Specialitiy

 




 


Oncology


 

 




  • Fertility
    Drugs and the Risk of Breast Cancer

    E
    Ricci, et al (Instituto di Richerche Farmacologiche
    ” Mario Negri,’ Milan, Italy; Universita degli
    Studi di Milano, Italy)

    Hum Reprod  14:
    1653-1655, 1999.


       

    Use of
    fertility drugs does not increase the risk of breast
    cancer.  These
    findings are consistent with the results of most, though
    not all, previous studies.

        

  • Fertility Drugs and the Risk of
    Breast and Ovarian Cancers : Results of a Long-term
    Follow-up Study
    .

    G Potashnik, et al (Ben-Gurion Univ of Negev, Beer Sheva,
    Israel;  Sheba
    Med Ctr, Tel Hashomer, Israel).

    Fertile Steril 71:853-859, 1999.

       

    The
    relationship between fertility drug use and the risk of
    breast and ovarian cancers has not been defined. 
    A historic-prospective cohort study was
    undertaken to investigate this association.

        

    Conclusions-
    The use of fertility drugs appears to be unassociated
    with an increased risk of breast cancer. 
    Women treated with human menopausal 
    gonadotropin alone had no malignant tumors. 
    These findings should be considered in light of
    the recent suggestion that clomiphene citrate may
    decrease the risk of breast cancer in infertile women.

       

    Editorial
    comment:

    The data from this long-term prospective study indicate
    that the use of ovulation-inducing agents is not
    associated with an increased risk of either breast or
    ovarian cancer.  Many
    women are concerned that the use of these agents may
    increase their risk of having these cancers. 
    Data accumulating from this and other studies
    indicate that such a relation does not exist.

       

  • MA
    Cobleigh, et al (Rush-Presbyterian-St Luke’s Med Ctr,
    Chicago)  

    Hormone Replacement Therapy and High S Phase in Breast Cancer

    JAMA 281: 1528-1530, 1999.

       

    Conclusion
    – Pre-existing clinically occult cancers may be promoted
    by the use of hormone replacement therapy, which may
    bring them to light sooner in their natural biological
    history.  This
    may account for the better survival of patients with
    breast cancer who have used hormone replacement therapy. 
    The use of hormone replacement therapy appears to
    stimulate growth of estrogen receptor-positive but not
    estrogen receptor-negative breast cancer. 
    There is an unknown prognostic significance in
    current hormone replacement therapy users who have
    estrogen receptor-positive tumors.

       

    Editorial
    comments:

    Some, but not all, observational epidemiologic studies
    indicate that the postmenopausal use of estrogen
    replacement is associated with an increased risk of
    diagnosis of breast cancer compared with women not
    taking estrogen.  Several
    studies have reported that survival rates of women in
    whom breast cancer develops postmenopausally is
    significantly greater among women taking estrogen than
    among age-matched controls with breast cancer who are
    not taking estrogen.

        

    Breast cancer with a high percentage of breast cells in S phase
    has been associated with a poor prognosis of the
    disease.  This
    study found that estrogen use was associated with a high
    frequency of S-phase cells in the treated breast
    cancers.  Since
    estrogen use is associated with a better prognosis for
    women with breast cancer, the authors speculate that
    estrogen may promote the growth of clinically occult
    cancers. These
    cancers are then treated earlier in their natural
    history than normally occurs, and survival rates are
    increased.  Thus
    estrogen does not initiate breast cancer but promotes
    the growth of an existing cancer so that it can be
    diagnosed and treated earlier in its natural history.

         

  • A
    Rosset, L Zografos, P Coucke, et al (Centre Hospitalier
    Universitaire Vaudois, Lausanne, Switzerland; Univ of
    Lausanne, Switzerland)


    Radiotherapy
    of Choroidal Metastases
    .

    Radiother Oncol 46:263-268, 1998.

        

    This
    is a review of the records of 58 consecutive patients
    undergoing external beam radiation therapy between 1970
    and 1993.  Patient
    ages ranged from 40 to 81 years.
    The primary tumor was breast carcinoma in 75%,
    lung carcinoma in 17%, gastrointestinal, gastrourinary,
    or unknown in the remainder.
    The median interval between the primary tumour
    and metastases was 55 months.
    Treatment consisted of megavoltage irradiation
    with a median prescribed dose of 35.5 Gy.

      

    Complete
    response rate at 3 months or more after Rx was 53%.
    In 62% of patients, visual acuity was improved or
    stabilized.  There
    were 5 complications: 3 cataracts, one retinopathy and
    one glaucoma.

        

    Doses
    greater than 35.5 Gy 
    provide significantly better tumor response and
    visual acuity. Whenever
    possible, a lens sparing technique should be used.

          

  • R
    Indudharan, T Arni, KK Myint, et al (Universiti Sains
    Malaysia, Kelantan; Hosp Tengku Ampuan Afzan, Kuantan,
    Malaysia)


    Lymphoblastic
    Lymphoma/Leukemia Presenting as Perichondritis of the
    Pinna.

    J Laryngol Otol 112: 592-594, 1998

      

    A
    patient treated for perichondritis of the pinna was
    eventually determined to have B-lineage lymphoblastic
    lymphoma evolving to a leukemic phase.
    There was no pre-existing immunodeficiency.

      

    Though
    lymphoma is the second most common malignancy of the
    head and neck region, the pinna as the extranodal site
    of lymphoma, has been previously reported only once.
    Hence the need to broaden one’s diagnostic
    horizon when inflammatory lesions do not heal within a
    reasonable period.

        

  • RC
    O’Reilly, SB Kapadia,  D.B. Kamerer (Univ of Pittsburgh, Pa)


    Primary
    Extracranial Meningioma of the Temporal Bone.

    Otolaryngol
    Head Neck Surg  118:690-694,
    1998.

       

    Though
    meningiomas typically occur intracranially, they may
    rarely arise de novo in the temporal bone.
    Because of the invasive nature of this tumor,
    surgical resection is difficult, and postoperative
    surveillance is necessary.

         

  • HM
    Dunniway, DB Welling (Ohio State Univ, Columbus)


    Intracranial
    Tumors Mimicking Benign Paroxysmal Positional Vertigo.

    Otolaryngol Head Neck Surg, 118:429-436, 1998.

       

    Benign positional vertigo may not always be benign,
    as indicated in this study where intracranial tumors
    were identified in five patients who presented as “
    benign paroxysmal vertigo.”

        

    When
    patients of “benign paroxysmal vertigo” do not
    improve after particle repositioning manoeuver, further
    assessment is needed to rule out intracranial new
    growths.

       

  • DW Cramer, RF Liberman, et al (Brigham and Women’s Hosp, Boston; Dartmouth-Hitchcock Med Ctr, Lebanon, NH)


    Genital Talc Exposure and Risk of Ovarian Cancer.



    Int J Cancer 81: 351-356, 1999.


      


    The group consisted of 563 women in eastern Massachusetts and New Hampshire with epithelial ovarian cancer, including tumors of borderline malignancy. With a control group of 523 randomly selected women.

      


    Findings: Patients were more likely than controls to have used talc as a body powder. Exposure appeared to be more harmful before the first live birth. The association was strongest for women with invasive serous cancers and weakest for those with mucinous tumors.

      


    Conclusions: This large population based case control study has demonstrated an association between the use of talcum powder in the genital region and ovarian cancer. Avoidance of talc in genital hygiene might reduce the occurrence of a highly lethal cancer by at least 10%. Formal public health warnings should be provided about the potential risk associated with the use of talcum powder in the genital region.

         

  • BY
    Karlan, RL Baldwin,. Et al (Univ of California, Los Angeles; Univ of Toronto)t


    Peritoneal Serous Papillary Carcinoma, a Phenotypic Variant of Familial Ovarian Cancer: Implications for Ovarian Cancer Screening.



    Am J Obstet gynecol 180: 917-928, 1999.


      


    During the administration of a familial ovarian cancer screening program that was begun in 1991 and based on the pedigrees of symptom-free volunteers, a disturbing number of “ovarian cancer” cases with bulky peritoneal carcinomatosis and normal-size ovaries, consistent with peritoneal serious papillary carcinoma were noted. These lesions may represent primary ovarian cancers that disseminated widely before ovarian enlargement or discrete tumors arising from multiple peritoneal surfaces predisposed to malignant transformation. These tumors’ clonality and association with BRCA1 and BRCA2 mutations were reported.

      


    It was found that those carrying BRCA mutations are at risk for both primary ovarian cancer and peritoneal serous papillary carcinoma. The latter is clearly not amenable to early detection by vaginal ultrasound screening. While prophylactic oophorectomy reduces the risk of these types of cancers by 50%, it, unfortunately, does not eliminate the risk.

        

  • A
    Obermair, A Handisurya, et al (Univ Hosp of Vienna; Gen Hosp Lainz, Vienna)


    The Relationship of Pretrement Serum Hemoglobin level to the Survival of Epithelial Ovarian Carcinoma Patients: A Prospective Review.



    Cancer 83: 726-731, 1998.


      


    In malignant solid tumors and a variety of hematologic malignancies, tumor anemia is common. There are no factors other than the malignant disease itself in a number of patients to explain the presence of anemia. Previous studies have shown a correlation between the prognosis in patients with a variety of malignancies and pretreatment hemoglobin levels. 

      


    This study comprises of 206 patients with untreated epithelial ovarian carcinoma who had surgery during a 10-year period. Serum hemoglobin value below 12g/dl was the definition of anemia.

      


    Authors conclude that overall survival of patients with ovarian carcinoma had an independent relationship with tumor anemia, after adjustment for established prognostic factors. Marked tumor anemia was considered an indicator of the presence of biologically aggressive tumor cell clones because no significant interaction could be found between the grade of anemia and chemotherapy.

       

  • JA Bridgewater, AE Nelstrop, et al (Mount Vernon Centre for Cancer Treatment, Northwood, England; Royal Marsden Hosp, London; Univ of Mississipi, Jackson; et al)


    Comparison of Standard and CA-125 Response Criteria in Patients With Epithelial Ovarian Cancer Treated with Platinum or
    Paclitaxel.



    J Clin Oncol 17: 501-508, 1999


       


    Background: The role of CA-125 in the assessment of patients undergoing second-line treatment with taxanes has been questioned. Some authorities doubt the reliability of CA-125 in the management of individual patients, and some have concluded that CA-125 cannot be used as a guide for determining response. CA-125 was evaluated as a measure of response in patients treated with paclitaxel.

      


    Methods: Data on 144 patients given paclitaxel in 4 different trials and 625 patients given platinum in 2 trials were analzyed, using precisely defined 50% and 75% reductions in CA-125 as responses. Standard and CA-125 response rates were compared.

      


    Conclusion: Precise 50% or 75% CA-125 response criteria are as sensitive as standard response criteria in evaluating treatment activity in patients with ovarian cancer. The standard measurement of complete response means disappearance of all disease or partial response more than 50% decrease.

      


    Though it is true CA-125 reduction 50-75% can be relied upon as response to the treatment of cancer with platinum or paclitaxel, the opposite does not hold true i.e. there can be disease response without a drop in CA-125.

       

  • M
    Markman, MF Brady, et al (Cleveland Clinic Found, Ohio; Roswell Park Cancer Inst., Buffalo, NY; Women’s Cancer Ctr of Northern California, Palo Alto; et al)


    Phase II Trial of Intraperitoneal Paclitaxel in Carcinoma of the Ovary, tube, and Peritoneum: A Gynecologic Oncology Group Study.



    J Clin Oncol 16: 2620-2624, 1998.




    Methods: Seventy-six eligible patients were enrolled in the trial. Eight-six percent were considered potentially cisplatin sensitive. In all patients, the largest residual disease was 0.5cmor less in maximum diameter at the end of second-look surgery. Some patients had been treated with paclitaxel previously. Treatment consisted of paclitaxel, 60mg/m2 intraperitoneal weekly for 16 weeks, followed by surgical assessment in patients with no evidence of disease progression.

      


    Findings : Fifty-three patients (70%) received all 16 planned treatment courses. Treatment was well tolerated. Microscopic disease at the beginning of intraperitoneal therapy had a complete response as defined by surgery.

      


    Authors conclude salvage intraperitoneal paclitaxel is active and tolerable in patients with microscopic residual ovarian, fallopian tube, or peritoneal cancer. The effect of such treatment on survival needs to be determined in a phase III trial.

      


    Editorial comment: Intraperitoneal therapy has yet to be shown an effective second-line treatment for most patients.

       

  • HD
    Homesley, BN Bundy, et al (Brookview Research Inc, Winston-Salem, NC; Roswell Park Cancer Inst, Buffalo, NY; Indiana Univ, Indianapolis)


    Bleomycin, Etoposide, and Cisplatin Combination Therapy of Ovarian Granulosa Cell Tumors and Other Stromal Malignancies: A Gynecologic Oncology Group Study.



    Gynecol Oncol 72: 131-137, 1999.


       


    Granulosa cell tumors represent about 8% of ovarian neoplasms and are more common in older women. These women usually present with early-stage disease. Patients with stage I tumors are usually treated with surgery, but those with advanced-stage tumors require adjunctive therapy. The efficacy and toxicity of a combination of bleomycin, etoposide, and cisplatin (BEP) as a first-line treatment for advanced or recurrent ovarian stromal cancers was investigated in a prospective trial.

      


    The study group consisted of 57 women with histologically confirmed stage II to IV or recurrent ovarian stromal tumors that had been incompletely resected. The patients were treated with BEP. 20 U/m2 on the day 1, etoposide 75mg/m2 from day 1 to day 5 and cisplatinum 20mg/m2 from day 1 to day 5 every 3 weeks for 4 courses.

      


    Findings: Of the 38 women who had second-look laparotomy at the end of the BEP treatment, 37% had negative findings. Grade 4 myelotoxicity occurred in 61% of the patients treated with the BEP.

      


    Authors conclude that BEP combination appears to be an effective first-line chemotherapy for advanced and recurrent ovarian stromal cancers.


  • Alam MDS, Kasagi K, Misaki T, et al [Kyoto Univ, Japan]

    Diagnostic Value of Technetium -99m Methoxyisobutyl Isonitrile [ 99m Tc-MIBI] Scintigraphy in Detecting Thyroid Cancer Metastases: A Critical Evaluation

    Thyroid 8: 1091-1100, 1998, Pg.215



    Many investigators consider that technetium – 99 methoxyisobutyl isonitrile [ 99m Tc-MIBI] scintigraphy should be used as a supplement to performing radioactive iodine whole-body scanning [ 131 I-WBS] and measuring serum thyroglobulin [Tg] levels in the detection of thyroid cancer metastases. 



    99m Tc-MIBI scintigraphy can be recommened as a first-line choice for detecting metastases in-patients with thyroid cancer. Its advantages over 131 I scintigraphy include better sensitivity in patients with remnant thyroid tissues, no need to restrict dietary iodide intake, and no need to discontinue exogenous thyroid hormones.



    Its shortcoming appears to be in imaging patients with small multiple lung metastases, in which case its sensitivity is similar to that of plain radiography.



       

  • Gelmon Karen – British Columbia Cancer Agency, Vancouver, British Columbia V5Z 4E6, Canada 

    ONE STEP FORWARD OR ONE STEP BACK WITH TAMOXIFEN?


    The Lancet,[ Vol 356], Number 9233, 9 September,2000, Pg. No 868.


      


    It is well recognized that tamoxifen is the drug of choice for treatment of breast cancer patients, both pre-menopausal and post- menopausal. It is also given in both localised and metastatic breast cancers. The only adverse reaction of tamoxifen is increased chances of endometrial cancer. The longer tamoxifen treatment, the greater is the chance of endometrial cancer. More importantly, endometrial cancer in patients who are receiving tamoxifen are more serious than in tamoxifen non users. 

      


    It becomes important to note that endometrial cancer occurs as a long term adverse effect. Therefore, prophylactic use of tamoxifen in persons, who do not have breast cancer should not be taken lightly. 

        

  • Franceschi Silvia, Munoz Nubia, Snijders J F – Unit of Field and Intervention Studies, International Agency for Research on Cancer, F-69372 Lyon Cedex 08, France : and Department of Pathology, Free University Hospital, Amsterdam, Netherlands


    How Strong and How wide is the Link Between Human Papillomavirus [HPV] and Oropharyngeal Cancer



    The Lancet,[ Vol  356], Number 9233, 9 September,2000,


      

    Human Papillomavirus [HPV] has now been established as an important cause of cancer cervix both squamous cell carcinoma and adenocarcinoma. It has now been shown that HPV-16 is commonly found in patients with cancer of the tonsils. Tonsils are situated between external and internal environment of the body, similar to cervix uterus and the etiology may be similar.

        

  • Caelyx approved in EC for cancer


    SCRIP No.2588, November 1st, 2000, pg.22


      


    Pegylated liposomal doxorubicin (Caelyx) also known as Doxil has been approved in the EC for ovarian cancer. It is administered intravenously once every 4 weeks. Although there have been concerns that results of clinical trials submitted to US NDA (FDA) were not very meaningful, there are no alternative advanced treatment options for ovarian cancer and the FDA advisory panel decided that the product may be useful.

       

  • GA Chung-Faye, DJ Kerr


    ABC of colorectal cancer Innovative treatment for colon cancer



    BMJ Vol.321, 2 December, 2001, pg.1397.


       


    Cancer of the colon is notorious for poor response to chemotherapy. However some new findings may be of interest. It has been postulated that colorectal cancer can be benefited by the use of NSAID in addition to their usual anticancer drugs. Although aspirin did not show any benefit in a clinical trial after 5 years of use, it has been suggested that a 10-year follow-up may be needed to show any significant effect. The only danger is G.I. bleeding which has to be weighed against any possible benefit in reduction of cancer mortality.

      


    Many immunological technologies have been used to augment the effect of anticancer drugs. The only proven drug is Levamisole in Duke-C colon cancer.

      


    Gene therapy is still at a very early stage. Crucial feature is the transfer of the gene, but the situation may improve with more effective gene transfer by using viruses.

       

  • All-trans retinoic acid
    (ATRA)

    AK Burnett, for the MRC Adult Leukaemia Working Party (Univ of Wales, Cardiff)


    Presenting White Blood Cell Count and Kinetics of Molecular Remission Predict Prognosis in Acute Promyelocytic Leukemia Treated With All Trans Retinoic Acid: Results of the Randomized MRC Trial.



    Blood 93: 4131-4143, 1999.


      


    Patients with acute promyelocytic leukaemia with low white blood cells count are treated by chemotherapy with reasonably good results. Combining ATRA with chemotherapy until complete remission, improves the prognosis. This benefit is seen only in patients with low white blood cell count. Patients with high blood cell count did not benefit from
    ATRA.

       

  • V
    Franciosi, G Cocconi, M Michiara, et al (Azienda Ospedaliera di Parma, Italy; et al)

    Front-Line Chemotherapy with Cisplatin and Etoposide for Patients with Brain Metastases from Breast Carcinoma,
    Non-small Cell Lung Carcinoma, or Malignant Melanoma: A Prospective Study.



    Cancer 85: 1599-1605, 1999.


       


    Previous studies have shown that combination of cisplatin and etoposide is highly active in patients with brain metastases from breast cancer. The rate of response was almost 40% in patients with metastasis in brain from breast cancer and 30% in brain metastasis from lung cancer. A very large percentage of brain metastasis in patients with breast cancer had a complete response radiologically and 7% with lung cancer also had this excellent response. However, brain metastases from melanoma did not respond to this chemotherapy

       

  • WJ
    Catalona, AW Partin, KM Slawin, et al (Washington Univ, St. Louis, Mo; Johns Hopkins Hosp, Baltimore Md; Baylor College of Medicine, Houston; et al) 

    Use of the Percentage of Free Prostate-specific Antigen to Enhance Differentiation of Prostate Cancer from Benign Prostatic Disease: A Prospective Multicenter Clinical Trial. 


    JAMA 279: 1542-1547, 1998.


       


    Free PSA percentage is a significant predictor of prostate cancer, with a sensitivity of 95% below a cutoff of 25%. Patients with prostate cancer and free PSA levels about the cutoff had less aggressive disease. Percentage of free PSA is an independent predictor of prostate cancer.

        

  • Katz D, Rothstein R, Schned A, et al [VA Med Ctr, White River Junction, Vt; Univ of Wisconsin, Madison; Dartmouth Hitchcock Med Ctr, Lebanon, NH; et al]

    The Development of Dysplasia and Adenocarcinoma During Endoscopic Surveillance of Barrett’s Esophagus 

    Am J Gastroenterol 93: 536-541, 1998, Pg. 224



    Most esophageal adenocarcinomas probably arise from premalignant Barett’s esophagus. Dysplasia is the best available indicator of malignant potential in Barrett’s epithelium. 



    Most of the patients suffer dyspepsia there were no cases of dysplasia among patients who had undergone antireflux surgery. High grade dysplasia and edenocarcinoma took more than two years to develop. Antireflux surgery may have a protective effect against progression to dysplasia. 

       

  • Walsh
    TJ, for the National Institute of Allergy and Infectious
    Diseases Mycoses Study Group [ Natl Cancer Inst,
    Bethesda, Md; et al]


    Liposomal Amphotericin B for
    Empirical Therapy in Patients with Persistent Fever and
    Neutropenia

    N
    Engl J Med 340: 764-771, 1999

      

    Patients
    with persistent neutropenia and fever require
    amphotericin B as empirical therapy. This study compared
    liposomal amphotericin B to conventional amphotericin B
    in such a patients cohort
    liposomal amphotericin B was as effective as
    conventional. However
    it was associated with fewer, fever breakthrough fungal
    infections, less infusion related toxicity, and less
    nephrotoxicity.

         


  • Dimeo
    FC, Stieglitz R-D, Novelli-Fischer U, et al [Freiburg
    Univ, Germany]


    Effects of Physical Activity on
    the Fatigue and Psychologic Status of Cancer Patients
    During Chemotherapy

    Cancer
    85: 2273-2277, 1999

       

    Loss
    of physical performance and fatigue are common problems
    for patients undergoing chemotherapy.

      

    This
    study compared patients receiving high dose chemotherapy
    followed by autologous peripheral blood stem cell
    transplant to exercise intervention or control. Those
    who exercised had decrease fatigue and improved
    psychological distress.

          

  • Sneed
    PK, Stauffer PR, McDermott MW, et al [Univ of
    California, San Francisco]


    Survival Benefit of
    Hyperthermia in a Prospective Randomized Trial of
    Brachytherapy Boost + Hyperthermia for
    Glioblastoma Multiforme

    Int
    J Radiat Oncol Biol Phys 40: 287-295, 1998

      

    Glioblastomas
    an aggressive brain tumor has median survival of about
    12 month radiation therapy and an additional
    brachytherapy boost to provide a high focal dose have
    been used earlier.

      

    This study of patient with supratentorial glioblastoma
    were assigned to radiotherapy bracytherapy and then with
    or without hyperthermia.

      

    Time
    to progression and survival were significantly longer in
    hyperthermic than non-hyperthermic group.

           

  • C.M.
    Malata, S.A. McIntosh and A.D. Purushotham [ Departments
    of Reconstructive and – General Surgery, Cambridge
    Breast Unit, Addenbrook’s Hospital, Cambridge, UK ]


    ImmediateBreast Reconstruction After
    Mastectomy for Cancer


    Br.
    Jour. of  Sur.
    Volume 87, No.11, November 2000, Pgs- 1455-1472


      

    Immediate
    breast reconstruction after mastectomy has increased
    over the past decade following unequivocal demonstration
    of its oncological safety and the availability of
    reliable methods of reconstruction. Broadly, it is
    undertaken in the treatment of breast cancer after
    prophylactic mastectomy in high-risk patients and in the
    management of treatment failure after breast conserving
    surgery and radiotherapy.

      

    Breast
    reconstruction can be 
    achieved reliably with a variety of techniques :-


      

    1. 
    Prosthetic Devices – Implants, classical expander
    implants or adjustable implants.

    2. 
    Autogenous
    Tissue Reconstruction – Transverse
    rectus abdominis myocutaneous flap [various types]

        
    Free 
    deep inferior epigastric perforator flap
    latissimus dorsi musculocutaneous flap.

    3. 
    Other
    autogenous tissue Techniques – Superior and inferior
    gluteal free flap, gluteal
    perforator free flap, lateral

         transverse thigh flap,
    Taylor-Rubens peri-iliac free flap

      

      Careful
    discussion and evaluation remains vital in choosing the
    correct technique for the individual patient.

     


    The
    aesthetic considerations [comparison with opposite
    breast] and psychological consideration must be looked
    into.

       

  • J.L.
    Poggio, D.M. Nagorney, A.G. Nascimento, C. Rowland,
    P.Kay, R.M. Young and J.H. Donohue [ Department of
    Surgery, Section of Anatomic Pathology and Section of
    Biostatistics, Mayo Clinic, 200 First Street, SW,
    Rochester, Minnesota 55905, USA

    Surgical Treatment of Adult Primary Hepatic Sarcoma

    Br.
    Jour. of  Sur.
    Volume 87, No.11, November 2000, Pgs- 1500-1505


     

    Primary
    sarcomas of the liver are extremely rare in adults.
    Optimal therapeutic approaches remain unclear.

     

    Twenty
    consecutive adults who are operated for hepatic sarcomas
    were reviewed. The ages ranged between 23 to 80 years.
    No predisposing causes could be found except in one who
    had a history of thorotrast exposure 23 years ago.

     

    19
    patients had hepatic resection and one patient had an
    orthotopic liver transplant. No patient was given
    neo-adjuvant chemotherapy but one patient had
    intra-operative radiotherapy.

      

    Leiomyosarcoma
    was the most common histologic carcinoma [ 5 out of 20]
    followed by malignant solitary fibrous tumour [4 cases]
    and epithelioid haemagioendothelioma [ 3 cases]. 14
    tumours were high grade sarcomas whereas 6 were low
    grade malignancies.

      

    Three
    patients developed local recurrences while 10 patients
    developed metastases and intrahepatic recurrence in 6
    patients were the predominant sites of initial treatment
    failure.

      

    Six
    patients received salvage chemotherapy.
    Histological grading was the only factor
    significantly associated with patient survival [ p=03].

      

    With
    complete resection, patient with high grade tumours had
    a 5 year survival rate of 18% compared with 80% for
    patients with low grade tumours. Overall survival rate
    was 37%.

     

    Surgical
    resection is the only effective therapy for primary
    hepatic sarcoma . Better adjuvant therapy is necessary
    for high grade malignancy owing to high failure rate
    with only surgery.

           

  • Goode
    RK, Auclair PL, et al (Armed Forces Inst of Pathology, Washington, DC: Natl Naval Dental Ctr, Washington, DC)

    Mucoepidermoid Carcinoma of the Major Salivary Glands: Clinical and Histopathologic Analysis of 234 Cases with Evaluation of Grading Criteria.

    Cancer 82: 1217-1224, 1998.

        

    High, intermediate and low grades have been reported. One study denotes the presence of cystic component of less than 10% is considered as high grade.

         

    In this study, 337 patients were analysed which included follow-up data. 84% were in parotid. 13% in submandibular gland and 3% in the sublingual gland. Four groups were formed Group I, survival free of disease. Group II, survival with local recurrence, Group III, survival with local metastases and Group IV, death of disease.

        

    This study identifies prognostic factors. Outcome varied significantly according to site and grade of the tumour. Metastases from submandibular glands were more frequent. The treatment should be based on clinical stage of the disease and histopathologic guide. Even low grade tumours in submandibular gland needs aggressive treatment and close follow-up

          

  • Laskawi R, Rodel R, et al (Univ of Gottingen, Germany)

    Retrospective Analysis of 35 Patients with Acinic Cell Carcinoma of the Parotid Gland.

    J OralMaxillofac Surg 56: 440-443, 1998.

        

    This is a rare tumour, occurs in late middle age commonly in females. Retrospectively studied because of its rarity. The study included 35 patients treated between 1945 and 1994. Surgery is the therapy of choice. The response to radiation is not favourable either to prevent recurrences or increase in survival period. The latter part is of particular interest in management.

         

  • Yang CY, Andersen PE, et al (Oregon Health Sciences Univ, Portland)

    Nodal Disease in Purely Glottic Carcinoma: Is Elective Neck Treatment Worthwhile?

    Laryngoscope 108: 1006-1008, 1998.

        

    All patients were included with glottic cancer between 1984 to 1994. Ninety-two patients were identified who had at least 2 yrs of follow-up for T stage, cord mobility, CT scan, nodal disease, lesion extension, treatment modality and tumour pathology. Recurrences were reviewed.

         

    Occult nodal disease with NO glottic carcinoma was low with 0% incidence in T1 and T2 stage disease and 19% in T3 and T4 stage disease. Only paratracheal level II and III nodes were at high risk. Therefore, elective neck dissection should be performed for advanced disease in case with low morbidity. CT scanning was not useful for staging in these patients.

         

  • Asakage T, Yokose T, Mukai K, et al (Natl Cancer Ctr Hosp East, Chiba, Japan; Tohoku Univ, Miyagi, Japan)

    Tumor Thickness Predicts Cervical Metastasis in Patients with State I/II Carcinoma of the Tongue.

    Cancer 82: 1443-1448, 1998

         

    The retrospective study included 44 patients with previously untreated stage I/II carcinoma of tongue involving the anterior two thirds of the tongues. They were treated by partial glossectomy only. Twenty-one patients had cervical metastasis and 23 were without. Tumour thickness and other variables were compared.

         

    Tumour thickness more than 4mm thickness are at higher risk of cervical metastases and were regarded as having latent metastasis. Conservative supramyohyoid neck dissection, as performed for T1N1 or T2N1 carcinoma of the tongue may be suitable.

         

    This article confirms depth of invasion in more predictive of cervical metastasis than T classification. Spiro et al suggested this even for 2mm thickness and more.

         

  • Cruz
    IB, Snijders PJF, Meijer CJ, et al (Univ Hosp Vrije Universiteit, Amsterdam; Academic Centre for Dentistry, Amsterdam)

    p53 Expression above the Basal Cell layer in Oral Mucosa is an Early Event of Malignant Transformation and Has Predictive Value for Developing Oral Squamous Cell Carcinoma.

    J Pathol 184: 360-368, 1998.

        

    Majority of oral squamous cell carcinoma have mutations in the oncogene p53.

         

    To determine the relationship, immunohistochemical staining was performed on 11 premalignant lesions in which carcinoma developed. Therefore, p53 expression appears on early event in the carcinogenesis of premalignant lesions. 

          

    This combined with histologic criteria of dysplasia is danger sign. If more continued studies demonstrate this, it will be of great value in the management of patients with dysplastic biopsy specimens.

        

  • Concomitant Radiotherapy with Mitomycin C and Bleomycin Compared with Radiotherapy Alone in Inoperable Head and Neck Cancer: Final Report.

    Int J Radiat Zakotnik B, Smid L, Budihna M, et al (Inst of Oncology, Ljubljana, Slovenia: Univ Dept. of Otorhinolaryngology and Cervicofacial Surgery, Ljubljana, Slovenia)

    Oncol Biol Phys 41: 1121-1127, 1998.

       

    Sixty-four patients were randomly treated in 2 groups. One group received radiotherapy alone and other group received radiotherapy with concomitant above mentioned chemotherapy.

       

    Other group receiving radiotherapy with concomitant chemotherapy had significantly higher complete remission, disease free survival and better survival rates.

         

  • Forrest LA, Schuller DE, Karanfilov B, et al (Ohio State Univ, Columbus)

    Update on Intraoperative Analysis of Mandibular Margins

    Am J Otolaryngol 18: 396-399, 1997

        

    In 61 patients with involvement of alvelous, the study of serial frozen section biopsy of the cancellous bone at the mandibular stump demonstrated 100% corelation, and thus the extent of resection of the mandibule could be decided accordingly.

         

    This article provides some evidence of the effectiveness of this technique in assessing resection.

        

  • De Stefani E, Boffetta P, Oreggia F, et al (Registro Nacional de Cancer, Montevideo Uruguay; Inernatl Agency for Research on Cancer, Lyon, France; Academia Nacional de Medicina, Montevideo, Uruguay, et al).

    Smoking Patterns and Cancer of the Oral Cavity and Pharynx: A Case-Control Study in Uruguay.

    Oral Oncol, Eur J Cancer 34: 340-346, 1998.

         

    Four hundred and twenty-five men with confirmed lesions and 427 hospitalized controls were studied.

         

    Smoking black tobacco cigarettes seems significant in oral and pharyngeal carcinogenesis. Risk was decreased with filter use and cessation of smoking. Black tobacco contained high tobacco-specific nitrosamines. A high tar content was noted in hand-rolled cigarettes thus combination has more risk of oral cancer.

        

    This interesting article can help physicians counseling their patients – particularly impact of tobacco type and use of filtered cigarettes.

        

  • Colletier
    PJ, Garden AS, Morrison WH, et al (Univ of Texas, Houston)

    Postoperative Radiation for Squamous Cell Carcinoma Metastatic to Cervical Lymph Nodes from an Unknown Primary Site: Outcomes and Patterns of Failure.

    Head Neck 20: 674-681, 1998.

         

    Out of 136 patients with cervical metastasis from unknown primary sites, 39 patients underwent excisional biopsy and rest of them various types of neck dissection. All received radiotherapy subsequently. 58 months follow-up was done.

        

    Excisional biopsy and radiotherapy offers excellent disease control and survival rates. Those with ECE (extracapsular extension) and multiple nodal involvement the results are not as good. Radiation should start within 3 to 4 weeks and should be of full required dose.

          

    Excisional biopsy did not have any reduction in disease control or survival rates. However, it should not be an argument in all cases. Detrimental effects of ECE and multiple nodal involvement is confirmed by this study further. R.A. Otto.

          

  • Simon D, Koehrle J, Reiners C, et al (Heinrich-Heine-Univ, Dusseldorf, Germany; Unvi of Wurzburg, Germany; Univ of Essen, Germany)

    Redifferentiation Therapy with Retinoids: Therapeutic Option for Advanced Follicular and Papillary Thyroid Carcinoma.

    World J Surg 22: 569-574, 1998.

           

    About 33% of differentiated thyroid carcinoma (DTC) show loss of differentiation during progression of disease and then become refractory to standard treatment.

        

    Retinoid treatment (13-cis-retinoic acid) reduces tumour growth and reinduces iodide uptake suggesting that redifferentiation in cancerous growth in (DTC). This is not so in on anaplastic cancer.

        

    A 65% response rate was shown among patients of advance DTC. Thyroglobulin levels always do not accompany this response. Therapy is well tolerated with few side effects. No conclusions as the survival rates have been drawn.

      

    This study has offered a ray of hope in the management of advanced DTC patients and further studies may offer better hopes. R.A. Otto.

         

  • Gimm O, Ukkat J, Dralle H (Martin-Luther-Univ Halle-Wittenberg, Germany)

    Determinative Factors of Biochemical Cure After Primary and Reoperative Surgery for Sporadic Medullary Thyroid Carcinoma.

    World J Surg 22: 562-568, 1998.

        

    Twenty-seven patients underwent total thyroidectomy and compartment based microdissection of nodes. Thirty-seven patients with continuously elevated serum calcitonin levels underwent 4-compartment lymphodectomy at reoperation.

        

    The report of 100% normalizaiton in serum of calcitonin levels in node negative and pT1 patients is notable. Postoperative calcitonic level is powerful prognostic factor. However, it is not clear whether the patients who are biochemically cured have better outcome. By correlating tumour size with the presence and location of lymph node metastasis, this study provides useful guidelines for the extent of nodal dissection necessary at the time of primary operation of Medullary Thyroid Carcinoma. R.A. Otto.

          

  • Dralle H, Gimm O, Simon D, et al (Martin-Luther-Universitat Halle-Wittenberg, Germany; Heinrich-Heine Universitat, Dusseldorf, Germany; Gemeinschaftspraxis Innere Medizin-Endokrinologie, Heildelberg, Germany; et al)

    Prophylactic Thyroidectomy in 75 Children and Adolescents with Hereditary Medullary Thyroid Carcinoma: German and Austrian Experience.

    World J Surg 22: 744-751, 1998.

         

    In 1993, the RET proto-oncogene was identified as responsible for hereditary medullary thyroid carcinoma (MTC), since then patients with MTC based genetic screening have achieved biochemical cure by undergoing prophylactic thyroidectomy which prevents MTC and lymph node metastasis from developing.

          

    – A major breakthrough in the diagnosis and treatment with identification of this genetic defect in thyroid tumours. Biochemical estimation of serum calcitonin to screen in no longer required. 

           

    These authors provide a sensible algorithm for management of these patients. The achievement in 96% patients of a biochemical cure is remarkable. Time will tell if biochemically curing these patients is superior. R.A. Otto.

           

  • Nilsson O, Lindeberg J, Zedenius J, et al (Karolinska Hosp, Stockholm; Lund Univ Hosp, Sweden; Uppsala Univ Hosp, Sweden)

    Anaplastic Giant Cell Carcinoma of the Thyroid Gland: Treatment and Survival Over a 25-Year Period.

    World J Surg 22: 725-730, 1998.

         

    Between 1930 and 1970, 50% of patients with ATC died within 3 months mainly by suffocation from the local tumour growth. Now only one similar death has occurred since 1989. Local tumour control has been achieved with debulking and pre and post operative doxorubicin and hyperfractionated accelerated radiotherapy.

                 

  • Patel PC, Pellitteri PK, Patel NM, et al (Penn State Geisinger Health System, Danville,Pa)

    Use of a Rapid Intraoperative Parathyroid Hormone Assay in the Surgical Management of Parathyroid Disease.

    Arch Otolaryngol Head Neck Surg 124: 559-562, 1998.

     

    During parathyroid surgery patients underwent neck exploration and the parathyroid hormone assay is done by preremoval of parathyroids and postremoval during operative procedure, thus guiding whether enough functioning of parathyroid tissue is removed. If adenoma is suspected then preoperative 99mTc-sestamibi scanning was used to localize.

           

    Thus combination of preoperative scanning and intraoperative parathyroid hormone assay can guide unilateral exploration of neck.

           

  • Dhingra
    JK, Zhang X, McMillan K, et al (Tufts Univ, Boston; Lahey Clinic Med Ctr, Burlington, Mass; Massachusetts Inst of Technology, Cambridge)

    Diagnosis of Head and Neck Precancerous Lesions in an Animal Model Using Fluorescence Spectroscopy.

    Laryngoscope 108: 471-475, 1998.

         

    This animal experiment using laser induced fluorescence spectroscopy demonstrated the utility in the diagnosis of premalignant lesions like leukoplakia or erythroplakia and histologically as metaplasia and dysplasia. 

         

    If this technique could be used to enhance over clinical skills (60%-80% reliability) such a tool could be very useful. G.R. Holt

        

  • London SD, Park SS, Gampper TJ, et al (Univ of Virginia, Charlottesville)

    Hyperbaric Oxygen for the Management of Radionecrosis of Bone and Cartilage.

    Laryngoscope 108: 1291-1296, 1998.

         

    Sixteen patients included in this study suggests good results with HBO therapy for the management of radionecrosis of the head and neck. Subjective and objective outcomes improved greatly.

           

    HBO therapy has become an important portion of the equation in the prevention and treatment of osteoradionecrosis and chondroradionecrosis.

             

  • F
    Fugt, MP Varyas, Z Zhaung, et al (NIH, Bethesda, Md)

    Utilisation
    of Molecular Genetics in the differentiation Between
    Adrenal cortical Adenomas and Carcinomas.

    Hum
    Pathol 28: 518-521, 1998.

     

    Background
    : With current advanced radiological techniques, small
    adrenal cortical lesions may be identified that are
    prone to misidentification.

     

    Methods
    : Specific areas of each histologic slide were
    microdissected and subjected to polymerase chain
    reaction (PCR)for loss of heterozygosity (LOH) of 5
    different tumor suppressor gene loci as follow

      

    1.                 
    P53 gene at chromosome  17p,

     

    2.                 
    P16 gene at chromosome 9p

     

    3.                 
    The neuroblastoma gene at 1p

     

    4.                 
    Von Hippel Lindav gene at chrom. 3p

     

    5.                 
    Retinoblastoma gene at 13q

     

    Results:
    None of the hyperplasias or adenomas showed LOH.

     

    -
    61% of adrenocortical carcinomas showed genetic
    alterations for at least 1 of the markers.

     

    LOH
    of P53 was seen in 44%

       

    1P
    was seen in 22%

        

    3P
    was seen in 22%

       

    9p
    was seen in 26%

        

    80%
    of informative cases showed LOH of the retinoblastoma
    gene.

       

    Conclusions
    : The most informative markers for adrenal malignancy
    are P53 and 13q.

         

  • H Miyake, H Nakamura, I Hara, et al (Kobe Univ;Japan; Kumamoto Univ, Japan) Multifocal Multifocal Renal Cell Carcinoma:
    Evidence for a Common Clonal Origin.

    Clin Cancer Res. 4: 2491, 1998.

        

    The controversy surrounding the use of Nephron sparing surgery for renal cell carcinoma has revolved around the observed 7% to 25% incidence of relatively small satellite tumors discovered at autopsy or upon careful examination of radical nephrectomy specimens from patients with clinically evident renal cell carcinoma.

         

    In this study, the authors studied 10 cases of renal cell carcinoma that were accompanied by smaller satellite tumors for LOH (Loss of Heterozygosity) at chromosome arms 3p, 6q, 8p, 9p, 9q and 14q. All tumors were less than 5cm. Primary and satellite lesions in 8 of 10 cases exhibited identical patterns of LOH.

        

    Similarity of LOH patterns in the main satellite tumors indicated that satellite tumors are the result of intrarenal metastasis rather than new separate primaries. In any series the satellite lesions are generally small and occurring within 2 cm of the index tumor. The satellite tumors measure 2-4mm. Many satellite lesions may be resected during a “radical partial nephrectomy” or may never reach the clinical horizon.

        

  • C.H.
    Yoo, S.H. Noh, D.W. Shin, S.H. Choi and J.S. Min [Department of Surgery, Yonsei University College of Medicine, 134 Shinchon-ku, 120-752, Seoul, Korea ]

    Recurrence Following Curative Resection for Gastric Carcinoma

    Br. J. of Sur., Volume 87, Number 2, February, 2000, Pg. 236-242



    The diagnosis and treatment of recurrent gastric carcinoma is difficult. This study was aimed at determining the risk factors for recurrence of gastric carcinoma and prognosis for these patients.

    508 cases of recurrent gastric carcinoma out of 2328 patients who underwent curative resection for gastric carcinoma were studied retrospectively by univariate and multivariate analysis.

       

    The mean time to recurrence was 21.8 months and peritoneal recurrence was the most common [45.9%]. Logistic regression analysis showed that serosal invasion and lymph node metastasis were risk factors for all recurrence and early recurrence [at 24 months or less]. In addition, independent risk factors involved in each recurrence pattern included younger age, infiltrative or diffuse type, undifferentiated tumour and total gastrectomy for peritoneal recurrence, older age and larger tumour size for disseminated haematogenous recurrence; and older age, larger tumour size, infiltrative or diffuse type, proximally located tumour and subtotal gastrectomy for locoregional recurrence. Other risk factors for early recurrence were infiltrative or diffuse type and total gastrectomy. 

       

    Re-operation for cure was possible in only 19 patients and the mean survival time after conservative treatment or palliative resection was less than 12 months.

       

    The risk factors can be predicted by the clinicopathological features of the primary tumour.

          

  • KS
    Hafez, AC Novick, BP Butler (Cleveland Clinic Foundation, Ohio)

    Management of Small Solitary Unilateral Renal Cell Carcinoma: Impact of Central Versus Peripheral Tumor Location.

    J. Urol 159: 1156-1160, 1998.

      

    Conclusion : No significant biological differences are evident between central and peripheral small solitary unilateral renal cell carcinomas.

      

    Nephron sparing surgery was technically more complicated among central renal cell carcinomas.

       

    Intraoperative ultrasonography may be a more important adjunct when approaching patients with central tumors.

           

  • Yotsuyanagi T, Nihei Y, Yokoi K, et al (Hirosaki Univ, Japan)

    Functional Reconstruction Using a Depressor Anguli Oris Musculocutaneous Flap for Large Lower Lip Defects, Especially for Elderly Patients.

    Plast Reconstr Surg 103: 850-856, 1999

       

    The most common lesion of the malignant lesions of oral cavity is lower lip squamous carcinoma.

      

    In planning the reconstruction of large excision defect the following factors should be kept in mind.

       

    – Maintenance of sphineteric action.

    – Retention of sensation.

    – A large enough opening for the mouth.

    – Acceptable cosmetic appearance.

      

    In surgical technique described – Nerve supply and Blood supply is well preserved.

         

  • Franceschi S, Levi F, La Vecchia C, et al (Centro di Riferimento Oncologico, Aviano, Italy; Registre Vaudois de Tumeurs, Lausanne, Switzerland; Instituto di Ricerche Farmacologiche “M Negri”, Milano, Italy; et al )

    Comparison of the Effect of Smoking and Alcohol Drinking Between Oral and Pharyngeal Cancer

    Int J Cancer 83: 1-4, 1999

      

    The relationship of exposure to alcohol and tobacco is established. However, the separate and combined effects of alcohol and tobacco between oral and pharyngeal cancer were compared in case-control investigation.

      

    274 patients with oral cancer and 364 with pharyngeal cancer, 1254 controls matched were studied. 

       

    Observation-Conclusion – Alcohol has a stronger effect on oral cancer than on pharyngeal cancer. This may help explain why oral cancer mortaility is rising in men from many developing countries after many years of declining.

      

  • J Meiron Thomas and Erica J Patocskai 

    The argument against sentinel node biopsy for malignant melanoma

    Its use should be confined to patients in clinical trials

    BMJ, 1July 2000, p.3

      

    In recent years, there has been a tendency to perform sentinel node biopsy in patients with malignant melanoma. It has been seen that 88.5% of patients with negative sentinel node biopsy remained free of the disease for 3 years as compared to 55.8% of patients with positive biopsy. The survival rate in patients with negative sentinel node biopsy is 93% as compared to 67% in those with a positive biopsy. However, there is no clear-cut criteria to justify sentinel node biopsy. Some reasons forwarded are that firstly the sentinel node biopsy is cheaper than elective lymph node dissection. The second argument is that a sentinel node biopsy can be used to dissect patient for adjuvant therapy. Thirdly a sentinel node biopsy may be used in selecting patients for complete node dissection.

      

    At the moment, sentinel node biopsy is usually restricted to patients in clinical trials.

       

  • Aquino SL, Chiles C, Halford P [Wake Forest Univ, Winston-Salem, NC]

    Distinction of Consolidative Bronchioloalveolar Carcinoma From Pneumonia- Do CT Criteria Work?

    AJR 171: 359-363, 1998

       

    About 30% of bronchioalveolar carcinomas [BACs] are of the consolidative type. Certain chest CT findings are reportedly helpful in identifying pulmonary consolidation as BAC.

      

    In addition to consolidation, the review focused on features such as nodules and ground-glass opacities; cysts, or cavities within the consolidation. 

      

    In the BAC group, all patients had consolidation, more often with a peripheral distribution. 

      

    Findings that were present significantly more often in patients with consolidative BAC were coexisting nodules and a peripheral pattern of consoliation.

      

    Consolidative BAC should be suspected in adult patients with normal immunity who had a nonresolving peripheral consolidative pneumonia, particularly when associated nodules are present.

         

  • Valji AM, Maziak DE, Shamji FM, et al [Ottawa Civic Hosp, Ont, Canada]

    Postoneumonectomy Syndrome: Recognition and Management

    Chest 114: 1766-1769, 1998

       

    Postpneumonectomy syndrome [PPS] is caused by extreme shift and rotation of the mediastinum after pneumonectomy. It can produce
    symptomatic proximal airway obstruction and airway trapping.

      

    Clinical diagnosis of PPS was made with the aid of chest radiographs, 2-dimensional echocardiography, pulmonary function tests, CT scans, and awake fiberoptic bronchoscopy.

       

    After complete mobilization of the mediastinum, anterior pericardiorrhaphy was done before the pericardium was anchored in the parasternal chest wall with suture. A Silastic prothesis filled with saline solution was placed to correct overshifting of the mediastinum.

       

    The diagnosis of PPS should be considered in all patients with progressive dyspnea after pneumonectomy. Repositioning of the mediastinum by means of a prosthesis filled with saline solution and anterior pericardiorrhaphy is a simple procedure and offers immediate and lasting symptomatic relief.

        

        

  • Marcia Hall Gordon J.S. Rustin

    Testicular Tumour Management

    Recent Advances in Surgery, Number 22, Year-1999, Pg. 173

      

    Many risk factors promoting the development of Germ Cell Tumours [ GCT] have been identified, the best known and most consistent being a history of cryptorchidism.

     

    Most patients present with symptoms relating to the affected testicle [e.g. swelling, pain or aching] and occasionally symptoms and signs referable to metastatic disease [e.g. back pain from retroperitoneal nodes, dyspnoea from pulmonary/mediastinal disease] or, less commonly, hormone-related gynaecomastia.

     

    In the low risk stage 1 GCT, with no treatment other than initial orchidectomy, the mainstay of management is close follow-up with fortnightly markers and regular imaging for metastatic disease. Adjuvant therapy of two cycles of bleomycin, etoposide and cisplatin [BEP] is an acceptable and justifiable way of virtually eliminating the risk of relapse.

     

    Seminoma is exquisitely radiosensitive and characteristically spreads via the lymphatic system, treatment aimed at the retroperitoneal /para-aortic nodes significantly reduces the risk of relapse.

      

    BEP currently remains the standard treatment.

      

    In pure seminoma, residual masses can be safely observed on serial scans and most will shrink and calcify over time; a growing mass, however, would indicate recurrent disease requiring further treatment.

      

    Mature teratoma must be surgically removed before it enlarges locally and becomes inoperable.

      

    Chemotherapy – induced acute toxicities in the treatment of testicular GCT are mostly transient. Fertility is adversely affected by chemotherapy, it usually returns to normal. Concern has been raised about the possible carcinogenic effects of chemotherapy in the long-term. Etoposide is known to be leukaemogenic and secondary tumours have been reported following etoposide containing therapy for GCT.

      

    The treatment of GCT overall has not changed a great deal in the last 5 years, although there is a trend toward more frequent use of chemotherapy in the earlier stages.

      

    Surgical conundrum is the benefits o orchidopexy to prevent the development of GCT only orchidopexy done at a very young age can reduce risk.

         

  • lam MDS, Kasagi K, Misaki T, et al [Kyoto Univ, Japan]

    Diagnostic Value of Technetium -99m Methoxyisobutyl Isonitrile [ 99m Tc-MIBI] Scintigraphy in Detecting Thyroid Cancer Metastases: A Critical Evaluation

    Thyroid 8: 1091-1100, 1998, Pg.215

       

    Many investigators consider that technetium – 99 methoxyisobutyl isonitrile [ 99m Tc-MIBI] scintigraphy should be used as a supplement to performing radioactive iodine whole-body scanning [ 131 I-WBS] and measuring serum thyroglobulin [Tg] levels in the detection of thyroid cancer metastases. 

     

    99m Tc-MIBI scintigraphy can be recommened as a first-line choice for detecting metastases in-patients with thyroid cancer. Its advantages over 131 I scintigraphy include better sensitivity in patients with remnant thyroid tissues, no need to restrict dietary iodide intake, and no need to discontinue exogenous thyroid hormones.

     

    Its shortcoming appears to be in imaging patients with small multiple lung metastases, in which case its sensitivity is similar to that of plain radiography.

            

  • Veling MC, Windmill I, Bumpous JM [Univ of Louisville, Ky]

    Sudden Hearing Loss as a Presenting Manifestation of Leukemia

    Otolaryngol Head Neck Surg 120:954-956, 1999

      

    ¨ Sudden loss of hearing is a rare presenting symptom in blood disorders.

    ¨ Tinnitus may be present, but no vertigo, nystagmus or cranial nerve palsys.

    ¨ Effusion in middle ears with intact tympanic membrane is found.

    ¨ Bone marrow examination is a must to diagnose leukemia.

    ¨ Audiograms which showed initial bilateral loss of hearing improved after treatment of leukemia.

    ¨ Usually, leukemia causes deafness in terminal stages.

          

  • Yim JH,Wick MR, Philpott GW, et al [Washington Univ, St Louis]

    Underlying Pathology in Mammary Paget’s Disease

    Ann Surg Oncol 4: 287-292, 1997

       

    Mastectomy has been the standard treatment, but recent studies have recommended radiotherapy with no resection. All patients had histologically confirmed Paget’s disease; 92% of patients had underlying carcinoma, either ductal carcinoma in situ, invasive ductal cancer, or both. Mammography failed to detect the multifocal lesions in 64% of patients with no palpable mass. Patients with a palpable mass were significantly more likely to have invasive cancer, multifocal lesions, and positive lymph nodes. 

      

    Most patients with mammary Paget’s disease have underlying multifocal carcinoma, including invasive lesions. Therefore, mastectomy remains the standard treatment.

            

  • Coveney E, Weltz CR, Greengrass R, et al [Duke Univ, Durham, NC]

    Use of Paravertebral Block Anesthesia in the Surgical Management of Breast Cancer : Experience in 156 Cases.

    Ann Surg 227: 496-501, 1998

      

    The most common surgical procedures used in the treatment of breast cancer are modified radical mastectomy and lumpectomy with axillary dissection. Typically general anesthesia is used for both procedures. Successful surgery was completed in 85% of the cases in paravertebral block alone. The need for medication for nausea and vomiting was greater in the general anesthesia group. and significantly more patients in the general anesthesia group required narcotic analgesia. 

       

    Patients undergoing major operations for breast cancer had minimal complications and a low rate of conversion to general anesthesia when paravertebral block was used. 

        

    This type of anesthetic as well as high thoracic, epidermal anesthetic, which may be somewhat trechnically easier on the patient. Can improve patient’s satisfaction reduce the need for narcotic, and shorten the length of stay in the hospital.

          

  • G.H. Sakorafas and A.G. Tsiotou [ Department of Surgery, 251 Hellenic Air Force Hospital, Messogion and Katehaki, Athens 115 25, Greece

    Genetic Predisposition to Breast Cancer : A Surgical Perspective

    Br. J. of Sur., Volume 87, Number 2, February, 2000, Pg. 149

       

    Molecular alterations in proto-oncogenes, tumour suppressor genes, and genes that function in DNA damage recognition and repair are considered to be the hallmarks of a carcinogenic process, including breast carcinogenesis.

      

    After a thorough review of literature the authors postulate that hereditary breast cancer accounts for 5-10 per cent of all breast cancer cases. About 90% of hereditary breast cancer involve mutation of BRCA1 and/or BRCA2 genes. Other cancer related genes [myc, c-erbB2, Tsg101 and Mdgi] are involved in breast carcinogenesis, but they do not give rise to familial breast cancer syndromes. Risk estimation is the most important clinical implication. Management options for the high-risk mutation carriers include cancer surveillance and preventive strategies [prophylactic surgery or chemoprevention].

      

    They conclude that despite inadequate knowledge about the genetic predisposition to breast cancer and its clinical implications, the demand for genetic testing is likely to increase. In addition to risk estimation, cancer surveillance and preventive strategies, gene therapy offers a new and theoretically attractive approach to breast cancer management.

          

  • U
    Chetty, W. Jack, R.J. Prescott, C. Tyler and A. Rodger, on behalf of the Edinburgh Breast Unit [ Correspondence to : Mr. U. Chetty, Edinburgh Breast Unit, Western General Hospital, Edinburgh EH4 2XU, UK]


    Management of the Axilla in Operable Breast Cancer Treated by Breast Conservation : a Randomized Clinical Trial



    Br. J. of Sur. Volume 87, Number 2, February, 2000, Pg. 163


       


    In the treatment of operable breast cancer by breast conservation, the extent of axillary dissection, the need for radiotherapy to the axilla and the morbidity associated with these procedures have not been assessed adequately.

        


    Patients with operable breast cancer were randomized to have level III axillary node clearance. Radiotherapy [RT] to the axilla was given selectively. RT was not given to those who had an axillary clearance. The first 54 patients were subjected to node sampling and RT. Subsequently only node positive patients were given RT. The morbidity, [upper limb volume, and circumference, and glenohumeral and scapular movements were assessed.

        


    No difference was found in local axillary or distant recurrence. There was no statistical difference in the 5-year survival ratio. The morbidity was least in those who had node sampling but no RT, to axilla. RT to axilla who had a node sample resulted in a significant reduction in range of movement of the shoulder. Surgical axillary clearance was associated with significant lymphoedema of the upper extremity.

         

  • Carolyn
    Westhoff, Debra Heller, et al (Department of Obstetrics & Gynaecology, New Jersey)


    Risk factors for hyperplasia-associated versus atrophy-associated endometrial carcinoma.



    Am J Obstet Gynecol, March 2000, 182: 506-8.


       


    Objective: Endometrial cancer can be divided into atrophy-associated and hyperplasia-associated subtypes. It has been suggested that these subtypes have different pathologic features and prognoses.

        


    Study Design: Hysterectomies performed in cases of endometrial carcinoma with evaluable benign endometrium on routine processing were reviewed, and clinical data were abstracted from medical records. Forty-eight subjects with atrophy-associated and 28 subjects with hyperplasia-associated cancers were studied.

      


    It was found younger age, higher weight, absence of cigarette smoking and earlier menarche in subjects with hyperplasia related cancers.

       


    Conclusions: Their findings support the idea that hyperplasia-associated endometrial cancer is estrogen-related but also suggest that atrophy-associated cases may result from a different causal pathway. Epidemiologic studies may yield more precise and accurate measures of association if atrophy-associated and hyperplasia-associated endometrial cancers are considered separately.

         

  • S. J. Pain and A.D. Purushotham [Cambridge Breast Unit, Addenbrooke’s Hospital, Cambridge , UK]

    Lymphoedema Following Surgery for Breast Cancer

    Br.Jour. of Surg. Volume 87, No.9, September 2000, Pgs. 1128-1141

      

    Lymphoedema is a common complication of breast cancer treatment, affecting almost 25% of cases. It can cause discomfort, cosmetic and functional problems. It is prone to episodic superficial infections.

      

    A systematic review of all published literature on this problem using the Medline and Cinahl databases with cross -referencing of major articles upto 1999 was undertaken.

      

    The aetiology and pathology of this condition is multifactorial and still not fully understood. Although conservative treatment can be very successful in palliation, it does not afford a cure. The place of surgery and pharmacotherapy remains unclear. Improved understanding of pathophysiology may assist in reducing the incidence of this condition or help to identify high risk cases in whom early conservative treatment may prove effective.

          

  • Gerrits
    CJH, Burris H, Schellens JHM, et al [ Univ Hosp Rotterdam, The Netherlands; Univ of Texas Health Sciences Ctr at san Antonio; SmithKline Beecham Pharmaceuticals, UK and USA

    Five Days of Oral Topotecan [Hycamtin TM, a Phase I and Pharmacological Study in Adult Patients With Solid Tumors

    Eur J Cancer 34: 1030-1035, 1998

      

    Topotecan., a specific inhibitor of topoisomerase I, is available in an oral formulation, with a 32% to 44% bioavailability in humans. This study of 29 patients with malignant solid tumors refractory to standard treatment received topotecan in escalating doses. The dose limiting toxicity grade IV granulocytopenia occurred at 2.7 mg/m2/day. The recommended dose for phase II trials is 2.3 mg/m2 /day or a fixed dose of 4 mg/day.

          

  • C.M. Wright, O.F. Dent, M. Barker, R.C. Newland, P.H. Chapuis, E.L. Bokey, J.P. Young, B.A. Leggett, J.R. Jass and G.A. Macdonald [ Department of Surgery, Princess Alexandra Hospital, Conjoint Gastroenterology Laboratory, Royal Brisbane Hospital Research Foundation Clinical Research Center, Department of Pathology , University of Queensland and Department of Medicine, University of Queensland and Clinical Sciences Unit, Queensland Institute of Medical Research, Brisbane, Queensland, Department of Sociology, Australian National University]

    Prognostic Significance of Extensive Microsatellite Instability in Sporadic Clinicopathological Stage C Colorectal Cancer

    Br.Jour. of Surg. Volume 87, No.9, September 2000, Pgs. 1197-1202

         

    Colorectal cancers exhibiting microsatellite instability [MSI] appear to have unique biological behaviour. This study analyses the association between extensive MSI [MSI-H], clinicopathological features and survival in an unselected, group of patients with Sporadic Australian Clinico-Pathological Stage [ACPS] C [tumour node metastasis stage III] colorectal cancer.

    255 patients who underwent resection for sporadic ACPS C colorectal cancer between 1986-1992 were studied. No chemotherapy was given and a minimum follow up period was 5 years. Archival normal and tumour DNA was extracted and amplified by polymerase chain reaction using a radioactive labeling technique. MSI-4 was defined as instability in 40 percent or more of seven markers.

      

    21 patients showed MSI-H. No association was found between MSI and age or sex. Tumours exhibiting MSI-H were more commonly right sided, larger and more likely to be high grade. After adjustment for age, sex, and other variables, patients with MSI-H had improved survival rates.

         

  • E.A. Baker, F.G. Bergin and D.J. Leaper [ Professorial Unit of Surgery, North Tees General Hospital, Stockton on Tees TS19 8PE, UK]

    Matrix Metalloproteinases, Their Tissue Inhibitors and Colorectal Cancer Staging

    Br.Jour. of Surg. Volume 87, No.9, September 2000, Pgs. 1215-1221

       

    Matrix metalloproteinases [MMPs] and their tissue inhibitors [TIMPs] are important in tumour invasion and metastases. This study measured the levels of MMPs and TIMPs and total MMP activity in colorectal tumour cases and compared them with normal and correlated with clinical and pathological staging.

    Gelatin zymography [MMP-2 and MMP-9] enzyme linked immnunosorbent assays [MMP-1, MIMP-3, TIMP-1 and TIMP-2] and quenched fluorescent substrate hydrolysis [total MMP activity] were employed in resection specimens from 50 patients, four with adenomas and 46 with colorectal cancer.

       

    The levels of active MMP-2 and MMP-9 and total MMP-1, MMP-3 MMP-9 and total MMP1, MMP3, and TIMP-3 were significantly greater in tumour tissue than in normal colon. However, TIMP-2 levels were significantly greater in normal tissue. The total MMP activity was greater in tumours. Correlations were found between MMP and TIMP levels and pathological tumor staging. MMP1 appeared to be most important as its concentration correlated positively with Dukes staging, tumor differentiation and lymphatic invasion.


       

  • T.
    Funai, H. Osugi, M. higashino and Kinoshita [ Second Department of Surgery, Osaka City University Medical School, 1-4-3, Asahi-machi, Abeno-ku, Osaka 545-8585, Japan]

    Estimation of Lymph Node Metastasis by Size in Patients with Intrathoracic Oesophageal Cancer

    Br.Jour. of Surg. Volume 87, No.9, September 2000, Pgs. 1234-1239

       

    The aim of this study was to establish criteria for the preoperative diagnosis of lymph node metastases based on size and shape of nodes.

       

    123 patients were studied. 6822 nodes were obtained by extended lymphadenectomy. The nodes were classified anatomically and their size was measured by the operating surgeon during or immediately after surgery. All were examined histologically and criteria for diagnosis of metastasis were evaluated.

       

    The size of the nodes varied by anatomical site. They were smallest in the neck and largest at the tracheal bifurcation. The cut off value for the diagnosis of metastases was 5 mm in the neck. 6 mm in the abdomen and 8 mm in the mediastinum, except for tracheal nodes. Lymph node 10 mm or larger tended to become spherical when involved by metastasis.

        

  • Paul A Vasey (CRC Dept of Medical Oncology, Univ. of Glasgow)

    Immunotherapy for renal carcinoma: theoretical basis and current standard of care

    Br.J.Clin. Pharmacol 50, 521-529.

       

    There is no internationally recognised standard therapy for metastatic renal cancer and patients are treated with IFA or rIL-2 monotherapy or combinations. New approaches are needed.

      

    There are a number of preclinical studies which suggest that simultaneous exposure to both interferons and retinoids can result in enhanced antiproliferative and differentiation effects, compared with either agent alone. The EORTC are conducting a randomised trial of IFA in combination with 13-cis retinoic acid, a natural metabolite of vitamin A which has anticancer activity through a number of mechanisms including antiangiogenesis, differentiation induction and inhibition of IL-6.

      

    Immunostimulation by exogenously administered cytokines serves to enhance the function of the existing host immune system, rather than act as a cytotoxic agent that will eradicate or cure a disease process such as cancer. Continued development and exploration of novel therapies such as antiangiogenic compounds (e.g. thalidomide), differentiating agents, and newer immuno-stimulating agents will hopefully improve the outlook for patients in the future.

        

  • Gideon
    Steinbach, Patrick M Lynch et al

    The Effect of Celecoxib, a cyclooxygenase-2 inhibitor, in familial adenomatous polyposis.

    New Eng J Med. Vol.342, June 29, 2000, pg. 1946.

       

    Patients with familial adenomatous polyposis have a nearly 100 percent risk of colorectal cancer. Chemo-preventive effects of NSAIDs may be related to their inhibition of cyclooxygenase-2.

      

    Authors studied the effect of celecoxib, a selective cyclooxygenase-2 inhibitor, on colorectal polyposis in patients with familial adenomatous polyposis. In a double-blind, placebo-controlled study, 77 patients were randomly assigned to treatment with celecoxib (100 or 400 mg twice daily) or placebo for 6 months. Patients underwent endoscopy at the beginning and end of the study. The number and size of the polyps were determined from photographs and videotapes, the response to treatment was expressed as the mean percent change from base line.

      

    It was concluded that in patients with familial adenomatous polyposis, 6 months of twice daily treatment with 400mg of celecoxib, leads to a significant reduction in the number of colorectal polyps.

         

  • Christoph C, Zielinski and Michael Hejna

    Warfarin for cancer prevention.

    New Eng Jr Med. Vol.342, No.26, June 29, 2000, pg.1991.

      

    Clear evidence has been provided of an association between idiopathic thromboembolism and development of cancer. The risk is significantly higher among patients less than 65 years of age than among those who are 65 or older.

      

    Heparin, aspirin and other NSAIDs and warfarin have been used experimentally for prevention and treatment of various tumours in animals and humans. There are impressive data that suggest that aspirin and other NSAIDs reduce the risk of colorectal cancer probably by suppressing the synthesis of cyclooxygenase-2 and proinflammatory prostaglandins.

       

    A prospective randomised Veterans Affairs Co-operative Study demonstrated that the use of warfarin led to a statistically significant prolongation of the time to disease progression and improved survival among patients with small-cell lung cancer but not among patients with non-small cell lung cancer or cancer of the head, neck, prostate or colon.

      

    Schulman and Lindmarker report in this journal the effect of anticoagulants on the development of cancer. It is likely that anticoagulants were not acting on preexisting, clinically overt tumours but, rather were preventing the development of new cancerous lesions. This interpretation originated in a previous investigation that studied the optimal duration of anticoagulant therapy after venous thromboembolism and concluded that 6 months was superior to 6 weeks.

      

    This study should raise the awareness of the risk of certain cancers in patients with idiopathic thromboembolism. The necessity of appropriate follow up in these patients is clear. Wafarin needs to be studied in controlled clinical trials, with the aim of assessing prevention rather than treatment of cancer. Persons with genetic or environmental risk for the specific cancers should be considered for such studies. Warfarin could be a drug to be added to the armamentarium of chemoprotective agents.

          

  • Sam Schulman and Per Lindmarker

    Incidence of cancer after prophylaxis with warfarin against recurrent venous thromboembolism.

    New Eng Jr Med. Vol.342, June 29, 2000, pg. 1953

       

    The length of time after an episode of venous thromboembolism during which the risk of newly diagnosed cancer is increased is not known, and whether vitamin K antagonists have an antineoplastic effect is controversial.

      

    In a prospective, randomized study of the duration of oral anticoagulation (6 weeks or 6 months) after a first episode of venous thromboembolism, patients were questioned annually about any newly diagnosed cancer. After a mean follow up of 8.1 years, authors used the Swedish Cancer Registry to identify all diagnoses of cancer and causes of death in the study population. The observed numbers of cases of cancer were compared with expected numbers based on national incidence rates, and the standardized incidence ratios were calculated.

       

    The conclusion was that the risk of newly diagnosed cancer after a first episode of venous thromboembolism is elevated during at least the following 2 years. Subsequently, the risk seems to be lower among patients treated with oral anticoagulants for 6 months than among those treated for 6 weeks.

          

  • Mark W. Onaitis, Paul M. Kirshbom, Thomas Z. Hayward, Frank J. Quayle, Jerome M. Feldman, Hilliard F. Seigler, and Douglas S. Tyler [ From the Departments of Surgery and Medicine, Duke University Medical Center, Dursham, North Carolina]

    Gastrointestinal Carcinoids : Characterization by Site of Origin and Hormone Production

    Annals of Surgery, Volume 232, Number 4, Pg. Nos. 549-556

       

    This study describes a large series of patients with carcinoid tumors in terms of their clinical features, hormonal diagnosis and survival.

       

    A prospective database of carcinoid tumour patients seen at Duke University Medical Center was kept from 1970 onwards.

       

    A retrospective review of medical records was done on this database to record clinical features, hormonal data, pathologic features and survival.

      

    Carcinoids at different sites had different clinical features. Rectal tumours presented with bleeding and midgut carcinoids with flushing diarrhea, and the carcinoid syndrome. 

       

    They had significantly higher levels of serotonin and its breakdown products, corresponding to higher metastatic tumor burdens. Although age, stage, region of origin and urinary levels of 5-HIAA predicted survival by univariate analysis; with a multivariate analysis only the latter there were independent predictors of survival. In patients with metastatic disease midgut tumours had better prognosis than foregut or hindgut
    tumours. 

       

  • Ambrosio Hernandez, Farin Smith, BS, QingDing Wang, Xiaofu Wang, BS, and B. Mark Evers [ From the department of Surgery, The University of Texas Medical Branch, Galveston, Texas]

    Assessment of Differential Gene Expression Patterns in Human Colon Cancers

    Annals of Surgery, Volume 232, Number 4, Pg. Nos. 530-541

       

    This study uses a novel genomic approach to determine differential gene expression patterns in colon cancers of different metastatic potential.

       

    Human colon cancer cells KM12C [derived from a Dukes B colon cancer] KML 4A [ a metastatic variant derived from KM12C] and KM20 [ derived from Dukes D Colon Cancer] were extracted for RNA. In addition RNA was extracted from normal colon primary cancer and hepatic metastasis in a patient with metastatic colon cancer. Gene expression patterns for approximately 1200 human genes were analyzed and compared by cDNA array techniques.

       

    Of the 1200 genes assessed in the KM cell lines,9 genes were noted to have more than threefold change in expression [either increased or decreased] in the more metastatic KML4A and KM20 cells compared with KM12C. There was more than threefold change in expression of 16 genes in metastatic colon cancer compared with normals.

       

    The authors have identified genes with expression levels that are altered with metastasis.

        

  • H. Tanaka, K. Hirohashi, S. Kubo, T. Shuto, I. Higaki and H. Kinoshita

    Preoperative Portal Vein Embolization Improves Prognosis of Right Hepatectomy for Hepatocellular Carcinoma in Patients with Impaired Hepatic Function

    Br.Jour. of Surg. Volume 87, No.7, July 2000, Pgs. 879-882

       

    Percutaneous transhepatic portal vein embolization [PTPE] increases the safety of subsequent major hepatectomy. This study aims to determine the effect of PTPE on long term prognosis after hepatectomy in patients with hepatocellular carcinoma [HCC].

        

    71 patients underwent hepatectomy for HCC. 33 patients [group 1] underwent preoperative PTPE and 38 patients [group 2] did not have this procedure. The patient were further divided according to the median tumour diameter [cut off 6 cm] and indocyanine green retention rate at 15 min [ICGR15] [cut-off 13%]. 

       

    The cumulative survival rate was significantly higher in group 1 then in group 2 in patients with an ICGR15 of at least 13%. Tumour-free survival rates were similar in both groups. Of patients with tumour recurrence after right hepatectomy, those in group 1 were more frequently subjected to further treatment. 

     

    Preoperative PTPE improves the prognosis after right hepatectomy for HCC in patients with impaired hepatic function although it does not prevent tumour recurrence.

       

  • T.M.D. Hughes, R.P. A’Hern and J.M. Thomas [ Melanoma and Sarcoma Unit, Royal Marsden Hospital, Fulham Road, London SW3 6JJ, UK]

    Prognosis and Surgical Management of Patients with Palpable Inguinal Lymph Node Metastases from Melanoma

    BJS, Volume 87, Number 7, July 2000, Pg. Nos. 892-901

      

    The aim of this study was to identify factors that influence the outcome of patients undergoing therapeutic groin dissection for clinically detectable melanoma lymph node metastases. 

       

    A retrospective study of 132 cases who underwent lymph node dissection [ inguinal] therapeutically.

    60 Patients had superficial inguinal lymph node [SLND] dissection and 72 had combined superficial inguinal and pelvic lymph node dissection [CLND]. 

      

    There was no difference in postoperative morbidity or major lymphoedema. The overall survival rate was 34% at 5 years. On univariate analysis age, the number of superficial inguinal nodes and presence of extra capsular spread had a significant impact on survival. The presence of or absence of pelvic lymph node metastases was a significant prognostic factor [ 19% vs. 47%].

       

    The prognosis of patients with clinically detectable melanoma metastases to the groin is variable and related to the biologic characteristics of each case. CLND provided additional prognostic information and optional regional control but no change in morbidity compared to
    SLND.

        

  • E.
    Rullier, F. Zerbib, C. Laurent, M. Caudry and J. Saric [ Departments of Digestive Surgery, Gastroenterology and Radiation Oncology, Saint-Andre Hospital, 33075 Bordeaux Cedex, France]

    Morbidity and Functional Outcome After Double Dynamic Graciloplasty for Anorectal Reconstruction

    BJS, Volume 87, Number 7, July 2000, Pg. Nos. 909-913

      

    The aim of this study was to evaluate the morbidity and functional results in a homogeneous series of patients undergoing double dynamic graciloplasty following APR for rectal cancer.

       

    15 patients[ 10 men and 5 women, mean age of 54 years range [ 39 to 77] underwent anorectal reconstruction with double dynamic graciloplasty after APR for low rectal cancer. 

       

    All patients had preoperative radiotherapy [ 15 Gy] and ten received adjuvant, chemotherapy, 8 had intraoperative radiotherapy [15 Gy] and ten received 

       

    adjuvant chemotherapy for six months. Surgery was performed in three stages : APR with coloperineal anastomosis and double graciloplasty; implantation of the stimulation 2 months later; and ileostomy closure after a training period.

      

    There was no operative death. At a mean of 28 months [3-48] of follow-up there was no local recurrence; 2 patients had lung metastases. Early and late morbidity occurred in 11 patients [mainly related to neosphinctor], mainly stenosis. Of 12 patients followed up for functional outcome. 7 were continent, 2 were incontinent and 3 had an abdominal colostomy [ 2 for incontinence and one for sepsis]. The restenosis required major surgery and had a poor outcome.

       

    The conclusion is that the double dynamic graciloplasty is associated with a high risk of neosphincter stenosis which may entail morbidity, reintervention and poor functional results. It is suggested that single dynamic graciloplasty should be used for anorectal reconstruction after APR.

      

  • D.C. Jenner , A. Middleton, W.M. Webb, R. Oommen and T. Bates [ The Breast Unit, William Harvey Hospital, Ashfold TN24 OLZ, UK]

    In-Hospital Delay in the Diagnosis of Breast Cancer

    BJS, Volume 87, Number 7, July 2000, Pg. Nos. 914-919

         

    Delay in the diagnosis of breast cancer may prejudice survival. The aim of this study was to determine the incidence, time trends and causes of delay in a dedicated breast clinic. 

        

    The interval between the first visit to the clinic and a definitive diagnosis, was recorded in 1004 patients with invasive breast cancer.

       

    There was a delay of 3 months or more in 42 cases [4.2%]. The median delay was 6 months and the median age at diagnosis was 53 years [range 27-89 years]. Triple assessment was undertaken in 30 patients. Ten did not have a needle biopsy and three patients did not have a mammography. The principal cause of delay was false negative or inadequate needle aspiration cytology [FNAC] in 19 patients, a failure of follow-up in 8 cases, failure of needle localization in two cases, FNAC not carried out in 4 cases, no clinical signs in five patients and one case who did not follow clinical advice. The annual incidence of delay in diagnosis did not change significantly over a 10 year interval.

       

    Triple assessment is not sufficiently sensitive to detect breast cancer and a small delay in diagnosis is inevitable with current techniques.

       

  • L. Jansen, M. H.E. Doting E.J.Th. Rutgers, J. de Vries, R.A. Valdes Olmos and O.E.Nieweg [ Departments of Surgery and Nuclear Medicine, The Netherlands Cancer Institute /Antoni van Leeuwenhock Hospital, Amsterdam and Department of Surgical Oncology, Groningen University Hospital, Groningen, The Netherlands]

    Clinical Relevance of Sentinel Lymph Nodes Outside the Axilla in Patients with Breast Cancer 

    BJS, Volume 87, Number 7, July 2000, Pg. Nos. 920-925

         

    Lymphatic mapping in patients with breast cancer can reveal sentinel lymph nodes that are not located at level I-II of the axilla. The clinical relevance of this is not fully understood.

       

    113 consecutive patients [T1-3 No Mo] with breast cancer were studied. Based on preoperative scintigraphy. Sentinel node biopsy was performed guided by a g probe and patent blue dye. All sentinel nodes that were visible were biopsied and examination of those nodes included step sections and staining with CAM5.2. Axillary node dissection was performed regardless of sentinal lymph node status.

       

    19% [ 21 cases] had sentinel lymph nodes outside level I-II of the axilla, mostly in the internal mammary chain. 22 of the 30 sentinel nodes at these sites were harvested. 3 patients had sentinel nodes only outside the axilla. 4 other patients had metastases outside the axilla. This changed postoperative treatment in 3 patients. No postoperative complication occurred.

       

    Biopsy of sentinel lymph nodes [19% of cases in this series] is technically demanding but the clinical impact was limited – treatment changed in only 3%.

      

  • Manel
    Esteller, Jesus Garcia Foncillas et al

    Inactivation of the DNA repair gene MGMT and the clinical response of gliomas to alkylating agents.

    New Eng J Med. Vol.343, Nov.9, 2000,pg.1350.

       

    Summary : The DNA repair enzyme O6-methyl-guanine-DNA methyltransferase (MGMT) inhibits the killing of tumour cells by alkylating agents. MGMT activity is controlled by a promoter and methylation of the promoter silences the gene in cancer and the cells no longer produce MGMT. Authors examined gliomas to determine whether methylation of the MGMT promoter is related to the responsiveness of the tumour to alkylating agents.



    MGMT promoter in tumour DNA was analysed by a specific PCR assay. Gliomas were obtained from patients treated with carmustine. Molecular data were correlated with the clinical outcome. MGMT promoter was methylated in 40% of gliomas and this was associated with regression of the tumour and prolonged overall and disease free survival. It was an independent and stronger prognostic factor than age, stage, tumour grade or performance status.



    The conclusion was that methylation of the MGMT promoter in gliomas is a useful predictor of responsiveness of the tumours to alkylating agents.

       



    Editorial :
    John N Weinsten, pg.1408

    Pharmacogenomics – Teaching old drugs new tricks.

    Summary: Traditionally, cancer treatments have been selected on the basis of tumour type, pathological features, clinical stage, the patient’s age and performance status and other nonmolecular considerations. The field of pharmacogenomics, through the study of large number of genes that influence drug activity, toxicity and metabolism, provides the opportunity to tailor drug treatments and to eliminate many of the uncertainties of current therapy for cancer.

      


    Strong support for this concept is provided by the study of genetic polymorphisms that influence drug metabolism. CYP2D6 affects metabolism of several drugs (beta-blockers, antidepressants, antipsychotics and opioids). Dihydropyrimidine dehydrogenase influences metabolism and therefore neurotoxicity of fluorouracil.

      


    Esteller and colleagues provide clinical evidence to explain the resistance of some gliomas to nitrosourea alkylating agents. Carmustine and other nitrosoureas kill by alkylating O6 position of guanine and thereby cross-linking adjacent strands of DNA. Formation of these cross-links can be prevented by MGMT, which rapidly reverses alkylation. About 30% of gliomas lack MGMT. A lack of MGMT appears to correlate with sensitivity to carmustine. Methylation of MGMT promoter could be used to predict responses to treatment with carmustine.

       


    Pharmacogenomics studies will produce benefits both for clinical research and standard practice. Potential advantages include discovery of better drugs, elimination of poor candidates early in the development process, and dramatic decrease in size and expense of clinical trials.

      

  • Ambrosio Hernandez, Farin Smith, BS, QingDing Wang, Xiaofu Wang, BS, and B. Mark Evers [ From the department of Surgery, The University of Texas Medical Branch, Galveston, Texas]

    Assessment of Differential Gene Expression Patterns in Human Colon Cancers

    Annals of Surgery, Volume 232, Number 4, Pg. Nos. 530-541

        

    This study uses a novel genomic approach to determine differential gene expression patterns in colon cancers of different metastatic potential.

       

    Human colon cancer cells KM12C [derived from a Dukes B colon cancer] KML 4A [ a metastatic variant derived from KM12C] and KM20 [ derived from Dukes D Colon Cancer] were extracted for RNA. In addition RNA was extracted from normal colon primary cancer and hepatic metastasis in a patient with metastatic colon cancer. Gene expression patterns for approximately 1200 human genes were analyzed and compared by cDNA array techniques.

       

    Of the 1200 genes assessed in the KM cell lines,9 genes were noted to have more than threefold change in expression [either increased or decreased] in the more metastatic KML4A and KM20 cells compared with KM12C. There was more than threefold change in expression of 16 genes in metastatic colon cancer compared with normals.

        

    The authors have identified genes with expression levels that are altered with metastasis.

       

  • Dorudi
    S, Kinrade E, Marshall NC, et al [ Royal London Hosp]

    Genetic Detection of Lymph Node Micrometastases in
    Patients with Colorectal Cancer


    Br J Surg 85: 98-100, 1998

          

    Undetected micro metastases are the most important cause
    of treatment failure in patients with putatively
    curative colorectal cancer surgery. The detection in the
    regional lymph node of mRNA expressed from cytokeratin
    [CK] 20 gene upstaged 4 of 15 patients. Following a
    resection for colorectal cancer. The CK 20 gene product
    being a cytokeratin is restricted to intestinal
    epithelium and is not likely to be expressed in the
    lymph node. The editor comments that these so called
    negative nodes by hematoxylin eosin may be placed into
    trials for adjuvant therapy once these molecular biology
    techniques are standardized and gained experience in
    clinical practice.

      

  • Delbeke
    D, Martin WH, Sandler MP, et al [ Vanderbilt Unit,
    Nashville, Tenn]

    Evaluation of Benign vs Malignant Hepatic Lesions
    with Positron Emission Tomography


    Arch Surg 133: 510-516, 1998

        

    The relatively low levels of glucose-6-phosphatase is
    most malignant cells results in accumulation and
    trapping of [18F] flurodeoxyglucose [FDG]
    intracellularly, & then visualizing the increased
    uptake. This technique of FDG PET has been used in 110
    consecutive patients with hepatic tumors of 1 cm or
    greater to differentiate between benign vs. Malignant
    lesions. All liver metastasis from adenocarcinoma or
    sarcoma and all cholangiocarcinomas showed increased
    uptake. Whereas hepatocellular carcinoma [HCC] had an
    increased FDG uptake in 16 of 23 patients and poor
    uptake in 7 of 23 with the exception of one abscess
    which had increased uptake. Rest all benign lesions
    revealed a poor uptake. The limitation of this technique
    is false positive in a minority of abscess and false
    negative in minority of HCC. FDG PET would also be
    useful in future for staging, detecting recurrences and
    monitoring response.

      

  • Sorensen HT, Mellemkjaer L, Steffensen
    FH, et al [ Univ of Aarhus, Denmark; Inst of Cancer
    Epidemiology, Copenhagen; Aalborg Hosp, Denmark]

    The Risk of a Diagnosis of Cancer After Primary Deep Venous Thrombosis or Pulmonary Embolism

    N Engl J Med 338: 1169-1173, 1998

       

    The relation between pulmonary embolism [PE], deep venous thrombosis
    [DVT] and cancer has been debated. This large study of 15,348 patients with DVT and 11,305 with PE revealed an increased risk of 1.3 for development of cancer. Although the risk was significantly elevated only during the first 6 months of follow-up. Pancreas, ovary, liver, and brain were most common sites of cancer in patients with
    thromboembolism. Exhaustive search for cancer in such patient was not of clinical benefit.

     

  • Narod
    SA, for the Hereditary Ovarian Cancer Clinical Study
    Group [Univ of Toronto; et al]

    Oral Contraceptives and the Risk of Hereditary
    Ovarian Cancer


    N Engl J Med 339: 424-428, 1998

       

    In this study 207 women with hereditary ovarian cancer
    and with a pathogenic mutation in either BRCA1 or BRCA2
    gene were studied along with 161 of their sisters. The
    study findings revealed women using oral contraceptive [OC]
    for 6 or more years had a 60% reduction in the risk of
    ovarian cancer. The use of OC protected against ovarian
    cancer among the carriers of both to BRCA1 or BRCA2
    mutation.

        

  • Lombard
    I, Vincent-Salomon, Validire P, et al [ Institut
    Curie,Paris; Institut Pasteur, Paris]

    Human Palillomavirus Genotype as a Major Determinant
    of the Course of Cervical Cancer


    J Clin Oncol 16: 2613-2619, 1998

       

    Human Papillomavirus [HPV] a venereally transmissible
    oncogenic agent, is a well known to be associated with
    of uterine cervix. In this study HPV DNA was extracted
    from frozen tumor specimens analyzed by Southern blot
    hybridization and polymerase chain reaction. 

      

    The genotype HPV 16 & HPV18 positive tumors had a
    disease free survival at 5 year of 58% and 38%
    respectively. A multivariate analysis recorded HPV-18
    related tumors with a relative risk of death that was
    2.4 times higher than were HPV-16 related tumors and a
    4.4 times higher than tumors related to other viral
    types. The editor comments that typing of HPV is clearly
    a prognostic indicator for individual patients with
    cervical cancer and further management of these patients
    would be through biological and immunological therapies
    directed against HPV associated carcinoma.

       

  • Penninx
    BWJH, Guralnik JM, Pahor M, et al [ Natl Inst on Aging,
    Bethesda, Md; Univ of Tennessee, Memphis; Istituto
    Nazionale Ricerca e Cura Per Gli Anziani, Florence,
    Italy; et al]

    Chronically Depressed Mood and Cancer Risk in Older
    Persons


    J Natl Cancer Inst 90: 1888-1893, 1998

         

    The associations of chronic depression with cancer in
    elderly patients was investigated. All participants in
    this study were 71 years or older.

       

    Depression of at least 6 years duration appears to be
    associated with an increased risk of cancer in elderly
    even when corrected for factors such as alcohol smoking,
    age, sex and race. The editor comments that depressed
    patients practice poorer health promoting behavior than
    non depressed and could be attributed to increased
    cancer risk.

        

  • Granovsky
    MO, Mueller BU, Nicholson HS, et al [ Natl Cancer Inst,
    Bethesda, Md; Children’s Hosp, Boston; Children’s Natl
    Med Ctr, Washington, DC]

    Cancer in Human Immunodeficiency Virus-Infected
    Children: A Case Series From the Children’s Cancer Group
    and the National Cancer Institute


    J Clin Oncol 16: 1729-1735, 1998

       

    The epidemiology of HIV-related cancer in adults has
    been well described but that in children is not well
    documented and hence this study reports the spectrum of
    malignancies in HIV infected children and their clinical
    outcome.

       

    Most [58%] of the children had acquired HIV vertically
    34% through blood or blood products transfusion.
    Non-Hodgkin’s lymphoma – 65% was the commonest followed
    by leiomyosarcomas – 17% and the others were acute
    leukemia. Kaposi’s sarcoma, Hodgkin’s disease vaginal
    carcinoma in situ tracheal neuroendocrine tumor. The
    median survival for NHL was 6 months and leiomyosarcoma
    – 12 months after diagnosis. The editor comments that
    with recent improvements in antiretroviral therapy and
    supportive care. More children are surviving the early
    complications of HIV and will subsequently develop
    malignancies.

        

  • Bennet
    CL, Ferreira MR, Davis TC, et al [ Chicago Veteran
    Affairs Administration Healthcare System-Lakeside
    Division; Lurie Cancer Ctr; Northwestern Univ, Chicago;
    et al

    Relation between Literacy, Race, and Stage of
    Presentation Among Low-Income Patients with Prostate
    Cancer


    J Clin Oncol 16: 3101-2104, 1998

       

    Advanced prostate cancer in a low income men is related
    to poor literacy skill has been brought out in this
    study. The black men were almost twice as likely as
    white men to have stage D prostate cancer at initial
    examination. The editor comments that the effectiveness
    of screening to detect cancer at the earlier stage
    depends on aggressiveness of the tumor, the cost
    effectiveness of screening and most importantly, the
    willingness of the patient to undergo screening. The
    importance of the literacy for the informed consent has
    direct implications in clinical trials.

         

  • deVere
    White RW, Deitch AD, Jackson AG, et al [ Univ of
    California, Davis; Northern California Cancer Ctr, union
    City; Howard Univ, Washington, DC]

    Racial Differences in Clinically Localized Prostate
    Cancers of Black and White Men


    J Urol 159: 1979-1983, 1998

      

    The investigative skill i.e prostate-specific antigen
    and proper records in cancer registries, are responsible
    for the increase in prostate cancer despite these a true
    rise in incidence of prostate cancer is noted. The
    highest incidence in the world is found among black men
    in Unites States; They have at younger age, large
    volume, higher stage and grade compared with white men.
    This study has correlated with biological markers i.e.
    deoxyribonucleic acid ploidy by DNA flow cytometry using
    propidium / expression of proliferation, as well as P53
    & bcl-2 . A monoclonal antibody cocktail for p53 and
    clone 124 antibody for bcl-2 were used for
    immunostaining after microwave antigen retrieval on the
    prostate biopsy specimens. The higher S phase fraction
    reflecting high proliferation and bcl-2 immnuno
    positively i.e. block to programmed cell death-
    characterize the aggressive prostate cancer of black
    men.

       

  • Andrea
    Mariani, Maurice J Webb, et al (Rochester, Minnesota, and Milan, Italy)

    Low-risk corpus cancer: Is lymphadenectomy or radiotherapy necessary?

    Am J Obstet Gynecol, vol.182, June 2000, p.1506-19

        


    Objective: The objective of this study was to find readily ascertainable intraoperative pathologic indicators that would discriminate a subgroup of early corpus cancers that would not require lymphadenectomy or adjuvant radiotherapy.

       


    Study Design: Between 1984 and 1993, a total of 328 patients with endometrial corpus cancer, grade 1 or 2 tumor, myometrial invasion £50%, and no intraoperative evidence of macroscopic extrauterine spread were treated surgically. Pelvic lymphadenectomy was performed in 187 cases (57%), and nodes were positive in nine cases (5%). Adjuvant radiotherapy was administered to 65 patients (20%). Median follow-up was 88 months.

       


    Results: The 5-year overall cancer-related and recurrence-free survivals were 97% and 96%, respectively. Primary tumor diameter and lymphatic or vascular invasion significantly affected longevity. No patient with tumor diameter £2cm had positive lymph nodes or died of disease.

       


    Conclusion: Patients who have International Federation of Gynecology and Obstetrics grade 1 or 2 endometrioid corpus cancer with greatest surface dimension £2cm, myometrial invasion £50%, and no intraoperative evidence of macroscopic disease can be treated optimally with hysterectomy only.

       

  • Moinpour CM, Savage MJ, Troxel A, et al [ Fred Hutchinson Cancer Research Ctr, Seattle; Mercy Med Ctr, Baltimore, Md; Columbia Presbyterian Cancer Ctr, New York; et al]

    Quality of Life in Advanced Prostate Cancer: Results of a Randomized Therapeutic Trial

    J Natl Cancer Inst 90: 1537-1544, 1998

        

    Palliative therapy of metastatic carcinoma prostate in 739 patients with prostate cancer metastasis to bone or soft tissue underwent bilateral orchiectomy. The patients then reviewed flutamide or placebo. The patient on flutamide had more diarrhea, worse emotional functioning and thereby poor quality of life outcomes than on placebo.

  • Socie G, for the Late Effects Working Committee of the International Bone Marrow Transplant Registry [Hopital Saint Louis, Paris]

    Long-term Survival and Late Deaths After Allogeneic Bone Marrow Transplantation

    N Engl J Med 341: 14-21, 1999



    This study of 6691 patients who underwent allogeneic or syngenic bone marrow transplant and were disease free for 2 years post transplant. The probability of survival at 5 years was 89%. Late deaths were less frequent [6% at 7 years] for aplastic anemia than for leukemia [ 12% at 7 years] and the mortality was due to chronic graft-versus-host disease and relapse respectively. 

       

  • MJ
    Byrne, JA Davidson, AW Musk, et al (Sir Charles Gairdner
    Hosp, Nedlands, Australia; Unvi of Western Australia,
    Nedlands)

    Cisplatin and Gemcitabin Treatment for Malignant
    Mesothelioma: A Phase II Study.

    J Clin Oncol 17: 25-30, 1999.

       

     Malignant mesothelioma, an aggressive tumor, is an
    uncommon tumor that is increasing in incidence. A Phase
    II Study of combined cisplatin and gemcitabine for the
    treatment has been reported herewith.

       

    Twenty-one patients, aged 46 to 74 years were enrolled
    in the study of which sixty-two percent had epithelial
    tumors, eighteen had tumor-node-metastasis (TNM) system
    stage III or IV. Treatment consisted of cisplatin being
    given as 100mg/m2, given intravenously on day 1 and
    gemcitabine 1000mg/m2 intravenously on days 1, 8, 15 of
    a 28-day cycle for 6 cycles. Pleural tumor was measured
    at 3 levels with CT scan at baseline; before the second,
    fourth, and sixth cycles; and every 2 months thereafter
    until the disease progression.

       

    The treatment of malignant pleural mesothelioma has been
    always controversial. For earlier stage disease being
    subjected to extrapleural pneumonectomy. For advanced
    disease, there are a number of chemotherapeutic agents
    that have demonstrated single-agents activity against
    malignant pleural  mesothelioma, but the response
    rate is only 15% to 20 %. This trial seems to have
    response rate of 47% i.e. 10 of 10 patients and is
    perhaps the highest ever reported. Consequently, several
    other centers are trying out the result of these studies
    so as to seen whether they are spurious or not.

       

  • H. Stephan Stoldt James G, Geraghty 

    Surgical Principles in the Management of Soft Tissue Sarcomas

    Recent Advances in Surgery, Number 22, Year – 1999

       

    Safe margins are as important to achieve as in any tumour type. Surgical resection remains the mainstay in management but pre- and postoperative radiotherapy, as well as brachytherapy, are important modalities of treatment, which may impact on the surgical approach to the tumour. 

        

    One important aspect related to the surgical management of soft tissue sarcoma concerns its staging. 

      

    It is better to carry out an incisional rather than an excisional biopsy. The exception to this rule is the small superficial lesion where it is simplest to excise the lesion. 

       

    The surgical management of sarcomas can be divided into marginal resection, radical resection, amputation, debulking and surgery combined with brachytherapy. 

      

    The challenge in sarcoma surgery is in achieving adequate resection of the tumour while preserving good functional outcome. A margin of at least 1 cm is required to achieve microscopic free margins.

      

    At present, the standard local treatment for Soft Tissue Sarcomas [STS] of the extremity is limb sparing surgery . Locoregional adjuvant therapy include isolated limb perfusion with chemotherapeutic agents hyperthermia alone and combined chemoradiation with hyperthermia. 

         

    The evidence demonstrates an advantage for preoperative compared to postoperative radiotherapy after surgery . It has been shown however that there are overall advantages for pre-operative radiotherapy, particularly in lesions over 5 cm in diameter. There is no proven benefit with brachytherapy.

         

    An unusual group of tumours called Desmoid tumours which are classified as benign do not metastasize but sometimes behave in a locally aggressive fashion. Due to their potential for an aggressive growth pattern, aggressive surgery is the treatment of choice.

        

  • M. R. Kell, D. C.Winter, G.C. O’Sullivan, F. Shanahan and H.P. Redmond 

    [Departments of Academic Surgery and Medicine, National University of Ireland, Cork University Hospital and ‘Mercy Hospital, Cork, Ireland]

    Biological Behaviour and Clinical Implications of Micrometastases

    Br. Jr. of Sur. Volume 87, No.12, December 2000, Pgs-1629-1639

         


    The most important prognostic determinant in cancer is the identification of designated tumor burden [metastases]. Micrometastases are microscopic (<2mm) deposits of malignant cells that are segregated spatially from the primary tumour and depend on neovascular formation (angiogenesis) to propogate.

    The literature on micrometastases and their implications in malignant melanoma and epithelial cancers is reviewed.

    Immunohistochemical and serial sectioning methods were used. Molecular techniques were reserved for blood samples and bone marrow aspirates.

         

    Detection of micrometastases in regional lymph nodes and/or bone marrow confers a poor prognosis in epithelial cancers. The concept of sentinel node biopsy combined with serial sectioning and dedicated screening for micrometastases may improve staging procedures. Strategies against angiogenesis may provide novel therapies to induce and maintain micrometastatic dormancy.

         

  • A
    Llaneza, F. Vizoso, J.C. Rodriguez, P. Raigoso, J.L. Garcia-Muniz, M.T. Allende and M. Garcia-Moran [ Department of Surgery and Nuclear Medicine, Hospital Central de Asturias, Oviedo and Department of Surgery, Hospital de Jove, Gijon, Spain]

    Hyaluronic Acid as Prognostic Marker in Resectable Colorectal Cancer

    Br. Jour. of Sur. Volume 87, No.12, December 2000, Pgs 1690-1696

       


    Hyaluronic Acid [HA] an extracellular high molecular mass polysaccharide, is thought to be involved in the growth and progression of malignant tumours. This study evaluates the cytosolic HA content in resectable colonic cancer, and its possible relationship with clinicopathological parameters of tumours and its prognostic significance.

        


    Cytosolic HA levels were examined by radiometric assay in 120 patients with resectable colorectal cancer. The mean follow up period was 33.4 months. The levels of cytosolic HA levels of tumours ranged widely from 3o to 29412 ng/mg protein. Intratumour HA levels were significantly correlated with Dukes Stage [P<0.005] and were higher in patients with advanced tumours [ mean (s.e.m.) 2695(446), 2858(293) and 5274(967) ng/mg protein for stages A-B and C respectively]. In addition, Cox multivariate analysis demonstrated that tumour HA levels >2000 ng/mg protein predicted shorter relapse free survival and overall survival period [both P<0.05].

        


    They conclude that there is a wide variability in cytosolic HA levels in colorectal cancers, which seems to be related to the biological heterogeneity of the tumours. High tumour cytosolic HA levels were associated with an unfavourable prognosis

      

  • Krouse JH 

    Staging of Inverted Papilloma

    Laryngoscope 2000: 110: 965-968

         

    Formerly medical maxillectomy through an external incision was treatment of choice as against that today endoscopy is the treatment followed by most of them. This is controversial because of an association of inverted papilloma with malignancy.

        

    This study utilized a literature review to develop a simple and easily applied staging system – based on endoscopic examination of the nasal cavity and CT scanning.

        

    The staging system is as follows:-

        

    Stage I – Disease is limited to nasal cavity.

    Stage II – It is limited to the ethmoid sinuses and medial and superior portion of the 

                  
    maxillary sinuses.

    Stage III – Involves the lateral or inferior aspects of maxillary sinuses or extension 

                   
    into the frontal or sphenoid sinuses.

    Stage IV – Involves tumour spread outside the confines of the nose.

         

  • Moreau PR 

    Laser Laryngeal Surgery

    Laryngoscope 2000; 110: 1000 – 1006

         


    This study is a retrospective analysis of 160 patients treated for laryngeal cancer with CO2 laser endoscopic microsurgery.

         

    Glottic tumours were treated with progressively more extensive cordectomies, extended if necessary to the contralateral cord. Supraglottic tumours had an excision limited to the vestibule, a trans-preepiglottic resection or a radical subglottic dissection. The results are as follows:-

        

    Five year survival was 97% for 98 tumours (infiltrative glottic tumours) and 100% for the 18 infiltrative supraglottic tumour and 27 in situ carcinoma. No local recurrences were noted in either group of 118 tumours (in whom two precancerous lesions were treated with a further excision) as in 27 in situ. Local control was thus 100%.

       

  • H
    Wunderlich, et al (Freidrich Schiller Univ, Jena Germany)

    Nephron Sparing Surgery for Renal Cell Carcinoma 4cm or less in diameter: Indicated or Under Treated ?

    J Urol 159: 1465-1469, 1998.

        

    Background : Radical Nephrectomy continues to be the standard treatment for localised unilateral renal cell carcinoma in patients with normal contralateral kidneys.

        

    The use of radical nephrectomy was retrospectively studied with respect to size and metastasis of renal cell carcinoma.

        

    Findings: The frequency of grade I renal cell carcinomas declined with increasing tumor diameter.

    The opposite was noted for grade 3. Tumor size was associated with lymph node and distant metastasis.

        

    Frequency of venous involvement increased along with increase in tumor size.

       

    Conclusion : The metastatic potential and biology of small renal cell carcinomas have not been established.

       

    To minimise the risk of recurrence Nephron sparing surgery might be limited to those with renal cell carcinomas of 20mm or less.

        

  • KS
    Hafez, AC Novick, BP Butler (Cleveland Clinic Foundation, Ohio)

    Management of Small Solitary Unilateral Renal Cell Carcinoma: Impact of Central Versus Peripheral Tumor Location.

    J. Urol 159: 1156-1160, 1998.

        

    Conclusion : No significant biological differences are evident between central and peripheral small solitary unilateral renal cell carcinomas.

       

    Nephron sparing surgery was technically more complicated among central renal cell carcinomas.

       

    Intraoperative ultrasonography may be a more important adjunct when approaching patients with central tumors.

       

  • H Miyake, H Nakamura, I Hara, et al (Kobe Univ;Japan; Kumamoto Univ, Japan) 

    Multifocal Renal Cell Carcinoma: Evidence for a Common Clonal Origin.


    Clin Cancer Res. 4: 2491, 1998.

        

    The controversy surrounding the use of Nephron sparing surgery for renal cell carcinoma has revolved around the observed 7% to 25% incidence of relatively small satellite tumors discovered at autopsy or upon careful examination of radical nephrectomy specimens from patients with clinically evident renal cell carcinoma.

        

    In this study, the authors studied 10 cases of renal cell carcinoma that were accompanied by smaller satellite tumors for LOH (Loss of Heterozygosity) at chromosome arms 3p, 6q, 8p, 9p, 9q and 14q. All tumors were less than 5cm. Primary and satellite lesions in 8 of 10 cases exhibited identical patterns of LOH.

       

    Similarity of LOH patterns in the main satellite tumors indicated that satellite tumors are the result of intrarenal metastasis rather than new separate primaries. In any series the satellite lesions are generally small and occurring within 2 cm of the index tumor. The satellite tumors measure 2-4mm. Many satellite lesions may be resected during a “radical partial nephrectomy” or may never reach the clinical horizon.

        

  • R. Edward Coleman (Professor of Radiology, Director of Nuclear Medicine and Vice-Chair, Department of Radiology, Duke University Medical Center, Durham, NC)

    PET is Now a Routine Clinical Procedure

    (Emeritus Editor’s Essay)

      

    Clinical PET imaging is having an impact on the medical care of patients. Although the technology was developed in the early 1970s along with MRI, it has only recently received recognition. It provides excellent physiologic and biochemical information as against MRI that gives only anatomical information.

      

    The economics of setting up a PET center was not viable until the 1990s. It requires a cyclotron, a tomograph, and a staff to support the chemistry for the production of FDG (a radiopharmaceutical which is the major reason for the progression of clinical PET). It is approximately 19% more sensitive and 13% more specific than CT.

       

    The growth of PET in USA has been phenomenal. From 83,000 studies done in 1998 to 172,000 studies in 2000. In the author’s division, more than one third of the revenue comes from PET.

       

    It can be anticipated to grow further. New radiopharmaceuticals are being developed to improve the sensitivity and specificity. When it is combined with CT scans, it will give a marked improvement in image quality.

       

    PET is making a major impact in nuclear medicine.

         

  • Mijnhout GS, Hooft L, van Tulder MW, et al (Vrije Universiteit, Amsterdam)

    How to Perform a Comprehensive Search for FDG-PET Literature

    Eur J Nucl Med 27:91-97, 2000

        

    PET scan with FDG is a useful imaging technique for a wide variety of pathologies especially in neoplasia.

        

    However there is a lack of guidelines for performing a literature search on this subject. A practical approach to this searching of electronic databases has been reported.

       

    This approach has increased the retrieval of FDG-PET studies. This would be easier if one standardizes the widely variable spelling of FDG. They recommend the medical subject be labeled as ‘Fluorodeoxyglucose F18’. 

         

  • Weber WA, Ziegler SI, Thodtmann R, et al (Technische Universitat Munchen, Germany)

    Reproducibility of Metabolic Measurements in Malignant Tumors Using FDG PET

    J Nucl Med 40:1771-1777, 1999

        

    Although, PET has been used to detect and stage tumors, its application in the quantitative measurements in malignant tumors, specifically with the use of FDG has not been studied.

      

    FDG-PET evaluations were done twice before the start of chemotherapy in a phase I study of new antineoplastic compounds. Standard uptake values (SUV), FDG net influx constants (K), glucose normalized SUVs (SUVgluc) and influx constants (Kgluc). The accuracy was judged by comparing each lesion and each patient at both examinations.

       

    FDG-PET provided highly reproducible values involving several parameters. It may therefore provide reliable evaluation of the efficacy of therapy for
    neoplasms.

         

  • Young H, for the European Organization for Research and Treatment of Cancer (EORTC) PET Study Group (Hammersmith Hosp, London; et al)

    Measurement of Clinical and Subclinical Tumour Response Using [18F]-Fluorodeoxyglucose and Positron Emission Tomography: Review and 1999 EORTC Recommendations

    Eur J Cancer 35:1773-1782, 1999

       

    A method for evaluating tumor 18F-FDG uptake and reporting of response data used by EORTC PET study group has been described.

        

    Six hours of starvation before the study is recommended. Insulin may be given at the physician’s discretion, good hydration and diazepam may be given for muscle relaxation.

       

    The optimal time after injection to record the uptake value and the optimal time between scans has not been standardized. Pre and post treatment scans are recommended for comparison.

       

    The recommendations made are not meant to be exclusive of other measurements.

         

  • Antoine
    JC, Cinotti L, Tilikete C, et al (Hospital de Bellevue, Saint-Etienne, France; Hospital Neurologique, Lyon, France) 

    [18F] Fluorodeoxyglucose and Positron Emission Tomography in the Diagnosis of Cancer in Patients With Paraneoplastic Neurological Syndrome and Anti-Hu Antibodies 

    Ann Neurol 48:105-108, 2000

       

    The diagnosis of paraneoplastic neurologic syndrome (PNS) and anti Hu antibodies is difficult. FDG-PET scanning is highly sensitive and specific in the detection of lung tumors as seen in this study of 15 patients.

       

    Whole body FDG-PET scanning was useful in the diagnosis of cancer in patients with PNS and anti Hu antibodies and with negative findings after an initial workup using radiologic approaches. 

        

  • Bohuslavizki
    KH, Klutmann S, Kroger S, et al (Univ Hosp Eppendorf, Hamburg, Germany; Phillips Univ, Marburg, Germany)

    FDG PET Detection of Unknown Primary Tumors

    J Nucl Med 41:816-822, 2000

        

    The value of FDG-PET scanning in detecting unknown primary cancer sites is studied.

       

    53 patients with metastatic cervical lymph adenopathy from an unknown primary site were studied.

       

    27 patients showed focal tracer uptakes corresponding to primary tumor sites in lungs, palatine tonsil, salivary glands, nasopharynx, oropharynx, maxillary sinus, or larynx. 2 patients had lesions in breast and ileocolonic region.

       

    6 of 17 patients showed false positive results. 26 patients did not show any suspicious lesions (none of them had primary tumors).

        

    FDG-PET may show unknown primary tumors in one third of all patients. It may also help guide biopsies for histologic assessment.

         

  • Vanuytsel
    LJ, Vansteenkiste JF, Stroobants SG, et al (Univ Hosp Gasthuisberg, Leuven, Belgium)

    The Impact of 18F-Fluoro-2-Deoxy-D-Glucose Positron Emission Tomography (FDG-PET) Lymph Node Staging on the Radiation Treatment Volumes in Patients With Non-Small Cell Lung Cancer

    Radiother Oncol 55:317-324, 2000

       

    The potential effects of a non-invasive lymph node staging procedure – 18F- FDG-PET combined with CT (PET-CT) were compared with CT alone in patients with non small cell lung cancer.

        

    Previously published data on prospective lymph node staging protocols has used imaging and surgical pathology data from 105 patients. 73 had positive lymph nodes on CT and/or PET. For each one, gross tumor volume (GTV) was defined. The completeness of tumor coverage was assessed with the available surgical data. Theoretical radiation treatment plans were then
    formulated.

       

    Tumor coverage improved from 75% to 89% with this method. Information obtained could have led to a change of the treatment volumes in 45 patients (62%).

          

    In non small cell lung cancer, for radiation therapy, improved tumor coverage will result from assessment of locoregional spread by PET. In some selectable patients, toxicity could be reduced by correct assessment.

          

  • Erasmus
    JJ, McAdams HP, Rossi SE, et al (Duke Univ, Durham, NC)

    FDG PET of Pleural Effusions in Patients With Non-small Cell Lung Cancer

    AJR 175:245-249, 2000

        

    Pleural effusions associated with non small cell lung cancer are not always malignant and therefore do not preclude potentially curative surgery. The ability of FDG-PET to distinguish between benign and malignant pleural effusions is investigated.

         

    25 patients with non small cell lung cancer with pleural effusions were evaluated. Pleural activity that was greater than background mediastinal activity on FDG-PET was considered a positive finding. These findings were correlated with the pathological findings.

         

    In 22 patients malignancy was verified by pathology. 21 of these had positive FDG-PET scans and 1 was negative. 3 cases had no malignancy on pathology FDG-PET showed positivity in one of them. The sensitivity of FDG-PET was 95% and specificity was 67%. The positive and negative predictive values were 95% and 67%. Its accuracy was 92%.

       

  • MJ Byrne, JA Davidson, AW Musk, et al (Sir Charles Gairdner Hosp, Nedlands, Australia; Univ of Western Australia, Nedlands)

    Cisplatin and Gemcitabine Treatment for Malignant Mesothelioma: A Phase II Study.

    J Clin Oncol 17: 25-30, 1999.

        


    Malignant mesothelioma, an aggressive tumor, is an uncommon tumor that is increasing in incidence. A Phase II study of the efficacy of combined cisplatin and gemcitabine for the treatment has been reported herewith.

        


    Twenty-one patients, aged 46 to 74 years were enrolled in the study of which sixty-two percent had epithelial tumors, eighteen had tumor-node-metastasis (TNM) system stage III or IV. Treatment consisted of cisplatin being given as 100mg/m2, given intravenously on day 1 and gemcitabine 1000mg/m2 intravenously on days1,8, 15 of a 28-day cycle for 6 cycles. Pleural tumor was measured at 3 levels with CT scan at baseline; before the second, fourth, and sixth cycles; and every 2 months thereafter until the disease progression.

      


    The treatment of malignant pleural mesothelioma has been always controversial. For earlier stage disease being subjected to extrapleural pneumonectomy. For advanced disease, there are a number of chemotherapeutic agents that have demonstrated single-agent activity against malignant pleural mesothelioma, but the response rate is only 15% to 20%. This trial seems to have response rate of 47% i.e. 10 of 10 patients and is perhaps the highest ever reported. Consequently, several other centers are trying out the results of these studies so as to seen whether they are spurious or not.

        

  • Guardiola P, for the International Collaboration for Transplantation in Agnogenic Myeloid Metaplasia (Hopital Saint-Louis, Paris; et al)

    Allogeneic Stem Cell Transplantation for Agnogenic Myeloid Metaplasia: A European Group for Blood and Marrow Transplantation, Societe Francaise de Greffe de Moelle, Gruppo Italiano per il Trapianto del Midollo Osseo, and Fred Hutchinson Cancer Research Center Collaborative Study

    Blood 93: 2831-2838, 1999

      

    Agnogenic myeloid metaplasia patients have a median survival of less than 3 years.

       

    This study is a multivariate analysis conducted retrospectively on 55 patients who received allogenic stem cell transplantation for AMM.

      

    The 1-year transplant-related mortality rate approached 30% and outcome was strongly affected by grade III-IV acute GVHD and extensive chronic GVHD and old age. Those with anemia and high degree of bone marrow fibrosis also faired poorly.

       

  • Palumbo A, Triolo S, Argentino C, et al (Universita di Torino, Italy)

    Dose-intensive Melphalan With Stem Cell Support (MEL 100) Is Superior to Standard Treatment in Elderly Myeloma Patients 

    Blood 94: 1248-1253, 1999

       

    The clinical relationship between dose intensity of melphalan and response rate have been noted in patients with multiple myeloma particularly in younger patients after 200mg/m2 (median age of 64 years).

       

    This study of 71 patients with multiple myeloma underwent 2 or 3 courses of melphalan 100mg/m2 followed by stem cell support. CR was better (47%) compared to 5% in patients given melphalan and prednisone (MP). The median overall survival was 56 months for MEL 100 group and 48 months for MP group. Hence even the elderly patients with multiple myeloma given MEL 100 had faired better compared with MP.

        

  • Raymond D. Pastore, Lawrence M. Pfeffer and David M. Nanus (Division of Hematology and Medical Oncology, Department of Medicine, Joan and Sanford I. Weill Medical College of Cornell University, New York, New York; Department of Pathology, University of Tennessee Health Science Center, Memphis, Tennessee; Department of Urology, Joan and Sanford I. Weill Medical College of Cornell University, New York, New York)

    Renal Cell Carcinoma and Interferon at the Millennium

    Cancer Investigation 2001 Vol. 19 (3) Pg. 281-291

       

    Advanced renal cell carcinoma (RCC) has a dismal outlook, less than 5% have 5 year survival. Interferons (IFN) were originally classified as per type of cells producing them. The type I IFN include Interferon IFN-a, IFN-b and IFN-w (omega). Type II is IFN-g. IFN-a has been used for metastatic RCC since 1983 complete and partial responses occurred in 26% of patients. This time to response is approximately 3 months whereas the median duration of response is 6-10 months. 

       

    As compared to medroxyprogesterone acetate one year survival and median survival was better with IFN-a.

       

    Another study of IFN-a and IL-2, and tamoxifen combination vs. single agent tamoxifen alone had no difference in survival.

      

    Addition of 5Fluorouracil to IFN-a + IL-2 also did not have any impact on progression free survival. Better outcome and response rates were possible when combining IFN-a with cisretinoic acid. The rate of IFN in adjuvant setting is unclear. The Memorial Sloan-Kettering Cancer Center identified five prognostic factors, Karnofsky performance status (less than 80%), increased serum LDH, anemia (hemoglobin < 13 g/dl), hypercalcemia, and no prior nephrectomy. A recent SWOG study has shown prior nephrectomy enables a survival advantage for IFN therapy.

       

  • Jon
    Sudbo, Wanja Kildal et al

    DNA content as a prognostic marker in patients with oral leukoplakia.

    New Eng Jr. Med. Vol.344, April.26, 2001, pg.1270.



    Oral leukoplakia may develop into squamous cell carcinoma, which has a poor prognosis. Risk factors for oral carcinoma have been identified, but there are no reliable predictors of the outcome in individual patients with oral leukoplakia. Authors identified 150 patients with oral leukoplakia that was classified as epithelial dysplasia and measured the nuclear DNA content (ploidy) of the lesions to determine whether DNA ploidy could be used to predict the clinical outcome. Biopsy specimens obtained at annual follow-up visits were graded histologically and classified with respect to DNA content in a blinded fashion. Disease-free survival was assessed in relation to DNA ploidy and the histologic grade.



    A carcinoma developed in 3% of patients with diploid (normal ) lesions, as compared to 84% of patients with aneuploid (abnormal) lesions at the time of initial diagnosis. Carcinoma developed in 60% of patients with tetraploid lesions (intermediate). The cumulative disease-free survival rate was 97% among the group with diploid lesions, 40% among the group with tetraploid lesions and 16% among the group with aneuploid lesions.



    The conclusion was that the DNA content in cells of oral leukoplakia can be used to predict the risk of oral carcinoma.

      

  • New Approaches to Cancer Therapy and Diagnosis 

        


    Gerald Shklar, and Se-Kyung Oh (Division of Oral Pathology, Department of Oral Medicine and Diagnostic Sciences, Harvard School of Dental Medicine, Boston, Massachusetts)

    Experimental Basis for Cancer Prevention by Vitamin E

    Cancer Investigation 2000 Vol. 18 (3) Pg. 214-222

        

    Recent clinical trials have demonstrated significant cancer preventive potential of vitamin E. Experimental cancer model such as hamster buccal pouch which closely resembles its human counterpart have shown significant inhibition of carcinogenesis with systemic administration of vitamin E.

        


    In addition the other properties documented were its well known antioxidant properties, immunoenhancer, activator of p53 tumor supressor gene and an inhibitor of tumor angiogenesis. 

         


    Animal studies are now being confirmed in humans. The low levels of vitamin E in serum and plasma were found to be associated with an increased risk of lung and cervical cancer and prostate cancer mortality. Vitamin E has been shown to reduce the toxicity of adriamycin and enhance the anticancer effect of melphalan. 

         

  • L
    Kjellberg, G Wadell, F. Bergman, et al ( Umed and Stockholm,
    Sweden )

    Regular disappearance of the human papillomavirus genome after conization of cervical dysplasia by carbon dioxide laser.

    Am J Obstet Gynecol, Nov.2000; 183: 1238-42

        

    Objective : To evaluate the effectiveness of treatment of cervical dysplasia by laser conization in relation to persistence of human papillomavirus after treatment.

        

    Study Design : Of 230 women referred to colposcopy because of an abnormal Papanicolaou smear, 149 women could be followed up for 3 years. A total of 108 women were treated by carbon dioxide laser excision, 4 women were treated by carbon dioxide laser evaporation, and 37 women were merely followed up. Cervical samples were taken before treatment and at follow-up 3 years later and were analyzed by nested general primer polymerase chain reaction for human papillomavirus deoxyribonucleic acid.

         

    Results : Among women treated by laser conization, 82(73.2%) had positive results for human papillomavirus deoxyribonucleic acid before treatment. Three women (2.7%) had a positive finding at follow-up, but no woman had the same human papillomavirus type on both occasions. 

         

    Eighty-eight women had grade1 to grade 3 cervical intraepithelial neoplasia before treatment, whereas during follow-up only 2 squamous cells atypias were found.

         

    Conclusion : The human papillomavirus genome present before treatment was regularly cleared, and there was also no recurrence of dysplasia. The results suggest that human papillomavirus testing is useful for monitoring the efficacy of treatment and that treatment modalities resulting in clearance of human papillomavirus should be favored.

       

  • B. P. L. Wijnhoven, W. N. M. Dinjens and M. Pignatelli (Departments of Surgery and Pathology, Erasmus University Medical Centre, Rotterdam, The Netherlands and Division of Histopathology, Department of Pathology and Microbiology, Bristol Royal Infirmary, Bristol, UK)

    E-Cadherin-Catenin Cell-Cell Adhesion Complex and Human Cancer

    Br J. Surg August 2000 Vol. 87 (8) Pg. 992-1005 

        

    The E-cadherin-catenin complex plays a crucial role in epithelial cell-cell adhesion and in the maintenance of tissue architecture. Perturbation in the expression or function of this complex results in loss of intercellular adhesion, with possible consequent cell transformation and tumour progression. 

        


    Disturbance in protein-protein interaction in the E-cadherin-catenin adhesion complex is one of the main events in the early and late steps of cancer development.

       


    It has long been known that cell-cell adhesion is generally reduced in human cancers. Reduced cell-cell adhesiveness is associated with loss of contact inhibition of proliferation, thereby allowing escape from growth control signals. Invasion and metastases, the most life-threatening properties of malignant tumours, are considered to be later, but critically important, carcinogenic steps.

       


    In recent years, there has been increasing interest in a large family of transmembrane glycoproteins, called cadherins, which are the prime mediators of calcium-dependant cell-cell adhesion in normal cells. 

      


    There is increasing evidence that modulation of this complex by different mechanisms is an important step in the initiation and progression of human cancers.

      


    E-cadherin is bound via series of undercoat proteins, the catenins, to the actin cytoskeleton. This linkage between transmembranous cadherins and actin filaments of the cytoskeleton is necessary to form strong cell-cell adhesion. 

      


    In general, E-cadherin and catenin staining is strong in well differentiated cancers that maintain their cell adhesiveness and are less invasive, but is reduced in poorly differentiated tumours which have lost their cell-cell adhesion and show strong invasive behaviour. 

     


    Direct evidence implicating E-cadherin in the development of metastases is based on the association between highly metastasizing carcinomas and low E-cadherin immunoreactivity. 

       


    To predict tumour invasion and metastasis in carcinomas, it is useful to investigate not just the expression of E-cadherin but also the expression of the catenins. 

      


    Since the function and expression of the E-cadherin-catenin complex is often reduced in cancer cells, it is suggested that restoration of the E-cadherin-catenin will lead to differentiation and anti-invasive properties. Several drugs have been described to alter the expression of E-cadherin, some of which are already used in the treatment of cancer. 

       


    At least in vitro, insulin-like growth factor 1, tamoxifen, taxol, retinoic acid and progestagens have been shown to upregulate the functions of the E-cadherin-catenin complex, including inhibition of invasion.

      


    Aspirin is probably the most intriguing. Non-steroidal ant-inflammatory drugs are potent preventive agents against colon cancer. Aspirin decreased the rate of tumour formation.

      


    Aspirin produces a decrease in intracellular b-catenin levels, suggesting that modulation of this protein is associated with tumour prevention.

       

    Inactivation of the E-cadherin-catenin cell-cell adhesion complex is mediated by genetic and epigenetic events that occur in both the early and late stages of carcinogenesis.

      


    Elucidation of the mechanisms underlying the changes in E-cadherin and catenin function may lead to the development of novel therapeutic approaches based on biochemical and genetic manipulation.

       

  •  W. P. Ceelen, U. Hesse, B. de Hemptinne and P. Pattyn (Department of Abdominal Surgery 2P4, Ghent University Hospital, De Pintelaan 185, B-9000 Ghent, Belgium)

    Hyperthermic Intraperitoneal Chemoperfusion in the Treatment of Locally Advanced Intra-Abdominal Cancer

    Br J. Surg August 2000 Vol. 87 (8) Pg. 1006-1015 

       

    Surgical treatment of intra-abdominal cancer is often followed by local recurrence. In a subgroup of patients, local recurrence is the sole site of disease, reflecting biologically low-grade malignancy. These patients might, therefore, benefit from local treatment.

      


    A growing body of experimental evidence supports the use of hyperthermia combined with chemotherapy as an adjunct to cytoreductive surgery.

      


    Traditionally, locoregional cancer recurrence with widespread peritoneal implantation has been difficult to treat, most patients undergoing palliative procedures or no surgery at all.

      


    Although intraperitoneal chemotherapy has been used alone or after surgery, taking advantage of the presence of a peritoneal-plasma barrier, its clinical efficacy is moderate. 

       


    Recently, cytoreductive surgery followed by hyperthermic intraperitoneal chemoperfusion (HIPEC) has been described for both treatment and prevention of locoregional cancer spread from various origins, a management plan based on the experimentally noted synergism between hyperthermia and several antineoplastic drugs.

       


    Hyperthermia Alone

       


    The tumoricidal properties of hyperthermia have been recognized since ancient times. The observation of spontaneous tumour regression in patients with hyperpyrexia led to the first clinical application of hyperthermia, which consisted of injection of pyrogenic substances in patients suffering from sarcoma. 

      


    Tumour cell inactivation is time and temperature dependent, and starts at 40-410 C. At temperatures above 430 C exponential inactivation of tumour cells occurs for most rodent cell lines, resembling the effect of ionizing radiation. Human tumour cell lines may be more sensitive to mild hyperthermia (41-420 C) than rodent cell lines.

      


    Hyperthermia with Chemotherapy

      


    Both experimentally and clinically, the antitumoral effect of various chemotherapeutic drugs is enhanced by hyperthermia. A possible disadvantage of the addition of hyperthermia is the induction of multidrug resistance gene (MDR1) expression. 

      


    Most clinical experience with hyperthermic chemoperfusion has involved mitomycin C (MMC) or platinum compounds. MMC is commonly used in the treatment of gastrointestinal cancer, usually in combination with other drugs. Platinum compounds are widely used in the treatment of epithelial ovarian cancer.

       


    Hyperthermia with Radiotherapy 

      


    Several randomized clinical studies have clearly demonstrated that hyperthermia and radiotherapy act synergistically on tumour tissue. 

      


    This synergism is explained by two phenomena observed in animal experiments. First, hyperthermia is cytotoxic to cells in an environment with low partial pressure of oxygen and pH44. Second, hyperthermic treatment at mild temperatures induces reoxygenation of tumour cells, rendering them more sensitive to the effects of radiation therapy. At higher temperatures (over 430 C) the opposite happens.

      


    The delivery of hyperthermia to the peritoneal surfaces by closed perfusion of a heated solution was first described in a clinical situation in 1980.

      


    Extensive cytoreduction followed by HIPEC is associated with considerable rates of morbidity and mortality, and the potential risks of the procedure must be weighed carefully against any potential benefit.

      


    Postoperative morbidity and death may, therefore, relate mainly to the extent and duration of surgery, and not to the hyperthermic perfusion itself.

       


    Peritoneal carcinomatosis is generally considered to be an incurable condition. However, a growing body of both experimental and clinical evidence supports the therapeutic and prophylactic use of HIPEC in patients without systemic disease.

       


    Many surgeons may not be familiar with the use of hyperthermia as an adjunct to surgery; the authors hope that this article will stimulate their interest.


      

  • N S Weiss, M A Rossing

    Oestrogen-replacement therapy and risk of ovarian cancer

    The Lancet, vol.358, August 11, 2001,p438

        

    Data presented in the American Cancer Society’s Cancer Prevention Study II, has clearly demonstrated that there is an increase risk of ovarian cancer after HRT and the increased risk remains for atleast 4 years after hormone has been discontinued. Secondly this increased risk of ovarian cancer becomes more important after HRT has been used for 10 years.

      

    The data on increased risk of ovarian cancer by using oestrogen progestagen combination therapy is at present an unknown factor and we may have to wait for 10 years for clarification.

       

  • Baerg J, Murphy JJ, Anderson R, et al (BC Children’s Hosp, Vancouver, Canada)

    Neutropenic Enteropathy: A 10-Year Review

    J Pediatr Surg 34: 1068-1071, 1999



    Neutropenic enteropathy following chemotherapy is associated with fever, abdominal pain and neutropenia. This is usually due to mucosal damage and preferred sites are terminal ileum and cecum.



    This study of 38 episodes of neutropenic enteropathy in 33 patients with hematologic malignancies receiving intensive chemotherapy. The treatment for all these patients was conservative i.e. fluid resuscitation, bowel rest, and broad-spectrum antibiotics. Surgery was performed for bowel perforation. 



    Most of the patients developing neutropenic enteropathy had received cytosine arabinoside and/or VP16. 



    Ninety-four percent survived, surgery was performed only for patients with bowel perforation, 12% required laprotomy and right hemicolectomy, all of them survived.

          

  • B F Cole, R D Gelber, et al 

    Polychemotherapy for early breast cancer: an overview of the randomized clinical trials with quality-adjusted survival analysis.

    The Lancet; 2001; 358: 277-86

         


    Polychemotherapy is inclusive of multiple anticancer agents and tamoxifen. It was tried in younger women (less than 50 years old) and separately among older women (50-69 years old). The findings of the trial favour adjuvant polychemotherapy in both younger women and older women especially in patients with estrogen receptors breast
    cancer.

       

  • S. J. Pain and A. D. Purushotham (Cambridge Breast Unit, Addenbrooke’s Hospital, Cambridge, UK)

    Lymphoedema Following Surgery for Breast Cancer

    BJS September 2000 Vol. 87 (9) Pg. 1128-1141

        


    Lymphoedema is a common complication of breast cancer treatment, affecting approximately a quarter of patients. Those affected can have an uncomfortable, unsightly and sometimes functionally impaired limb prone to episodes of superficial infection. The aetiology, pathophysiology and management of these patients is poorly understood. 

        


    Lymphoedema has been described as ‘a progressive pathologic state or condition characterized by chronic inflammatory fibromatosis and hypertrophy of the hypodermal and dermal connective tissues.

         


    There exists the extremely rare but potentially fatal possibility of secondary lymphangiosarcoma (Stewart-Treves syndrome).

        


    Axillary clearance, as commonly advocated, provides a guide to prognosis, assists in planning adjuvant systemic therapy and minimizes axillary recurrence; there is emerging evidence to suggest an impact on survival.

        


    Arm swelling in the early postoperative period is commonly observed and tends to settle spontaneously within a matter of weeks. Lymphoedema may, however, develop months or years after this (an interval of over 20 years has been reported), with around 75 per cent of cases occurring in the first year after operation.

         


    Onset may be gradual, or rapid. Patients occasionally identify a precipitating factor, such as a minor infection following a cut or graze, or a greater than usual degree of exercise involving the arm. 

        


    There remain, however, a number of questions regarding arm oedema following breast cancer surgery.

         


    1. Why do some women develop this complication while others do not?

    2. What explains the latent period preceding the onset of oedema?

    3. Why is it that certain sections of the arm are ‘spared’?

    4. Why is it so difficult to create artificial models of lymphoedema in animals, employing far greater surgical trauma than that involved in breast cancer treatment?

         


    Oedema is defined as the accumulation of interstitial fluid in abnormally large amounts. This can occur as a result of one of a number of physiological changes: (a) an increase in filtration pressure caused either locally by arteriolar dilation or venular constriction, or more globally by increased arterial inflow or elevated venous pressure; 

    (b) a reduction in the osmotic pressure gradient resulting from either a decrease in plasma proteins or an increase in osmotically active material in the interstitium; 

    (c) an increase in capillary permeability mediated by ‘lymphagogues’ such as substance P, histamines and kinins; and

    (d) a reduction in the flow of lymph

        


    Kissin et al found the prevalence of swelling following axillary sampling and irradiation to be equivalent to that following clearance of the axilla, and there is general agreement that the combination of surgery and radiotherapy to the axilla is best avoided, with quoted prevalence rates more than double those for surgery alone.

        


    There are other factors contributing to the aetiology of lymphoedema, with alterations noted in arterial inflow, venous return and plasma osmolality, as well as the intriguing possibility of the presence of lymphaticovenous communications. 

        


    Treatment strategies for lymphoedema fall into three main groups: conservative measures, drug treatment and surgery. At present, conservative measures form the mainstay of management, with surgery reserved for resistant cases (if at all). The place of pharmacological therapy is still unclear. 

         


    The principles of conservative treatment of lymphoedema remain unchanged from the middle of the nineteenth century, with attention to the areas of hygiene, massage, compression, and remedial exercises.

        


    There is no place for the use of diuretics in the treatment of lymphoedema; these drugs may even exacerbate the problem by increasing the protein concentration in the interstitium, thus enhancing the stimulus to inflammation and fibrosis. 

         


    Surgery for lymphoedema is usually reserved for cases resistant to conservative measures. Operations may be divided into two groups, namely debulking procedures and attempts to influence lymphatic drainage. 

         


    In 1962, Cockett and Goodwin described the anastomosis of a dilated lumbar lymphatic to the spermatic vein to treat a case of chyluria. Subsequent development of microsurgical techniques has enabled lymphaticovenous anastomosis to emerge as a potential treatment of arm lymphoedema. 

         


    At present lymphoedema following surgery for breast cancer remains a poorly understood and incurable problem. With cure an unrealistic possibility at present, emphasis should be placed on prevention. It may also be that postoperative changes, demonstrated in the latent phase before the development of swelling, might identify those in whom lymphoedema is most likely to occur. Early prophylactic initiation of conservative treatment measures may then prove more efficient than their institution when swelling has become established.

       

  • Clinical Trials 




    Stephen Tyring, Robert Belanger, Werner Bezwoda, Per Ljungman, Ron Boon, and Robin L. Saltzman for the Collaborative Famciclovir Immunocompromised Study Group (University of Texas Medical Branch, Galveston, Texas; Hospital Maisonneuve-Rosemont, Montreal, Quebec, Canada; Johannesburg Hospital, Parktown, Johannesburg, South Africa; Department of Hematology, Huddinge University Hospital, Karolinska Institute, Huddinge, Sweden; SmithKline Beecham Pharmaceuticals, New Frontiers Science Park, Harlow, Essex, UK; SmithKline Beecham Pharmaceuticals, Collegeville, Pennsylvania) 

    A Randomized, Double-Blind Trial of Famciclovir Versus Acyclovir for the Treatment of Localized Dermatomal Herpes Zoster in Immunocompromised Patients 

    Cancer Investigation 2001 Vol. 19 (1) Pg. 13-22

         


    This study of 148 patients with clinical evidence of localized herpes zoster in patients who were immunocompromised following bone marrow or organ transplantation or oncology (chemotherapy) treatment received either oral famciclovir 500 mg thrice daily or acyclovir 800 mg five times daily for 10 days.

          


    Efficacy and safety data revealed equivalent results, thus famciclovir was well tolerated with a safety profile comparable to that of acyclovir.

          

  • L. E. Schnipper and T. B. Strom 

    Editorial: A Magic Bullet For Cancer – How Near and How far?

    The New England Journal of Medicine Vol. 345(4), 26 July 2001; Pg. 283-84

           

    Since even humanized chimeric monoclonal antibodies often provoke antibodies that nullify the therapeutic effects of engineered immunoglobulins, a way of making fully human antibodies in vitro has been sought.

          

    The most notable success to date has been achieved with rituximab, a humanized monoclonal antibody against the B-cell-specific antigen CD20. In patients with low-grade B-cell lymphoma who relapse after the usual therapy, rituximab frequently results in complete or partial remissions.

         

    In some patients with low-grade lymphoma, rituximab plus chemotherapy eliminates all detectable cells. 

           

    A different approach entails fusing the DNA sequences encoding antigen-binding antibody fragments with genes for bacterial toxins.

           

    CD22, a surface antigen of B cells, was genetically fused to a truncated pseudomonas toxin protein containing the translocation and toxin moieties. This genetically engineered immunotoxin was used to treat patients with hairy-cell leukemia, a B-cell neoplasm with abundant expression of surface CD22. In this trial, the anti-CD22 immunotoxin induced complete remissions in 69 percent of patients.

           

    Similar results have also been found with use of a fusion protein combining diphtheria toxin and interleukin-2 in patients with T-cell lymphomas that express interleukin-2 receptors.

            

    Despite the uncertainties and unsolved problems, the authors are confident that tumor-specific immunotherapy is more than a distant promise.

         

  • Reiter A, Schrappe M, Tiemann M, et al (Medizinische Hochschule, Hannover, Germany; Christian-Albrechts-Universitat, Kiel, Germany; Humboldt Univ Berlin; et al)

    Improved Treatment Results in Childhood B-Cell Neoplasms With Tailored Intensification of Therapy: A Report of the Berlin-Frankfurt-Munster Group Trial NHL-BFM 90

    Blood 94: 3294-3306, 1999

         

    This study of patients up to 18 years and newly diagnosed with Non Hodgkin lymphoma or acute B-cell leukemia were stratified into 3 groups.

        


    R1-completely resected received two, 5-day courses of chemotherapy including intermediate-dose methotrexate, dexamethasone, oxazophorins, etoposide, cytarabine, doxorubicin, and intrathecal therapy. 

         


    Patients in group R2 had extraabdominal primary tumors only or an abdominal tumor with LDH > 500 U/L. These patients received 4 courses of chemotherapy including high-dose methotrexate.

          


    Those in third group R3 with abdominal primary and systemic involvement (bone marrow, CNS, or multifocal bone disease). These patients received VI courses of high dose methotrexate. 

         


    This therapy strategy demonstrated a high degree of effectiveness for patients with Burkitt-type lymphoma or acute B-cell leukemia and also for patients with diffuse large B-cell lymphomas. Intensification of therapy can significantly improve outcome for patients with childhood B-cell neoplasms.

           

  • Per Eystein
    Lfnning 

    Aromatase Inhibitors and Inactivators in Breast Cancer 

    BMJ, Vol.323 (7318), 20 October 2001, Pg. 880-881

               

    Summary : Aminoglutethimide, a first generation aromatase inhibitor, was used for the treatment of breast cancer 3 decades ago. Although its antitumour effect was similar to that of tamoxifen, its use was limited because of severe side effects.

          

    Introduction of the 3rd generation aromatase inhibitors anastrozole and letrozole was a great leap forward. While aminoglutethimide and 2nd generation compounds reduced oestrogen synthesis by 85-90%, the 3rd generation compounds effectively inhibit oestrogen synthesis by 97-99%.

            

  • Amar Alwitry and Iain Gardner

    Minerva 

    BMJ, Vol.323, 20 October, Pg. 944

           

    Summary : This is a case report of tamoxifen induced retinopathy in a 64 year old woman taking tamoxifen 20 mg/day for 8 years. The incidence of tamoxifen retinopathy is about 6% among patients who have taken the drug for 5 years. Stopping treatment prevents further deterioration but rarely allows complete recovery of visual function.

          

  • Shulin Li

    IL-12 based therapy of malignancies

    Drugs of Today, Sept.2001, vol.37, pg.629-737.

      

    Interleukin-12 (IL-12) is an important molecule that triggers the activation of natural killer (NK) cells and T-cells, the development of T helper type 1(Th1) cells and the expression of antiangiogenic genes. Novel methods for IL-12 delivery include cell-based ex vivo gene therapy, viral vector-based gene therapy and DNA plasmid-based nonviral gene therapy. IL-12 electroporation gene therapy may hold some promise for tumors accessible by electrode, such as head and neck cancer, breast cancer, prostate cancer and melanoma. Codelivery of other therapeutic genes with IL-12 may enhance the therapeutic effect and reduce the level of IL-12 required for efficacy. All three approaches to IL-12 gene therapy are under clinical investigation. The preliminary results indicate that IL-12 gene therapy is safe and is not associated with any major clinical toxicity.

       

  • Enrico Crucitta, Nathalia Locopo, et al

    The Role of Letrozole (Femara®) in Breast Cancer Therapy: A Clinical Review.

    Drugs of Today, Sept.2001, 37(9): 639-644

       

    Letrozole is a third-generation aromatase inhibitor for use in postmenopausal women with hormonal-sensitive breast cancer. This drug was found to reduce or effectively shrink tumors in a significant number of such patients. It exhibits antitumor activity at a relatively low daily dose, and is highly potent and selective and well tolerated. Results from recent phase III clinical studies have confirmed the efficacy and the key role of this drug in the therapy of advanced breast cancer in postmenopausal women.

       

    Moreover, letrozole demonstrated higher activity and lower toxicity compared to tamoxifen in the first-line therapy of postmenopausal women affected with advanced breast cancer. However, it also represents a valid option in second-line therapy after tamoxifen failure. New data on this agent in adjuvant or neoadjuvant treatment also suggest efficacy in the treatment of early breast cancer.                                                                                      

                                        

  • Carlos L Arteaga  

    Foreword – Epidermal Growth Factor receptor – Trageted approaches for anticancer therapy: Focus on ZD1839        

    Drug – Supplement no.1, 2000, vol.60     

                                    

    Epidermal growth factor receptor (EGFR) is the cellular homologue of a mutant constitutively active, oncogenic tyrosine kinase that induced tumours in animals. The EGFR requires activation by binding of ligand, while its cellular effects depend on activation of its intrinsic tyrosine kinase activity.       

                                              

    This basic knowledge has led to the development of several antireceptor approaches which are the subject of the articles. One has been the development of antibodies against the receptors ectodomain. A second powerful approach has been the generation of ATP-mimetics that compete with ATP for binding to the receptor’s tyrosine kinase pocket and thus disable its function. One of these promising small molecules, ZD 1839, is discussed in the supplement.               

                                                                                                                                         

  • Eric K Rowinsky                                               

    The Pursuit of Optimal Outcomes in Cancer Therapy in a New Age of Rationally Designed Target-Based Anticancer Agents.                          

    Drugs Supplement 2000, vol.60, supplement 1, pg.1                        

                                                                                                          

    The recent development of a plethora of rationally designed target-based anticancer agents has opened up new opportunities and extraoridinary therapeutic challenges. Since these agents appear primarily to target malignant cells, they can be expected to be less toxic at clinically effective doses than the cytotoxic agents. Among the various types of rationally designed target based agents are those that target strategic facets of cell growth signal transduction, angiogenesis, metastatsis and cell cycle regulation .                          



    Table 1. Rationally derived molecular anticancer approaches requiring novel clinical development paradigms.


        
    General
    target                 
    Specific target                             
    Therapeutic agent





















    Signal transduction

    Growth factor receptor

    Antibodies against erbB/family (EGFR, HER2).Small molecule inhibitors of
    receptor tyrosine kinases (ERB family, EGFR, HER2,
    PDGF)

    Ras

    Small molecule inhibitors of farnesyltransferase
    Antisense oligonucleotides (K-Ras, H-Ras, N-Ras)

    Raf   

    Antisense oligonucleotides

    MAPK

    Small molecules

    Rapaymycin-sensitive
    and

    Rapamycin analogs

    P13K/ Akt pathways

    Small molecule inhibitors

    Malignant angiogenesis and
    Metastasis

    VEGF

    Antibodies
    Small molecular inhibitors of VEGF receptortyrosine kinasesNatural products
    Ribozymes

    Matrix metalloproteinases

    Small molecules

    Integrins 

    Small molecules, peptides,
    peptide cytotoxic conjugates

    Apoptosis-Survival

    BCL-2 

    Antisense

    BCR/ABL

    Small molecules,inhibitors of tyrosine

    kinase

    Death receptors (TNF and
    Other death receptor Families)

    Small molecules

    Tumor suppressor gene function. 

    p53

    Viral vectors with p53 to restore
    Function.Viral vectors that selectively kill cells
    With mutant p53

    Tumour differentiation

    Polyamines 

    Polyamine inhibitors

    Retinoid receptors

    Retinoids

    Cell cycle checkpoint
    control 

    CDKs

    Small molecule kinase inhibitors


    CKDs
    = cyclin-dependent kinases; EGFR
    = epidermal growth factor receptor; MAPK=
    mitogen-


    Activated
    protein kinase; PDGF= platelet derived growth factor; TNF= tumour necrosis factor; VEGF=
    vascular endothelial growth factor.

                             


  • Jose Baselga and Steven D Averbuch                  

    ZD1839 (‘Iressa’) 1,2 as an Anticancer Agent               

    Drugs Supplement 2000, vol.60, suppl.1, pg.33-40 

                        

    ZD1839 (‘Iressa’)1,2 is an orally active, selective epidermal growth factor receptor-tyrosine kinase inhibitor which blocks signal transduction pathways implicated in the proliferation and survival of cancer cells and other host dependent processes promoting cancer growth. In preclinical studies, ZD1839 produced reversible growth inhibition and growth delay in a wide range of tumour cell lines and human tumour xenografts. Moreover, this activity was enhanced when ZD1839 was coadministered with cytotoxic agents. Preliminary results from phase I trials in patients with advanced disease and a wide variety of tumour types suggest that ZD1839 has an acceptable tolerability profile and promising clinical efficacy, particularly in non-small cell lung cancer (NSCLC). ZD1839 is currently in phase III clinical development for the treatment of advanced NSCLC. In addition, further trials are ongoing or planned in a number of other tumour types.          

                      

    ZD1839 (‘Iressa’)1,2, an anilinoquinazoline, is an orally active, selective EGFR tyrosine kinase inhibitor (TKI) which is currently under clinical evaluation in phase II to III clinical trials in patients with cancer. Preclinical data for ZD1839 strongly support the possibility of potentiating the antitumour activity of conventional chemotherapy with agents that selectively block the
    EGFR.    

  • Michael McCarthy


    Targeted drugs taken center stage at US Cancer Meeting


    Lancet, vol.357, May 19, 2001, pg.1593

                                     

    Researchers attending this year’s annual meeting of the American Society of Clinical Oncology (ASCO) were clearly excited by results of several early phase I and phase II trials that suggest that new drugs that target specific molecular abnormalities in cancer cells may be extremely potent weapons against various cancers.    

                                                            

    These new drugs, which target abnormal growth factor receptors and other cancer-causing proteins, will change the way doctors treat cancer in much the same way the discovery of antibiotics changed the way doctors treated infections, said Larry Norton head of the Division of Solid Tumour Oncology at Memorial Sloan-Kettering Cancer Centre (New York)   

                                                      

    The studies that gained the greatest attention were trials of the compound imatinib mesylate. This drug,which is being marketed in the USA as Gleevec, was granted accelerated approval by the US Food and Drug Administration (FDA) after it had been shown to be extremely potent against chronic myelogenous leukaemia (CML). The compound is a small molecule that blocks an abnormal tyrosine kinase, BCL-ABL, that seems to be the key molecular defect leading to uncontrolled cell growth in CML.  

                                                        

    Earlier this year, Brian Druker of Oregon Health Sciences University (Portland, OR, USA) reported the results of a dose-escalating phase I study that indicated that a dose of 300 mg per day induced complete haematological responses in 53 of 54 patients for whom standard CML treatment with interferon ? had previously been ineffective or not tolerated. And a related study showed the drug could also induce responses in patients with CML and acute lymphoblastic leukaemia who were in blast crises.                                    

                                                         

    The new studies presented at the ASCO meeting were phase I and phase II trials of imatinib mesylate in patients with a rare form of tumours, called gastrointestinal stromal tumours (GISTs) which arise from the precursor cells of the connective tissue of the gut. Another abnormal tyrosine kinase growth factor, C-KIT, is thought to play a key role in the pathogenesis of these tumours. GISTs usually do not respond to chemotherapy or radiation therapy and if not resected successfully are usually rapidly fatal.

                                                 

    In another phase II trial reported at the meeting, cetuximab was found to shrink metastatic colorectal cancer tumours in patients with chemotherapy-resistant disease. Cetuximab is a monoclonal antibody that blocks epidermal growth factor receptors (EGFR), cell membrane proteins found in colon and several other tumours that when stimulated drive cancer cell division and protect the cells from apoptosis. All of the 121 patients in the trial had tumours that had failed to respond to courses of standard chemotherapy with fluorouracil and irinotecan. All patients had tumours that expressed EGFR.    

                                                             

    In the trial, the patients were treated with irinotecan again but this time in combination with cetuximab. 27 (22.5%) of the patients had a partial response, which was defined as a greater than 50% reduction in tumour size.  

                                                                                                           

    Results from the trials of the antiangiogenesis drugs were less encouraging. Several trials suggested that the drugs clearly have antitumour activity but that the extent of the activity will vary not only from patient to patient but from tumour to tumour and even within a tumour.

      

  • P.A.McKelvie, M. Daniel (Melbourne, Victoria, Australia)

    Impression cytology following mitomycin C therapy for ocular surface squamous neoplasia.

    BJO 2001; 85: 1115-1119

      

    Though topical mitomycin C (MMC) therapy has been used for treatment of ocular surface squamous neoplasia (OSSN) since 1994, relatively few studies have reported the cellular changes in ocular surface following
    MMC.

      

    Hence, using Millipore filters at intervals between 4 and 17 weeks after starting MMC, the authors studied impression cytology in 4 patients with OSSN and compared them with pretreatment cytology.

      

    It was found that MMC induced changes of cytomegaly, cytoplasmic vacuolation, nucleomegaly with nuclear wrinkling, and binucleation or multinucleation in some cells in all samples. These changes resembled those seen following radiation therapy in uterine cervix. The predominant form of cell death was apoptosis with fewer cells showing necrosis.

     

    MMC related changes may persist in ocular surface epithelium for at least 8 months following therapy.

      

  • E
    G Kemp, A N Harnett, et al (Gartnavel Gen Hospital,
    Glasgow, UK)

    Preoperative Topical and Intraoperative Local
    Mitomycin C Adjuvant Therapy in the Management of Ocular
    Surface Neoplasias


    BJO, January 2002; 86(1); 31-34

      

    The authors reviewed case notes of 11 patients receiving
    mitomycin C adjuvant therapy as 0.04% drops, four times
    daily in 2 weekly courses preoperatively and/or a single
    intraoperative appplication of 0.4 mg/ml of mitomycin C.

      

    The histopathology of the cases

    (1) conjunctival primary acquired melanosis,

    (2) conjunctival melanomas

    (3) sebaceous cell carcinomas with conjunctival
    intraepithelial spread, and

    (4) conjunctival intraepithelial squamous neoplasias.
    Seven patients had limited local excision of the
    residual tumor mass and one had cryotherapy.

      

    All 11 patients showed a favorable response to mitomycin
    C adjuvant therapy. The therapy was well tolerated.

      



 

 

Specialitiy

 

 

  • Fertility Drugs and the Risk of Breast Cancer
    E Ricci, et al (Instituto di Richerche Farmacologiche ” Mario Negri,’ Milan, Italy; Universita degli Studi di Milano, Italy)
    Hum Reprod  14: 1653-1655, 1999.
       
    Use of fertility drugs does not increase the risk of breast cancer.  These findings are consistent with the results of most, though not all, previous studies.
        

  • Fertility Drugs and the Risk of Breast and Ovarian Cancers : Results of a Long-term Follow-up Study.
    G Potashnik, et al (Ben-Gurion Univ of Negev, Beer Sheva, Israel;  Sheba Med Ctr, Tel Hashomer, Israel).
    Fertile Steril 71:853-859, 1999.
       
    The relationship between fertility drug use and the risk of breast and ovarian cancers has not been defined.  A historic-prospective cohort study was undertaken to investigate this association.
        
    Conclusions- The use of fertility drugs appears to be unassociated with an increased risk of breast cancer.  Women treated with human menopausal  gonadotropin alone had no malignant tumors.  These findings should be considered in light of the recent suggestion that clomiphene citrate may decrease the risk of breast cancer in infertile women.
       
    Editorial comment: The data from this long-term prospective study indicate that the use of ovulation-inducing agents is not associated with an increased risk of either breast or ovarian cancer.  Many women are concerned that the use of these agents may increase their risk of having these cancers.  Data accumulating from this and other studies indicate that such a relation does not exist.
       

  • MA Cobleigh, et al (Rush-Presbyterian-St Luke’s Med Ctr, Chicago)  
    Hormone Replacement Therapy and High S Phase in Breast Cancer
    JAMA 281: 1528-1530, 1999.
       
    Conclusion – Pre-existing clinically occult cancers may be promoted by the use of hormone replacement therapy, which may bring them to light sooner in their natural biological history.  This may account for the better survival of patients with breast cancer who have used hormone replacement therapy.  The use of hormone replacement therapy appears to stimulate growth of estrogen receptor-positive but not estrogen receptor-negative breast cancer.  There is an unknown prognostic significance in current hormone replacement therapy users who have estrogen receptor-positive tumors.
       
    Editorial comments: Some, but not all, observational epidemiologic studies indicate that the postmenopausal use of estrogen replacement is associated with an increased risk of diagnosis of breast cancer compared with women not taking estrogen.  Several studies have reported that survival rates of women in whom breast cancer develops postmenopausally is significantly greater among women taking estrogen than among age-matched controls with breast cancer who are not taking estrogen.
        
    Breast cancer with a high percentage of breast cells in S phase has been associated with a poor prognosis of the disease.  This study found that estrogen use was associated with a high frequency of S-phase cells in the treated breast cancers.  Since estrogen use is associated with a better prognosis for women with breast cancer, the authors speculate that estrogen may promote the growth of clinically occult cancers. These cancers are then treated earlier in their natural history than normally occurs, and survival rates are increased.  Thus estrogen does not initiate breast cancer but promotes the growth of an existing cancer so that it can be diagnosed and treated earlier in its natural history.
         

  • A Rosset, L Zografos, P Coucke, et al (Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland; Univ of Lausanne, Switzerland)
    Radiotherapy of Choroidal Metastases.
    Radiother Oncol 46:263-268, 1998.
        
    This is a review of the records of 58 consecutive patients undergoing external beam radiation therapy between 1970 and 1993.  Patient ages ranged from 40 to 81 years. The primary tumor was breast carcinoma in 75%, lung carcinoma in 17%, gastrointestinal, gastrourinary, or unknown in the remainder. The median interval between the primary tumour and metastases was 55 months. Treatment consisted of megavoltage irradiation with a median prescribed dose of 35.5 Gy.
      
    Complete response rate at 3 months or more after Rx was 53%. In 62% of patients, visual acuity was improved or stabilized.  There were 5 complications: 3 cataracts, one retinopathy and one glaucoma.
        
    Doses greater than 35.5 Gy  provide significantly better tumor response and visual acuity. Whenever possible, a lens sparing technique should be used.
          

  • R Indudharan, T Arni, KK Myint, et al (Universiti Sains Malaysia, Kelantan; Hosp Tengku Ampuan Afzan, Kuantan, Malaysia)
    Lymphoblastic Lymphoma/Leukemia Presenting as Perichondritis of the Pinna.
    J Laryngol Otol 112: 592-594, 1998
      
    A patient treated for perichondritis of the pinna was eventually determined to have B-lineage lymphoblastic lymphoma evolving to a leukemic phase. There was no pre-existing immunodeficiency.
      
    Though lymphoma is the second most common malignancy of the head and neck region, the pinna as the extranodal site of lymphoma, has been previously reported only once. Hence the need to broaden one’s diagnostic horizon when inflammatory lesions do not heal within a reasonable period.
        

  • RC O’Reilly, SB Kapadia,  D.B. Kamerer (Univ of Pittsburgh, Pa)
    Primary Extracranial Meningioma of the Temporal Bone.
    Otolaryngol Head Neck Surg  118:690-694, 1998.
       
    Though meningiomas typically occur intracranially, they may rarely arise de novo in the temporal bone. Because of the invasive nature of this tumor, surgical resection is difficult, and postoperative surveillance is necessary.
         

  • HM Dunniway, DB Welling (Ohio State Univ, Columbus)
    Intracranial Tumors Mimicking Benign Paroxysmal Positional Vertigo.
    Otolaryngol Head Neck Surg, 118:429-436, 1998.
       
    Benign positional vertigo may not always be benign, as indicated in this study where intracranial tumors were identified in five patients who presented as “ benign paroxysmal vertigo.”
        
    When patients of “benign paroxysmal vertigo” do not improve after particle repositioning manoeuver, further assessment is needed to rule out intracranial new growths.
       

  • DW Cramer, RF Liberman, et al (Brigham and Women’s Hosp, Boston; Dartmouth-Hitchcock Med Ctr, Lebanon, NH)
    Genital Talc Exposure and Risk of Ovarian Cancer.
    Int J Cancer 81: 351-356, 1999.
      
    The group consisted of 563 women in eastern Massachusetts and New Hampshire with epithelial ovarian cancer, including tumors of borderline malignancy. With a control group of 523 randomly selected women.
      
    Findings: Patients were more likely than controls to have used talc as a body powder. Exposure appeared to be more harmful before the first live birth. The association was strongest for women with invasive serous cancers and weakest for those with mucinous tumors.
      
    Conclusions: This large population based case control study has demonstrated an association between the use of talcum powder in the genital region and ovarian cancer. Avoidance of talc in genital hygiene might reduce the occurrence of a highly lethal cancer by at least 10%. Formal public health warnings should be provided about the potential risk associated with the use of talcum powder in the genital region.
         

  • BY Karlan, RL Baldwin,. Et al (Univ of California, Los Angeles; Univ of Toronto)t
    Peritoneal Serous Papillary Carcinoma, a Phenotypic Variant of Familial Ovarian Cancer: Implications for Ovarian Cancer Screening.
    Am J Obstet gynecol 180: 917-928, 1999.
      
    During the administration of a familial ovarian cancer screening program that was begun in 1991 and based on the pedigrees of symptom-free volunteers, a disturbing number of “ovarian cancer” cases with bulky peritoneal carcinomatosis and normal-size ovaries, consistent with peritoneal serious papillary carcinoma were noted. These lesions may represent primary ovarian cancers that disseminated widely before ovarian enlargement or discrete tumors arising from multiple peritoneal surfaces predisposed to malignant transformation. These tumors’ clonality and association with BRCA1 and BRCA2 mutations were reported.
      
    It was found that those carrying BRCA mutations are at risk for both primary ovarian cancer and peritoneal serous papillary carcinoma. The latter is clearly not amenable to early detection by vaginal ultrasound screening. While prophylactic oophorectomy reduces the risk of these types of cancers by 50%, it, unfortunately, does not eliminate the risk.
        

  • A Obermair, A Handisurya, et al (Univ Hosp of Vienna; Gen Hosp Lainz, Vienna)
    The Relationship of Pretrement Serum Hemoglobin level to the Survival of Epithelial Ovarian Carcinoma Patients: A Prospective Review.
    Cancer 83: 726-731, 1998.
      
    In malignant solid tumors and a variety of hematologic malignancies, tumor anemia is common. There are no factors other than the malignant disease itself in a number of patients to explain the presence of anemia. Previous studies have shown a correlation between the prognosis in patients with a variety of malignancies and pretreatment hemoglobin levels. 
      
    This study comprises of 206 patients with untreated epithelial ovarian carcinoma who had surgery during a 10-year period. Serum hemoglobin value below 12g/dl was the definition of anemia.
      
    Authors conclude that overall survival of patients with ovarian carcinoma had an independent relationship with tumor anemia, after adjustment for established prognostic factors. Marked tumor anemia was considered an indicator of the presence of biologically aggressive tumor cell clones because no significant interaction could be found between the grade of anemia and chemotherapy.
       

  • JA Bridgewater, AE Nelstrop, et al (Mount Vernon Centre for Cancer Treatment, Northwood, England; Royal Marsden Hosp, London; Univ of Mississipi, Jackson; et al)
    Comparison of Standard and CA-125 Response Criteria in Patients With Epithelial Ovarian Cancer Treated with Platinum or Paclitaxel.
    J Clin Oncol 17: 501-508, 1999
       
    Background: The role of CA-125 in the assessment of patients undergoing second-line treatment with taxanes has been questioned. Some authorities doubt the reliability of CA-125 in the management of individual patients, and some have concluded that CA-125 cannot be used as a guide for determining response. CA-125 was evaluated as a measure of response in patients treated with paclitaxel.
      
    Methods: Data on 144 patients given paclitaxel in 4 different trials and 625 patients given platinum in 2 trials were analzyed, using precisely defined 50% and 75% reductions in CA-125 as responses. Standard and CA-125 response rates were compared.
      
    Conclusion: Precise 50% or 75% CA-125 response criteria are as sensitive as standard response criteria in evaluating treatment activity in patients with ovarian cancer. The standard measurement of complete response means disappearance of all disease or partial response more than 50% decrease.
      
    Though it is true CA-125 reduction 50-75% can be relied upon as response to the treatment of cancer with platinum or paclitaxel, the opposite does not hold true i.e. there can be disease response without a drop in CA-125.
       

  • M Markman, MF Brady, et al (Cleveland Clinic Found, Ohio; Roswell Park Cancer Inst., Buffalo, NY; Women’s Cancer Ctr of Northern California, Palo Alto; et al)
    Phase II Trial of Intraperitoneal Paclitaxel in Carcinoma of the Ovary, tube, and Peritoneum: A Gynecologic Oncology Group Study.
    J Clin Oncol 16: 2620-2624, 1998.

    Methods: Seventy-six eligible patients were enrolled in the trial. Eight-six percent were considered potentially cisplatin sensitive. In all patients, the largest residual disease was 0.5cmor less in maximum diameter at the end of second-look surgery. Some patients had been treated with paclitaxel previously. Treatment consisted of paclitaxel, 60mg/m2 intraperitoneal weekly for 16 weeks, followed by surgical assessment in patients with no evidence of disease progression.
      
    Findings : Fifty-three patients (70%) received all 16 planned treatment courses. Treatment was well tolerated. Microscopic disease at the beginning of intraperitoneal therapy had a complete response as defined by surgery.
      
    Authors conclude salvage intraperitoneal paclitaxel is active and tolerable in patients with microscopic residual ovarian, fallopian tube, or peritoneal cancer. The effect of such treatment on survival needs to be determined in a phase III trial.
      
    Editorial comment: Intraperitoneal therapy has yet to be shown an effective second-line treatment for most patients.
       

  • HD Homesley, BN Bundy, et al (Brookview Research Inc, Winston-Salem, NC; Roswell Park Cancer Inst, Buffalo, NY; Indiana Univ, Indianapolis)
    Bleomycin, Etoposide, and Cisplatin Combination Therapy of Ovarian Granulosa Cell Tumors and Other Stromal Malignancies: A Gynecologic Oncology Group Study.
    Gynecol Oncol 72: 131-137, 1999.
       
    Granulosa cell tumors represent about 8% of ovarian neoplasms and are more common in older women. These women usually present with early-stage disease. Patients with stage I tumors are usually treated with surgery, but those with advanced-stage tumors require adjunctive therapy. The efficacy and toxicity of a combination of bleomycin, etoposide, and cisplatin (BEP) as a first-line treatment for advanced or recurrent ovarian stromal cancers was investigated in a prospective trial.
      
    The study group consisted of 57 women with histologically confirmed stage II to IV or recurrent ovarian stromal tumors that had been incompletely resected. The patients were treated with BEP. 20 U/m2 on the day 1, etoposide 75mg/m2 from day 1 to day 5 and cisplatinum 20mg/m2 from day 1 to day 5 every 3 weeks for 4 courses.
      
    Findings: Of the 38 women who had second-look laparotomy at the end of the BEP treatment, 37% had negative findings. Grade 4 myelotoxicity occurred in 61% of the patients treated with the BEP.
      
    Authors conclude that BEP combination appears to be an effective first-line chemotherapy for advanced and recurrent ovarian stromal cancers.

  • Alam MDS, Kasagi K, Misaki T, et al [Kyoto Univ, Japan]
    Diagnostic Value of Technetium -99m Methoxyisobutyl Isonitrile [ 99m Tc-MIBI] Scintigraphy in Detecting Thyroid Cancer Metastases: A Critical Evaluation
    Thyroid 8: 1091-1100, 1998, Pg.215

    Many investigators consider that technetium – 99 methoxyisobutyl isonitrile [ 99m Tc-MIBI] scintigraphy should be used as a supplement to performing radioactive iodine whole-body scanning [ 131 I-WBS] and measuring serum thyroglobulin [Tg] levels in the detection of thyroid cancer metastases. 

    99m Tc-MIBI scintigraphy can be recommened as a first-line choice for detecting metastases in-patients with thyroid cancer. Its advantages over 131 I scintigraphy include better sensitivity in patients with remnant thyroid tissues, no need to restrict dietary iodide intake, and no need to discontinue exogenous thyroid hormones.

    Its shortcoming appears to be in imaging patients with small multiple lung metastases, in which case its sensitivity is similar to that of plain radiography.

       

  • Gelmon Karen – British Columbia Cancer Agency, Vancouver, British Columbia V5Z 4E6, Canada 
    ONE STEP FORWARD OR ONE STEP BACK WITH TAMOXIFEN?
    The Lancet,[ Vol 356], Number 9233, 9 September,2000, Pg. No 868.
      
    It is well recognized that tamoxifen is the drug of choice for treatment of breast cancer patients, both pre-menopausal and post- menopausal. It is also given in both localised and metastatic breast cancers. The only adverse reaction of tamoxifen is increased chances of endometrial cancer. The longer tamoxifen treatment, the greater is the chance of endometrial cancer. More importantly, endometrial cancer in patients who are receiving tamoxifen are more serious than in tamoxifen non users. 
      
    It becomes important to note that endometrial cancer occurs as a long term adverse effect. Therefore, prophylactic use of tamoxifen in persons, who do not have breast cancer should not be taken lightly. 
        

  • Franceschi Silvia, Munoz Nubia, Snijders J F – Unit of Field and Intervention Studies, International Agency for Research on Cancer, F-69372 Lyon Cedex 08, France : and Department of Pathology, Free University Hospital, Amsterdam, Netherlands
    How Strong and How wide is the Link Between Human Papillomavirus [HPV] and Oropharyngeal Cancer
    The Lancet,[ Vol  356], Number 9233, 9 September,2000,
      
    Human Papillomavirus [HPV] has now been established as an important cause of cancer cervix both squamous cell carcinoma and adenocarcinoma. It has now been shown that HPV-16 is commonly found in patients with cancer of the tonsils. Tonsils are situated between external and internal environment of the body, similar to cervix uterus and the etiology may be similar.
        

  • Caelyx approved in EC for cancer
    SCRIP No.2588, November 1st, 2000, pg.22
      
    Pegylated liposomal doxorubicin (Caelyx) also known as Doxil has been approved in the EC for ovarian cancer. It is administered intravenously once every 4 weeks. Although there have been concerns that results of clinical trials submitted to US NDA (FDA) were not very meaningful, there are no alternative advanced treatment options for ovarian cancer and the FDA advisory panel decided that the product may be useful.
       

  • GA Chung-Faye, DJ Kerr
    ABC of colorectal cancer Innovative treatment for colon cancer
    BMJ Vol.321, 2 December, 2001, pg.1397.
       
    Cancer of the colon is notorious for poor response to chemotherapy. However some new findings may be of interest. It has been postulated that colorectal cancer can be benefited by the use of NSAID in addition to their usual anticancer drugs. Although aspirin did not show any benefit in a clinical trial after 5 years of use, it has been suggested that a 10-year follow-up may be needed to show any significant effect. The only danger is G.I. bleeding which has to be weighed against any possible benefit in reduction of cancer mortality.
      
    Many immunological technologies have been used to augment the effect of anticancer drugs. The only proven drug is Levamisole in Duke-C colon cancer.
      
    Gene therapy is still at a very early stage. Crucial feature is the transfer of the gene, but the situation may improve with more effective gene transfer by using viruses.
       

  • All-trans retinoic acid (ATRA)
    AK Burnett, for the MRC Adult Leukaemia Working Party (Univ of Wales, Cardiff)
    Presenting White Blood Cell Count and Kinetics of Molecular Remission Predict Prognosis in Acute Promyelocytic Leukemia Treated With All Trans Retinoic Acid: Results of the Randomized MRC Trial.
    Blood 93: 4131-4143, 1999.
      
    Patients with acute promyelocytic leukaemia with low white blood cells count are treated by chemotherapy with reasonably good results. Combining ATRA with chemotherapy until complete remission, improves the prognosis. This benefit is seen only in patients with low white blood cell count. Patients with high blood cell count did not benefit from ATRA.
       

  • V Franciosi, G Cocconi, M Michiara, et al (Azienda Ospedaliera di Parma, Italy; et al)
    Front-Line Chemotherapy with Cisplatin and Etoposide for Patients with Brain Metastases from Breast Carcinoma, Non-small Cell Lung Carcinoma, or Malignant Melanoma: A Prospective Study.
    Cancer 85: 1599-1605, 1999.
       
    Previous studies have shown that combination of cisplatin and etoposide is highly active in patients with brain metastases from breast cancer. The rate of response was almost 40% in patients with metastasis in brain from breast cancer and 30% in brain metastasis from lung cancer. A very large percentage of brain metastasis in patients with breast cancer had a complete response radiologically and 7% with lung cancer also had this excellent response. However, brain metastases from melanoma did not respond to this chemotherapy
       

  • WJ Catalona, AW Partin, KM Slawin, et al (Washington Univ, St. Louis, Mo; Johns Hopkins Hosp, Baltimore Md; Baylor College of Medicine, Houston; et al) 
    Use of the Percentage of Free Prostate-specific Antigen to Enhance Differentiation of Prostate Cancer from Benign Prostatic Disease: A Prospective Multicenter Clinical Trial. 
    JAMA 279: 1542-1547, 1998.
       
    Free PSA percentage is a significant predictor of prostate cancer, with a sensitivity of 95% below a cutoff of 25%. Patients with prostate cancer and free PSA levels about the cutoff had less aggressive disease. Percentage of free PSA is an independent predictor of prostate cancer.
        

  • Katz D, Rothstein R, Schned A, et al [VA Med Ctr, White River Junction, Vt; Univ of Wisconsin, Madison; Dartmouth Hitchcock Med Ctr, Lebanon, NH; et al]
    The Development of Dysplasia and Adenocarcinoma During Endoscopic Surveillance of Barrett’s Esophagus 
    Am J Gastroenterol 93: 536-541, 1998, Pg. 224

    Most esophageal adenocarcinomas probably arise from premalignant Barett’s esophagus. Dysplasia is the best available indicator of malignant potential in Barrett’s epithelium. 

    Most of the patients suffer dyspepsia there were no cases of dysplasia among patients who had undergone antireflux surgery. High grade dysplasia and edenocarcinoma took more than two years to develop. Antireflux surgery may have a protective effect against progression to dysplasia. 
       

  • Walsh TJ, for the National Institute of Allergy and Infectious Diseases Mycoses Study Group [ Natl Cancer Inst, Bethesda, Md; et al]
    Liposomal Amphotericin B for Empirical Therapy in Patients with Persistent Fever and Neutropenia
    N Engl J Med 340: 764-771, 1999
      
    Patients with persistent neutropenia and fever require amphotericin B as empirical therapy. This study compared liposomal amphotericin B to conventional amphotericin B in such a patients cohort liposomal amphotericin B was as effective as conventional. However it was associated with fewer, fever breakthrough fungal infections, less infusion related toxicity, and less nephrotoxicity.
         

  • Dimeo FC, Stieglitz R-D, Novelli-Fischer U, et al [Freiburg Univ, Germany]
    Effects of Physical Activity on the Fatigue and Psychologic Status of Cancer Patients During Chemotherapy
    Cancer 85: 2273-2277, 1999
       
    Loss of physical performance and fatigue are common problems for patients undergoing chemotherapy.
      
    This study compared patients receiving high dose chemotherapy followed by autologous peripheral blood stem cell transplant to exercise intervention or control. Those who exercised had decrease fatigue and improved psychological distress.
          

  • Sneed PK, Stauffer PR, McDermott MW, et al [Univ of California, San Francisco]
    Survival Benefit of Hyperthermia in a Prospective Randomized Trial of Brachytherapy Boost + Hyperthermia for Glioblastoma Multiforme
    Int J Radiat Oncol Biol Phys 40: 287-295, 1998
      
    Glioblastomas an aggressive brain tumor has median survival of about 12 month radiation therapy and an additional brachytherapy boost to provide a high focal dose have been used earlier.
      
    This study of patient with supratentorial glioblastoma were assigned to radiotherapy bracytherapy and then with or without hyperthermia.
      
    Time to progression and survival were significantly longer in hyperthermic than non-hyperthermic group.
           

  • C.M. Malata, S.A. McIntosh and A.D. Purushotham [ Departments of Reconstructive and – General Surgery, Cambridge Breast Unit, Addenbrook’s Hospital, Cambridge, UK ]
    ImmediateBreast Reconstruction After Mastectomy for Cancer
    Br. Jour. of  Sur. Volume 87, No.11, November 2000, Pgs- 1455-1472
      
    Immediate breast reconstruction after mastectomy has increased over the past decade following unequivocal demonstration of its oncological safety and the availability of reliable methods of reconstruction. Broadly, it is undertaken in the treatment of breast cancer after prophylactic mastectomy in high-risk patients and in the management of treatment failure after breast conserving surgery and radiotherapy.
      
    Breast reconstruction can be  achieved reliably with a variety of techniques :-
      
    1.  Prosthetic Devices – Implants, classical expander implants or adjustable implants.

    2.  Autogenous Tissue Reconstruction – Transverse rectus abdominis myocutaneous flap [various types]
        
    Free  deep inferior epigastric perforator flap latissimus dorsi musculocutaneous flap.

    3.  Other autogenous tissue Techniques – Superior and inferior gluteal free flap, gluteal perforator free flap, lateral
         transverse thigh flap, Taylor-Rubens peri-iliac free flap
      
      Careful discussion and evaluation remains vital in choosing the correct technique for the individual patient.
     
    The aesthetic considerations [comparison with opposite breast] and psychological consideration must be looked into.
       

  • J.L. Poggio, D.M. Nagorney, A.G. Nascimento, C. Rowland, P.Kay, R.M. Young and J.H. Donohue [ Department of Surgery, Section of Anatomic Pathology and Section of Biostatistics, Mayo Clinic, 200 First Street, SW, Rochester, Minnesota 55905, USA
    Surgical Treatment of Adult Primary Hepatic Sarcoma
    Br. Jour. of  Sur. Volume 87, No.11, November 2000, Pgs- 1500-1505
     
    Primary sarcomas of the liver are extremely rare in adults. Optimal therapeutic approaches remain unclear.
     
    Twenty consecutive adults who are operated for hepatic sarcomas were reviewed. The ages ranged between 23 to 80 years. No predisposing causes could be found except in one who had a history of thorotrast exposure 23 years ago.
     
    19 patients had hepatic resection and one patient had an orthotopic liver transplant. No patient was given neo-adjuvant chemotherapy but one patient had intra-operative radiotherapy.
      
    Leiomyosarcoma was the most common histologic carcinoma [ 5 out of 20] followed by malignant solitary fibrous tumour [4 cases] and epithelioid haemagioendothelioma [ 3 cases]. 14 tumours were high grade sarcomas whereas 6 were low grade malignancies.
      
    Three patients developed local recurrences while 10 patients developed metastases and intrahepatic recurrence in 6 patients were the predominant sites of initial treatment failure.
      
    Six patients received salvage chemotherapy. Histological grading was the only factor significantly associated with patient survival [ p=03].
      
    With complete resection, patient with high grade tumours had a 5 year survival rate of 18% compared with 80% for patients with low grade tumours. Overall survival rate was 37%.
     
    Surgical resection is the only effective therapy for primary hepatic sarcoma . Better adjuvant therapy is necessary for high grade malignancy owing to high failure rate with only surgery.
           

  • Goode RK, Auclair PL, et al (Armed Forces Inst of Pathology, Washington, DC: Natl Naval Dental Ctr, Washington, DC)
    Mucoepidermoid Carcinoma of the Major Salivary Glands: Clinical and Histopathologic Analysis of 234 Cases with Evaluation of Grading Criteria.
    Cancer 82: 1217-1224, 1998.
        
    High, intermediate and low grades have been reported. One study denotes the presence of cystic component of less than 10% is considered as high grade.
         
    In this study, 337 patients were analysed which included follow-up data. 84% were in parotid. 13% in submandibular gland and 3% in the sublingual gland. Four groups were formed Group I, survival free of disease. Group II, survival with local recurrence, Group III, survival with local metastases and Group IV, death of disease.
        
    This study identifies prognostic factors. Outcome varied significantly according to site and grade of the tumour. Metastases from submandibular glands were more frequent. The treatment should be based on clinical stage of the disease and histopathologic guide. Even low grade tumours in submandibular gland needs aggressive treatment and close follow-up
          

  • Laskawi R, Rodel R, et al (Univ of Gottingen, Germany)
    Retrospective Analysis of 35 Patients with Acinic Cell Carcinoma of the Parotid Gland.
    J OralMaxillofac Surg 56: 440-443, 1998.
        
    This is a rare tumour, occurs in late middle age commonly in females. Retrospectively studied because of its rarity. The study included 35 patients treated between 1945 and 1994. Surgery is the therapy of choice. The response to radiation is not favourable either to prevent recurrences or increase in survival period. The latter part is of particular interest in management.
         

  • Yang CY, Andersen PE, et al (Oregon Health Sciences Univ, Portland)
    Nodal Disease in Purely Glottic Carcinoma: Is Elective Neck Treatment Worthwhile?
    Laryngoscope 108: 1006-1008, 1998.
        
    All patients were included with glottic cancer between 1984 to 1994. Ninety-two patients were identified who had at least 2 yrs of follow-up for T stage, cord mobility, CT scan, nodal disease, lesion extension, treatment modality and tumour pathology. Recurrences were reviewed.
         
    Occult nodal disease with NO glottic carcinoma was low with 0% incidence in T1 and T2 stage disease and 19% in T3 and T4 stage disease. Only paratracheal level II and III nodes were at high risk. Therefore, elective neck dissection should be performed for advanced disease in case with low morbidity. CT scanning was not useful for staging in these patients.
         

  • Asakage T, Yokose T, Mukai K, et al (Natl Cancer Ctr Hosp East, Chiba, Japan; Tohoku Univ, Miyagi, Japan)
    Tumor Thickness Predicts Cervical Metastasis in Patients with State I/II Carcinoma of the Tongue.
    Cancer 82: 1443-1448, 1998
         
    The retrospective study included 44 patients with previously untreated stage I/II carcinoma of tongue involving the anterior two thirds of the tongues. They were treated by partial glossectomy only. Twenty-one patients had cervical metastasis and 23 were without. Tumour thickness and other variables were compared.
         
    Tumour thickness more than 4mm thickness are at higher risk of cervical metastases and were regarded as having latent metastasis. Conservative supramyohyoid neck dissection, as performed for T1N1 or T2N1 carcinoma of the tongue may be suitable.
         
    This article confirms depth of invasion in more predictive of cervical metastasis than T classification. Spiro et al suggested this even for 2mm thickness and more.
         

  • Cruz IB, Snijders PJF, Meijer CJ, et al (Univ Hosp Vrije Universiteit, Amsterdam; Academic Centre for Dentistry, Amsterdam)
    p53 Expression above the Basal Cell layer in Oral Mucosa is an Early Event of Malignant Transformation and Has Predictive Value for Developing Oral Squamous Cell Carcinoma.
    J Pathol 184: 360-368, 1998.
        
    Majority of oral squamous cell carcinoma have mutations in the oncogene p53.
         
    To determine the relationship, immunohistochemical staining was performed on 11 premalignant lesions in which carcinoma developed. Therefore, p53 expression appears on early event in the carcinogenesis of premalignant lesions. 
          
    This combined with histologic criteria of dysplasia is danger sign. If more continued studies demonstrate this, it will be of great value in the management of patients with dysplastic biopsy specimens.
        

  • Concomitant Radiotherapy with Mitomycin C and Bleomycin Compared with Radiotherapy Alone in Inoperable Head and Neck Cancer: Final Report.
    Int J Radiat Zakotnik B, Smid L, Budihna M, et al (Inst of Oncology, Ljubljana, Slovenia: Univ Dept. of Otorhinolaryngology and Cervicofacial Surgery, Ljubljana, Slovenia)
    Oncol Biol Phys 41: 1121-1127, 1998.
       
    Sixty-four patients were randomly treated in 2 groups. One group received radiotherapy alone and other group received radiotherapy with concomitant above mentioned chemotherapy.
       
    Other group receiving radiotherapy with concomitant chemotherapy had significantly higher complete remission, disease free survival and better survival rates.
         

  • Forrest LA, Schuller DE, Karanfilov B, et al (Ohio State Univ, Columbus)
    Update on Intraoperative Analysis of Mandibular Margins
    Am J Otolaryngol 18: 396-399, 1997
        
    In 61 patients with involvement of alvelous, the study of serial frozen section biopsy of the cancellous bone at the mandibular stump demonstrated 100% corelation, and thus the extent of resection of the mandibule could be decided accordingly.
         
    This article provides some evidence of the effectiveness of this technique in assessing resection.
        

  • De Stefani E, Boffetta P, Oreggia F, et al (Registro Nacional de Cancer, Montevideo Uruguay; Inernatl Agency for Research on Cancer, Lyon, France; Academia Nacional de Medicina, Montevideo, Uruguay, et al).
    Smoking Patterns and Cancer of the Oral Cavity and Pharynx: A Case-Control Study in Uruguay.
    Oral Oncol, Eur J Cancer 34: 340-346, 1998.
         
    Four hundred and twenty-five men with confirmed lesions and 427 hospitalized controls were studied.
         
    Smoking black tobacco cigarettes seems significant in oral and pharyngeal carcinogenesis. Risk was decreased with filter use and cessation of smoking. Black tobacco contained high tobacco-specific nitrosamines. A high tar content was noted in hand-rolled cigarettes thus combination has more risk of oral cancer.
        
    This interesting article can help physicians counseling their patients – particularly impact of tobacco type and use of filtered cigarettes.
        

  • Colletier PJ, Garden AS, Morrison WH, et al (Univ of Texas, Houston)
    Postoperative Radiation for Squamous Cell Carcinoma Metastatic to Cervical Lymph Nodes from an Unknown Primary Site: Outcomes and Patterns of Failure.
    Head Neck 20: 674-681, 1998.
         
    Out of 136 patients with cervical metastasis from unknown primary sites, 39 patients underwent excisional biopsy and rest of them various types of neck dissection. All received radiotherapy subsequently. 58 months follow-up was done.
        
    Excisional biopsy and radiotherapy offers excellent disease control and survival rates. Those with ECE (extracapsular extension) and multiple nodal involvement the results are not as good. Radiation should start within 3 to 4 weeks and should be of full required dose.
          
    Excisional biopsy did not have any reduction in disease control or survival rates. However, it should not be an argument in all cases. Detrimental effects of ECE and multiple nodal involvement is confirmed by this study further. R.A. Otto.
          

  • Simon D, Koehrle J, Reiners C, et al (Heinrich-Heine-Univ, Dusseldorf, Germany; Unvi of Wurzburg, Germany; Univ of Essen, Germany)
    Redifferentiation Therapy with Retinoids: Therapeutic Option for Advanced Follicular and Papillary Thyroid Carcinoma.
    World J Surg 22: 569-574, 1998.
           
    About 33% of differentiated thyroid carcinoma (DTC) show loss of differentiation during progression of disease and then become refractory to standard treatment.
        
    Retinoid treatment (13-cis-retinoic acid) reduces tumour growth and reinduces iodide uptake suggesting that redifferentiation in cancerous growth in (DTC). This is not so in on anaplastic cancer.
        
    A 65% response rate was shown among patients of advance DTC. Thyroglobulin levels always do not accompany this response. Therapy is well tolerated with few side effects. No conclusions as the survival rates have been drawn.
      
    This study has offered a ray of hope in the management of advanced DTC patients and further studies may offer better hopes. R.A. Otto.
         

  • Gimm O, Ukkat J, Dralle H (Martin-Luther-Univ Halle-Wittenberg, Germany)
    Determinative Factors of Biochemical Cure After Primary and Reoperative Surgery for Sporadic Medullary Thyroid Carcinoma.
    World J Surg 22: 562-568, 1998.
        
    Twenty-seven patients underwent total thyroidectomy and compartment based microdissection of nodes. Thirty-seven patients with continuously elevated serum calcitonin levels underwent 4-compartment lymphodectomy at reoperation.
        
    The report of 100% normalizaiton in serum of calcitonin levels in node negative and pT1 patients is notable. Postoperative calcitonic level is powerful prognostic factor. However, it is not clear whether the patients who are biochemically cured have better outcome. By correlating tumour size with the presence and location of lymph node metastasis, this study provides useful guidelines for the extent of nodal dissection necessary at the time of primary operation of Medullary Thyroid Carcinoma. R.A. Otto.
          

  • Dralle H, Gimm O, Simon D, et al (Martin-Luther-Universitat Halle-Wittenberg, Germany; Heinrich-Heine Universitat, Dusseldorf, Germany; Gemeinschaftspraxis Innere Medizin-Endokrinologie, Heildelberg, Germany; et al)
    Prophylactic Thyroidectomy in 75 Children and Adolescents with Hereditary Medullary Thyroid Carcinoma: German and Austrian Experience.
    World J Surg 22: 744-751, 1998.
         
    In 1993, the RET proto-oncogene was identified as responsible for hereditary medullary thyroid carcinoma (MTC), since then patients with MTC based genetic screening have achieved biochemical cure by undergoing prophylactic thyroidectomy which prevents MTC and lymph node metastasis from developing.
          
    – A major breakthrough in the diagnosis and treatment with identification of this genetic defect in thyroid tumours. Biochemical estimation of serum calcitonin to screen in no longer required. 
           
    These authors provide a sensible algorithm for management of these patients. The achievement in 96% patients of a biochemical cure is remarkable. Time will tell if biochemically curing these patients is superior. R.A. Otto.
           

  • Nilsson O, Lindeberg J, Zedenius J, et al (Karolinska Hosp, Stockholm; Lund Univ Hosp, Sweden; Uppsala Univ Hosp, Sweden)
    Anaplastic Giant Cell Carcinoma of the Thyroid Gland: Treatment and Survival Over a 25-Year Period.
    World J Surg 22: 725-730, 1998.
         
    Between 1930 and 1970, 50% of patients with ATC died within 3 months mainly by suffocation from the local tumour growth. Now only one similar death has occurred since 1989. Local tumour control has been achieved with debulking and pre and post operative doxorubicin and hyperfractionated accelerated radiotherapy.
                 

  • Patel PC, Pellitteri PK, Patel NM, et al (Penn State Geisinger Health System, Danville,Pa)
    Use of a Rapid Intraoperative Parathyroid Hormone Assay in the Surgical Management of Parathyroid Disease.
    Arch Otolaryngol Head Neck Surg 124: 559-562, 1998.
     
    During parathyroid surgery patients underwent neck exploration and the parathyroid hormone assay is done by preremoval of parathyroids and postremoval during operative procedure, thus guiding whether enough functioning of parathyroid tissue is removed. If adenoma is suspected then preoperative 99mTc-sestamibi scanning was used to localize.
           
    Thus combination of preoperative scanning and intraoperative parathyroid hormone assay can guide unilateral exploration of neck.
           

  • Dhingra JK, Zhang X, McMillan K, et al (Tufts Univ, Boston; Lahey Clinic Med Ctr, Burlington, Mass; Massachusetts Inst of Technology, Cambridge)
    Diagnosis of Head and Neck Precancerous Lesions in an Animal Model Using Fluorescence Spectroscopy.
    Laryngoscope 108: 471-475, 1998.
         
    This animal experiment using laser induced fluorescence spectroscopy demonstrated the utility in the diagnosis of premalignant lesions like leukoplakia or erythroplakia and histologically as metaplasia and dysplasia. 
         
    If this technique could be used to enhance over clinical skills (60%-80% reliability) such a tool could be very useful. G.R. Holt
        

  • London SD, Park SS, Gampper TJ, et al (Univ of Virginia, Charlottesville)
    Hyperbaric Oxygen for the Management of Radionecrosis of Bone and Cartilage.
    Laryngoscope 108: 1291-1296, 1998.
         
    Sixteen patients included in this study suggests good results with HBO therapy for the management of radionecrosis of the head and neck. Subjective and objective outcomes improved greatly.
           
    HBO therapy has become an important portion of the equation in the prevention and treatment of osteoradionecrosis and chondroradionecrosis.
             

  • F Fugt, MP Varyas, Z Zhaung, et al (NIH, Bethesda, Md)
    Utilisation of Molecular Genetics in the differentiation Between Adrenal cortical Adenomas and Carcinomas.
    Hum Pathol 28: 518-521, 1998.
     
    Background : With current advanced radiological techniques, small adrenal cortical lesions may be identified that are prone to misidentification.
     
    Methods : Specific areas of each histologic slide were microdissected and subjected to polymerase chain reaction (PCR)for loss of heterozygosity (LOH) of 5 different tumor suppressor gene loci as follow
      
    1.                  P53 gene at chromosome  17p,
     
    2.                  P16 gene at chromosome 9p
     
    3.                  The neuroblastoma gene at 1p
     
    4.                  Von Hippel Lindav gene at chrom. 3p
     
    5.                  Retinoblastoma gene at 13q
     
    Results: None of the hyperplasias or adenomas showed LOH.
     
    - 61% of adrenocortical carcinomas showed genetic alterations for at least 1 of the markers.
     
    LOH of P53 was seen in 44%
       
    1P was seen in 22%
        
    3P was seen in 22%
       
    9p was seen in 26%
        
    80% of informative cases showed LOH of the retinoblastoma gene.
       
    Conclusions : The most informative markers for adrenal malignancy are P53 and 13q.
         

  • H Miyake, H Nakamura, I Hara, et al (Kobe Univ;Japan; Kumamoto Univ, Japan) Multifocal Multifocal Renal Cell Carcinoma: Evidence for a Common Clonal Origin.
    Clin Cancer Res. 4: 2491, 1998.
        
    The controversy surrounding the use of Nephron sparing surgery for renal cell carcinoma has revolved around the observed 7% to 25% incidence of relatively small satellite tumors discovered at autopsy or upon careful examination of radical nephrectomy specimens from patients with clinically evident renal cell carcinoma.
         
    In this study, the authors studied 10 cases of renal cell carcinoma that were accompanied by smaller satellite tumors for LOH (Loss of Heterozygosity) at chromosome arms 3p, 6q, 8p, 9p, 9q and 14q. All tumors were less than 5cm. Primary and satellite lesions in 8 of 10 cases exhibited identical patterns of LOH.
        
    Similarity of LOH patterns in the main satellite tumors indicated that satellite tumors are the result of intrarenal metastasis rather than new separate primaries. In any series the satellite lesions are generally small and occurring within 2 cm of the index tumor. The satellite tumors measure 2-4mm. Many satellite lesions may be resected during a “radical partial nephrectomy” or may never reach the clinical horizon.
        

  • C.H. Yoo, S.H. Noh, D.W. Shin, S.H. Choi and J.S. Min [Department of Surgery, Yonsei University College of Medicine, 134 Shinchon-ku, 120-752, Seoul, Korea ]
    Recurrence Following Curative Resection for Gastric Carcinoma
    Br. J. of Sur., Volume 87, Number 2, February, 2000, Pg. 236-242

    The diagnosis and treatment of recurrent gastric carcinoma is difficult. This study was aimed at determining the risk factors for recurrence of gastric carcinoma and prognosis for these patients.
    508 cases of recurrent gastric carcinoma out of 2328 patients who underwent curative resection for gastric carcinoma were studied retrospectively by univariate and multivariate analysis.
       
    The mean time to recurrence was 21.8 months and peritoneal recurrence was the most common [45.9%]. Logistic regression analysis showed that serosal invasion and lymph node metastasis were risk factors for all recurrence and early recurrence [at 24 months or less]. In addition, independent risk factors involved in each recurrence pattern included younger age, infiltrative or diffuse type, undifferentiated tumour and total gastrectomy for peritoneal recurrence, older age and larger tumour size for disseminated haematogenous recurrence; and older age, larger tumour size, infiltrative or diffuse type, proximally located tumour and subtotal gastrectomy for locoregional recurrence. Other risk factors for early recurrence were infiltrative or diffuse type and total gastrectomy. 
       
    Re-operation for cure was possible in only 19 patients and the mean survival time after conservative treatment or palliative resection was less than 12 months.
       
    The risk factors can be predicted by the clinicopathological features of the primary tumour.
          

  • KS Hafez, AC Novick, BP Butler (Cleveland Clinic Foundation, Ohio)
    Management of Small Solitary Unilateral Renal Cell Carcinoma: Impact of Central Versus Peripheral Tumor Location.
    J. Urol 159: 1156-1160, 1998.
      
    Conclusion : No significant biological differences are evident between central and peripheral small solitary unilateral renal cell carcinomas.
      
    Nephron sparing surgery was technically more complicated among central renal cell carcinomas.
       
    Intraoperative ultrasonography may be a more important adjunct when approaching patients with central tumors.
           

  • Yotsuyanagi T, Nihei Y, Yokoi K, et al (Hirosaki Univ, Japan)
    Functional Reconstruction Using a Depressor Anguli Oris Musculocutaneous Flap for Large Lower Lip Defects, Especially for Elderly Patients.
    Plast Reconstr Surg 103: 850-856, 1999
       
    The most common lesion of the malignant lesions of oral cavity is lower lip squamous carcinoma.
      
    In planning the reconstruction of large excision defect the following factors should be kept in mind.
       
    – Maintenance of sphineteric action.
    – Retention of sensation.
    – A large enough opening for the mouth.
    – Acceptable cosmetic appearance.
      
    In surgical technique described – Nerve supply and Blood supply is well preserved.
         

  • Franceschi S, Levi F, La Vecchia C, et al (Centro di Riferimento Oncologico, Aviano, Italy; Registre Vaudois de Tumeurs, Lausanne, Switzerland; Instituto di Ricerche Farmacologiche “M Negri”, Milano, Italy; et al )
    Comparison of the Effect of Smoking and Alcohol Drinking Between Oral and Pharyngeal Cancer
    Int J Cancer 83: 1-4, 1999
      
    The relationship of exposure to alcohol and tobacco is established. However, the separate and combined effects of alcohol and tobacco between oral and pharyngeal cancer were compared in case-control investigation.
      
    274 patients with oral cancer and 364 with pharyngeal cancer, 1254 controls matched were studied. 
       
    Observation-Conclusion – Alcohol has a stronger effect on oral cancer than on pharyngeal cancer. This may help explain why oral cancer mortaility is rising in men from many developing countries after many years of declining.
      

  • J Meiron Thomas and Erica J Patocskai 
    The argument against sentinel node biopsy for malignant melanoma
    Its use should be confined to patients in clinical trials
    BMJ, 1July 2000, p.3
      
    In recent years, there has been a tendency to perform sentinel node biopsy in patients with malignant melanoma. It has been seen that 88.5% of patients with negative sentinel node biopsy remained free of the disease for 3 years as compared to 55.8% of patients with positive biopsy. The survival rate in patients with negative sentinel node biopsy is 93% as compared to 67% in those with a positive biopsy. However, there is no clear-cut criteria to justify sentinel node biopsy. Some reasons forwarded are that firstly the sentinel node biopsy is cheaper than elective lymph node dissection. The second argument is that a sentinel node biopsy can be used to dissect patient for adjuvant therapy. Thirdly a sentinel node biopsy may be used in selecting patients for complete node dissection.
      
    At the moment, sentinel node biopsy is usually restricted to patients in clinical trials.
       

  • Aquino SL, Chiles C, Halford P [Wake Forest Univ, Winston-Salem, NC]
    Distinction of Consolidative Bronchioloalveolar Carcinoma From Pneumonia- Do CT Criteria Work?
    AJR 171: 359-363, 1998
       
    About 30% of bronchioalveolar carcinomas [BACs] are of the consolidative type. Certain chest CT findings are reportedly helpful in identifying pulmonary consolidation as BAC.
      
    In addition to consolidation, the review focused on features such as nodules and ground-glass opacities; cysts, or cavities within the consolidation. 
      
    In the BAC group, all patients had consolidation, more often with a peripheral distribution. 
      
    Findings that were present significantly more often in patients with consolidative BAC were coexisting nodules and a peripheral pattern of consoliation.
      
    Consolidative BAC should be suspected in adult patients with normal immunity who had a nonresolving peripheral consolidative pneumonia, particularly when associated nodules are present.
         

  • Valji AM, Maziak DE, Shamji FM, et al [Ottawa Civic Hosp, Ont, Canada]
    Postoneumonectomy Syndrome: Recognition and Management
    Chest 114: 1766-1769, 1998
       
    Postpneumonectomy syndrome [PPS] is caused by extreme shift and rotation of the mediastinum after pneumonectomy. It can produce symptomatic proximal airway obstruction and airway trapping.
      
    Clinical diagnosis of PPS was made with the aid of chest radiographs, 2-dimensional echocardiography, pulmonary function tests, CT scans, and awake fiberoptic bronchoscopy.
       
    After complete mobilization of the mediastinum, anterior pericardiorrhaphy was done before the pericardium was anchored in the parasternal chest wall with suture. A Silastic prothesis filled with saline solution was placed to correct overshifting of the mediastinum.
       
    The diagnosis of PPS should be considered in all patients with progressive dyspnea after pneumonectomy. Repositioning of the mediastinum by means of a prosthesis filled with saline solution and anterior pericardiorrhaphy is a simple procedure and offers immediate and lasting symptomatic relief.
        
        

  • Marcia Hall Gordon J.S. Rustin
    Testicular Tumour Management
    Recent Advances in Surgery, Number 22, Year-1999, Pg. 173
      
    Many risk factors promoting the development of Germ Cell Tumours [ GCT] have been identified, the best known and most consistent being a history of cryptorchidism.
     
    Most patients present with symptoms relating to the affected testicle [e.g. swelling, pain or aching] and occasionally symptoms and signs referable to metastatic disease [e.g. back pain from retroperitoneal nodes, dyspnoea from pulmonary/mediastinal disease] or, less commonly, hormone-related gynaecomastia.
     
    In the low risk stage 1 GCT, with no treatment other than initial orchidectomy, the mainstay of management is close follow-up with fortnightly markers and regular imaging for metastatic disease. Adjuvant therapy of two cycles of bleomycin, etoposide and cisplatin [BEP] is an acceptable and justifiable way of virtually eliminating the risk of relapse.
     
    Seminoma is exquisitely radiosensitive and characteristically spreads via the lymphatic system, treatment aimed at the retroperitoneal /para-aortic nodes significantly reduces the risk of relapse.
      
    BEP currently remains the standard treatment.
      
    In pure seminoma, residual masses can be safely observed on serial scans and most will shrink and calcify over time; a growing mass, however, would indicate recurrent disease requiring further treatment.
      
    Mature teratoma must be surgically removed before it enlarges locally and becomes inoperable.
      
    Chemotherapy – induced acute toxicities in the treatment of testicular GCT are mostly transient. Fertility is adversely affected by chemotherapy, it usually returns to normal. Concern has been raised about the possible carcinogenic effects of chemotherapy in the long-term. Etoposide is known to be leukaemogenic and secondary tumours have been reported following etoposide containing therapy for GCT.
      
    The treatment of GCT overall has not changed a great deal in the last 5 years, although there is a trend toward more frequent use of chemotherapy in the earlier stages.
      
    Surgical conundrum is the benefits o orchidopexy to prevent the development of GCT only orchidopexy done at a very young age can reduce risk.
         

  • lam MDS, Kasagi K, Misaki T, et al [Kyoto Univ, Japan]
    Diagnostic Value of Technetium -99m Methoxyisobutyl Isonitrile [ 99m Tc-MIBI] Scintigraphy in Detecting Thyroid Cancer Metastases: A Critical Evaluation
    Thyroid 8: 1091-1100, 1998, Pg.215
       
    Many investigators consider that technetium – 99 methoxyisobutyl isonitrile [ 99m Tc-MIBI] scintigraphy should be used as a supplement to performing radioactive iodine whole-body scanning [ 131 I-WBS] and measuring serum thyroglobulin [Tg] levels in the detection of thyroid cancer metastases. 
     
    99m Tc-MIBI scintigraphy can be recommened as a first-line choice for detecting metastases in-patients with thyroid cancer. Its advantages over 131 I scintigraphy include better sensitivity in patients with remnant thyroid tissues, no need to restrict dietary iodide intake, and no need to discontinue exogenous thyroid hormones.
     
    Its shortcoming appears to be in imaging patients with small multiple lung metastases, in which case its sensitivity is similar to that of plain radiography.
            

  • Veling MC, Windmill I, Bumpous JM [Univ of Louisville, Ky]
    Sudden Hearing Loss as a Presenting Manifestation of Leukemia
    Otolaryngol Head Neck Surg 120:954-956, 1999
      
    ¨ Sudden loss of hearing is a rare presenting symptom in blood disorders.
    ¨ Tinnitus may be present, but no vertigo, nystagmus or cranial nerve palsys.
    ¨ Effusion in middle ears with intact tympanic membrane is found.
    ¨ Bone marrow examination is a must to diagnose leukemia.
    ¨ Audiograms which showed initial bilateral loss of hearing improved after treatment of leukemia.
    ¨ Usually, leukemia causes deafness in terminal stages.
          

  • Yim JH,Wick MR, Philpott GW, et al [Washington Univ, St Louis]
    Underlying Pathology in Mammary Paget’s Disease
    Ann Surg Oncol 4: 287-292, 1997
       
    Mastectomy has been the standard treatment, but recent studies have recommended radiotherapy with no resection. All patients had histologically confirmed Paget’s disease; 92% of patients had underlying carcinoma, either ductal carcinoma in situ, invasive ductal cancer, or both. Mammography failed to detect the multifocal lesions in 64% of patients with no palpable mass. Patients with a palpable mass were significantly more likely to have invasive cancer, multifocal lesions, and positive lymph nodes. 
      
    Most patients with mammary Paget’s disease have underlying multifocal carcinoma, including invasive lesions. Therefore, mastectomy remains the standard treatment.
            

  • Coveney E, Weltz CR, Greengrass R, et al [Duke Univ, Durham, NC]
    Use of Paravertebral Block Anesthesia in the Surgical Management of Breast Cancer : Experience in 156 Cases.
    Ann Surg 227: 496-501, 1998
      
    The most common surgical procedures used in the treatment of breast cancer are modified radical mastectomy and lumpectomy with axillary dissection. Typically general anesthesia is used for both procedures. Successful surgery was completed in 85% of the cases in paravertebral block alone. The need for medication for nausea and vomiting was greater in the general anesthesia group. and significantly more patients in the general anesthesia group required narcotic analgesia. 
       
    Patients undergoing major operations for breast cancer had minimal complications and a low rate of conversion to general anesthesia when paravertebral block was used. 
        
    This type of anesthetic as well as high thoracic, epidermal anesthetic, which may be somewhat trechnically easier on the patient. Can improve patient’s satisfaction reduce the need for narcotic, and shorten the length of stay in the hospital.
          

  • G.H. Sakorafas and A.G. Tsiotou [ Department of Surgery, 251 Hellenic Air Force Hospital, Messogion and Katehaki, Athens 115 25, Greece
    Genetic Predisposition to Breast Cancer : A Surgical Perspective
    Br. J. of Sur., Volume 87, Number 2, February, 2000, Pg. 149
       
    Molecular alterations in proto-oncogenes, tumour suppressor genes, and genes that function in DNA damage recognition and repair are considered to be the hallmarks of a carcinogenic process, including breast carcinogenesis.
      
    After a thorough review of literature the authors postulate that hereditary breast cancer accounts for 5-10 per cent of all breast cancer cases. About 90% of hereditary breast cancer involve mutation of BRCA1 and/or BRCA2 genes. Other cancer related genes [myc, c-erbB2, Tsg101 and Mdgi] are involved in breast carcinogenesis, but they do not give rise to familial breast cancer syndromes. Risk estimation is the most important clinical implication. Management options for the high-risk mutation carriers include cancer surveillance and preventive strategies [prophylactic surgery or chemoprevention].
      
    They conclude that despite inadequate knowledge about the genetic predisposition to breast cancer and its clinical implications, the demand for genetic testing is likely to increase. In addition to risk estimation, cancer surveillance and preventive strategies, gene therapy offers a new and theoretically attractive approach to breast cancer management.
          

  • U Chetty, W. Jack, R.J. Prescott, C. Tyler and A. Rodger, on behalf of the Edinburgh Breast Unit [ Correspondence to : Mr. U. Chetty, Edinburgh Breast Unit, Western General Hospital, Edinburgh EH4 2XU, UK]
    Management of the Axilla in Operable Breast Cancer Treated by Breast Conservation : a Randomized Clinical Trial
    Br. J. of Sur. Volume 87, Number 2, February, 2000, Pg. 163
       
    In the treatment of operable breast cancer by breast conservation, the extent of axillary dissection, the need for radiotherapy to the axilla and the morbidity associated with these procedures have not been assessed adequately.
        
    Patients with operable breast cancer were randomized to have level III axillary node clearance. Radiotherapy [RT] to the axilla was given selectively. RT was not given to those who had an axillary clearance. The first 54 patients were subjected to node sampling and RT. Subsequently only node positive patients were given RT. The morbidity, [upper limb volume, and circumference, and glenohumeral and scapular movements were assessed.
        
    No difference was found in local axillary or distant recurrence. There was no statistical difference in the 5-year survival ratio. The morbidity was least in those who had node sampling but no RT, to axilla. RT to axilla who had a node sample resulted in a significant reduction in range of movement of the shoulder. Surgical axillary clearance was associated with significant lymphoedema of the upper extremity.
         

  • Carolyn Westhoff, Debra Heller, et al (Department of Obstetrics & Gynaecology, New Jersey)
    Risk factors for hyperplasia-associated versus atrophy-associated endometrial carcinoma.
    Am J Obstet Gynecol, March 2000, 182: 506-8.
       
    Objective: Endometrial cancer can be divided into atrophy-associated and hyperplasia-associated subtypes. It has been suggested that these subtypes have different pathologic features and prognoses.
        
    Study Design: Hysterectomies performed in cases of endometrial carcinoma with evaluable benign endometrium on routine processing were reviewed, and clinical data were abstracted from medical records. Forty-eight subjects with atrophy-associated and 28 subjects with hyperplasia-associated cancers were studied.
      
    It was found younger age, higher weight, absence of cigarette smoking and earlier menarche in subjects with hyperplasia related cancers.
       
    Conclusions: Their findings support the idea that hyperplasia-associated endometrial cancer is estrogen-related but also suggest that atrophy-associated cases may result from a different causal pathway. Epidemiologic studies may yield more precise and accurate measures of association if atrophy-associated and hyperplasia-associated endometrial cancers are considered separately.
         

  • S. J. Pain and A.D. Purushotham [Cambridge Breast Unit, Addenbrooke’s Hospital, Cambridge , UK]
    Lymphoedema Following Surgery for Breast Cancer
    Br.Jour. of Surg. Volume 87, No.9, September 2000, Pgs. 1128-1141
      
    Lymphoedema is a common complication of breast cancer treatment, affecting almost 25% of cases. It can cause discomfort, cosmetic and functional problems. It is prone to episodic superficial infections.
      
    A systematic review of all published literature on this problem using the Medline and Cinahl databases with cross -referencing of major articles upto 1999 was undertaken.
      
    The aetiology and pathology of this condition is multifactorial and still not fully understood. Although conservative treatment can be very successful in palliation, it does not afford a cure. The place of surgery and pharmacotherapy remains unclear. Improved understanding of pathophysiology may assist in reducing the incidence of this condition or help to identify high risk cases in whom early conservative treatment may prove effective.
          

  • Gerrits CJH, Burris H, Schellens JHM, et al [ Univ Hosp Rotterdam, The Netherlands; Univ of Texas Health Sciences Ctr at san Antonio; SmithKline Beecham Pharmaceuticals, UK and USA
    Five Days of Oral Topotecan [Hycamtin TM, a Phase I and Pharmacological Study in Adult Patients With Solid Tumors
    Eur J Cancer 34: 1030-1035, 1998
      
    Topotecan., a specific inhibitor of topoisomerase I, is available in an oral formulation, with a 32% to 44% bioavailability in humans. This study of 29 patients with malignant solid tumors refractory to standard treatment received topotecan in escalating doses. The dose limiting toxicity grade IV granulocytopenia occurred at 2.7 mg/m2/day. The recommended dose for phase II trials is 2.3 mg/m2 /day or a fixed dose of 4 mg/day.
          

  • C.M. Wright, O.F. Dent, M. Barker, R.C. Newland, P.H. Chapuis, E.L. Bokey, J.P. Young, B.A. Leggett, J.R. Jass and G.A. Macdonald [ Department of Surgery, Princess Alexandra Hospital, Conjoint Gastroenterology Laboratory, Royal Brisbane Hospital Research Foundation Clinical Research Center, Department of Pathology , University of Queensland and Department of Medicine, University of Queensland and Clinical Sciences Unit, Queensland Institute of Medical Research, Brisbane, Queensland, Department of Sociology, Australian National University]
    Prognostic Significance of Extensive Microsatellite Instability in Sporadic Clinicopathological Stage C Colorectal Cancer
    Br.Jour. of Surg. Volume 87, No.9, September 2000, Pgs. 1197-1202
         
    Colorectal cancers exhibiting microsatellite instability [MSI] appear to have unique biological behaviour. This study analyses the association between extensive MSI [MSI-H], clinicopathological features and survival in an unselected, group of patients with Sporadic Australian Clinico-Pathological Stage [ACPS] C [tumour node metastasis stage III] colorectal cancer.
    255 patients who underwent resection for sporadic ACPS C colorectal cancer between 1986-1992 were studied. No chemotherapy was given and a minimum follow up period was 5 years. Archival normal and tumour DNA was extracted and amplified by polymerase chain reaction using a radioactive labeling technique. MSI-4 was defined as instability in 40 percent or more of seven markers.
      
    21 patients showed MSI-H. No association was found between MSI and age or sex. Tumours exhibiting MSI-H were more commonly right sided, larger and more likely to be high grade. After adjustment for age, sex, and other variables, patients with MSI-H had improved survival rates.
         

  • E.A. Baker, F.G. Bergin and D.J. Leaper [ Professorial Unit of Surgery, North Tees General Hospital, Stockton on Tees TS19 8PE, UK]
    Matrix Metalloproteinases, Their Tissue Inhibitors and Colorectal Cancer Staging
    Br.Jour. of Surg. Volume 87, No.9, September 2000, Pgs. 1215-1221
       
    Matrix metalloproteinases [MMPs] and their tissue inhibitors [TIMPs] are important in tumour invasion and metastases. This study measured the levels of MMPs and TIMPs and total MMP activity in colorectal tumour cases and compared them with normal and correlated with clinical and pathological staging.
    Gelatin zymography [MMP-2 and MMP-9] enzyme linked immnunosorbent assays [MMP-1, MIMP-3, TIMP-1 and TIMP-2] and quenched fluorescent substrate hydrolysis [total MMP activity] were employed in resection specimens from 50 patients, four with adenomas and 46 with colorectal cancer.
       
    The levels of active MMP-2 and MMP-9 and total MMP-1, MMP-3 MMP-9 and total MMP1, MMP3, and TIMP-3 were significantly greater in tumour tissue than in normal colon. However, TIMP-2 levels were significantly greater in normal tissue. The total MMP activity was greater in tumours. Correlations were found between MMP and TIMP levels and pathological tumor staging. MMP1 appeared to be most important as its concentration correlated positively with Dukes staging, tumor differentiation and lymphatic invasion.
       

  • T. Funai, H. Osugi, M. higashino and Kinoshita [ Second Department of Surgery, Osaka City University Medical School, 1-4-3, Asahi-machi, Abeno-ku, Osaka 545-8585, Japan]
    Estimation of Lymph Node Metastasis by Size in Patients with Intrathoracic Oesophageal Cancer
    Br.Jour. of Surg. Volume 87, No.9, September 2000, Pgs. 1234-1239
       
    The aim of this study was to establish criteria for the preoperative diagnosis of lymph node metastases based on size and shape of nodes.
       
    123 patients were studied. 6822 nodes were obtained by extended lymphadenectomy. The nodes were classified anatomically and their size was measured by the operating surgeon during or immediately after surgery. All were examined histologically and criteria for diagnosis of metastasis were evaluated.
       
    The size of the nodes varied by anatomical site. They were smallest in the neck and largest at the tracheal bifurcation. The cut off value for the diagnosis of metastases was 5 mm in the neck. 6 mm in the abdomen and 8 mm in the mediastinum, except for tracheal nodes. Lymph node 10 mm or larger tended to become spherical when involved by metastasis.
        

  • Paul A Vasey (CRC Dept of Medical Oncology, Univ. of Glasgow)
    Immunotherapy for renal carcinoma: theoretical basis and current standard of care
    Br.J.Clin. Pharmacol 50, 521-529.
       
    There is no internationally recognised standard therapy for metastatic renal cancer and patients are treated with IFA or rIL-2 monotherapy or combinations. New approaches are needed.
      
    There are a number of preclinical studies which suggest that simultaneous exposure to both interferons and retinoids can result in enhanced antiproliferative and differentiation effects, compared with either agent alone. The EORTC are conducting a randomised trial of IFA in combination with 13-cis retinoic acid, a natural metabolite of vitamin A which has anticancer activity through a number of mechanisms including antiangiogenesis, differentiation induction and inhibition of IL-6.
      
    Immunostimulation by exogenously administered cytokines serves to enhance the function of the existing host immune system, rather than act as a cytotoxic agent that will eradicate or cure a disease process such as cancer. Continued development and exploration of novel therapies such as antiangiogenic compounds (e.g. thalidomide), differentiating agents, and newer immuno-stimulating agents will hopefully improve the outlook for patients in the future.
        

  • Gideon Steinbach, Patrick M Lynch et al
    The Effect of Celecoxib, a cyclooxygenase-2 inhibitor, in familial adenomatous polyposis.
    New Eng J Med. Vol.342, June 29, 2000, pg. 1946.
       
    Patients with familial adenomatous polyposis have a nearly 100 percent risk of colorectal cancer. Chemo-preventive effects of NSAIDs may be related to their inhibition of cyclooxygenase-2.
      
    Authors studied the effect of celecoxib, a selective cyclooxygenase-2 inhibitor, on colorectal polyposis in patients with familial adenomatous polyposis. In a double-blind, placebo-controlled study, 77 patients were randomly assigned to treatment with celecoxib (100 or 400 mg twice daily) or placebo for 6 months. Patients underwent endoscopy at the beginning and end of the study. The number and size of the polyps were determined from photographs and videotapes, the response to treatment was expressed as the mean percent change from base line.
      
    It was concluded that in patients with familial adenomatous polyposis, 6 months of twice daily treatment with 400mg of celecoxib, leads to a significant reduction in the number of colorectal polyps.
         

  • Christoph C, Zielinski and Michael Hejna
    Warfarin for cancer prevention.
    New Eng Jr Med. Vol.342, No.26, June 29, 2000, pg.1991.
      
    Clear evidence has been provided of an association between idiopathic thromboembolism and development of cancer. The risk is significantly higher among patients less than 65 years of age than among those who are 65 or older.
      
    Heparin, aspirin and other NSAIDs and warfarin have been used experimentally for prevention and treatment of various tumours in animals and humans. There are impressive data that suggest that aspirin and other NSAIDs reduce the risk of colorectal cancer probably by suppressing the synthesis of cyclooxygenase-2 and proinflammatory prostaglandins.
       
    A prospective randomised Veterans Affairs Co-operative Study demonstrated that the use of warfarin led to a statistically significant prolongation of the time to disease progression and improved survival among patients with small-cell lung cancer but not among patients with non-small cell lung cancer or cancer of the head, neck, prostate or colon.
      
    Schulman and Lindmarker report in this journal the effect of anticoagulants on the development of cancer. It is likely that anticoagulants were not acting on preexisting, clinically overt tumours but, rather were preventing the development of new cancerous lesions. This interpretation originated in a previous investigation that studied the optimal duration of anticoagulant therapy after venous thromboembolism and concluded that 6 months was superior to 6 weeks.
      
    This study should raise the awareness of the risk of certain cancers in patients with idiopathic thromboembolism. The necessity of appropriate follow up in these patients is clear. Wafarin needs to be studied in controlled clinical trials, with the aim of assessing prevention rather than treatment of cancer. Persons with genetic or environmental risk for the specific cancers should be considered for such studies. Warfarin could be a drug to be added to the armamentarium of chemoprotective agents.
          

  • Sam Schulman and Per Lindmarker
    Incidence of cancer after prophylaxis with warfarin against recurrent venous thromboembolism.
    New Eng Jr Med. Vol.342, June 29, 2000, pg. 1953
       
    The length of time after an episode of venous thromboembolism during which the risk of newly diagnosed cancer is increased is not known, and whether vitamin K antagonists have an antineoplastic effect is controversial.
      
    In a prospective, randomized study of the duration of oral anticoagulation (6 weeks or 6 months) after a first episode of venous thromboembolism, patients were questioned annually about any newly diagnosed cancer. After a mean follow up of 8.1 years, authors used the Swedish Cancer Registry to identify all diagnoses of cancer and causes of death in the study population. The observed numbers of cases of cancer were compared with expected numbers based on national incidence rates, and the standardized incidence ratios were calculated.
       
    The conclusion was that the risk of newly diagnosed cancer after a first episode of venous thromboembolism is elevated during at least the following 2 years. Subsequently, the risk seems to be lower among patients treated with oral anticoagulants for 6 months than among those treated for 6 weeks.
          

  • Mark W. Onaitis, Paul M. Kirshbom, Thomas Z. Hayward, Frank J. Quayle, Jerome M. Feldman, Hilliard F. Seigler, and Douglas S. Tyler [ From the Departments of Surgery and Medicine, Duke University Medical Center, Dursham, North Carolina]
    Gastrointestinal Carcinoids : Characterization by Site of Origin and Hormone Production
    Annals of Surgery, Volume 232, Number 4, Pg. Nos. 549-556
       
    This study describes a large series of patients with carcinoid tumors in terms of their clinical features, hormonal diagnosis and survival.
       
    A prospective database of carcinoid tumour patients seen at Duke University Medical Center was kept from 1970 onwards.
       
    A retrospective review of medical records was done on this database to record clinical features, hormonal data, pathologic features and survival.
      
    Carcinoids at different sites had different clinical features. Rectal tumours presented with bleeding and midgut carcinoids with flushing diarrhea, and the carcinoid syndrome. 
       
    They had significantly higher levels of serotonin and its breakdown products, corresponding to higher metastatic tumor burdens. Although age, stage, region of origin and urinary levels of 5-HIAA predicted survival by univariate analysis; with a multivariate analysis only the latter there were independent predictors of survival. In patients with metastatic disease midgut tumours had better prognosis than foregut or hindgut tumours. 
       

  • Ambrosio Hernandez, Farin Smith, BS, QingDing Wang, Xiaofu Wang, BS, and B. Mark Evers [ From the department of Surgery, The University of Texas Medical Branch, Galveston, Texas]
    Assessment of Differential Gene Expression Patterns in Human Colon Cancers
    Annals of Surgery, Volume 232, Number 4, Pg. Nos. 530-541
       
    This study uses a novel genomic approach to determine differential gene expression patterns in colon cancers of different metastatic potential.
       
    Human colon cancer cells KM12C [derived from a Dukes B colon cancer] KML 4A [ a metastatic variant derived from KM12C] and KM20 [ derived from Dukes D Colon Cancer] were extracted for RNA. In addition RNA was extracted from normal colon primary cancer and hepatic metastasis in a patient with metastatic colon cancer. Gene expression patterns for approximately 1200 human genes were analyzed and compared by cDNA array techniques.
       
    Of the 1200 genes assessed in the KM cell lines,9 genes were noted to have more than threefold change in expression [either increased or decreased] in the more metastatic KML4A and KM20 cells compared with KM12C. There was more than threefold change in expression of 16 genes in metastatic colon cancer compared with normals.
       
    The authors have identified genes with expression levels that are altered with metastasis.
        

  • H. Tanaka, K. Hirohashi, S. Kubo, T. Shuto, I. Higaki and H. Kinoshita
    Preoperative Portal Vein Embolization Improves Prognosis of Right Hepatectomy for Hepatocellular Carcinoma in Patients with Impaired Hepatic Function
    Br.Jour. of Surg. Volume 87, No.7, July 2000, Pgs. 879-882
       
    Percutaneous transhepatic portal vein embolization [PTPE] increases the safety of subsequent major hepatectomy. This study aims to determine the effect of PTPE on long term prognosis after hepatectomy in patients with hepatocellular carcinoma [HCC].
        
    71 patients underwent hepatectomy for HCC. 33 patients [group 1] underwent preoperative PTPE and 38 patients [group 2] did not have this procedure. The patient were further divided according to the median tumour diameter [cut off 6 cm] and indocyanine green retention rate at 15 min [ICGR15] [cut-off 13%]. 
       
    The cumulative survival rate was significantly higher in group 1 then in group 2 in patients with an ICGR15 of at least 13%. Tumour-free survival rates were similar in both groups. Of patients with tumour recurrence after right hepatectomy, those in group 1 were more frequently subjected to further treatment. 
     
    Preoperative PTPE improves the prognosis after right hepatectomy for HCC in patients with impaired hepatic function although it does not prevent tumour recurrence.
       

  • T.M.D. Hughes, R.P. A’Hern and J.M. Thomas [ Melanoma and Sarcoma Unit, Royal Marsden Hospital, Fulham Road, London SW3 6JJ, UK]
    Prognosis and Surgical Management of Patients with Palpable Inguinal Lymph Node Metastases from Melanoma
    BJS, Volume 87, Number 7, July 2000, Pg. Nos. 892-901
      
    The aim of this study was to identify factors that influence the outcome of patients undergoing therapeutic groin dissection for clinically detectable melanoma lymph node metastases. 
       
    A retrospective study of 132 cases who underwent lymph node dissection [ inguinal] therapeutically.
    60 Patients had superficial inguinal lymph node [SLND] dissection and 72 had combined superficial inguinal and pelvic lymph node dissection [CLND]. 
      
    There was no difference in postoperative morbidity or major lymphoedema. The overall survival rate was 34% at 5 years. On univariate analysis age, the number of superficial inguinal nodes and presence of extra capsular spread had a significant impact on survival. The presence of or absence of pelvic lymph node metastases was a significant prognostic factor [ 19% vs. 47%].
       
    The prognosis of patients with clinically detectable melanoma metastases to the groin is variable and related to the biologic characteristics of each case. CLND provided additional prognostic information and optional regional control but no change in morbidity compared to SLND.
        

  • E. Rullier, F. Zerbib, C. Laurent, M. Caudry and J. Saric [ Departments of Digestive Surgery, Gastroenterology and Radiation Oncology, Saint-Andre Hospital, 33075 Bordeaux Cedex, France]
    Morbidity and Functional Outcome After Double Dynamic Graciloplasty for Anorectal Reconstruction
    BJS, Volume 87, Number 7, July 2000, Pg. Nos. 909-913
      
    The aim of this study was to evaluate the morbidity and functional results in a homogeneous series of patients undergoing double dynamic graciloplasty following APR for rectal cancer.
       
    15 patients[ 10 men and 5 women, mean age of 54 years range [ 39 to 77] underwent anorectal reconstruction with double dynamic graciloplasty after APR for low rectal cancer. 
       
    All patients had preoperative radiotherapy [ 15 Gy] and ten received adjuvant, chemotherapy, 8 had intraoperative radiotherapy [15 Gy] and ten received 
       
    adjuvant chemotherapy for six months. Surgery was performed in three stages : APR with coloperineal anastomosis and double graciloplasty; implantation of the stimulation 2 months later; and ileostomy closure after a training period.
      
    There was no operative death. At a mean of 28 months [3-48] of follow-up there was no local recurrence; 2 patients had lung metastases. Early and late morbidity occurred in 11 patients [mainly related to neosphinctor], mainly stenosis. Of 12 patients followed up for functional outcome. 7 were continent, 2 were incontinent and 3 had an abdominal colostomy [ 2 for incontinence and one for sepsis]. The restenosis required major surgery and had a poor outcome.
       
    The conclusion is that the double dynamic graciloplasty is associated with a high risk of neosphincter stenosis which may entail morbidity, reintervention and poor functional results. It is suggested that single dynamic graciloplasty should be used for anorectal reconstruction after APR.
      

  • D.C. Jenner , A. Middleton, W.M. Webb, R. Oommen and T. Bates [ The Breast Unit, William Harvey Hospital, Ashfold TN24 OLZ, UK]
    In-Hospital Delay in the Diagnosis of Breast Cancer
    BJS, Volume 87, Number 7, July 2000, Pg. Nos. 914-919
         
    Delay in the diagnosis of breast cancer may prejudice survival. The aim of this study was to determine the incidence, time trends and causes of delay in a dedicated breast clinic. 
        
    The interval between the first visit to the clinic and a definitive diagnosis, was recorded in 1004 patients with invasive breast cancer.
       
    There was a delay of 3 months or more in 42 cases [4.2%]. The median delay was 6 months and the median age at diagnosis was 53 years [range 27-89 years]. Triple assessment was undertaken in 30 patients. Ten did not have a needle biopsy and three patients did not have a mammography. The principal cause of delay was false negative or inadequate needle aspiration cytology [FNAC] in 19 patients, a failure of follow-up in 8 cases, failure of needle localization in two cases, FNAC not carried out in 4 cases, no clinical signs in five patients and one case who did not follow clinical advice. The annual incidence of delay in diagnosis did not change significantly over a 10 year interval.
       
    Triple assessment is not sufficiently sensitive to detect breast cancer and a small delay in diagnosis is inevitable with current techniques.
       

  • L. Jansen, M. H.E. Doting E.J.Th. Rutgers, J. de Vries, R.A. Valdes Olmos and O.E.Nieweg [ Departments of Surgery and Nuclear Medicine, The Netherlands Cancer Institute /Antoni van Leeuwenhock Hospital, Amsterdam and Department of Surgical Oncology, Groningen University Hospital, Groningen, The Netherlands]
    Clinical Relevance of Sentinel Lymph Nodes Outside the Axilla in Patients with Breast Cancer 
    BJS, Volume 87, Number 7, July 2000, Pg. Nos. 920-925
         
    Lymphatic mapping in patients with breast cancer can reveal sentinel lymph nodes that are not located at level I-II of the axilla. The clinical relevance of this is not fully understood.
       
    113 consecutive patients [T1-3 No Mo] with breast cancer were studied. Based on preoperative scintigraphy. Sentinel node biopsy was performed guided by a g probe and patent blue dye. All sentinel nodes that were visible were biopsied and examination of those nodes included step sections and staining with CAM5.2. Axillary node dissection was performed regardless of sentinal lymph node status.
       
    19% [ 21 cases] had sentinel lymph nodes outside level I-II of the axilla, mostly in the internal mammary chain. 22 of the 30 sentinel nodes at these sites were harvested. 3 patients had sentinel nodes only outside the axilla. 4 other patients had metastases outside the axilla. This changed postoperative treatment in 3 patients. No postoperative complication occurred.
       
    Biopsy of sentinel lymph nodes [19% of cases in this series] is technically demanding but the clinical impact was limited – treatment changed in only 3%.
      

  • Manel Esteller, Jesus Garcia Foncillas et al
    Inactivation of the DNA repair gene MGMT and the clinical response of gliomas to alkylating agents.
    New Eng J Med. Vol.343, Nov.9, 2000,pg.1350.
       
    Summary : The DNA repair enzyme O6-methyl-guanine-DNA methyltransferase (MGMT) inhibits the killing of tumour cells by alkylating agents. MGMT activity is controlled by a promoter and methylation of the promoter silences the gene in cancer and the cells no longer produce MGMT. Authors examined gliomas to determine whether methylation of the MGMT promoter is related to the responsiveness of the tumour to alkylating agents.

    MGMT promoter in tumour DNA was analysed by a specific PCR assay. Gliomas were obtained from patients treated with carmustine. Molecular data were correlated with the clinical outcome. MGMT promoter was methylated in 40% of gliomas and this was associated with regression of the tumour and prolonged overall and disease free survival. It was an independent and stronger prognostic factor than age, stage, tumour grade or performance status.

    The conclusion was that methylation of the MGMT promoter in gliomas is a useful predictor of responsiveness of the tumours to alkylating agents.
       
    Editorial : John N Weinsten, pg.1408
    Pharmacogenomics – Teaching old drugs new tricks.
    Summary: Traditionally, cancer treatments have been selected on the basis of tumour type, pathological features, clinical stage, the patient’s age and performance status and other nonmolecular considerations. The field of pharmacogenomics, through the study of large number of genes that influence drug activity, toxicity and metabolism, provides the opportunity to tailor drug treatments and to eliminate many of the uncertainties of current therapy for cancer.
      
    Strong support for this concept is provided by the study of genetic polymorphisms that influence drug metabolism. CYP2D6 affects metabolism of several drugs (beta-blockers, antidepressants, antipsychotics and opioids). Dihydropyrimidine dehydrogenase influences metabolism and therefore neurotoxicity of fluorouracil.
      
    Esteller and colleagues provide clinical evidence to explain the resistance of some gliomas to nitrosourea alkylating agents. Carmustine and other nitrosoureas kill by alkylating O6 position of guanine and thereby cross-linking adjacent strands of DNA. Formation of these cross-links can be prevented by MGMT, which rapidly reverses alkylation. About 30% of gliomas lack MGMT. A lack of MGMT appears to correlate with sensitivity to carmustine. Methylation of MGMT promoter could be used to predict responses to treatment with carmustine.
       
    Pharmacogenomics studies will produce benefits both for clinical research and standard practice. Potential advantages include discovery of better drugs, elimination of poor candidates early in the development process, and dramatic decrease in size and expense of clinical trials.
      

  • Ambrosio Hernandez, Farin Smith, BS, QingDing Wang, Xiaofu Wang, BS, and B. Mark Evers [ From the department of Surgery, The University of Texas Medical Branch, Galveston, Texas]
    Assessment of Differential Gene Expression Patterns in Human Colon Cancers
    Annals of Surgery, Volume 232, Number 4, Pg. Nos. 530-541
        
    This study uses a novel genomic approach to determine differential gene expression patterns in colon cancers of different metastatic potential.
       
    Human colon cancer cells KM12C [derived from a Dukes B colon cancer] KML 4A [ a metastatic variant derived from KM12C] and KM20 [ derived from Dukes D Colon Cancer] were extracted for RNA. In addition RNA was extracted from normal colon primary cancer and hepatic metastasis in a patient with metastatic colon cancer. Gene expression patterns for approximately 1200 human genes were analyzed and compared by cDNA array techniques.
       
    Of the 1200 genes assessed in the KM cell lines,9 genes were noted to have more than threefold change in expression [either increased or decreased] in the more metastatic KML4A and KM20 cells compared with KM12C. There was more than threefold change in expression of 16 genes in metastatic colon cancer compared with normals.
        
    The authors have identified genes with expression levels that are altered with metastasis.
       

  • Dorudi S, Kinrade E, Marshall NC, et al [ Royal London Hosp]
    Genetic Detection of Lymph Node Micrometastases in Patients with Colorectal Cancer
    Br J Surg 85: 98-100, 1998
          
    Undetected micro metastases are the most important cause of treatment failure in patients with putatively curative colorectal cancer surgery. The detection in the regional lymph node of mRNA expressed from cytokeratin [CK] 20 gene upstaged 4 of 15 patients. Following a resection for colorectal cancer. The CK 20 gene product being a cytokeratin is restricted to intestinal epithelium and is not likely to be expressed in the lymph node. The editor comments that these so called negative nodes by hematoxylin eosin may be placed into trials for adjuvant therapy once these molecular biology techniques are standardized and gained experience in clinical practice.
      

  • Delbeke D, Martin WH, Sandler MP, et al [ Vanderbilt Unit, Nashville, Tenn]
    Evaluation of Benign vs Malignant Hepatic Lesions with Positron Emission Tomography
    Arch Surg 133: 510-516, 1998
        
    The relatively low levels of glucose-6-phosphatase is most malignant cells results in accumulation and trapping of [18F] flurodeoxyglucose [FDG] intracellularly, & then visualizing the increased uptake. This technique of FDG PET has been used in 110 consecutive patients with hepatic tumors of 1 cm or greater to differentiate between benign vs. Malignant lesions. All liver metastasis from adenocarcinoma or sarcoma and all cholangiocarcinomas showed increased uptake. Whereas hepatocellular carcinoma [HCC] had an increased FDG uptake in 16 of 23 patients and poor uptake in 7 of 23 with the exception of one abscess which had increased uptake. Rest all benign lesions revealed a poor uptake. The limitation of this technique is false positive in a minority of abscess and false negative in minority of HCC. FDG PET would also be useful in future for staging, detecting recurrences and monitoring response.
      

  • Sorensen HT, Mellemkjaer L, Steffensen FH, et al [ Univ of Aarhus, Denmark; Inst of Cancer Epidemiology, Copenhagen; Aalborg Hosp, Denmark]
    The Risk of a Diagnosis of Cancer After Primary Deep Venous Thrombosis or Pulmonary Embolism
    N Engl J Med 338: 1169-1173, 1998
       
    The relation between pulmonary embolism [PE], deep venous thrombosis [DVT] and cancer has been debated. This large study of 15,348 patients with DVT and 11,305 with PE revealed an increased risk of 1.3 for development of cancer. Although the risk was significantly elevated only during the first 6 months of follow-up. Pancreas, ovary, liver, and brain were most common sites of cancer in patients with thromboembolism. Exhaustive search for cancer in such patient was not of clinical benefit.
     

  • Narod SA, for the Hereditary Ovarian Cancer Clinical Study Group [Univ of Toronto; et al]
    Oral Contraceptives and the Risk of Hereditary Ovarian Cancer
    N Engl J Med 339: 424-428, 1998
       
    In this study 207 women with hereditary ovarian cancer and with a pathogenic mutation in either BRCA1 or BRCA2 gene were studied along with 161 of their sisters. The study findings revealed women using oral contraceptive [OC] for 6 or more years had a 60% reduction in the risk of ovarian cancer. The use of OC protected against ovarian cancer among the carriers of both to BRCA1 or BRCA2 mutation.
        

  • Lombard I, Vincent-Salomon, Validire P, et al [ Institut Curie,Paris; Institut Pasteur, Paris]
    Human Palillomavirus Genotype as a Major Determinant of the Course of Cervical Cancer
    J Clin Oncol 16: 2613-2619, 1998
       
    Human Papillomavirus [HPV] a venereally transmissible oncogenic agent, is a well known to be associated with of uterine cervix. In this study HPV DNA was extracted from frozen tumor specimens analyzed by Southern blot hybridization and polymerase chain reaction. 
      
    The genotype HPV 16 & HPV18 positive tumors had a disease free survival at 5 year of 58% and 38% respectively. A multivariate analysis recorded HPV-18 related tumors with a relative risk of death that was 2.4 times higher than were HPV-16 related tumors and a 4.4 times higher than tumors related to other viral types. The editor comments that typing of HPV is clearly a prognostic indicator for individual patients with cervical cancer and further management of these patients would be through biological and immunological therapies directed against HPV associated carcinoma.
       

  • Penninx BWJH, Guralnik JM, Pahor M, et al [ Natl Inst on Aging, Bethesda, Md; Univ of Tennessee, Memphis; Istituto Nazionale Ricerca e Cura Per Gli Anziani, Florence, Italy; et al]
    Chronically Depressed Mood and Cancer Risk in Older Persons
    J Natl Cancer Inst 90: 1888-1893, 1998
         
    The associations of chronic depression with cancer in elderly patients was investigated. All participants in this study were 71 years or older.
       
    Depression of at least 6 years duration appears to be associated with an increased risk of cancer in elderly even when corrected for factors such as alcohol smoking, age, sex and race. The editor comments that depressed patients practice poorer health promoting behavior than non depressed and could be attributed to increased cancer risk.
        

  • Granovsky MO, Mueller BU, Nicholson HS, et al [ Natl Cancer Inst, Bethesda, Md; Children’s Hosp, Boston; Children’s Natl Med Ctr, Washington, DC]
    Cancer in Human Immunodeficiency Virus-Infected Children: A Case Series From the Children’s Cancer Group and the National Cancer Institute
    J Clin Oncol 16: 1729-1735, 1998
       
    The epidemiology of HIV-related cancer in adults has been well described but that in children is not well documented and hence this study reports the spectrum of malignancies in HIV infected children and their clinical outcome.
       
    Most [58%] of the children had acquired HIV vertically 34% through blood or blood products transfusion. Non-Hodgkin’s lymphoma – 65% was the commonest followed by leiomyosarcomas – 17% and the others were acute leukemia. Kaposi’s sarcoma, Hodgkin’s disease vaginal carcinoma in situ tracheal neuroendocrine tumor. The median survival for NHL was 6 months and leiomyosarcoma – 12 months after diagnosis. The editor comments that with recent improvements in antiretroviral therapy and supportive care. More children are surviving the early complications of HIV and will subsequently develop malignancies.
        

  • Bennet CL, Ferreira MR, Davis TC, et al [ Chicago Veteran Affairs Administration Healthcare System-Lakeside Division; Lurie Cancer Ctr; Northwestern Univ, Chicago; et al
    Relation between Literacy, Race, and Stage of Presentation Among Low-Income Patients with Prostate Cancer
    J Clin Oncol 16: 3101-2104, 1998
       
    Advanced prostate cancer in a low income men is related to poor literacy skill has been brought out in this study. The black men were almost twice as likely as white men to have stage D prostate cancer at initial examination. The editor comments that the effectiveness of screening to detect cancer at the earlier stage depends on aggressiveness of the tumor, the cost effectiveness of screening and most importantly, the willingness of the patient to undergo screening. The importance of the literacy for the informed consent has direct implications in clinical trials.
         

  • deVere White RW, Deitch AD, Jackson AG, et al [ Univ of California, Davis; Northern California Cancer Ctr, union City; Howard Univ, Washington, DC]
    Racial Differences in Clinically Localized Prostate Cancers of Black and White Men
    J Urol 159: 1979-1983, 1998
      
    The investigative skill i.e prostate-specific antigen and proper records in cancer registries, are responsible for the increase in prostate cancer despite these a true rise in incidence of prostate cancer is noted. The highest incidence in the world is found among black men in Unites States; They have at younger age, large volume, higher stage and grade compared with white men. This study has correlated with biological markers i.e. deoxyribonucleic acid ploidy by DNA flow cytometry using propidium / expression of proliferation, as well as P53 & bcl-2 . A monoclonal antibody cocktail for p53 and clone 124 antibody for bcl-2 were used for immunostaining after microwave antigen retrieval on the prostate biopsy specimens. The higher S phase fraction reflecting high proliferation and bcl-2 immnuno positively i.e. block to programmed cell death- characterize the aggressive prostate cancer of black men.
       

  • Andrea Mariani, Maurice J Webb, et al (Rochester, Minnesota, and Milan, Italy)
    Low-risk corpus cancer: Is lymphadenectomy or radiotherapy necessary?
    Am J Obstet Gynecol, vol.182, June 2000, p.1506-19
        

    Objective: The objective of this study was to find readily ascertainable intraoperative pathologic indicators that would discriminate a subgroup of early corpus cancers that would not require lymphadenectomy or adjuvant radiotherapy.
       
    Study Design: Between 1984 and 1993, a total of 328 patients with endometrial corpus cancer, grade 1 or 2 tumor, myometrial invasion £50%, and no intraoperative evidence of macroscopic extrauterine spread were treated surgically. Pelvic lymphadenectomy was performed in 187 cases (57%), and nodes were positive in nine cases (5%). Adjuvant radiotherapy was administered to 65 patients (20%). Median follow-up was 88 months.
       
    Results: The 5-year overall cancer-related and recurrence-free survivals were 97% and 96%, respectively. Primary tumor diameter and lymphatic or vascular invasion significantly affected longevity. No patient with tumor diameter £2cm had positive lymph nodes or died of disease.
       
    Conclusion: Patients who have International Federation of Gynecology and Obstetrics grade 1 or 2 endometrioid corpus cancer with greatest surface dimension £2cm, myometrial invasion £50%, and no intraoperative evidence of macroscopic disease can be treated optimally with hysterectomy only.
       

  • Moinpour CM, Savage MJ, Troxel A, et al [ Fred Hutchinson Cancer Research Ctr, Seattle; Mercy Med Ctr, Baltimore, Md; Columbia Presbyterian Cancer Ctr, New York; et al]
    Quality of Life in Advanced Prostate Cancer: Results of a Randomized Therapeutic Trial
    J Natl Cancer Inst 90: 1537-1544, 1998
        
    Palliative therapy of metastatic carcinoma prostate in 739 patients with prostate cancer metastasis to bone or soft tissue underwent bilateral orchiectomy. The patients then reviewed flutamide or placebo. The patient on flutamide had more diarrhea, worse emotional functioning and thereby poor quality of life outcomes than on placebo.

  • Socie G, for the Late Effects Working Committee of the International Bone Marrow Transplant Registry [Hopital Saint Louis, Paris]
    Long-term Survival and Late Deaths After Allogeneic Bone Marrow Transplantation
    N Engl J Med 341: 14-21, 1999

    This study of 6691 patients who underwent allogeneic or syngenic bone marrow transplant and were disease free for 2 years post transplant. The probability of survival at 5 years was 89%. Late deaths were less frequent [6% at 7 years] for aplastic anemia than for leukemia [ 12% at 7 years] and the mortality was due to chronic graft-versus-host disease and relapse respectively. 
       

  • MJ Byrne, JA Davidson, AW Musk, et al (Sir Charles Gairdner Hosp, Nedlands, Australia; Unvi of Western Australia, Nedlands)
    Cisplatin and Gemcitabin Treatment for Malignant Mesothelioma: A Phase II Study.
    J Clin Oncol 17: 25-30, 1999.
       
     Malignant mesothelioma, an aggressive tumor, is an uncommon tumor that is increasing in incidence. A Phase II Study of combined cisplatin and gemcitabine for the treatment has been reported herewith.
       
    Twenty-one patients, aged 46 to 74 years were enrolled in the study of which sixty-two percent had epithelial tumors, eighteen had tumor-node-metastasis (TNM) system stage III or IV. Treatment consisted of cisplatin being given as 100mg/m2, given intravenously on day 1 and gemcitabine 1000mg/m2 intravenously on days 1, 8, 15 of a 28-day cycle for 6 cycles. Pleural tumor was measured at 3 levels with CT scan at baseline; before the second, fourth, and sixth cycles; and every 2 months thereafter until the disease progression.
       
    The treatment of malignant pleural mesothelioma has been always controversial. For earlier stage disease being subjected to extrapleural pneumonectomy. For advanced disease, there are a number of chemotherapeutic agents that have demonstrated single-agents activity against malignant pleural  mesothelioma, but the response rate is only 15% to 20 %. This trial seems to have response rate of 47% i.e. 10 of 10 patients and is perhaps the highest ever reported. Consequently, several other centers are trying out the result of these studies so as to seen whether they are spurious or not.
       

  • H. Stephan Stoldt James G, Geraghty 
    Surgical Principles in the Management of Soft Tissue Sarcomas
    Recent Advances in Surgery, Number 22, Year – 1999
       
    Safe margins are as important to achieve as in any tumour type. Surgical resection remains the mainstay in management but pre- and postoperative radiotherapy, as well as brachytherapy, are important modalities of treatment, which may impact on the surgical approach to the tumour. 
        
    One important aspect related to the surgical management of soft tissue sarcoma concerns its staging. 
      
    It is better to carry out an incisional rather than an excisional biopsy. The exception to this rule is the small superficial lesion where it is simplest to excise the lesion. 
       
    The surgical management of sarcomas can be divided into marginal resection, radical resection, amputation, debulking and surgery combined with brachytherapy. 
      
    The challenge in sarcoma surgery is in achieving adequate resection of the tumour while preserving good functional outcome. A margin of at least 1 cm is required to achieve microscopic free margins.
      
    At present, the standard local treatment for Soft Tissue Sarcomas [STS] of the extremity is limb sparing surgery . Locoregional adjuvant therapy include isolated limb perfusion with chemotherapeutic agents hyperthermia alone and combined chemoradiation with hyperthermia. 
         
    The evidence demonstrates an advantage for preoperative compared to postoperative radiotherapy after surgery . It has been shown however that there are overall advantages for pre-operative radiotherapy, particularly in lesions over 5 cm in diameter. There is no proven benefit with brachytherapy.
         
    An unusual group of tumours called Desmoid tumours which are classified as benign do not metastasize but sometimes behave in a locally aggressive fashion. Due to their potential for an aggressive growth pattern, aggressive surgery is the treatment of choice.
        

  • M. R. Kell, D. C.Winter, G.C. O’Sullivan, F. Shanahan and H.P. Redmond 
    [Departments of Academic Surgery and Medicine, National University of Ireland, Cork University Hospital and ‘Mercy Hospital, Cork, Ireland]
    Biological Behaviour and Clinical Implications of Micrometastases
    Br. Jr. of Sur. Volume 87, No.12, December 2000, Pgs-1629-1639
         
    The most important prognostic determinant in cancer is the identification of designated tumor burden [metastases]. Micrometastases are microscopic (<2mm) deposits of malignant cells that are segregated spatially from the primary tumour and depend on neovascular formation (angiogenesis) to propogate.
    The literature on micrometastases and their implications in malignant melanoma and epithelial cancers is reviewed.
    Immunohistochemical and serial sectioning methods were used. Molecular techniques were reserved for blood samples and bone marrow aspirates.
         
    Detection of micrometastases in regional lymph nodes and/or bone marrow confers a poor prognosis in epithelial cancers. The concept of sentinel node biopsy combined with serial sectioning and dedicated screening for micrometastases may improve staging procedures. Strategies against angiogenesis may provide novel therapies to induce and maintain micrometastatic dormancy.
         

  • A Llaneza, F. Vizoso, J.C. Rodriguez, P. Raigoso, J.L. Garcia-Muniz, M.T. Allende and M. Garcia-Moran [ Department of Surgery and Nuclear Medicine, Hospital Central de Asturias, Oviedo and Department of Surgery, Hospital de Jove, Gijon, Spain]
    Hyaluronic Acid as Prognostic Marker in Resectable Colorectal Cancer
    Br. Jour. of Sur. Volume 87, No.12, December 2000, Pgs 1690-1696
       
    Hyaluronic Acid [HA] an extracellular high molecular mass polysaccharide, is thought to be involved in the growth and progression of malignant tumours. This study evaluates the cytosolic HA content in resectable colonic cancer, and its possible relationship with clinicopathological parameters of tumours and its prognostic significance.
        
    Cytosolic HA levels were examined by radiometric assay in 120 patients with resectable colorectal cancer. The mean follow up period was 33.4 months. The levels of cytosolic HA levels of tumours ranged widely from 3o to 29412 ng/mg protein. Intratumour HA levels were significantly correlated with Dukes Stage [P<0.005] and were higher in patients with advanced tumours [ mean (s.e.m.) 2695(446), 2858(293) and 5274(967) ng/mg protein for stages A-B and C respectively]. In addition, Cox multivariate analysis demonstrated that tumour HA levels >2000 ng/mg protein predicted shorter relapse free survival and overall survival period [both P<0.05].
        
    They conclude that there is a wide variability in cytosolic HA levels in colorectal cancers, which seems to be related to the biological heterogeneity of the tumours. High tumour cytosolic HA levels were associated with an unfavourable prognosis
      

  • Krouse JH 
    Staging of Inverted Papilloma
    Laryngoscope 2000: 110: 965-968
         
    Formerly medical maxillectomy through an external incision was treatment of choice as against that today endoscopy is the treatment followed by most of them. This is controversial because of an association of inverted papilloma with malignancy.
        
    This study utilized a literature review to develop a simple and easily applied staging system – based on endoscopic examination of the nasal cavity and CT scanning.
        
    The staging system is as follows:-
        
    Stage I – Disease is limited to nasal cavity.
    Stage II – It is limited to the ethmoid sinuses and medial and superior portion of the 
                   maxillary sinuses.
    Stage III – Involves the lateral or inferior aspects of maxillary sinuses or extension 
                    into the frontal or sphenoid sinuses.
    Stage IV – Involves tumour spread outside the confines of the nose.
         

  • Moreau PR 
    Laser Laryngeal Surgery
    Laryngoscope 2000; 110: 1000 – 1006
         

    This study is a retrospective analysis of 160 patients treated for laryngeal cancer with CO2 laser endoscopic microsurgery.
         
    Glottic tumours were treated with progressively more extensive cordectomies, extended if necessary to the contralateral cord. Supraglottic tumours had an excision limited to the vestibule, a trans-preepiglottic resection or a radical subglottic dissection. The results are as follows:-
        
    Five year survival was 97% for 98 tumours (infiltrative glottic tumours) and 100% for the 18 infiltrative supraglottic tumour and 27 in situ carcinoma. No local recurrences were noted in either group of 118 tumours (in whom two precancerous lesions were treated with a further excision) as in 27 in situ. Local control was thus 100%.
       

  • H Wunderlich, et al (Freidrich Schiller Univ, Jena Germany)
    Nephron Sparing Surgery for Renal Cell Carcinoma 4cm or less in diameter: Indicated or Under Treated ?
    J Urol 159: 1465-1469, 1998.
        
    Background : Radical Nephrectomy continues to be the standard treatment for localised unilateral renal cell carcinoma in patients with normal contralateral kidneys.
        
    The use of radical nephrectomy was retrospectively studied with respect to size and metastasis of renal cell carcinoma.
        
    Findings: The frequency of grade I renal cell carcinomas declined with increasing tumor diameter.
    The opposite was noted for grade 3. Tumor size was associated with lymph node and distant metastasis.
        
    Frequency of venous involvement increased along with increase in tumor size.
       
    Conclusion : The metastatic potential and biology of small renal cell carcinomas have not been established.
       
    To minimise the risk of recurrence Nephron sparing surgery might be limited to those with renal cell carcinomas of 20mm or less.
        

  • KS Hafez, AC Novick, BP Butler (Cleveland Clinic Foundation, Ohio)
    Management of Small Solitary Unilateral Renal Cell Carcinoma: Impact of Central Versus Peripheral Tumor Location.
    J. Urol 159: 1156-1160, 1998.
        
    Conclusion : No significant biological differences are evident between central and peripheral small solitary unilateral renal cell carcinomas.
       
    Nephron sparing surgery was technically more complicated among central renal cell carcinomas.
       
    Intraoperative ultrasonography may be a more important adjunct when approaching patients with central tumors.
       

  • H Miyake, H Nakamura, I Hara, et al (Kobe Univ;Japan; Kumamoto Univ, Japan) 
    Multifocal Renal Cell Carcinoma: Evidence for a Common Clonal Origin.
    Clin Cancer Res. 4: 2491, 1998.
        
    The controversy surrounding the use of Nephron sparing surgery for renal cell carcinoma has revolved around the observed 7% to 25% incidence of relatively small satellite tumors discovered at autopsy or upon careful examination of radical nephrectomy specimens from patients with clinically evident renal cell carcinoma.
        
    In this study, the authors studied 10 cases of renal cell carcinoma that were accompanied by smaller satellite tumors for LOH (Loss of Heterozygosity) at chromosome arms 3p, 6q, 8p, 9p, 9q and 14q. All tumors were less than 5cm. Primary and satellite lesions in 8 of 10 cases exhibited identical patterns of LOH.
       
    Similarity of LOH patterns in the main satellite tumors indicated that satellite tumors are the result of intrarenal metastasis rather than new separate primaries. In any series the satellite lesions are generally small and occurring within 2 cm of the index tumor. The satellite tumors measure 2-4mm. Many satellite lesions may be resected during a “radical partial nephrectomy” or may never reach the clinical horizon.
        

  • R. Edward Coleman (Professor of Radiology, Director of Nuclear Medicine and Vice-Chair, Department of Radiology, Duke University Medical Center, Durham, NC)
    PET is Now a Routine Clinical Procedure
    (Emeritus Editor’s Essay)
      
    Clinical PET imaging is having an impact on the medical care of patients. Although the technology was developed in the early 1970s along with MRI, it has only recently received recognition. It provides excellent physiologic and biochemical information as against MRI that gives only anatomical information.
      
    The economics of setting up a PET center was not viable until the 1990s. It requires a cyclotron, a tomograph, and a staff to support the chemistry for the production of FDG (a radiopharmaceutical which is the major reason for the progression of clinical PET). It is approximately 19% more sensitive and 13% more specific than CT.
       
    The growth of PET in USA has been phenomenal. From 83,000 studies done in 1998 to 172,000 studies in 2000. In the author’s division, more than one third of the revenue comes from PET.
       
    It can be anticipated to grow further. New radiopharmaceuticals are being developed to improve the sensitivity and specificity. When it is combined with CT scans, it will give a marked improvement in image quality.
       
    PET is making a major impact in nuclear medicine.
         

  • Mijnhout GS, Hooft L, van Tulder MW, et al (Vrije Universiteit, Amsterdam)
    How to Perform a Comprehensive Search for FDG-PET Literature
    Eur J Nucl Med 27:91-97, 2000
        
    PET scan with FDG is a useful imaging technique for a wide variety of pathologies especially in neoplasia.
        
    However there is a lack of guidelines for performing a literature search on this subject. A practical approach to this searching of electronic databases has been reported.
       
    This approach has increased the retrieval of FDG-PET studies. This would be easier if one standardizes the widely variable spelling of FDG. They recommend the medical subject be labeled as ‘Fluorodeoxyglucose F18’. 
         

  • Weber WA, Ziegler SI, Thodtmann R, et al (Technische Universitat Munchen, Germany)
    Reproducibility of Metabolic Measurements in Malignant Tumors Using FDG PET
    J Nucl Med 40:1771-1777, 1999
        
    Although, PET has been used to detect and stage tumors, its application in the quantitative measurements in malignant tumors, specifically with the use of FDG has not been studied.
      
    FDG-PET evaluations were done twice before the start of chemotherapy in a phase I study of new antineoplastic compounds. Standard uptake values (SUV), FDG net influx constants (K), glucose normalized SUVs (SUVgluc) and influx constants (Kgluc). The accuracy was judged by comparing each lesion and each patient at both examinations.
       
    FDG-PET provided highly reproducible values involving several parameters. It may therefore provide reliable evaluation of the efficacy of therapy for neoplasms.
         

  • Young H, for the European Organization for Research and Treatment of Cancer (EORTC) PET Study Group (Hammersmith Hosp, London; et al)
    Measurement of Clinical and Subclinical Tumour Response Using [18F]-Fluorodeoxyglucose and Positron Emission Tomography: Review and 1999 EORTC Recommendations
    Eur J Cancer 35:1773-1782, 1999
       
    A method for evaluating tumor 18F-FDG uptake and reporting of response data used by EORTC PET study group has been described.
        
    Six hours of starvation before the study is recommended. Insulin may be given at the physician’s discretion, good hydration and diazepam may be given for muscle relaxation.
       
    The optimal time after injection to record the uptake value and the optimal time between scans has not been standardized. Pre and post treatment scans are recommended for comparison.
       
    The recommendations made are not meant to be exclusive of other measurements.
         

  • Antoine JC, Cinotti L, Tilikete C, et al (Hospital de Bellevue, Saint-Etienne, France; Hospital Neurologique, Lyon, France) 
    [18F] Fluorodeoxyglucose and Positron Emission Tomography in the Diagnosis of Cancer in Patients With Paraneoplastic Neurological Syndrome and Anti-Hu Antibodies 
    Ann Neurol 48:105-108, 2000
       
    The diagnosis of paraneoplastic neurologic syndrome (PNS) and anti Hu antibodies is difficult. FDG-PET scanning is highly sensitive and specific in the detection of lung tumors as seen in this study of 15 patients.
       
    Whole body FDG-PET scanning was useful in the diagnosis of cancer in patients with PNS and anti Hu antibodies and with negative findings after an initial workup using radiologic approaches. 
        

  • Bohuslavizki KH, Klutmann S, Kroger S, et al (Univ Hosp Eppendorf, Hamburg, Germany; Phillips Univ, Marburg, Germany)
    FDG PET Detection of Unknown Primary Tumors
    J Nucl Med 41:816-822, 2000
        
    The value of FDG-PET scanning in detecting unknown primary cancer sites is studied.
       
    53 patients with metastatic cervical lymph adenopathy from an unknown primary site were studied.
       
    27 patients showed focal tracer uptakes corresponding to primary tumor sites in lungs, palatine tonsil, salivary glands, nasopharynx, oropharynx, maxillary sinus, or larynx. 2 patients had lesions in breast and ileocolonic region.
       
    6 of 17 patients showed false positive results. 26 patients did not show any suspicious lesions (none of them had primary tumors).
        
    FDG-PET may show unknown primary tumors in one third of all patients. It may also help guide biopsies for histologic assessment.
         

  • Vanuytsel LJ, Vansteenkiste JF, Stroobants SG, et al (Univ Hosp Gasthuisberg, Leuven, Belgium)
    The Impact of 18F-Fluoro-2-Deoxy-D-Glucose Positron Emission Tomography (FDG-PET) Lymph Node Staging on the Radiation Treatment Volumes in Patients With Non-Small Cell Lung Cancer
    Radiother Oncol 55:317-324, 2000
       
    The potential effects of a non-invasive lymph node staging procedure – 18F- FDG-PET combined with CT (PET-CT) were compared with CT alone in patients with non small cell lung cancer.
        
    Previously published data on prospective lymph node staging protocols has used imaging and surgical pathology data from 105 patients. 73 had positive lymph nodes on CT and/or PET. For each one, gross tumor volume (GTV) was defined. The completeness of tumor coverage was assessed with the available surgical data. Theoretical radiation treatment plans were then formulated.
       
    Tumor coverage improved from 75% to 89% with this method. Information obtained could have led to a change of the treatment volumes in 45 patients (62%).
          
    In non small cell lung cancer, for radiation therapy, improved tumor coverage will result from assessment of locoregional spread by PET. In some selectable patients, toxicity could be reduced by correct assessment.
          

  • Erasmus JJ, McAdams HP, Rossi SE, et al (Duke Univ, Durham, NC)
    FDG PET of Pleural Effusions in Patients With Non-small Cell Lung Cancer
    AJR 175:245-249, 2000
        
    Pleural effusions associated with non small cell lung cancer are not always malignant and therefore do not preclude potentially curative surgery. The ability of FDG-PET to distinguish between benign and malignant pleural effusions is investigated.
         
    25 patients with non small cell lung cancer with pleural effusions were evaluated. Pleural activity that was greater than background mediastinal activity on FDG-PET was considered a positive finding. These findings were correlated with the pathological findings.
         
    In 22 patients malignancy was verified by pathology. 21 of these had positive FDG-PET scans and 1 was negative. 3 cases had no malignancy on pathology FDG-PET showed positivity in one of them. The sensitivity of FDG-PET was 95% and specificity was 67%. The positive and negative predictive values were 95% and 67%. Its accuracy was 92%.
       

  • MJ Byrne, JA Davidson, AW Musk, et al (Sir Charles Gairdner Hosp, Nedlands, Australia; Univ of Western Australia, Nedlands)
    Cisplatin and Gemcitabine Treatment for Malignant Mesothelioma: A Phase II Study.
    J Clin Oncol 17: 25-30, 1999.
        
    Malignant mesothelioma, an aggressive tumor, is an uncommon tumor that is increasing in incidence. A Phase II study of the efficacy of combined cisplatin and gemcitabine for the treatment has been reported herewith.
        
    Twenty-one patients, aged 46 to 74 years were enrolled in the study of which sixty-two percent had epithelial tumors, eighteen had tumor-node-metastasis (TNM) system stage III or IV. Treatment consisted of cisplatin being given as 100mg/m2, given intravenously on day 1 and gemcitabine 1000mg/m2 intravenously on days1,8, 15 of a 28-day cycle for 6 cycles. Pleural tumor was measured at 3 levels with CT scan at baseline; before the second, fourth, and sixth cycles; and every 2 months thereafter until the disease progression.
      
    The treatment of malignant pleural mesothelioma has been always controversial. For earlier stage disease being subjected to extrapleural pneumonectomy. For advanced disease, there are a number of chemotherapeutic agents that have demonstrated single-agent activity against malignant pleural mesothelioma, but the response rate is only 15% to 20%. This trial seems to have response rate of 47% i.e. 10 of 10 patients and is perhaps the highest ever reported. Consequently, several other centers are trying out the results of these studies so as to seen whether they are spurious or not.
        

  • Guardiola P, for the International Collaboration for Transplantation in Agnogenic Myeloid Metaplasia (Hopital Saint-Louis, Paris; et al)
    Allogeneic Stem Cell Transplantation for Agnogenic Myeloid Metaplasia: A European Group for Blood and Marrow Transplantation, Societe Francaise de Greffe de Moelle, Gruppo Italiano per il Trapianto del Midollo Osseo, and Fred Hutchinson Cancer Research Center Collaborative Study
    Blood 93: 2831-2838, 1999
      
    Agnogenic myeloid metaplasia patients have a median survival of less than 3 years.
       
    This study is a multivariate analysis conducted retrospectively on 55 patients who received allogenic stem cell transplantation for AMM.
      
    The 1-year transplant-related mortality rate approached 30% and outcome was strongly affected by grade III-IV acute GVHD and extensive chronic GVHD and old age. Those with anemia and high degree of bone marrow fibrosis also faired poorly.
       

  • Palumbo A, Triolo S, Argentino C, et al (Universita di Torino, Italy)
    Dose-intensive Melphalan With Stem Cell Support (MEL 100) Is Superior to Standard Treatment in Elderly Myeloma Patients 
    Blood 94: 1248-1253, 1999
       
    The clinical relationship between dose intensity of melphalan and response rate have been noted in patients with multiple myeloma particularly in younger patients after 200mg/m2 (median age of 64 years).
       
    This study of 71 patients with multiple myeloma underwent 2 or 3 courses of melphalan 100mg/m2 followed by stem cell support. CR was better (47%) compared to 5% in patients given melphalan and prednisone (MP). The median overall survival was 56 months for MEL 100 group and 48 months for MP group. Hence even the elderly patients with multiple myeloma given MEL 100 had faired better compared with MP.
        

  • Raymond D. Pastore, Lawrence M. Pfeffer and David M. Nanus (Division of Hematology and Medical Oncology, Department of Medicine, Joan and Sanford I. Weill Medical College of Cornell University, New York, New York; Department of Pathology, University of Tennessee Health Science Center, Memphis, Tennessee; Department of Urology, Joan and Sanford I. Weill Medical College of Cornell University, New York, New York)
    Renal Cell Carcinoma and Interferon at the Millennium
    Cancer Investigation 2001 Vol. 19 (3) Pg. 281-291
       
    Advanced renal cell carcinoma (RCC) has a dismal outlook, less than 5% have 5 year survival. Interferons (IFN) were originally classified as per type of cells producing them. The type I IFN include Interferon IFN-a, IFN-b and IFN-w (omega). Type II is IFN-g. IFN-a has been used for metastatic RCC since 1983 complete and partial responses occurred in 26% of patients. This time to response is approximately 3 months whereas the median duration of response is 6-10 months. 
       
    As compared to medroxyprogesterone acetate one year survival and median survival was better with IFN-a.
       
    Another study of IFN-a and IL-2, and tamoxifen combination vs. single agent tamoxifen alone had no difference in survival.
      
    Addition of 5Fluorouracil to IFN-a + IL-2 also did not have any impact on progression free survival. Better outcome and response rates were possible when combining IFN-a with cisretinoic acid. The rate of IFN in adjuvant setting is unclear. The Memorial Sloan-Kettering Cancer Center identified five prognostic factors, Karnofsky performance status (less than 80%), increased serum LDH, anemia (hemoglobin < 13 g/dl), hypercalcemia, and no prior nephrectomy. A recent SWOG study has shown prior nephrectomy enables a survival advantage for IFN therapy.
       

  • Jon Sudbo, Wanja Kildal et al
    DNA content as a prognostic marker in patients with oral leukoplakia.
    New Eng Jr. Med. Vol.344, April.26, 2001, pg.1270.

    Oral leukoplakia may develop into squamous cell carcinoma, which has a poor prognosis. Risk factors for oral carcinoma have been identified, but there are no reliable predictors of the outcome in individual patients with oral leukoplakia. Authors identified 150 patients with oral leukoplakia that was classified as epithelial dysplasia and measured the nuclear DNA content (ploidy) of the lesions to determine whether DNA ploidy could be used to predict the clinical outcome. Biopsy specimens obtained at annual follow-up visits were graded histologically and classified with respect to DNA content in a blinded fashion. Disease-free survival was assessed in relation to DNA ploidy and the histologic grade.

    A carcinoma developed in 3% of patients with diploid (normal ) lesions, as compared to 84% of patients with aneuploid (abnormal) lesions at the time of initial diagnosis. Carcinoma developed in 60% of patients with tetraploid lesions (intermediate). The cumulative disease-free survival rate was 97% among the group with diploid lesions, 40% among the group with tetraploid lesions and 16% among the group with aneuploid lesions.

    The conclusion was that the DNA content in cells of oral leukoplakia can be used to predict the risk of oral carcinoma.
      

  • New Approaches to Cancer Therapy and Diagnosis 
        
    Gerald Shklar, and Se-Kyung Oh (Division of Oral Pathology, Department of Oral Medicine and Diagnostic Sciences, Harvard School of Dental Medicine, Boston, Massachusetts)
    Experimental Basis for Cancer Prevention by Vitamin E
    Cancer Investigation 2000 Vol. 18 (3) Pg. 214-222
        
    Recent clinical trials have demonstrated significant cancer preventive potential of vitamin E. Experimental cancer model such as hamster buccal pouch which closely resembles its human counterpart have shown significant inhibition of carcinogenesis with systemic administration of vitamin E.
        
    In addition the other properties documented were its well known antioxidant properties, immunoenhancer, activator of p53 tumor supressor gene and an inhibitor of tumor angiogenesis. 
         
    Animal studies are now being confirmed in humans. The low levels of vitamin E in serum and plasma were found to be associated with an increased risk of lung and cervical cancer and prostate cancer mortality. Vitamin E has been shown to reduce the toxicity of adriamycin and enhance the anticancer effect of melphalan. 
         

  • L Kjellberg, G Wadell, F. Bergman, et al ( Umed and Stockholm, Sweden )
    Regular disappearance of the human papillomavirus genome after conization of cervical dysplasia by carbon dioxide laser.
    Am J Obstet Gynecol, Nov.2000; 183: 1238-42
        
    Objective : To evaluate the effectiveness of treatment of cervical dysplasia by laser conization in relation to persistence of human papillomavirus after treatment.
        
    Study Design : Of 230 women referred to colposcopy because of an abnormal Papanicolaou smear, 149 women could be followed up for 3 years. A total of 108 women were treated by carbon dioxide laser excision, 4 women were treated by carbon dioxide laser evaporation, and 37 women were merely followed up. Cervical samples were taken before treatment and at follow-up 3 years later and were analyzed by nested general primer polymerase chain reaction for human papillomavirus deoxyribonucleic acid.
         
    Results : Among women treated by laser conization, 82(73.2%) had positive results for human papillomavirus deoxyribonucleic acid before treatment. Three women (2.7%) had a positive finding at follow-up, but no woman had the same human papillomavirus type on both occasions. 
         
    Eighty-eight women had grade1 to grade 3 cervical intraepithelial neoplasia before treatment, whereas during follow-up only 2 squamous cells atypias were found.
         
    Conclusion : The human papillomavirus genome present before treatment was regularly cleared, and there was also no recurrence of dysplasia. The results suggest that human papillomavirus testing is useful for monitoring the efficacy of treatment and that treatment modalities resulting in clearance of human papillomavirus should be favored.
       

  • B. P. L. Wijnhoven, W. N. M. Dinjens and M. Pignatelli (Departments of Surgery and Pathology, Erasmus University Medical Centre, Rotterdam, The Netherlands and Division of Histopathology, Department of Pathology and Microbiology, Bristol Royal Infirmary, Bristol, UK)
    E-Cadherin-Catenin Cell-Cell Adhesion Complex and Human Cancer
    Br J. Surg August 2000 Vol. 87 (8) Pg. 992-1005 
        
    The E-cadherin-catenin complex plays a crucial role in epithelial cell-cell adhesion and in the maintenance of tissue architecture. Perturbation in the expression or function of this complex results in loss of intercellular adhesion, with possible consequent cell transformation and tumour progression. 
        
    Disturbance in protein-protein interaction in the E-cadherin-catenin adhesion complex is one of the main events in the early and late steps of cancer development.
       
    It has long been known that cell-cell adhesion is generally reduced in human cancers. Reduced cell-cell adhesiveness is associated with loss of contact inhibition of proliferation, thereby allowing escape from growth control signals. Invasion and metastases, the most life-threatening properties of malignant tumours, are considered to be later, but critically important, carcinogenic steps.
       
    In recent years, there has been increasing interest in a large family of transmembrane glycoproteins, called cadherins, which are the prime mediators of calcium-dependant cell-cell adhesion in normal cells. 
      
    There is increasing evidence that modulation of this complex by different mechanisms is an important step in the initiation and progression of human cancers.
      
    E-cadherin is bound via series of undercoat proteins, the catenins, to the actin cytoskeleton. This linkage between transmembranous cadherins and actin filaments of the cytoskeleton is necessary to form strong cell-cell adhesion. 
      
    In general, E-cadherin and catenin staining is strong in well differentiated cancers that maintain their cell adhesiveness and are less invasive, but is reduced in poorly differentiated tumours which have lost their cell-cell adhesion and show strong invasive behaviour. 
     
    Direct evidence implicating E-cadherin in the development of metastases is based on the association between highly metastasizing carcinomas and low E-cadherin immunoreactivity. 
       
    To predict tumour invasion and metastasis in carcinomas, it is useful to investigate not just the expression of E-cadherin but also the expression of the catenins. 
      
    Since the function and expression of the E-cadherin-catenin complex is often reduced in cancer cells, it is suggested that restoration of the E-cadherin-catenin will lead to differentiation and anti-invasive properties. Several drugs have been described to alter the expression of E-cadherin, some of which are already used in the treatment of cancer. 
       
    At least in vitro, insulin-like growth factor 1, tamoxifen, taxol, retinoic acid and progestagens have been shown to upregulate the functions of the E-cadherin-catenin complex, including inhibition of invasion.
      
    Aspirin is probably the most intriguing. Non-steroidal ant-inflammatory drugs are potent preventive agents against colon cancer. Aspirin decreased the rate of tumour formation.
      
    Aspirin produces a decrease in intracellular b-catenin levels, suggesting that modulation of this protein is associated with tumour prevention.
       
    Inactivation of the E-cadherin-catenin cell-cell adhesion complex is mediated by genetic and epigenetic events that occur in both the early and late stages of carcinogenesis.
      
    Elucidation of the mechanisms underlying the changes in E-cadherin and catenin function may lead to the development of novel therapeutic approaches based on biochemical and genetic manipulation.
       

  •  W. P. Ceelen, U. Hesse, B. de Hemptinne and P. Pattyn (Department of Abdominal Surgery 2P4, Ghent University Hospital, De Pintelaan 185, B-9000 Ghent, Belgium)
    Hyperthermic Intraperitoneal Chemoperfusion in the Treatment of Locally Advanced Intra-Abdominal Cancer
    Br J. Surg August 2000 Vol. 87 (8) Pg. 1006-1015 
       
    Surgical treatment of intra-abdominal cancer is often followed by local recurrence. In a subgroup of patients, local recurrence is the sole site of disease, reflecting biologically low-grade malignancy. These patients might, therefore, benefit from local treatment.
      
    A growing body of experimental evidence supports the use of hyperthermia combined with chemotherapy as an adjunct to cytoreductive surgery.
      
    Traditionally, locoregional cancer recurrence with widespread peritoneal implantation has been difficult to treat, most patients undergoing palliative procedures or no surgery at all.
      
    Although intraperitoneal chemotherapy has been used alone or after surgery, taking advantage of the presence of a peritoneal-plasma barrier, its clinical efficacy is moderate. 
       
    Recently, cytoreductive surgery followed by hyperthermic intraperitoneal chemoperfusion (HIPEC) has been described for both treatment and prevention of locoregional cancer spread from various origins, a management plan based on the experimentally noted synergism between hyperthermia and several antineoplastic drugs.
       
    Hyperthermia Alone
       

    The tumoricidal properties of hyperthermia have been recognized since ancient times. The observation of spontaneous tumour regression in patients with hyperpyrexia led to the first clinical application of hyperthermia, which consisted of injection of pyrogenic substances in patients suffering from sarcoma. 
      
    Tumour cell inactivation is time and temperature dependent, and starts at 40-410 C. At temperatures above 430 C exponential inactivation of tumour cells occurs for most rodent cell lines, resembling the effect of ionizing radiation. Human tumour cell lines may be more sensitive to mild hyperthermia (41-420 C) than rodent cell lines.
      
    Hyperthermia with Chemotherapy
      
    Both experimentally and clinically, the antitumoral effect of various chemotherapeutic drugs is enhanced by hyperthermia. A possible disadvantage of the addition of hyperthermia is the induction of multidrug resistance gene (MDR1) expression. 
      
    Most clinical experience with hyperthermic chemoperfusion has involved mitomycin C (MMC) or platinum compounds. MMC is commonly used in the treatment of gastrointestinal cancer, usually in combination with other drugs. Platinum compounds are widely used in the treatment of epithelial ovarian cancer.
       
    Hyperthermia with Radiotherapy 
      

    Several randomized clinical studies have clearly demonstrated that hyperthermia and radiotherapy act synergistically on tumour tissue. 
      
    This synergism is explained by two phenomena observed in animal experiments. First, hyperthermia is cytotoxic to cells in an environment with low partial pressure of oxygen and pH44. Second, hyperthermic treatment at mild temperatures induces reoxygenation of tumour cells, rendering them more sensitive to the effects of radiation therapy. At higher temperatures (over 430 C) the opposite happens.
      
    The delivery of hyperthermia to the peritoneal surfaces by closed perfusion of a heated solution was first described in a clinical situation in 1980.
      
    Extensive cytoreduction followed by HIPEC is associated with considerable rates of morbidity and mortality, and the potential risks of the procedure must be weighed carefully against any potential benefit.
      
    Postoperative morbidity and death may, therefore, relate mainly to the extent and duration of surgery, and not to the hyperthermic perfusion itself.
       
    Peritoneal carcinomatosis is generally considered to be an incurable condition. However, a growing body of both experimental and clinical evidence supports the therapeutic and prophylactic use of HIPEC in patients without systemic disease.
       
    Many surgeons may not be familiar with the use of hyperthermia as an adjunct to surgery; the authors hope that this article will stimulate their interest.
      

  • N S Weiss, M A Rossing
    Oestrogen-replacement therapy and risk of ovarian cancer
    The Lancet, vol.358, August 11, 2001,p438
        
    Data presented in the American Cancer Society’s Cancer Prevention Study II, has clearly demonstrated that there is an increase risk of ovarian cancer after HRT and the increased risk remains for atleast 4 years after hormone has been discontinued. Secondly this increased risk of ovarian cancer becomes more important after HRT has been used for 10 years.
      
    The data on increased risk of ovarian cancer by using oestrogen progestagen combination therapy is at present an unknown factor and we may have to wait for 10 years for clarification.
       

  • Baerg J, Murphy JJ, Anderson R, et al (BC Children’s Hosp, Vancouver, Canada)
    Neutropenic Enteropathy: A 10-Year Review
    J Pediatr Surg 34: 1068-1071, 1999

    Neutropenic enteropathy following chemotherapy is associated with fever, abdominal pain and neutropenia. This is usually due to mucosal damage and preferred sites are terminal ileum and cecum.

    This study of 38 episodes of neutropenic enteropathy in 33 patients with hematologic malignancies receiving intensive chemotherapy. The treatment for all these patients was conservative i.e. fluid resuscitation, bowel rest, and broad-spectrum antibiotics. Surgery was performed for bowel perforation. 

    Most of the patients developing neutropenic enteropathy had received cytosine arabinoside and/or VP16. 

    Ninety-four percent survived, surgery was performed only for patients with bowel perforation, 12% required laprotomy and right hemicolectomy, all of them survived.
          

  • B F Cole, R D Gelber, et al 
    Polychemotherapy for early breast cancer: an overview of the randomized clinical trials with quality-adjusted survival analysis.
    The Lancet; 2001; 358: 277-86
         
    Polychemotherapy is inclusive of multiple anticancer agents and tamoxifen. It was tried in younger women (less than 50 years old) and separately among older women (50-69 years old). The findings of the trial favour adjuvant polychemotherapy in both younger women and older women especially in patients with estrogen receptors breast cancer.
       

  • S. J. Pain and A. D. Purushotham (Cambridge Breast Unit, Addenbrooke’s Hospital, Cambridge, UK)
    Lymphoedema Following Surgery for Breast Cancer
    BJS September 2000 Vol. 87 (9) Pg. 1128-1141
        
    Lymphoedema is a common complication of breast cancer treatment, affecting approximately a quarter of patients. Those affected can have an uncomfortable, unsightly and sometimes functionally impaired limb prone to episodes of superficial infection. The aetiology, pathophysiology and management of these patients is poorly understood. 
        
    Lymphoedema has been described as ‘a progressive pathologic state or condition characterized by chronic inflammatory fibromatosis and hypertrophy of the hypodermal and dermal connective tissues.
         
    There exists the extremely rare but potentially fatal possibility of secondary lymphangiosarcoma (Stewart-Treves syndrome).
        
    Axillary clearance, as commonly advocated, provides a guide to prognosis, assists in planning adjuvant systemic therapy and minimizes axillary recurrence; there is emerging evidence to suggest an impact on survival.
        
    Arm swelling in the early postoperative period is commonly observed and tends to settle spontaneously within a matter of weeks. Lymphoedema may, however, develop months or years after this (an interval of over 20 years has been reported), with around 75 per cent of cases occurring in the first year after operation.
         
    Onset may be gradual, or rapid. Patients occasionally identify a precipitating factor, such as a minor infection following a cut or graze, or a greater than usual degree of exercise involving the arm. 
        
    There remain, however, a number of questions regarding arm oedema following breast cancer surgery.
         
    1. Why do some women develop this complication while others do not?
    2. What explains the latent period preceding the onset of oedema?
    3. Why is it that certain sections of the arm are ‘spared’?
    4. Why is it so difficult to create artificial models of lymphoedema in animals, employing far greater surgical trauma than that involved in breast cancer treatment?
         
    Oedema is defined as the accumulation of interstitial fluid in abnormally large amounts. This can occur as a result of one of a number of physiological changes: (a) an increase in filtration pressure caused either locally by arteriolar dilation or venular constriction, or more globally by increased arterial inflow or elevated venous pressure; 
    (b) a reduction in the osmotic pressure gradient resulting from either a decrease in plasma proteins or an increase in osmotically active material in the interstitium; 
    (c) an increase in capillary permeability mediated by ‘lymphagogues’ such as substance P, histamines and kinins; and
    (d) a reduction in the flow of lymph
        
    Kissin et al found the prevalence of swelling following axillary sampling and irradiation to be equivalent to that following clearance of the axilla, and there is general agreement that the combination of surgery and radiotherapy to the axilla is best avoided, with quoted prevalence rates more than double those for surgery alone.
        
    There are other factors contributing to the aetiology of lymphoedema, with alterations noted in arterial inflow, venous return and plasma osmolality, as well as the intriguing possibility of the presence of lymphaticovenous communications. 
        
    Treatment strategies for lymphoedema fall into three main groups: conservative measures, drug treatment and surgery. At present, conservative measures form the mainstay of management, with surgery reserved for resistant cases (if at all). The place of pharmacological therapy is still unclear. 
         
    The principles of conservative treatment of lymphoedema remain unchanged from the middle of the nineteenth century, with attention to the areas of hygiene, massage, compression, and remedial exercises.
        
    There is no place for the use of diuretics in the treatment of lymphoedema; these drugs may even exacerbate the problem by increasing the protein concentration in the interstitium, thus enhancing the stimulus to inflammation and fibrosis. 
         
    Surgery for lymphoedema is usually reserved for cases resistant to conservative measures. Operations may be divided into two groups, namely debulking procedures and attempts to influence lymphatic drainage. 
         
    In 1962, Cockett and Goodwin described the anastomosis of a dilated lumbar lymphatic to the spermatic vein to treat a case of chyluria. Subsequent development of microsurgical techniques has enabled lymphaticovenous anastomosis to emerge as a potential treatment of arm lymphoedema. 
         
    At present lymphoedema following surgery for breast cancer remains a poorly understood and incurable problem. With cure an unrealistic possibility at present, emphasis should be placed on prevention. It may also be that postoperative changes, demonstrated in the latent phase before the development of swelling, might identify those in whom lymphoedema is most likely to occur. Early prophylactic initiation of conservative treatment measures may then prove more efficient than their institution when swelling has become established.
       

  • Clinical Trials 
    Stephen Tyring, Robert Belanger, Werner Bezwoda, Per Ljungman, Ron Boon, and Robin L. Saltzman for the Collaborative Famciclovir Immunocompromised Study Group (University of Texas Medical Branch, Galveston, Texas; Hospital Maisonneuve-Rosemont, Montreal, Quebec, Canada; Johannesburg Hospital, Parktown, Johannesburg, South Africa; Department of Hematology, Huddinge University Hospital, Karolinska Institute, Huddinge, Sweden; SmithKline Beecham Pharmaceuticals, New Frontiers Science Park, Harlow, Essex, UK; SmithKline Beecham Pharmaceuticals, Collegeville, Pennsylvania) 
    A Randomized, Double-Blind Trial of Famciclovir Versus Acyclovir for the Treatment of Localized Dermatomal Herpes Zoster in Immunocompromised Patients 
    Cancer Investigation 2001 Vol. 19 (1) Pg. 13-22
         
    This study of 148 patients with clinical evidence of localized herpes zoster in patients who were immunocompromised following bone marrow or organ transplantation or oncology (chemotherapy) treatment received either oral famciclovir 500 mg thrice daily or acyclovir 800 mg five times daily for 10 days.
          
    Efficacy and safety data revealed equivalent results, thus famciclovir was well tolerated with a safety profile comparable to that of acyclovir.
          

  • L. E. Schnipper and T. B. Strom 
    Editorial: A Magic Bullet For Cancer – How Near and How far?
    The New England Journal of Medicine Vol. 345(4), 26 July 2001; Pg. 283-84
           
    Since even humanized chimeric monoclonal antibodies often provoke antibodies that nullify the therapeutic effects of engineered immunoglobulins, a way of making fully human antibodies in vitro has been sought.
          
    The most notable success to date has been achieved with rituximab, a humanized monoclonal antibody against the B-cell-specific antigen CD20. In patients with low-grade B-cell lymphoma who relapse after the usual therapy, rituximab frequently results in complete or partial remissions.
         
    In some patients with low-grade lymphoma, rituximab plus chemotherapy eliminates all detectable cells. 
           
    A different approach entails fusing the DNA sequences encoding antigen-binding antibody fragments with genes for bacterial toxins.
           
    CD22, a surface antigen of B cells, was genetically fused to a truncated pseudomonas toxin protein containing the translocation and toxin moieties. This genetically engineered immunotoxin was used to treat patients with hairy-cell leukemia, a B-cell neoplasm with abundant expression of surface CD22. In this trial, the anti-CD22 immunotoxin induced complete remissions in 69 percent of patients.
           
    Similar results have also been found with use of a fusion protein combining diphtheria toxin and interleukin-2 in patients with T-cell lymphomas that express interleukin-2 receptors.
            
    Despite the uncertainties and unsolved problems, the authors are confident that tumor-specific immunotherapy is more than a distant promise.
         

  • Reiter A, Schrappe M, Tiemann M, et al (Medizinische Hochschule, Hannover, Germany; Christian-Albrechts-Universitat, Kiel, Germany; Humboldt Univ Berlin; et al)
    Improved Treatment Results in Childhood B-Cell Neoplasms With Tailored Intensification of Therapy: A Report of the Berlin-Frankfurt-Munster Group Trial NHL-BFM 90
    Blood 94: 3294-3306, 1999
         
    This study of patients up to 18 years and newly diagnosed with Non Hodgkin lymphoma or acute B-cell leukemia were stratified into 3 groups.
        
    R1-completely resected received two, 5-day courses of chemotherapy including intermediate-dose methotrexate, dexamethasone, oxazophorins, etoposide, cytarabine, doxorubicin, and intrathecal therapy. 
         
    Patients in group R2 had extraabdominal primary tumors only or an abdominal tumor with LDH > 500 U/L. These patients received 4 courses of chemotherapy including high-dose methotrexate.
          
    Those in third group R3 with abdominal primary and systemic involvement (bone marrow, CNS, or multifocal bone disease). These patients received VI courses of high dose methotrexate. 
         
    This therapy strategy demonstrated a high degree of effectiveness for patients with Burkitt-type lymphoma or acute B-cell leukemia and also for patients with diffuse large B-cell lymphomas. Intensification of therapy can significantly improve outcome for patients with childhood B-cell neoplasms.
           

  • Per Eystein Lfnning 
    Aromatase Inhibitors and Inactivators in Breast Cancer 
    BMJ, Vol.323 (7318), 20 October 2001, Pg. 880-881
               
    Summary : Aminoglutethimide, a first generation aromatase inhibitor, was used for the treatment of breast cancer 3 decades ago. Although its antitumour effect was similar to that of tamoxifen, its use was limited because of severe side effects.
          
    Introduction of the 3rd generation aromatase inhibitors anastrozole and letrozole was a great leap forward. While aminoglutethimide and 2nd generation compounds reduced oestrogen synthesis by 85-90%, the 3rd generation compounds effectively inhibit oestrogen synthesis by 97-99%.
            

  • Amar Alwitry and Iain Gardner
    Minerva 
    BMJ, Vol.323, 20 October, Pg. 944
           
    Summary : This is a case report of tamoxifen induced retinopathy in a 64 year old woman taking tamoxifen 20 mg/day for 8 years. The incidence of tamoxifen retinopathy is about 6% among patients who have taken the drug for 5 years. Stopping treatment prevents further deterioration but rarely allows complete recovery of visual function.
          

  • Shulin Li
    IL-12 based therapy of malignancies
    Drugs of Today, Sept.2001, vol.37, pg.629-737.
      
    Interleukin-12 (IL-12) is an important molecule that triggers the activation of natural killer (NK) cells and T-cells, the development of T helper type 1(Th1) cells and the expression of antiangiogenic genes. Novel methods for IL-12 delivery include cell-based ex vivo gene therapy, viral vector-based gene therapy and DNA plasmid-based nonviral gene therapy. IL-12 electroporation gene therapy may hold some promise for tumors accessible by electrode, such as head and neck cancer, breast cancer, prostate cancer and melanoma. Codelivery of other therapeutic genes with IL-12 may enhance the therapeutic effect and reduce the level of IL-12 required for efficacy. All three approaches to IL-12 gene therapy are under clinical investigation. The preliminary results indicate that IL-12 gene therapy is safe and is not associated with any major clinical toxicity.
       

  • Enrico Crucitta, Nathalia Locopo, et al
    The Role of Letrozole (Femara®) in Breast Cancer Therapy: A Clinical Review.
    Drugs of Today, Sept.2001, 37(9): 639-644
       
    Letrozole is a third-generation aromatase inhibitor for use in postmenopausal women with hormonal-sensitive breast cancer. This drug was found to reduce or effectively shrink tumors in a significant number of such patients. It exhibits antitumor activity at a relatively low daily dose, and is highly potent and selective and well tolerated. Results from recent phase III clinical studies have confirmed the efficacy and the key role of this drug in the therapy of advanced breast cancer in postmenopausal women.
       
    Moreover, letrozole demonstrated higher activity and lower toxicity compared to tamoxifen in the first-line therapy of postmenopausal women affected with advanced breast cancer. However, it also represents a valid option in second-line therapy after tamoxifen failure. New data on this agent in adjuvant or neoadjuvant treatment also suggest efficacy in the treatment of early breast cancer.                                                                                      
                                        

  • Carlos L Arteaga  
    Foreword – Epidermal Growth Factor receptor – Trageted approaches for anticancer therapy: Focus on ZD1839        
    Drug – Supplement no.1, 2000, vol.60     
                                    
    Epidermal growth factor receptor (EGFR) is the cellular homologue of a mutant constitutively active, oncogenic tyrosine kinase that induced tumours in animals. The EGFR requires activation by binding of ligand, while its cellular effects depend on activation of its intrinsic tyrosine kinase activity.       
                                              
    This basic knowledge has led to the development of several antireceptor approaches which are the subject of the articles. One has been the development of antibodies against the receptors ectodomain. A second powerful approach has been the generation of ATP-mimetics that compete with ATP for binding to the receptor’s tyrosine kinase pocket and thus disable its function. One of these promising small molecules, ZD 1839, is discussed in the supplement.               
                                                                                                                                         

  • Eric K Rowinsky                                               
    The Pursuit of Optimal Outcomes in Cancer Therapy in a New Age of Rationally Designed Target-Based Anticancer Agents.                          
    Drugs Supplement 2000, vol.60, supplement 1, pg.1                        
                                                                                                          
    The recent development of a plethora of rationally designed target-based anticancer agents has opened up new opportunities and extraoridinary therapeutic challenges. Since these agents appear primarily to target malignant cells, they can be expected to be less toxic at clinically effective doses than the cytotoxic agents. Among the various types of rationally designed target based agents are those that target strategic facets of cell growth signal transduction, angiogenesis, metastatsis and cell cycle regulation .                          

    Table 1. Rationally derived molecular anticancer approaches requiring novel clinical development paradigms.


         General target                  Specific target                              Therapeutic agent


    Signal transduction

    Growth factor receptor

    Antibodies against erbB/family (EGFR, HER2).Small molecule inhibitors of receptor tyrosine kinases (ERB family, EGFR, HER2, PDGF)

    Ras

    Small molecule inhibitors of farnesyltransferase Antisense oligonucleotides (K-Ras, H-Ras, N-Ras)

    Raf   

    Antisense oligonucleotides

    MAPK

    Small molecules

    Rapaymycin-sensitive and

    Rapamycin analogs

    P13K/ Akt pathways

    Small molecule inhibitors

    Malignant angiogenesis and Metastasis

    VEGF

    Antibodies Small molecular inhibitors of VEGF receptortyrosine kinasesNatural products Ribozymes

    Matrix metalloproteinases

    Small molecules

    Integrins 

    Small molecules, peptides, peptide cytotoxic conjugates

    Apoptosis-Survival

    BCL-2 

    Antisense

    BCR/ABL

    Small molecules,inhibitors of tyrosine

    kinase

    Death receptors (TNF and Other death receptor Families)

    Small molecules

    Tumor suppressor gene function. 

    p53

    Viral vectors with p53 to restore Function.Viral vectors that selectively kill cells With mutant p53

    Tumour differentiation

    Polyamines 

    Polyamine inhibitors

    Retinoid receptors

    Retinoids

    Cell cycle checkpoint control 

    CDKs

    Small molecule kinase inhibitors


    CKDs = cyclin-dependent kinases; EGFR = epidermal growth factor receptor; MAPK= mitogen-

    Activated protein kinase; PDGF= platelet derived growth factor; TNF= tumour necrosis factor; VEGF= vascular endothelial growth factor.

                             


  • Jose Baselga and Steven D Averbuch                  
    ZD1839 (‘Iressa’) 1,2 as an Anticancer Agent               
    Drugs Supplement 2000, vol.60, suppl.1, pg.33-40 
                        
    ZD1839 (‘Iressa’)1,2 is an orally active, selective epidermal growth factor receptor-tyrosine kinase inhibitor which blocks signal transduction pathways implicated in the proliferation and survival of cancer cells and other host dependent processes promoting cancer growth. In preclinical studies, ZD1839 produced reversible growth inhibition and growth delay in a wide range of tumour cell lines and human tumour xenografts. Moreover, this activity was enhanced when ZD1839 was coadministered with cytotoxic agents. Preliminary results from phase I trials in patients with advanced disease and a wide variety of tumour types suggest that ZD1839 has an acceptable tolerability profile and promising clinical efficacy, particularly in non-small cell lung cancer (NSCLC). ZD1839 is currently in phase III clinical development for the treatment of advanced NSCLC. In addition, further trials are ongoing or planned in a number of other tumour types.          
                      
    ZD1839 (‘Iressa’)1,2, an anilinoquinazoline, is an orally active, selective EGFR tyrosine kinase inhibitor (TKI) which is currently under clinical evaluation in phase II to III clinical trials in patients with cancer. Preclinical data for ZD1839 strongly support the possibility of potentiating the antitumour activity of conventional chemotherapy with agents that selectively block the EGFR.    

  • Michael McCarthy
    Targeted drugs taken center stage at US Cancer Meeting
    Lancet, vol.357, May 19, 2001, pg.1593
                                     
    Researchers attending this year’s annual meeting of the American Society of Clinical Oncology (ASCO) were clearly excited by results of several early phase I and phase II trials that suggest that new drugs that target specific molecular abnormalities in cancer cells may be extremely potent weapons against various cancers.    
                                                            
    These new drugs, which target abnormal growth factor receptors and other cancer-causing proteins, will change the way doctors treat cancer in much the same way the discovery of antibiotics changed the way doctors treated infections, said Larry Norton head of the Division of Solid Tumour Oncology at Memorial Sloan-Kettering Cancer Centre (New York)   
                                                      
    The studies that gained the greatest attention were trials of the compound imatinib mesylate. This drug,which is being marketed in the USA as Gleevec, was granted accelerated approval by the US Food and Drug Administration (FDA) after it had been shown to be extremely potent against chronic myelogenous leukaemia (CML). The compound is a small molecule that blocks an abnormal tyrosine kinase, BCL-ABL, that seems to be the key molecular defect leading to uncontrolled cell growth in CML.  
                                                        
    Earlier this year, Brian Druker of Oregon Health Sciences University (Portland, OR, USA) reported the results of a dose-escalating phase I study that indicated that a dose of 300 mg per day induced complete haematological responses in 53 of 54 patients for whom standard CML treatment with interferon ? had previously been ineffective or not tolerated. And a related study showed the drug could also induce responses in patients with CML and acute lymphoblastic leukaemia who were in blast crises.                                    
                                                         
    The new studies presented at the ASCO meeting were phase I and phase II trials of imatinib mesylate in patients with a rare form of tumours, called gastrointestinal stromal tumours (GISTs) which arise from the precursor cells of the connective tissue of the gut. Another abnormal tyrosine kinase growth factor, C-KIT, is thought to play a key role in the pathogenesis of these tumours. GISTs usually do not respond to chemotherapy or radiation therapy and if not resected successfully are usually rapidly fatal.
                                                 
    In another phase II trial reported at the meeting, cetuximab was found to shrink metastatic colorectal cancer tumours in patients with chemotherapy-resistant disease. Cetuximab is a monoclonal antibody that blocks epidermal growth factor receptors (EGFR), cell membrane proteins found in colon and several other tumours that when stimulated drive cancer cell division and protect the cells from apoptosis. All of the 121 patients in the trial had tumours that had failed to respond to courses of standard chemotherapy with fluorouracil and irinotecan. All patients had tumours that expressed EGFR.    
                                                             
    In the trial, the patients were treated with irinotecan again but this time in combination with cetuximab. 27 (22.5%) of the patients had a partial response, which was defined as a greater than 50% reduction in tumour size.  
                                                                                                           
    Results from the trials of the antiangiogenesis drugs were less encouraging. Several trials suggested that the drugs clearly have antitumour activity but that the extent of the activity will vary not only from patient to patient but from tumour to tumour and even within a tumour.
      

  • P.A.McKelvie, M. Daniel (Melbourne, Victoria, Australia)
    Impression cytology following mitomycin C therapy for ocular surface squamous neoplasia.
    BJO 2001; 85: 1115-1119
      
    Though topical mitomycin C (MMC) therapy has been used for treatment of ocular surface squamous neoplasia (OSSN) since 1994, relatively few studies have reported the cellular changes in ocular surface following MMC.
      
    Hence, using Millipore filters at intervals between 4 and 17 weeks after starting MMC, the authors studied impression cytology in 4 patients with OSSN and compared them with pretreatment cytology.
      
    It was found that MMC induced changes of cytomegaly, cytoplasmic vacuolation, nucleomegaly with nuclear wrinkling, and binucleation or multinucleation in some cells in all samples. These changes resembled those seen following radiation therapy in uterine cervix. The predominant form of cell death was apoptosis with fewer cells showing necrosis.
     
    MMC related changes may persist in ocular surface epithelium for at least 8 months following therapy.
      

  • E G Kemp, A N Harnett, et al (Gartnavel Gen Hospital, Glasgow, UK)
    Preoperative Topical and Intraoperative Local Mitomycin C Adjuvant Therapy in the Management of Ocular Surface Neoplasias
    BJO, January 2002; 86(1); 31-34
      
    The authors reviewed case notes of 11 patients receiving mitomycin C adjuvant therapy as 0.04% drops, four times daily in 2 weekly courses preoperatively and/or a single intraoperative appplication of 0.4 mg/ml of mitomycin C.
      
    The histopathology of the cases
    (1) conjunctival primary acquired melanosis,
    (2) conjunctival melanomas
    (3) sebaceous cell carcinomas with conjunctival intraepithelial spread, and
    (4) conjunctival intraepithelial squamous neoplasias. Seven patients had limited local excision of the residual tumor mass and one had cryotherapy.
      
    All 11 patients showed a favorable response to mitomycin C adjuvant therapy. The therapy was well tolerated.
      

 

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