Peter K Sand, Harvey Winkler, Dawn W Blackhurst and Partick J Culligan, Evanston, Illinois, and Greenville, South Carolina
A prospective randomized study comparing modified Burch retropubic urethropexy and suburethral sling for treatment of genuine stress incontinence with low-pressure urethra.
Am J Obstet Gynecol 2000; 182:30-4.
The aim of this study was to compare a modified Burch procedure with a suburethral sling for the treatment of stress incontinence complicated by a low-pressure urethra.
Thirty-six women with stress incontinence, low-pressure urethra, and urethral hypermobility (straining cotton swab angle ³ 30°) were randomly assigned to undergo either a modified Burch procedure (n=19) or a suburethral sling (n=17). Objective and subjective cure rates at 3 months after the operation were the primary outcome measures. Comparison of groups were performed with the student t test for independent groups, and proportions were compared with the Fisher exact test.
After the operation the 2 groups had statistically similar cure rates and voiding function. Urethral closure pressure, pressure transmission ratios, and maximum detrusor pressure during voiding were significantly higher in the sling group.
At 3 months there were no clinically significant differences between the groups treated with suburethral sling and modified Burch procedures.
The Burch procedure and its various modifications all work by creating a shelf of endopelvic connective tissue and vaginal tissue at the level of the bladder neck and fastening it to the iliopectineal ligament. The basic design for sling procedures is placement of a nonabsorbable autologous or heterogous piece of material under the urethrovesical junction and anchoring it either to the retropubic structures or the abdominal wall structures or to both. Because sling procedures have been associated with higher rates of postoperative voiding dysfunction, they are commonly reserved for patients with complicated stress incontinence resulting at least partially from intrinsic urethral sphincteric weakness or damage.
The authors found that the group of women with urethral closure pressures £ 20cm H2O had a 54% objective failure rate at 3 months after the operation, compared with an 18% objective failure rate in the group with higher closure pressures. They concluded that patients with such low-pressure urethras might be better served by sling procedures for the correction of stress incontinence.
Subsequent experience has suggested that tying the Burch sutures more tightly could improve the success rates without causing the voiding dysfunction typically attributed to suburethral slings.
Material and methods:
Patients found to have genuine stress incontinence with urethral hypermobility, a maximum urethral closure pressure of £ 20cm H2O in the sitting position, and no significant anterior pelvic support defects were eligible for enrollment.
37 women were prospectively allocated in a randomized fashion to undergo either a modified Burch retropubic urethropexy or a suburethral sling.
The Burch procedures were performed with four 2-0 polytetrafluoroethylene sutures. When the time came for the tying of the Burch sutures, the subjects were taken out of a Trendelenberg position, and a cotton swab applicator was placed in the urethral meatus to the level of the urethrovesical junction. The sutures were then tied such that the cotton swab made a -10° to -20° angle with the horizontal, as measured with a goniometer. Other than in this study, our standard tension on Burch sutures creates a 0° to -5° angle with the horizontal.
All sling procedures were performed with a continuous polytetraflouroethylene strip running from the rectus fascia into the retropubic space and beneath the urethra at the level of the urethrovesical junction. Sling tension was also determined by cotton swab testing. All slings were placed under minimal tension such that the resting angle of the urethra was 0° to 10°.
A patient was considered to have an objective cure of stress incontinence if there was no leakage of urine at maximum cystometric capacity while coughing or performing Valsalva maneuvers in either the sitting or standing position during urodynamic studies.
After the operation the maximum detrusor pressure during voiding in the sling group (28.8 ± 8.0 cm H2O; P=.04) was significantly higher than that in the Burch group (21.3 ± 8.0 cm H2O). Both maximum urethral closure pressures (P =0008) and pressure transmission ratios (P=.001) were significantly higher in the sling group.
Lesley ME McCowan, Jane E Harding, Alistair B Roberts, Sarah E Barker, Cassandra Ford, and Alistair W Stewart. (Dept. of Obstetrics & Gynaecology, Univ of Auckland).
A Pilot Randomized Controlled Trial of Two Regimens of Fetal Surveillance for Small-for-Gestational-Age Fetuses with Normal Results of Umbilical Artery Doppler Velocimetry.
Am J Obstet Gynecol 2000; 182:81-6.
Objective : This study was undertaken to determine whether the frequency of fetal surveillance could be safely reduced from twice weekly to fortnightly in the case of small-for-gestational-age fetuses with normal results of umbilical artery Doppler velocimetry studies.
Study Design: Pregnant women between 24 and 36 weeks’ gestation (n=167) with small-for-gestational-age fetuses and normal results of umbilical artery Doppler velocimetry studies were randomly allocated to undergo twice-weekly or fortnightly fetal surveillance. Statistical analysis was carried out according to intention to treat.
Results: Eighty-five women were randomly assigned to undergo twice-weekly fetal surveillance and 82 were randomly assigned to undergo fortnightly fetal surveillance. Those randomly assigned to twice-weekly surveillance were delivered 4 days earlier (264 vs 268 days; P= .04) and were more likely to have labor induced (n=70, 82%, vs n=54, 66%; P= .02) than those randomly assigned to fortnightly surveillance. Fifty-four babies (23%) were admitted to the neonatal nursery, but there were no differences in neonatal morbidity between the groups.
Conclusions: Maternal intervention (induction) was more common in the twice-weekly group. No differences in neonatal outcomes were detected. A much larger trial is required to determine the safety and potential benefits of less frequent surveillance of small-for gestational-age fetuses with normal results of umbilical artery Doppler velocimetry studies.
Patrick Rozenberg, Francois Goffinet, Mahdie Hessabi, Sage-Femme (Dept. of Gynecology & Obstetrics, Poissy Hospital, University Paris V).
Comparison of the Bishop score, ultrasonographically measured cervical length, and fetal fibronectin assay in predicting time until delivery and type of delivery at term.
Am J Obstet Gynecol 2000; 182:108-13.
Objective : The authors aim was to compare the Bishop score, fetal fibronectin assays, and ultrasonographic measurement of cervical length to determine the best markers for time until spontaneous labour at term and risk of cesarean delivery, especially for the indication of lack of progress of dilatation.
Study Design: This prospective study included 128 singleton vertex pregnancies with no clinical evidence of membrane rupture or regular contractions and a prenatal consultation between 39 weeks 4 days’ gestation and measured cervical length by transvaginal ultrasonography. The end points were the percentage of patients with a spontaneous onset of labour in the week after these tests and type of delivery.
Results: The spontaneous onset of labour within a 7day period was closely associated with a Bishop score ³6 and with a cervical length £ 26mm but not with a positive result of the fetal fibronectin assay. On the other hand, vaginal delivery was significantly associated with the fibronectin assay result but not with either the Bishop score or cervical length.
Conclusions: The Bishop score and ultrasonographic measurement of cervical length are valuable for predicting the onset of spontaneous labour within 7 days, whereas the fetal fibronectin assay is useful for evaluating the risk of cesarean delivery. These tests thus provide different physiologic data that are useful for different purposes.
Several studies have shown that a finding of absence of fetal fibronectin in cervicovaginal secretions is useful in predicting the risk of postterm birth. The duration of the first phase of labour is significantly lower among patients with fetal fibronectin in the secretions.
Pelage J-P, Le Dref O, Mateo J, et al [Hopital Lariboisiere, Paris]
Life-threatening Primary Postpartum Hemorrhage: Treatment with Emergency Selective Arterial Embolization
Radiology 208: 359-362, 1998
All patients had intractable hemorrhage that could not be controlled by vaginal packing or uterotonic drugs.
Emergency selective arterial embolization is safe and effective for treating intractable primary postpartum hemorrhage. With arterial embolization, high-risk surgery can be avoided and the patients reproductive ability can be maintained.
Despite the seemingly ideal nature of gelfoam as an embolic agent in this setting, the authors substituted polyvinyl alcohol in some patients because of the fear of transmitting Creutzfeldt-Jakob disease with the former.
Thurmond AS, Brandt KR, Gorrill MJ [ Legacy Meridian Park Hosp, Tualatin, Ore: Oregon Health Sciences Univ, Portland; Mayo Clinic, Rochester, Minn]
Tubal Obstruction After Ligation Reversal Surgery : Results of Catheter Recanalization
Radiology 210: 747-750, 1999
For women desiring reversal of sterilization by fallopian ligation, surgery consists of careful resection of the damaged segment of tube and anastomosis.
All underwent transcervical fluoroscopically guided catheter recanalization using standard coaxial technique. Selective salpingography was done to confirm recanalization.
Fluoroscopically guided catheterization successfully recanalizes 68% of tubal obstruction in women with ligation reversal surgery.
Thistlewaite PA, Tarazi RY, Giordano FJ, et al [Univ of California, San Deigo]
Surgical Management of Spontaneous Left Main Coronary Artery Dissection
Ann Thorac Surg 66: 258-260, 1998
Spontaneous coronary artery dissection is a rare cause of ischemic heart disease and sudden death. It occurs predominantly in healthy, young women in the third trimester of pregnancy or in the early postpartum period. Cardiac risk factors are usually absent. Early recognition is essential because coronary artery bypass grafting may be life saving. Woman, 34, 12 weeks postpartum,was first seen after 18 hours of chest pain, with acute anterior wall myocardial infarction. Cardiac catheterization revealed a dissection of the left coronary artery extending into the left anterior descending artery. She underwent urgent bypass grafting, with bluish hemorrhage noticed over the left main coronary artery and distal left descending coronary artery, at operation. She was discharged on the sixth postoperative day. Transthoracic echocardiography after two months, indicated improvement in both wall motion and ejection fraction.
Most cases of primary coronary dissection occur in peripartum women without known cardiovascular risk factors. Young patients seen with acute ischemic symptoms should be considered for urgent angiography. If left main coronary artery dissection is detected, bypass grafting is safe and effective. Rapid diagnosis and surgical intervention are lifesaving.
RF Vale, MS Baggish, (Northwestern Univ, Chicago; Good Samaritan Med Ctr, Cincinnati, Ohio)
Endometrial Carcinoma After Endometrial Ablation: High-Risk Factors Predicting its Occurrence.
Am J Obstet Gynecol 179: 569-572, 1998.
Carcinoma of the endometrium has been described in 8 women who underwent endometrial ablation.
Patient Selection: Dysfunctional uterine bleeding that does not respond to medical treatment and has no anatomic cause is the indication for endometrial ablation. Therefore, a complete examination to rule out malignant conditions must be part of the selection criteria for these patients.
Findings: Of the 8 patients reported in the literature with endometrial carcinoma after endometrial ablation, most had several risk factors for endometrial neoplasia. These factors were diabetes mellitus and obesity in 6 patients, hypertension in 3, postmenopausal bleeding unresponsive to hormone treatment in 6, carcinoma of the colon or polycystic ovary disease in 5, endometrial complex hyperplasia in 5, failure of progestin treatment in 5 and persistent hyperplasia on biopsy in 5 patients. In this high-risk group of patients, hysterectomy would be a better choice of treatment.
Conclusions: For those women with risk factors for endometrial carcinoma, a preablation biopsy demonstrating normal endometrium is necessary. Persistent hyperplasia which does not respond to hormone therapy is an indication that hysterectomy should be considered.
Editorial comment: The authors note that adequate endometrial evaluation, including hysteroscopy and endometrial sampling should be performed prior to the procedure. In case of endometrial hyperplasia if the patient is a poor operative candidate, ablation may be done. However, periodic long-term follow-up which probably should include vaginal ultrasound, and if possible, endometrial sampling of the residual endometrium should be performed.
E Weiderpass, JA Baron, H-O Adami, et al (Karolinska Inst, Stockholm, Sweden; Dartmouth Med School, Hanover, NH; Falun Hosp, Sweden; et al)
Low-Potency Oestrogen and Risk of Endometrial Cancer: A Case-Control Study.
Lancet 353: 1824-1828, 1999
Urogenital symptoms in postmenopausal women, which occur commonly, may be relieved by low-potency estrogen formulations given orally or vaginally. Such formulations are thought to have few, if any, adverse effects on the endometrium. However, the risk of endometrial neoplasia has not been established. The occurrence of endometrial cancer among postmenopausal women in Sweden was investigated in a nation wide, population based, case-control study.
Methods: Data on hormone replacement were obtained from 789 women with endometrial cancer and 3368 population control subjects. After a histologic review, 80 cases, were reclassified as endometrial atypical hyperplasia.
Findings: A multivariate analysis, with adjustment for covariates, showed that the oral use of estriol, 1 to 2 mg daily, increased the relative risk of endometrial cancer and endometrial atypical hyperplasia. Compared with “never use,” at least 5 years of use had an odds ratio of 3.0 for endometrial cancer and 8.3 for endometrial atypical hyperplasia. The association was stronger for well-differentiated cancers, and cancers with limited invasion. This excess relative risk declined rapidly after treatment was stopped. Vaginal application of low-potency estrogen formulations was only weakly associated with the relative risk of endometrial neoplasia.
The authors suggest adding of a progestogen to protect the women who are on low-dose estrogen.
Editorial comment : Estrogen alone is indeed a risk factor for endometrial neoplasia.
K Fukuda, M Mori, M Uchiyama, et al (Saga Med School, Japan)
Preoperative Cervical Cytology in Endometrial Carcinoma and its Clinicopathologic Relevance.
Gynecol Oncol 72: 273-277, 1999.
The study group consisted of a series of 99 consecutive patients age 31 to 86 years with primary endometrial carcinoma. Cervical cytologic smears were examined before surgical treatment. The average follow-up was 5.8 years. Of the 99 patients, 17.2% died of their primary disease during follow-up.
Findings: Normal cervical cytology was detected in 68 patients, suspicious cervical cytology was detected in 1 patient, and malignant cytology was detected in 30 patients. There was no association between cervical cytology and patient’s age or peritoneal cytology. Univariate analysis demonstrated that preoperative cervical cytology was related to survival.
Conclusion : Patients with endometrial carcinoma who have suspicious or malignant preoperative cervical cytologic smears are at increased of advanced high stage, invasive, and metastatic cancer. This indicates that cervical cytology can play a useful role in the preoperative analysis of endometrial cancer. However, multivariate analysis indicated that cervical cytology was not an independent prognostic factor and probably should not influence treatment decisions.
Editorial comment: DuBesheter notes that the authors report that positive cervical cytology had a positive predictive value of 45% for nodal spread. However, the negative predictive value in the literature ranges from 77% to 94%. In other words, nodal spread is unlikely in the presence of normal cervical cytology. DuBeshter makes a convincing argument that this knowledge is good enough that Ultrasound, MRI and frozen section, all expensive tests, to determine myometrial invasion are probably not that helpful.
A Zelmanowicz, A Hildresheim, et al (Natl Cancer Inst, Bethesda, Md; Johns Hopkins Med Institutions, Baltimore, Md; Bowman Gray School of Medicine, Winston-Salem, NC et al)
Evidence for a Common Etiology for Endometrial Carcinomas and Malignant Mixed Mullerian Tumors.
Gynecol Oncol 69: 253-257, 1998.
There are 3 categories of uterine malignant tumors: carcinomas, sarcomas and carcinosarcomas or malignant mixed mullerian tumors (MMMTs).
The authors found that obesity, exogenous estrogen use and nulliparity were associated with increased risk of both tumor types. MMMT patients were more likely to be black. Oral contraceptive use was protective for both types of tumors. Current smokers had a reduced risk of endometrial carcinoma, but former smokers had an increased risk of MMMT.
Conclusion: This study indicates that the risk factors for endometrial carcinoma and malignant mixed mullerian tumors are similar. This suggests that the pathogenesis of these 2 types of endometrial tumors may be similar. MMMTs may represent carcinomas that have secondarily developed sarcomatous differentiation. Confirmation of these findings in larger studies is required.
KM Greven, RB D”Agostino Jr, et al (Wake forest Univ Winston-Salem, NC; Delaware County Regional Cancer Ctr, Drexel Hill Pa; Thomas Jefferson Univ, Philadelphia)
Is there a role for a Brachytherapy Vaginal Cuff Boost in the Adjuvant Management of Patients with Uterine-confined Endometrial Cancer ?
Int J Radiat Oncol Biol Phys 42: 101-104, 1998.
Adjuvant pelvic radiation is often the treatment used for women with uterine-confined endometrial cancer with prognostic factors predictive of recurrence. For these women, the addition of a brachytherapy vaginal cuff boost is controversial. A comparison was made of patients receiving external beam radiation therapy alone and women receiving this therapy with brachytherapy vaginal cuff boost.
The authors have come to the conclusion that for pelvic control or disease-free survival in patients with stage I or II endometrial cancer, there is no suggestion that the addition of a vaginal cuff brachytherapy boost to pelvic radiation is beneficial. A positive result is unlikely to be seen by prospective randomized trials designed to study external irradiation alone versus external beam radiation plus vaginal brachytherapy. To improve disease-free survival in patients at risk for recurrence, protocol development for uterine-confined corpus cancer should focus on identifying patients at risk as well as other means of augmenting external beam irradiation therapy, such as the addition of chemotherapy, because this therapy alone provides excellent pelvic control.
MF Weiss, PP Connell, et al (Univ of Chicago)
External Pelvic Radiation Therapy in Stage IC Endometrial Carcinoma
Obstet Gynecol 93: 599-602, 1999
Patients with endometrial carcinoma who have deep myometrial invasion without extrauterine disease (stage IC) usually receive postoperative radiation therapy, consisting of external beam whole pelvic irradiation and vaginal brachytherapy.
The study group consisted of 61 women, aged 44 to 87 years, with a diagnosis of stage IC endometrial carcinoma who were treated with postoperative pelvic radiation alone between June 1986 and June 1995.
Findings: the 5-year actuarial disease-free survival rate was 86.7% and overall survival was 97.6% in this patient group. There were no local recurrences. Ten patients had distant metastases.
Conclusions: the results of this retrospective study suggest that women with stage IC endometrial carcinoma treated with surgery and adjuvant pelvic radiation, without vaginal brachytherapy, achieve excellent local cancer control. More research is needed on methods to control distant metastases in this patient group.
Editorial comment: As emphasized by the authors such additional treatment like vaginal brachytherapy leads to more vaginal stenosis, runs the risk of increased radiation complications, and most importantly provides no therapeutic advantage.
One patient did get a lateral pelvic wall recurrence, but the main problem is recurrent distal disease, which was observed in 10 (16%) of the patients.
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.
R Lehner, R Wenzi, et al (Univ of Vienna; Hosp Lainz, Vienna)
Influence of Delayed Staging Laparotomy After Laparoscopic Removal of Ovarian Masses Later Found Malignant.
Obstet Gynecol 92: 967-971, 1998
Seventy patients were reviewed who had undergone attempted laparoscopic excision of a suspected benign ovarian mass, which was later proved by tissue and biopsy specimens to be malignant. In 22 patients, laparotomy was performed immediately after laparoscopy (immediate laparotomy group). Of the remaining patients, 22 underwent laparotomy 17 days or less after the initial examination and in 24 the delay between laparoscopy and laparotomy was more than 17 days.
Findings: Early-stage ovarian cancer was significantly more prevalent among patients in the immediate and early laparotomy groups compared with those in the late laparotomy group (59% and 71%, respectively).
Conclusions – Patients whose laparotomy was delayed more than 17 days after laparoscopy had a significantly increased risk of more advanced disease, probably because of tumor cell dissemination caused by the laparoscopy.
Dr. Ingle’s comment: I have not understood why the authors have kept such an odd number of 17 days as cut-off line, probably this was appropriate for their particular group of patients.
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.
JA Carlson, R Ambros, et al (Albany Med College, NY)
Vulvar Lichen Sclerosus and Squamous Cell Carcinoma: A Cohort, Case Control, and Investigational Study with Historical Perspective; Implications for Chronic Inflammation and Sclerosis in the Development of Neoplasia.
Hum Pathol 29: 932-948, 1998.
Background: Vulvar lichen sclerosus (LS) is an inflammatory dermatosis characterized by chronic sclerosis. There is no consensus about the relationship between LS and squamous cell carcinoma (SCC), although the conditions are known to occur together. Lichen sclerosus could be associated with carcinogenesis through chronic inflammation and proliferation. To evaluate the relationship between LS and SCC, clinicopathologic studies were performed on 32 symptomatic vulvar LS patients and 60 patients with vulvar SCC.
A Review of the patients of 1 gynecologist from 1980-1996 identified 32 LS patients. A further group of 60 patients, with invasive vulvar SCC excised at the Albany Medical Center from 1980 to 1995 and with follow-up available also formed part of the study group.
Findings: Among the 32 LS patients, 9% developed vulvar intraepithelial neoplasia (VIN) and 21% developed invasive SCC. Symptomatic LS was detected an average of 4 years before diagnosis of carcinoma. Vulvar LS had significantly higher expression of p53 and aneuploidy than any of the 3 control groups.
Authors conclude that the compiled frequency of SCC in association with LS was 4.5% with an average of 10 years of LS before diagnosis of SCC. The chronic inflammation and proliferation of LS can lead to genomic instability.
Editorial comments: Tumors associated with LS tended to be clitoral in location. They also tended to occur in older patients, with a mean age of 74 versus 65 in the non-LS group.
ZS Tuncer, MR Bernstein, et al (Harvard Med School, Boston
Outcome of Pregnancies Occurring Before Completion of Human Chorionic Gonadotropin Follow-up in Patients with Persistent Gestational Trophoblastic Tumor.
Gynecol Oncol 73: 345-347, 1999.
A chart review identified 43 women with gestational trophoblastic tumor (GTT) who conceived before standard hCG follow-up was completed during the period from 1973 to 1998. The mean interval from hCG remission to new pregnancy was 6.3 months. Of the remaining 29 patients, 75.9% delivered live infants at term and 10.3% had preterm delivery.
Conclusions : Pregnancies occurring before standard hCG follow-up is completed in women treated for gestational trophoblastic tumor may continue under close observation. Most such pregnancies have favorable outcomes. However, there is a low but important risk of delayed diagnosis of tumor relapse during early pregnancy.
Editorial comments: It appears that the risk of disease is low, but it certainly exists for those who undertake pregnancy sooner than 1 year after therapy for GTT.
P Harrkki-Siren, J Sjoberg, A Tiitinen (Helsinki Univ)
Urinary Tract Injuries After Hysterectomy
Obstet Gynecol 92: 113-118, 1998.
Introduction: In gynecologic surgery, urinary tract injuries are among the most serious complications. About 75% of all ureteral injuries are caused by gynecologic procedures.
There were 142 urinary tract injuries after hysterectomy that were reportd during a 5-year period, and these were retrospectively analyzed. During this study period, 62379 hysterectomies were performed.
Results : After all hysterectomies, the total incidence of ureteral injury was 1 of 1000 procedures: 13.9 of 1000 after laparoscopic, 0.4 of 1000 after total abdominal, 0.3 of 1000 after supracervical abdominal and 0.2 of 1000 after vaginal hysterectomy. Bladder injury there were 1.3 of 1000 procedures, 65% of reported bladder injuries were fistulas. The incidence was 2.2 of 1000 after laparoscopic hysterectomy; 1 of 1000 after total abdominal, 0 of 1000 after supracervical abdominal, and 0.2 of 1000 after vaginal hysterectomy.
Conclusion: After laparoscopic hysterectomy, the risk of ureteral injury and even bladder injury is higher than with traditional hysterectomies.
Editorial comment: The rates reported from Finland for laparoscopic procedures are much higher perhaps because the technique is comparatively new. As noted in the conclusion, if the patient is a good candidate for a vaginal hysterectomy there is no reason to change the operation to a laparoscopic procedure.
Notelovitz Morris, Cassel Diane, Hille Darcy, et al, Gainesville, Florida, Collegeville, Pennyslvania, and Antony, France.
Efficacy of continuous sequential transdermal estradiol and norethindrone acetate in relieving vasomotor symptoms associated with menopause.
Am J of Obstet & Gynec., Jan 2000p.7-12
The physiologic state of menopause is characterized by a progressive loss of ovarian function, with a resulting decrease in circulating estrogen concentration. The classic symptoms of estrogen deficiency after natural or surgical menopause are periods of episodic flushing and sweating. These symptoms, which are reported to develop in approximately 70% to 80% of postmenopausal women, appear to be directly correlated with the degree of estrogen deficiency. Hormone replacement therapy with oral or transdermal estrogen has been shown to be effective in alleviating the vasomotor symptoms of menopause and also in reducing associated risks of cardiovascular mortality and bone fractures. If given unopposed, however, the doses of estrogen required to provide symptom relief and protective benefits can increase the risk of endometrial hyperplasia and carcinoma. The addition of progestins to hormone replacement therapy regimens has been shown to successfully prevent such adverse endometrial effects without compromising the benefits of estrogen therapy.
Transdermal estrogen delivery systems for postmenopausal estrogen deficiency may have advantages with respect to oral therapy, such as improved convenience, controlled sustained release of estrogen, predictable absorption, lack of gastrointestinal side effects, circumvention of first-pass circulation through the liver, lower biliary cholesterol saturation index, slower metabolism to less-active estrogens, and potentially better compliance than with oral regimens. Moreover, a more physiologically appropriate estrogen/estradiol ratio is obtained and maintained than is achieved with oral hormonal replacement therapy regimens. It has been anticipated that transdermal delivery of progestins could confer similar advantages.
Preliminary experience with a combination estrogen plus progestin transdermal system suggested that administration in a sequentially worn regimen of a combination patch with an estrogen-only patch can successfully relieve menopausal symptoms and provide good cycle control. Norethindrone acetate, a progestin commonly used in hormone replacement therapy regimens, displays skin flux characteristics favorable for transdermal delivery. This study was designed to evaluate the efficacy of 3 dosage levels of transdermal norethindrone acetate (140,250, and 400 mg/d) when administered sequentially with continuous transdermal estradiol (50 mg/d) in reducing moderate to severe vasomotor symptoms associated with menopause.
Study design: This was a 12-week double-blind trial of 220 healthy postmenopausal women with ³8 moderate to severe hot flushes and sweating episodes per day. Wom en were randomly assigned to wear transdermal placebo patches or a transdermal patch releasing 50 mg/day 17b-estradiol alone (Vivelle) for days 1 to 14 of each cycle and a combination patch releasing 50 mg/day 17b-estradiol plus 1 of 3 dosage levels (140, 240 or 400 mg/day) of norethindorne acetate (combipatch) for days 15 through 28.
Result : There was a significant reduction by the second week in the mean number of daily hot flushes from baseline to end point with all 3 doses of estradiol plus norethindrone acetate compared with placebo. Significant reductions in the mean intensity of hot flushes and sweating were also noted with estradiol plus norethindrone acetate compared with placebo. The incidences of adverse events with all 3 doses of estradiol plus norethindrone acetate and with placebo were comparable.
Conclusion: An estradiol plus norethindrone acetate transdermal delivery system administered in a continuous sequential regimen with transdermal estradiol was well tolerated and effective for the treatment of moderate to severe vasomotor symptoms in postmenopausal women.
RA Lobo, HZ Zacur, P Caubel, and R Lane. (The Columbia Presbyterian Medical Center, the Johns Hopkins Medical Institutions, and the R.W. Johnson Pharmaceutical Research Institute US).
A Novel Intermittent Regimen of Norgestimate to Preserve the Beneficial Effects of 17b-estradiol on Lipid and Lipoprotein Profiles.
Am J Obstet Gynecol 2000; 182:41-9.
Objective : This study was undertaken to evaluate the effects of 3 dosage levels of intermittent norgestimate plus a constant dose of 17b-estradiol on blood lipid and lipoprotein concentrations in 236 postmenopausal women.
Study Design : In this multicenter, double-blind, parallel group trial the subjects were randomly assigned to receive 1mg estradiol daily or 1mg estradiol daily plus intermittent (3 days off and 3 days on) doses of 30mg, 90mg, or 180mg norgestimate for 360 days.
Results: The regimens of 1mg estradiol plus 30mg norgestimate and 1mg estradiol plus 90mg norgestimate increased concentrations of high-density lipoprotein cholesterol, HDL2 high-density lipoprotein cholesterol, HDL3 high-density lipoprotein cholesterol (except the regimen of 1mg estradiol plus 30 mg norgestimate at 7 months), and apolipoprotein apo A-1. They decreased total cholesterol concentration, low-density lipoprotein cholesterol concentration, low-density lipoprotein/high-densitylipoprotein ratio, apolipoprotein apo-B concentration, and Lp (a) lipoprotein concentration, and they attenuated estradiol-induced increases in triglyceride concentrations. In contrast, the regimen of 1mg estradiol plus 180 mg norgestimate reduced concentrations of high-density lipoprotein cholesterol, high-density lipoprotein HDL3 cholesterol, and apolipoprotein apo A-1 at 7 months and increased the low-density lipoprotein/high-density lipoprotein ratio at 7 months.
Conclusions: An intermittent regimen of norgestimate at 30 or 90 mg daily administered for 3 days off followed by 3 days on preserved the beneficial lipid and lipoprotein changes induced by continuous therapy with 1mg 17b-estradiol daily; however, 180 mg norgestimate did not do so.
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.
Berit Gull, S.A. Carlsson, et al (Department of Obstetrics & Gynaecology, Sahlgrenska University Hosptial, Goteborg, Sweden)
Transvaginal ultrasonography of the endometrium in women with postmenopasual bleeding: Is it always necessary to perform an endometrial biopsy?
Am J Obstet Gynecol, March 2000;182: 509-15
Study Design: Transvaginal ultrasonography was performed in 361 women aged ³50 years who were referred because of postmenopausal bleeding or irregular bleeding during hormone replacement therapy. If endometrial thickness was £4mm, a Papanicolaou cervical smear was performed and the woman was reexamined with transvaginal ultrasonography after 4 and 12 months. Subjects were also instructed to return if they had recurrent bleeding, in which case transvaginal ultrasonography was performed and an endometrial biopsy specimen was obtained. Women with an endometrial thickness ³ 5 mm underwent either curettage or endometrial biopsy.
Conclusion : If the false-negative rate of endometrial biopsy techniques is taken into account, then the combination of transvaginal ultrasonography and cervical cytologic examination is an adequate form of management for women with postmenopausal bleeding or irregular bleeding during hormone replacement therapy as long as endometrial thickness is £ 4 mm. A randomised prospective study is necessary to verify this finding.
Comment: Endometrial cancer was diagnosed in 0.6% of the women who had an endometrial thickness £ 4mm versus 18.7% among the women who had an endometrial thickness > 5mm. This figure includes an endometrial metastasis from a primary breast cancer and hence women with endometrial thickness of >5mm should have endometrial study in addition to clinical examination and ultrasonography.
Dannie J Gentry, Michael S Baggish, et al (Department of Obstetrics & Gynaecology, Cincinnati, Ohio)
The effects of loop excision of the transformation zone on cervical length: Implications for pregnancy.
Am J Obstet Gynecol March 2000, 182: 516-20
Objective: This study was undertaken to determine whether previously described significant and quantitative cervical shortening caused by loop excision of the transformation zone persists after 3 months of healing.
Study Design: A prospective study was designed in which 20 patients were enrolled. Each underwent transvaginal ultrasonography for determination of cervical length before the loop excision of the transformation zone and ³ 3 months after the loop excision of the transformation zone.
Conclusion : After adequate healing time after loop excision of the transformation zone, the length of the cervix, as measured by transvaginal ultrasonography, does not appear to remain shortened.
Catharina AH Janssen, Piet C Scholten, et al (Utrecht, The Netherlands)
The effect of low-dose 3-keto-desogestrel added to a copper-releasing intrauterine contraceptive device on menstrual blood loss: A double-blind, dose-finding, placebo controlled study.
Am J Obstet Gynecol March 2000; 182: 575-81
Study Design: A double-blind group comparative study was designed in which 203 healthy women with or without menorrhagia were enrolled and randomized to four different Multiload Cu250 intrauterine contraceptive devices, releasing 0 (control), 1.5, 3, or 6 mg of 3-keto-desogestrel daily. Menstrual blood loss, hemoglobin, and serum ferritin levels were determined before and during treatment.
Results: All 3 keto-desogestrel copper intrauterine contraceptive devices reduced menstrual blood loss significantly, causing a reduction of up to 30 to 40mL after 12 months of use. All women with essential menorrhagia were considered to have been successfully treated after 6 months of use. Serum ferritin levels rose with all three 3-keto-desogestrel-loaded devices.
Conclusion: A Multiload Cu250 intrauterine contraceptive device releasing 1.5 mg of 3 keto-desogestrel daily is able to reduce menstrual blood loss to a very low level and to replete body iron stores in women with or without menorrhagia. Higher doses have no superior effect.
David C G Skegg
Editorial – Third generation oral contraceptives – Caution is still justified.
BMJ, Vol.321, July 22, 2000, pg.190-191
In October 1995, the Committee on Safety of medicines in UK warned that oral contraceptives containing desogestrel or gestodene carried a small increase in risk of venous thromboembolism compared with older preparations. Four well-designed studies gave the picture that women using 3rd generation oral contraceptives (OCs) had about twice the risk of venous thromboembolism of women using preparations containing levonorgestrel. These conclusions have been debated extensively.
The absolute risks are small, but are they of no consequence ? Studies in Britain and New Zealand, where 3rd generation pills have been commonly used, estimate that the annual death rate from idiopathic venous thromboembolism in users of OC is about 1 in 100,000. Thus, the risk of dying of a woman using the pill for 2-3 years is of the same order of magnitude as the risk of fatal aplastic anaemia in a patient treated with chloramphenicol. Non-fatal events which can still have serious consequences may be at least 30 times more common.
A Randomized Trial on the Use of Ultrasonogrpahy or Office Hysteroscopy for Endometrial Assessment in Postmenopausal Patients with Breast Cancer who were Treated with Tamoxifen.
D Timmerman, J Deprest, et al (Univ Hosp. Leuven, Belgium)
Am J Obstet Gynecol 179:62-70, 1998.
The mortality rate in women with breast cancer has been reduced by tamoxifen and this drug is currently the hormonal treatment of choice. About 1 million women are taking tamoxifen in the United States currently. There is now an increased interest in the potential side effects of tamoxifen, particularly because it is used as a prophylactic agent against breast cancer.
There were 53 postmenopausal women with breast cancer who had no vaginal bleeding and who had taken tamoxifen at 20 or 40 mg/day for at least 6 months.
Results – Endometrial cancer was found in 2 women. In both patients, endometrial cancer was detected only by transvaginal. One woman had primary and other had breast secondary. At least 1 polyp was found in 26 women. All 47 polyps were benign. There was no significant difference among the women who had polyps with regard to their age, body mass, months of tamoxifen intake, or their cumulative dose. The sensitivity of transvaginal ultrasound was 90% and the specificity was 100%. For office hysteroscopy, the sensitivity was 77% and the specificity was 92%.
Some patients could not have office hysteroscopy due to cervical stenosis i.e. 19% of patients in the study.
Hwa Sook Moon, Young Joo Choi et al (Department of Obstetrics and Gynecology, Centre for Reproductive Medicine and Laparoscopic Surgery, Moon Hwa Hospital)
New Simple Endoscopic Operations for Interstitial Pregnancies
Am J Obstet Gynaecol, 182(1) Part 1, p.114-121
Interstitial or cornual pregnancy is a rare form of ectopic pregnancy. In previous reports it accounted for 2% to 4% of all ectopic pregnancies, and it occurs once in every 2500 to 5000 live births. There is a 2% to 5% mortality rate. In general, interstitial pregnancies are diagnosed later in gestation, and if rupture occurs, hemorrhage is profound. Traditional treatment has consisted of cornual resection or hysterectomy by laparotomy. Methods of diagnosis and treatment have posed difficulties; however, the development of ultrasonography and serum human chorionic gonadotropin (hCG) measurement have allowed earlier diagnosis. Furthermore, endoscopic technology and methotrexate have allowed minimally invasive treatment. Many successful endoscopic managements for early interstitial pregnancy have been reported by several authors. In the previous reports most authors used the electric cauterization method for bleeding control and cornual incision. Some authors have performed cornual excision. Some applied multiple procedures for hemostasis.
For the successful management of interstitial pregnancy, we expect minimal blood loss during the operation, an observed decrease in the serum hCG level, and early resumption of menstruation after operation. The outcome of subsequent pregnancy is very important for women who want future pregnancy. Patients with interstitial pregnancies who have been treated conservatively may have a risk of uterine rupture in subsequent pregnancies; however, limited information is available.
This study was performed retrospectively to provide information on the endoscopic management of interstitial pregnancy, to introduce simple and safe surgical techniques, and to report the outcomes of subsequent pregnancies.
Study Design :This is an uncontrolled retrospective review of 24 patients treated for interstitial pregnancies through endoscopic operations with 14 to 72 months of follow-up at a large urban medical center. Blood loss, operation time, changes of serum human chorionic gonadotropin levels, the resumption of menstruation, and subsequent pregnancy after operation were analyzed.
Results : Among 24 interstitial pregnancies, 3 had ruptured at the time of operation and 21 had not ruptured. Treatment consisted of either the vasopressin and electric cauterization method, the endoloop before evacuation of the conceptus method, or the encircling suture before evacuation of the conceptus method. The blood loss and operation time (mean ± SD) for unruptured cases were 133 ± 134 mL and 51.6 ± 7.6 minutes in the vasopressin and electric cauterization group (n=3), 32 ± 22mL and 28.5 ± 6.4 minutes in the endoloop group (n=15), and 40 ± 17mL and 35.0 ± 5.0 minutes in the encircling suture group (n=3). In 3 patients with ruptured pregnancy treated with the endoloop method, the blood loss and operation time (mean ± SD) were 1100 ± 854 mL and 82.5 ± 51.6 minutes. Any of these operative methods resulted in rapid decline of serum human chorionic gonadotropin levels within 1 week with the exception of 1 case, in which the endoloop method was used; this patient needed additional treatment with methotrexate. Seventeen patients desired pregnancy in the future, and 15 eventually became pregnant. One of these 15 pregnancies ended in an ectopic pregnancy on the opposite side 6 months after the interstitial pregnancy. Three ended in a spontaneous abortion and 11 were delivered by elective cesarean section at term before labor started. Operative records of cesarean section in 8 patients delivered at our institution showed little or no adhesions or defect in the cornual area of the previous operation.
Conclusion: the endoloop method and the encircling suture method are simple, safe, effective and nearly bloodless. There were no uterine ruptures in the pregnancies subsequent to these methods of endoscopic management.
Ahmet A Baschat and Carl P Weiner, (Department of Obstetrics, Gynecology and Reproductive Sciences, University of Maryland).
Umbilical artery Doppler screening for detection of the small fetus in need of antepartum surveillance.
Am J Obstet Gynecol 182(1), Part I, p. 154-8.
Detection of fetal hypoxemia is the prime goal of antenatal surveillance, and intrauterine fetal growth restriction (IUGR) is among the most common risk factors for chronic fetal hypoxemia. Fetuses measured as being small for gestational age on ultrasonography are routinely evaluated with weekly nonstress tests or biophysical profiles specifically in search of evidence of hypoxic fetal distress. Yet the positive predictive value of ultrasonographic biometry for diagnosis of IUGR approximates only 50%. Thus half of the ultrasonographically small fetuses are not truly at risk, and their selection for testing dramatically increases the cost of health care.
Knowledge of increased umbilical artery (UA) Doppler – determined resistance is associated with a reduction in perinatal morbidity and mortality when applied to populations at high risk for an adverse perinatal outcome. Relatively unexplored is the use of Doppler to select fetuses who might benefit from weekly surveillance because their ultransonographic biometric results suggest IUGR. The purpose of this study was to determine whether an abnormal UA resistance both improves the diagnostic accuracy of IUGR and identifies the fetus who is at risk for chronic hypoxemic distress and thus in need of antenatal surveillance. If true, this application of Doppler velocimetry would reduce the total population in need of weekly antenatal testing by improving specificity and thus lower the cost of antenatal chart without sacrificing outcome.
Study Design: Three hundred eight fetuses with either an ultrasonographic weight estimate < 10th percentile for gestational age or an abdominal circumference <2.5th percentile for gestational age or both of these had an umbilical artery Doppler measurement of the systolic/diastolic ratio. A systolic/diastolic ratio >90th percentile for gestation was considered abnormal. The incidences of a birth weight < 10th percentile, fetal distress, and metabolic acidemia were recorded fore both groups (normal vs abnormal umbilical artery Doppler).
Results : Only the umbilical artery systolic/diastolic ratio predicted perinatal outcome in the group of fetuses who were presumed to be small for gestational age. Those 138 fetuses with elevated umbilical artery systolic/diastolic ratios had lower umbilical artery and vein pH values at birth (artery, 7.23 ± 0.08 vs 7.25 ± 0.1; P<.02; vein, 7.31 ± 0.01 vs. 7.34 ± 0.09; P =.01), an increased likelihood of fetal distress consistent with chronic hypoxemia (26.3% vs 8.6%; P<.0001), more admissions to the neonatal intensive care unit (40.7% vs 30.7%; P < .005), and a higher incidence of respiratory distress (66% vs 27.3%; P < .03).
However, it is important that no fetus with a normal Doppler flow measurement was delivered with a metabolic acidemia associated with chronic hypoxemia. Further, the likelihood of a false-positive diagnosis of intrauterine growth restriction was increased in the group with a normal umbilical artery Doppler resistance.
Conclusion: Antenatal surveillance may be unnecessary in fetuses with suspected intrauterine growth restriction if the umbilical artery systolic/diastolic ratio and amniotic fluid volume are normal, because the complications that occur are intrapartum. If these findings are confirmed in prospective trials, the cost implication of reducing the number of antenatal surveillance tests administered I this group of patients is great.
Robert L Goldenberg, Anita Das, for the National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network, Birmingham, Alabama and Washington.
Fetal Fibronectin and bacterial vaginosis in smokers and nonsmokers.
Am J Obstet Gynecol 2000; 182: 164-6.
The National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network previously reported that there was a statistically significant association between the detection of fetal fibronectin and the presence of bacterial vaginosis. This relationship was subsequently confirmed but with the added observation that the relationship was statistically significant only among women who smoked during pregnancy. If this latter observation is indeed true and bacterial vaginosis predicts elevated fetal fibronectin levels only among women who smoke, this could suggest how 2 different risk factors for preterm birth might interact with each other.
To determine whether maternal smoking influences the relationship between bacterial vaginosis and fetal fibronectin, the presence of cervical or vaginal fetal fibronectin, the presence of bacterial vaginosis and smoking status were determined for 2899 women at 24 weeks’ gestation. Fetal fibronectin was more common among women with bacterial vaginosis, but maternal smoking did not increase the likelihood that women with bacterial vaginosis would have fetal fibronectin detected. A previously reported impact of maternal smoking status on the relationship between bacterial vaginosis and fetal fibronectin thus was not confirmed.
Anna Locatelli, Maria Giovanna Piccoli, et al (Divisione di Ostetricia e Ginecologia, Istitutio di scienze Biomediche San Gerardo, and the Departments of Obstetrics and Gynecology and Pharmacology and Biostatistics, Georgetown University Medical Center.
Critical appraisal of the use of nuchal fold thickness measurements for the prediction of Down Syndrome.
Am J Obstet Gynecol 2000; 182: 192-7
Maternal serum analyte levels have been used successfully to adjust the maternal age-associated probability of fetal trisomy 21 throughout the reproductive years. Ultrasonography offers another noninvasive means of selecting candidates for prenatal diagnosis of Down syndrome by using markers that are more frequently present in aneuploid fetuses than in euploid fetuses. Among the second-trimester ultrasonographic markers proposed, nuchal fold thickness has been consistently shown to be reproducible, to be easy to obtain, and to have a predictive ability that is independent of the other markers. A nuchal fold thickness ³6mm during the early second trimester has been reported to be the best ultrasonographic predictor of fetal chromosomal abnormalities and of trisomy 21 in particular. However, nuchal fold thickness has been shown to be correlated with gestational age. Therefore use of a single threshold across the early second trimester may not optimize the predictive ability of this marker. In addition, use of a single threshold of nuchal fold thickness independently from the prior probability (e.g. maternal age ) does not allow adjustment of the sensitivity and the false-positive rate according to the individual patient’s risk-level.
To obviate the confounding effect of gestational age on nuchal fold thickness and to allow calculation of posterior probabilities of Down syndrome on the basis of individual previously assessed risk, the authors analyzed a cohort sample of women undergoing a second trimester genetic sonogram. They then used the differences between the observed and expected nuchal fold thickness at each gestational age to calculate likelihood ratios.
Study Design: Nuchal fold thickness was measured at ultrasonographic examination at 14 to 22 weeks’ gestation without previous knowledge of the fetal karyotype. Nuchal cystic hygromas were excluded from anal4sis. Statistical analyses included correlation, logistic regression to control for other ultrasonographic predictors of trisomy 21 and for maternal age, receiver operating characteristic curve, and likelihood ratios. P< .05 was considered significant.
Results : Mean gestational age at ultrasonography was 16.9 weeks gestation (range 14-22 weeks’ gestation0. Mean (±SD) nuchal fold thickness in fetuses with trisomy 21 (4.7 ± 1.6mm; n=29) was greater than in euploid fetuses (3.2 ± 0.9; n-780; p <.001). Logistic regression analysis established that nuchal fold thickness was a signficant predictor of trisomy 21 independent botyh of the other ultrasonographic markers and of maternal age (P< .001). Regression analysis showed that nuchal fold thickness was significantly correlated with gestational age among both fetuses with trisomy 21 and euploid fetuses and that the regression line of fetuses with trisomy 21 had a slope similar to that of euploid fetuses. The difference between observed and expected nuchal fold thicknesses on the basis of th ebiparietal diameter (as a function of gestational age) was used to obviate the confounding effect of gestational age. Differences between observed and expected nuchal fold thicknesses were then used to calculate likelihood ratios. These likelihood ratios could then be multiplied by the individual prior probability to obtain a patient – specific Down syndrome probability.
Conclusion: Nuchal fold thickness is correlated with gestational age in both euploid fetuses and fetuses with Down syndrome. Use of the difference between observed and expected nuchal fold thicknesses to determine likelihood ratios allows the calculation of individual posterior probabilities of Down syndrome that take into consideration both gestational age and maternal age.
Anthony M Vintzileous, Cande V Ananth et al (Piscataway, New Jersey and farmington, Connecticut)
Routine second-trimester ultrasonography in the United States: A Cost benefit analysis.
Am J Obstet Gynecol, March 2000, 182: 655-60.
Objective: The objective of this study was to perform a cost-benefit analysis of routine second-trimester screening ultrasonography in the United States as compared with performing ultrasonography only in the presence of indications.
Study Design: It was assumed that 1 million pregnant women are available annually who otherwise would not have an indication for an ultrasonographic examination. Cost savings from early detection and therapeutic abortion were considered only for fetal conditions for which lifetime cost estimates are available, including spina bifida, major cardiac disease, cleft lip or palate, renal agenesis or dysgenesis, urinary obstruction, lower or upper limb reduction, omphalocele, gastroschisis, and diaphragmatic hernia. Two separate cost-benefit analyses were considered with the range of fetal anomaly detection rates before 24 weeks’ gestation as reported by tertiary and non-tertiary centers in the Routine Antenatal Diagnostic Imaging with Ultrasound (RADIUS) trial. Potential cost savings from averting treatment for preterm labor and postdate gestations were also considered.
Results: The ratio of savings to cost was between 1.35 and 1.70 (savings of $1.35 – $1.70 per $1 spent) if the ultrasonographic examinations were performed in tertiary care centers. The ratio of savings to cost was between 0.40 and 0.74 (loss of $0.26-$0.60 per $1 spent) if the examinations were performed in nontertiary centers. If the screening ultrasonography was performed in tertiary centers, the expected annual net benefits were estimated $97 to 189 million. If ultrasonographic screening was performed in nontertiary centers, the expected annual net losses were estimated at $69 to 161 million.
Conclusion: Routine second-trimester ultrasonographic screening appears to be associated with net benefits only if the ultrasonography is performed in tertiary care centers.
Bernard Gonik, Alberta Walker and Michele Grimm (Detroit, Michigan)
Mathematic modeling of forces associated with shoulder dystocia: A comparison of endogenous and exogenous sources.
Am J Obstet Gynecol, March 2000; 182: 689-91
Objective: A mathematic model was developed to estimate the compressive pressure on the fetal neck overlying the roots of the brachial plexus by the symphysis pubis during a shoulder dystocia event. The induced pressure was calculated for both exogenous (clinician applied) and endogenous (maternal and uterine) forces during the second stage of labor.
Study Design: Intrauterine pressure and clinician applied force data were taken from the existing literature. A free-body diagram was generated and equilibrium equations were used to calculate the contact pressure between the base of the fetal neck and the symphysis pubis during a shoulder dystocia event.
Results: Clinician applied traction to the fetal head (exogenous force) led to an estimated contact pressure of 22.9kPa between the fetal neck and the symphysis pubis. In contrast, uterine and maternal expulsive efforts (endogenous forces) resulted in contact pressures that ranged from 91.1 to 202.5kPa. The estimated pressures resulting from endogenous forces are 4 to 9 times greater than the value calculated for clinician applied forces.
Conclusion: Neonatal brachial plexus injury is not a priori explained by iatrogenically induced excessive traction. Spontaneous endogenous forces may contribute substantially to this type of neonatal trauma.
R Schellenberg for the Study Group
Treatment for the premenstrual syndrome with agnus castus fruit extract: prospective, randomized, placebo controlled study.
BMJ, Jan.20, 2001, pg.134.
Objective of the study was to compare the efficacy and tolerability of agnus castus fruit (Vitex agnus castus) with placebo for women with premenstrual syndrome. This is a randomized double-blind, placebo-controlled parallel group study over 3 menstrual cycles. Agnus castus dry extract tablets or matching placebo were administered in the dose of one tablet daily.
Main efficacy variable was change from baseline to end of 3rd cycle in women’s self-assessment of irritability, mood alteration, anger, headache, breast fullness and other menstrual symptoms including bloating.
The study-concluded that dry extract of agnus castus fruit is an effective and well-tolerated treatment for the relief of symptoms of premenstrual syndrome.
Andrew W Horne, John O White, Department of Reproductive Medicine and Science, Imperial College School of Medicine, London.
The endometrium and embryo implantation – A receptive endometrium depends on more than hormonal influences.
BMJ, 25 November , 2000, 321; pg. 1301-2
How embryos attach and implant remains a mystery. Implantation represents the remarkable synchronization between the development of the embryo and the differentiation of the endometrium. A study by Hertig et al in 1956 found that embryos found in the uterus before the 20th day of menstrual cycle were not attached to endometrium and after the 21st day of menstrual cycle were attached. During in-vitro fertilisation , treatment embryos replaced before the 20th day may implant and those replaced after the 24th day do not . Electron microscopy has identified epithelial protrusions into the uterine cavity - called ‘pinopodes’ which appear between day 19 and day 21 .
Regulation of anti-adhesion molecules such as mucin glycoproteins is important , it also needs adhesion molecules such as integrins, cadherins, and the immunoglobulins presence of certain integrins has been proposed as a means of distinguishing receptive endometrium from non-receptive.
The embryo is not passive and spatiotemporal expression of embryonic proteins and their influence on endometrium may prove to be critical.
Rose PG, Adler LP, Rodriguez M, et al [ Ireland Cancer Ctr, Cleveland, Ohio, Univ Hosps of Cleveland, Ohio; Case Western Reserve Univ, Cleveland, Ohio]
Positron Emission Tomography for Evaluating Para-aortic Nodal Metastasis in Locally Advanced Cervical Cancer Before Surgical Staging: A Surgicopathologic Study
J Clin Oncol 17: 41-45, 1999
Locally advanced cancer of the cervix at presentation have para -aortic lymph node involvement in 25%, which becomes the most important indicator of recurrence.
20mCi of 2-[18F] fluoro-2-deoxy -D-glucose [FDG] uptake in para-aortic LN by PET is seen in 91% of cervical tumors. Yielding a positive predictor value of 75% and negative predictor value of 92% and a relative risk of 9.0 for metastatic disease. The editor comments that identifying the para-aortic LN would allow modification of radiation therapy field to include such site of disease.
Kaplan RC, Heckbert SR, et al (Univ of Washington, Seattle; Fred Hutchinson Cancer Research Ctr, Seattle; Group Health Cooperative of Puget Sound, Seattle)
Postmenopausal Estrogens and Risk of Myocardial Infarction in Diabetic Women.
Diabetes Care 21: 1117-1121, 1998.
Methods : Two hundred twelve postmenopausal treated for diabetes who experienced a fatal or nonfatal myocardial infarction (MI) incident between 1986 and 1994 made up the case group. One hundred twenty-two women treated for diabetes with no previous MI constituted the control group. Estrogen use was determined from computerized pharmacy data and medical records. Adjustments were made for cardiovascular risk factors.
It was concluded that the use of postmenopausal estrogens does not appear to increase the risk of MI for women with diabetes. In fact, sustained estrogen use may be beneficial.
Gambacciani M, Ciaponi M, Cappagli B, et al (Univ of Pisa, Italy)
Climacteric Modifications in Body Weight and Fat Tissue Distribution
Climacteric 2: 37-44, 1999
Methods : A total of 1075 untreated healthy women underwent total body fat tissue mass and distribution analysis by the dual energy x-ray method. Three hundred eighty women were premenopausal; 263, perimenopausal; and 432, postmenopausal.
Conclusions : Perimenopausal impairment of ovarian function may result in fat accumulation and android fat distribution. Maintaining a normal menstrual function apparently protects against the increase in body weight and android fat distribution.
Pascot A, Lemieux S, Lemieux I, et al (Laval Univ, Ste-Foy, Quebec)
Age-Related Increase in Visceral Adipose Tissue and Body Fat and the Metablic Risk Profile of Premenopausal Women.
Diabetes Care 22: 1471-1478, 1999
Methods : The study included 122 young women (mean age, 27.4 years) and 52 middle-age, premenopausal women (mean age, 49.5 years), with a normal menstrual cycle. Body composition, adipose tissue distribution, plasma lipoprotein-lipid levels, glucose tolerance and plasma insulin concentrations in the group of young women were compared with the same variables in the middle-aged women.
Conclusions : Even before menopause onset, an age-related deterioration in the metabolic risk profile and an increase in visceral adipose tissue deposition in middle-aged women is apparently present. The current data also support the notion that the age-related increase in visceral adipose tissue accumulation is a significant contributor to deterioration of the cardiovascular disease risk profile observed in premenopausal women with aging.
Editorial comments : Even in premenopausal women, the effects of aging on body fat distribution are evident.
Anthony B Chin, R E Bristow, Lisa M Korst et al (Dept. Obstet and Gynecology, Cedar Sinai Medical Center, Suite, Beverly Blvd, Los Angeles)
The significance of atypical glandular cells on routine cervical cytologic testing in a community-based population.
Am J Obstet Gynecol, vol.182, 6, pg.1278-82
The authors sought to determine the follow-up rate of women with glandular atypia on routine Papanicolaou smears in a community-based population and to describe the associated pathologic findings.
Study Design : Over a 12 month period, all patients with Papanicolaou smears with atypical glandular cells of undetermined significance were reviewed for demographic and clinical characteristics and followed up for a period of 12 to 24 months.
Conclusion: The incidence of atypical glandular cells of undetermined significance on Papanicolaou smears in this community based population was 0.29%, which is consistent with estimates from institute based populations. Nearly 50% of women studied were not followed up with tissue biopsy. Of those with a tissue biopsy, 61% had positive findings, including 5 with cancer. Although postmenopausal status and abnormal vaginal bleeding were associated with endometrial or glandular disease, studies of larger patient populations should be conducted to examine potential risk factors for these conditions.
William H Hindle, Raquel D Arias, et al (Univ of Southern California School of Medicine, Los Angeles)
Lack of utility in clinical practice of cytologic examination of nonbloody cyst fluid from palpable breast cysts.
Am J Obstet Gynecol, 182(6),pg.1300 -5
Objective : This study was undertaken to answer the following question: Does cytologic evaluation of nonbloody fluid aspirated from breast cysts contribute to appropriate clinical management?
Study Design: A retrospective review of palpable breast cyst fluid cytologic reports and associated medical records was undertaken to determine whether the cytologic findings affected patient management. Breast cyst size, fluid volume, fluid color, and patient age were abstracted from 689 medical records (1988-1999) of women whose palpable cysts had been aspirated at the Breast Diagnostic Center, Women’s and Children’s Hospital, Los Angeles. These observations were correlated with the fluid cytologic reports.
Results : Except for frankly bloody fluid, all breast fluid cytologic reports listed the results as a cellular, inadequate for cytologic diagnosis, or no malignant cells identified.
Conclusion: In clinical practice only frankly bloody fluid should be submitted for cytologic analysis. All other cyst fluid should be discarded.
Philip H Henderson, MaryFran Sowers, et al (Longview, Washington, and Ann Arbor, Michigan)
Bone mineral density in grand multiparous women with extended lactation.
Am J Obstet Gynecol, June 2000, 182: 1371-7)
Objective : The authors sought to assess whether the accumulation of multiple, frequent pregnancies and the accompanying repeated extended lactation events was a risk factor for low bone mineral density and osteoporosis.
Study Design: The study population consisted of 30 grand multiparous women who had borne at least 6 children and lactated for at least 6 months with each child, as well as 6 nulliparous, premenopausal women. The medical history included the delivery data, birth outcome, infant birth weight, and number of months lactated for each pregnancy, as well as other health information. Bone mineral density of the lumbar spine, femoral neck, and radius was measured with the Hologic QDR 4500-C dual-energy x-ray absorptiometry scanner.
Results : The 2 study groups did not differ in terms of body mass index, history of smoking, or family history of osteoporosis and fracture, although the parous group was, on average, 8 years older than the nulliparous group (P<.05). The accumulation of repeated pregnancy and lactation events without a recovery interval was not associated with lowered bone mineral density or the presence of osteoporosis or osteopenia.
Conclusions: This study suggests that bone mineral density levels can be sustained
in the presence of the rapidly changing hormone environment associated with multiple pregnancies accompanying lactation events without a “recovery” interval.
J J Klutke, Susanne Ramos (Los Angeles, California)
Urodynamic outcome after surgery for severe prolapse and potential stress incontinence
Am J Obstet Gynecol,2000; 182: 1378-81
Objective : Women with severe prolapse may be paradoxically continent because of kinking of the urethra. It is currently a common practice to perform urethropexy in women who demonstrate stress incontinence on preoperative reduction of the prolapse with a pessary. The authors compared the urodynamic outcome after reconstructive operations that included suspending urethropexy with outcomes after those that did not.
Study Design: A review was performed of the charts of the Gynecologic Urology Clinic at Los Angeles County-University of Southern California Women’s and Children’s Hospital from 1991- 1997 of patients with grade III uterovaginal prolapse or procidentia in whom the pessary test was used to determine whether urethropexy was included in the reconstructive operation. Urodynamic outcomes were compared statistically with the Fisher exact test, and P =.05 denoted statistical significance.
Results: Fifty-five patients underwent urethropexy in addition to repair of the prolapse, and 70 underwent reconstruction alone. Twenty-three patients in the first group and 20 in the second were available for a mean urodynamic follow-up of 3.5 years. In the urethropexy group 7(30%) patients had de novo detrusor instability and 1 (4%) had stress incontinence. In the reconstruction-only group 1(5%) patient had detrusor instability and none had stress incontinence.
Conclusions: Preoperative barrier testing is useful in identifying patients who do not require an antiincontinence procedure. Prophylactic Burch retropubic urethropexy increases the incidence of bladder instability.
A L Nelson, RM Sinow and David Oliak (Torrance, California)
Transrectal ultrasonographically guided drainage of gynecologic pelvic abscesses
Am J Obstet Gynecol 2000; 182: 1382-8
Objective : This study assessed the feasibility of ultrasonographically guided transrectal aspiration of gynecologic pelvic abscesses to treat patients for whom intravenous antibiotic therapies failed and whose abscesses were not optimally amenable to colpotomy drainage or transabdominal or transvaginal ultrasonographically guided aspiration.
Study Design: This was a retrospective review of the first 15 women with pelvic abscesses that resulted from salpingitis or complications of gynecologic surgery who underwent transrectal pelvic abscess drainage after failure of antibiotic therapy.
Results : Purulent material was aspirated from the abscesses in 14 of the 15 women. All 14 women with aspirated material were successfully treated with real-time ultrasonographically guided transrectal drainage; only 4 of the 14 had indwelling catheter placement.
Conclusion: Ultrasonographically guided transrectal drainage of gynecologic pelvic abscesses is a safe and effective treatment of pelvic abscesses for women who do not have an adequate response to antibiotic therapy.
Material and Methods:
If the transrectal route was found to be desirable, diagnostic transrectal ultrasonography was performed with the patient in a left lateral decubitus postion with either a 7-MHz side-fire, end-fire or 30° off-angle end-fire transducer.
Local anesthesia with local lidocaine gel or 1% lidocaine injected into the rectal wall was used to reduce pain from the needle. The end-fire or off-angle end-fire transducer with an attached needle guide was reintroduced into the rectum.
L R Hickok (Seattle, Washington)
Hysteroscopic treatment of the uterine septum: A clinician’s experience
Am J Obstet Gynecol 2000; 182: 1414-20
Objective: The author reviewed his experience with the diagnosis and hysteroscopic treatment of uterine septa.
Study Design: This article is a retrospective review of cases from 1992-1999. A septate uterus was diagnosed in a total of 40 patients, and all were treated by hysteroscopic resection.
Results: The rate of preoperative pregnancy loss was 77.4%, and the uncomplicated delivery rate was 6.5%. After hysteroscopic septum resection 21 patients reported a total of 22 pregnancies with an 18.2% miscarriage rate and a 77.3% uncomplicated delivery rate.
Conclusion: Hysteroscopic treatment of uterine septa is a safe, simple and effective procedure. It can be used for all types of uterine septa, it attains optimal obstetric outcomes, and it should be undertaken whenever a uterine septum is diagnosed.
Discussion: Dr. Lorna A Marshall – Like every other report on this topic, this one is limited by its design. It compares a group of women who are examined because of failed reproduction with these same women after treatment. We know that a certain number of women will have a successful pregnancy in the presence of a uterine septum. In fact, that number may increase with each subsequent pregnancy in the untreated patient. There is currently no published clinical trial on uterine septa that compares pregnancy rate and pregnancy outcome in a treated and an untreated group. The ability to perform such a clinical trial has been limited by the need to do a laproscopy to provide reassurance that the uterus is externally unified.
Electrocautery may cause thermal damage that may negatively affect endometrial development or result in a weakened myometrium and uterine rupture in a subsequent pregnancy. In addition, uterine perforation during cauterization may entail a risk of severe thermal damage to intra-abdominal structures.
Uterine rupture during a subsequent pregnancy has been reported after hysteroscopic metroplasty complicated by perforation with microscissors. It has also been reported after an uncomplicated procedure with the KTP laser used to excise the septum. No cases of uterine rupture after resectoscopic removal of a septum have been reported.
Surgery for a septate uterus should not be substituted for other treatments for infertility.
Dr. Robert Israel comments that it is unnecessary to resect the septum; incising the septum is quite straightforward.
At present there is no substitute for diagnostic laparoscopy with regard to ascertaining the type of uterine anomaly or the condition of other pelvic organs or in identifying uterine perforations promptly, should they occur.
Kimberly Kraus, James Fanning
Prospective trial of early feeding and bowel stimulation after radical hysterectomy
Am J Obstet Gynecol,May 2001, vol.182(5), p.996-8
Objective: In an attempt to decrease hospital stay the authors performed a prospective trail of aggressive bowel stimulation and early postoperative feeding after radical hysterectomy.
Study Design: In a prospective trial of 20 consecutive patients undergoing class 3 radical hysterectomy. Feeding of a clear liquid diet and bowel stimulation with oral 66% sodium phosphate solution (Fleet Phosphosoda) were instituted on postoperative day 1. Patients were discharged after passage of flatus or stool.
Results: Median time to discharge was 3.5 days. No patients had emesis, ileus, or bowel obstruction. The decrease in hospital stay with respect to those in our previous trial with traditional postoperative feeding and our original study on postoperative bowel stimulation was statistically significant.
Conclusion: Aggressive bowel stimulation with Fleet Phospho-Soda and early feeding after radical hysterectomy resulted in early return of bowel function and early discharge without significant intestinal complication.
M. I. Shamonki, W F Ziegler, et al (Burlington, Vermont)
Prediction of endometrial ablation success according to perioperative findings
Am J Obstet & Gynecol, 2000; 182: 1005-7
Objective : The aim of this study was to determine which factors in the perioperative period influence the success of endometrial ablation in alleviating menorrhagia.
Study Design: The authors performed a retrospective chart review of 120 women aged 27 to 49 years who underwent endometrial ablation after 2 months of preoperative treatment with danazol (Danocrine, 800mg/d orally) or leuprolide (Lupron 3.75mg in one intramuscular injection each month). Patients who required medical management or additional operations to control the vaginal bleeding during follow-up (median follow-up, 37 weeks) were considered to have ablation failures.
Results: Sixty-three percent of patients (76/120) had a successful procedure. The chance of success was greater if a cavity of normal appearance was found (odds ratio, 2.3; P=.04). The finding of an intramural fibroid before the procedure resulted in a reduced trend toward success (odds ratio, 0.4; P=.06). The use of danazol pretreatment improved the rate of success overall (odds ratio, 2.2; P=.05) and especially among women <40 years old (P =.01).
Conclusion: Perioperative findings may provide useful information in counseling patients regarding endometrial ablation. Success is greater among patients with a normal intrauterine cavity and after preoperative treatment with danazol.
Nadine M. Antonelli, Sandra J Diehl and Jeffrey W Wright
A randomized trial of intravaginal nonoxynol 9 versus oral metronidazole in the treatment of vaginal trichomoniasis.
Am J Obstet Gynecol, May 2000, 182(3), p.1008-10
Objective : This study was undertaken to investigate the efficacy of nonoxynol 9 suppositories in the treatment of vaginal trichomoniasis.
Study Design: In this prospective comparison trial 46 women with documented motile trichomonads found on a wet preparation were randomly assigned to one of two treatment arms: (1) a single oral dose of 2g metronidazole and (2) a single 150-mg nonoxynol 9 suppository placed intravaginally for 3 consecutive nights. Cure was determined by a repeated wet preparation examination. After its first year, the study was terminated because of the poor efficacy of the nonoxynol 9 suppositories.
Results: Results were available for 33 patients. Three of 17 patients treated with nonoxynol 9 had negative wet preparation results at retest (17.65 cure rate). All women with nonoxynol 9 failures who were evaluated after treatment with 2g metronidazole had negative wet preparation results.
Conclusion : Intravaginal nonoxynol 9 at the tested dose and by the tested method of delivery was not an effective cure for vaginal trichomoniasis.
Susan L Hendrix, V Schimp, et al (Detroit, Michigan)
The legendary superior strength of the Pfannenstiel incision: A myth?
Am J Obstet Gynecol. Vol.182, June 2000, p.1446-51
Objective : This study was undertaken to determine whether there is a difference in the frequency of fascial dehiscence between midline vertical lower abdominal and pfannenstiel incisions among women undergoing obstetric and gynecologic operations.
Study Design: A case-control study of 48 cases of fascial dehiscence complicating 17,995 major operations (8950 cesarean deliveries and 9405 gynecologic procedures) during a 6 year period at Wayne State University Hutzel Hospital, Detroit, was performed.
Results: Among the 48 patients who underwent repair of fascial dehiscence after a major obstetric or gynecologic operation, 27 were from the obstetric service and 21 were from the benign and cancer gynecologic services. Wound dehiscence occurred in 10 vertical incisions and 17 Pfannenstiel incisions among the obstetric patients and in 12 vertical and 9 Pfannenstiel incisions among the gynecologic patients. The risk for dehiscence incision (P=.39, 2-tailed). This finding was true for all patients (odds ration, 1.3; 95% confidence interval, 0.7-2.6), obstetric patients (odds ratio, 1.3; 95% confidence interval, 0.5-3.4), and gynecologic patients (odds ratio, 1.5;95% confidence interval, 0.5-4.0). Forty-seven of the 48 case patients had documented wound infections, compared with 1 of the 144 control subjects (P<.001, odds ratio, 37.8; 95% confidence interval, 14.8-96.8)
Conclusion: Wound infection was the most important risk factor for fascial dehiscence among women who underwent major obstetric and gynecologic operations. Our results do not support the long-held belief that Pfannenstiel incisions are stronger than lower abdominal vertical incisions and reduce the risk for fascial dehiscence.
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.
A M Weber, M D Walters and MR Piedmonte (cleveland, Ohio)
Sexual function and vaginal anatomy in women before and after surgery for pelvic organ prolapse and urinary incontinence.
Am J Obstet Gynecol, vol.182, June 2000, p.1610-5)
Objective: To describe sexual function in women before and after surgery for either prolapse or urinary incontinence, or both.
Study Design: Women completed questionnaires, and vaginal dimensions were measured before and at least 6 months after surgery for prolapse or incontinence. Comparisons were made with signed-rank tests for the McNemar test.
Results : Eighty-one (49%) of 165 women were sexually active before and after surgery; their mean age was 54.0 ± 9.9 years. Mean frequency of intercourse did not change. Dyspareunia was reported by 6(8%) women preoperatively and 15(19%) women after surgery; dyspareunia persisted postoperatively in 1 woman, developed in 14, and resolved in 5 (P=.04). Dyspareunia occurred in 14 (26%) of 53 women after posterior colporrhaphy (P=.01) and in 8 (38%) of 21 women who had Burch colposusupension and posterior colporrhaphy performed together (P=.02). Vaginal dimensions decreased slightly after surgery; however, this did no correlate with any change in sexual function. Preoperatively, 66 (82%) women were satisfied with their sexual relationships, compared with 71(89%) who were satisfied postoperatively.
Comment: This study is limited by its observational design, which precludes definite conclusions, about cause and effect of observed changes.
Conclusion: Sexual function and satisfaction improved or did not change in most women after surgery for either prolapse or urinary incontinence, or both. However, the combination of Burch colposusupension and posterior colporrhaphy was especially likely to result in dyspareunia.
S R Goldstein, New York
Drugs for the gynecologist to prescribe in the prevention of breast cancer: Current status and future trends.
Am J Obstet Gynecol, May 2000; 182 : 1121-6
In the United States there are more than 180,000 new cases of breast cancer diagnosed annually. It is the most common cancer in women. A lifetime risk of death from breast cancer is 3.6% or 1 in 28. Approximately, 50% of women in whom the disease develops have no identifiable risk factors other than being female and aging.
After 10 years of hormone replacement therapy, there was an increased risk of >30% for new onset breast cancer. Although breast cancer accounts for <4% of all deaths among women, 40% of those polled believed it to be the most common cause of death. Actually, almost 1 in 2 women will die of some form of cardiovascular disease compared with the previously stated incidence of 1 in 28 women who will die of a malignancy of the breast.
Tamoxifen is the most widely prescribed antineoplastic drug in the world, with approximately 10 million woman years of experience. It was approved by the Food and Drug Administration (FDA) in 1978. Although initially approved for the treatment of metastatic breast cancer in postmenopausal women, it is now indicated as the hormonal treatment of choice for both early and advanced breast cancer in women of all ages. It has consistently been shown to increase disease-free survival and overall survival in virtually all adjuvant studies.
Treatment for 5 years reduced the recurrence rate by 50% and the annual death rate by 28%.
Breast cancer prevention:
Tamoxifen reduced the risk of contralateral breast cancer by 47% after 5 years of adjuvant treatment. Thus the preclinical in vitro and animal models coupled with clinical data, together with tamoxifen’s favourable effects on skeleton remodeling and lipid levels, led to the development of a series of chemopreventive trials with tamoxifen in both the United State and Europe.
The National Surgical Adjuvant Breast and Bowel Project (NSABP) launched its breast cancer prevention trial (BCPT) in 1992. Tamoxifen reduced the incidence of invasive breast cancer by 49% (P<.00001). Tamoxifen reduced the incidence of noninvasive breast cancer by 50% (P=.002)
Rayson Marsden trial:
This was one of two European tamoxifen breast cancer prevention trials that did not confirm the NSABP results.
Italian Tamoxifen Prevention Study:
The Italian Tamoxifen Prevention Study also did not confirm the NSABP findings.
Effects of tamoxifen on healthy women:
There was a statistically significant increase in the number of women with development of cataracts who then underwent cataract surgery.
Although the overall risk of endometrial cancer associated with tamoxifen therapy in healthy women, as evidenced by the results of the BCPT, showed a relative risk of 2.53, when further analyzed by age, the relative risk in women >50 years old was 4.01.
There was no statistically significant increase in either pulmonary embolism or deep vein thrombosis in women <50 years old.
An interim analysis of a 2-year Canadian study presented at the North American Menopause Society in 1997 and submitted to the FDA advisory panel in November 1997 showed that there were no endometrial proliferation, no hyperplasia, and no discontinuations because of vaginal bleeding with raloxifene. When raloxifene was compared to placebo, there were no differences in endometrial thickness, endoluminal masses, proliferation or hyperplasia. It was FDA approved for prevention of osteoporosis in December 1997. Its indication was extended to treatment of osteoporosis in October 1999.
Breast cancer is a very prevalent disease. It is perceived by women as their most feared disease. Selective estrogen receptor modulators (SERMs) are potent estrogen antagonists in breast tissue. Tamoxifen has a long history of benefit in women with breast cancer. Tamoxifen significantly reduces both invasive and noninvasive breast cancer in healthy women at risk. However, it increases the risk of endometrial carcinoma, hyperplasia, and polyps in women >50 years old. Tamoxifen was approved for breast cancer prevention in women at high risk in October 1998. Raloxifene, a second-generation SERM, is approved for prevention and treatment of postmenopausal osteoporosis. Raloxifene is a pure estrogen antagonist in the uterus in postmenopausal women. In animal and human studies raloxifene seems to have effects on breast tissue and breast cancer incidence that are similar to those of tamoxifen. Controlled, randomized trials show a significant reduction in invasive breast cancer with raloxifene when measured as a secondary end point. The STAR (Study of Tamoxifen and Raloxifene) trial will be a 5-year blinded study comparing the two agents in >22,000 women at 300 sites in the United States and Canada.
Currently, in my opinion tamoxifen is definitely indicated for women with ductal carcinoma in situ who do not choose surgical treatment, women with lobular carcinoma in situ or atypical hyperplasia, premenopausal women at sufficient risk, and postmenopausal women at sufficient risk who have undergone a hysterectomy.
Women should understand that tamoxifen reduces the incidence of breast cancer, but may not eliminate risk. The recommendation is for 5 years of therapy at a dosage of 20mg/d.
The American College of Obstetricians and Gynecologists takes the position that patients on a regimen of tamoxifen should have an annual pelvic examination with Papnicolaou smear. They further state, “Any bleeding should be evaluated thoroughly.
A Imai, A Takagi and T Tamaya (Gifu, Japan)
Gonadotropin-releasing hormone analog repairs reduced endometrial cell apoptosis in endometrioisis in vivo.
Am J Obstet Gynecol, May 2000; 182: 1142-6.
Objective: Impaired sensitivity of endometrial tissue to spontaneous apoptosis in women with endometriosis contributes to the abnormal implantation and growth of endometrium at ectopic sites. Our purpose was to examine the effect of gonadotropin-releasing hormone analog, widely used in the treatment of endometriosis, on the reduced rate of endometrial apoptosis in endometriosis.
Study Design: Paired ectopic and eutopic endometrial tissue specimens were obtained from 13 patients with endometriosis, and control samples were taken from 8 patients with uterine myoma. Apoptotic cell death was assessed biochemically and morphologically with an enzyme-linked immunoassay and Hoechst No. 33342 staining of deoxyribonucleic acid fragment, respectively.
Results : Spontaneous apoptosis was significantly lower in ectopic and eutopic endometrial tissue from patients with endometriosis (0.22 ± 0.082 in absorbance) than in endometrial tissue from control subjects (0.52 ± 0.483)(P<0.001). Incubation with a gonadotropin-releasing hormone analog (1 mmol/L) increased the apoptotic rate of endometrial cells from patients with endometriosis to 0.56 ± 0.501 (P.001). The effect of this gonadotropin-releasing hormone revealed a dose dependency; a half-maximal effect occurred with 10nmol/L; however, the control endometrium was not affected.
Conclusion: Exposure to gonadotropin-releasing hormone results in changes of the sensitivity of endometriotic endometrium to spontaneous apoptosis; these changes in sensitivity may, in turn, release endometrial cells from resistance to apoptosis and result in reduced survival and growth. This phenomenon could, at least in part, account for the therapeutic action of gonadotropin releasing hormone analog on endometriosis.
Abbey B. Berenson, Mariam R, Chacko, et al [ From the Department of Obstetrics and Gynecology, University of Texas Medical Branch, the Department of Pediatrics, Baylor College of Medicine, and the Department of Psychology, Mayo Clinic and Medical School]
A Case-control Study of Anatomic Changes Resulting from Sexual Abuse
Am J. Obstet Gynecol April 2000, Volume 182, Number 4, Pgs. 820-834
Objective – Our goal was to identify vulvar and hymenal characteristics associated with sexual abuse among female children between the ages of 3 and 8 years.
Study Design – Using a case-control study design, we examined and photographed the external genitalia of 192 prepubertal children with a history of penetration and 200 children who denied prior abuse. Bivariate analyses were conducted by x2, the Fisher exact test., and the Student t test to assess differences in vulvar and hymenal features between groups.
Results – Vaginal discharge was observed more frequently in abused children [p=.01]. No difference was noted in the percentage of abused versus nonabused children with labial agglutination, increased vascularity, linea vestibularis, friability, a perineal depression, or a hymenal bump, tag, longitudinal intravaginal ridge, external ridge, band, or superficial notch. Furthermore, the mean number of each of these features per child did not differ between groups. A hymenal transection, perforation, or deep notch was observed in 4 children, all of whom were abused.
Conclusion – The genital examination of the abused child rarely differs from that of the nonabused child. Thus legal experts should focus on the child’s history as the primary evidence of abuse.
Marya G, Zlatnik, John A, Copland, Kirk Ives, and Melvyn S. Soloff, [ From the Division of Maternal-Fetal Medicine, The Department of Obstetrics and Gynecology, The Department of General Surgery, and the Sealy Center for Molecular Science, University of Texas Medical Branch ]
Functional Oxytocin Receptors in a Human Endometrial Cell Line
Am J. Obstet Gynecol April 2000, Volume 182, Number 4, Pgs. 850-855
Objective – Our goal was to demonstrate expression and functionality of oxytocin receptors in a human endometrial cell line. This cell line could then be used for further investigation of the role of oxytocin in reproductive function at the cellular level.
Study Design – Oxytocin receptor messenger ribonucleic acid expression was determined by reverse transcriptase -polymerase chain reaction deoxyribonucleic acid amplification with ribonucleic acid from confluent ishikawa cells. Ligand binding to whole cells was evaluated by nonlinear regression analysis with an iodinated oxytocin antagonist. The coupling of the oxytocin receptor to signaling pathways was evaluated by measuring oxytocin-stimulated increases in intracellular calcium concentration, phosphorylation of ERK2 [extracellular -regulated protein kinase 2] mitogen-activated protein Kinase, and prostaglandin E2 release.
Results – Polyacrylamide gel electrophoresis of the reverse transcriptase – polymerase chain reaction products demonstrated the presence of oxytocin receptor messenger ribonucleic acid in Ishikwawa cells. Ligand binding analysis of these cells demonstrated a single class of noninteracting sites, with a Bmax [maximal number of binding sites] of 77.7 fmol/mg deoxyribonucleic acid and an apparent dissociation constant of 8.3 x 10-11 mol/L. Stimulation with 100-nmol/L oxytocin antagonist. Treatment of cells with oxytocin for 10 minutes resulted in a marked increase in the phosphorylation of ERK2, as determined by Western blot analysis, and a 5-fold increase in prostaglandin E2 release.
Conclusion – This study is the first to demonstrate functional oxytocin receptors in an established human endometrial cell line. This cell line will be useful in elucidating the mechanisms of action of oxytocin in the reproductive tract at the molecular level.
Louis Weinstein and Brian Ullery (Toledo, Ohio)
Identification of at-risk women for osteoporosis screening
Am J Obstet Gynecol, Sept.2000, 183:547-9
A total of 1610 women completed a questionnaire that evaluated their risk factors for osteoporosis. A dual energy x-ray absorptiometry scan followed. Analysis of data was performed by the 2-tailed c2 test and multivariate logistic regression. Age was directly related to osteoporosis, whereas weight was inversely related. Also, the lack of use of any estrogen was significantly related to the presence of osteoporosis.
E C Samuelsson, FT Arne Victor and K F Svardsudd, (Uppsala and Ostersund, Sweden)
Five-year incidence and remission rates of female urinary incontinence in a Swedish population less than 65 years old.
Am J Obstet Gynecol, Sept.2000; 183: 568-74
Objective: The authors sought to determine the incidence and remission rates of urinary incontinence in a population-based sample of women.
Study Design: A total of 382 (87.6%) of 436 eligible women aged 20 to 59 years answered a questionnaire and underwent a gynecologic examination at baseline and were followed up approximately 5 years later.
Results: Urinary incontinence was present in 23.6% of women at baseline and in 27.5% at follow-up. The mean annual incidence rate of incontinence was 2.9%, and the mean annual incidence rate of incontinence weekly or more often was 0.5%. Women that were receiving estrogen at baseline were more likely than other women to have incontinence during follow-up. The mean annual remission rate among the 90 women who were incontinent at baseline was 5.9%. The annual net increase of incontinence in the study population was 0.82%.
Conclusion: Female urinary incontinence seems to be a dynamic condition with a relatively high rate of spontaneous remission, a fact of which physicians should be aware when assessing and planning prevention and treatment strategies.
Vaccine against cervical cancer virus passes phase I trials
BMJ, Vol.322, March 3, 2001, p.510
Cervical cancer affects over 400,000 women a year worldwide and results in the death of 200,000 of them. It is caused by infections with oncogenic strains of the human papillomavirus. This virus is sexually transmitted.
A vaccine against HPV16, the most prevalent strain of the human papillomavirus found in cervical cancers, has passed phase I trials.
Henderson-Smart, Leila Duley, David Henderson, Smart et al
Antiplatelet drugs for prevention of pre-eclampsia and its consequences: systematic review.
BMJ, Vol.322, Feb.10, 2001. P.329
The cause of pre-eclampsia remains unknown, but it is associated with deficient intravascular production of prostacyclin, a vasodilator and excessive production of thromboxane, a platelet derived vascoconstrictor and stimulant of platelet aggregation. These observations led to the hypothesis that antiplatelet drugs might prevent or delay development of pre-eclampsia. This systematic review was done to assess the effects of antiplatelet drugs for prevention of pre-eclampsia and its complications.
The review included randomised trials involving women at risk of pre-eclampsia and its complications allocated to antiplatelet drugs, versus placebo or no antiplatet drug.
The conclusion was that antiplatelet drugs, largely low dose aspirin, have small to moderate benefits when used for prevention of pre-eclampsia.
Sheena McCormack, Richard Hayes et al
Microbicides in HIV prevention
BMJ, Vol.322, Feb. 17, 2001, p.410-413
Although the use of condoms has slowly increased in countries most severely affected by the HIV epidemic, many vulnerable women are unable to ensure they are used. An effective and affordable vaginal microbicide, whose use could be controlled by women, would represent an important addition to the armamentarium against HIV infection. This article examines current progress in microbicide development and discusses their future role in HIV control.
Potential microbicides currently in human trials:
Product groups and active agents Anti-STI Spermicidal Human trials
Broad spectrum activity
STI = sexually transmitted infection. NA = not assessed. * known to be cytotoxic to HIV
P Hartge, R.Hayes, D.Reding et al (Bethesda, Maryland, Salt Lake City, Utah and Marshfield, Wisconsin)
Complex ovarian cysts in postmenopausal women are not associated with ovarian cancer risk factors.
Preliminary data from the Prostate, Lung, Colon and Ovarian Cancer Screening Trial.
Am J Obstet Gynecol, Nov.2000; 183: 1232-7
Objective : Whether asymptomatic ovarian abnormalities detected on ultrasonography in postmenopausal women are precursors to ovarian cancer.
Study Design : The transvaginal ultrasonographic findings from the initial examination of 20,000 postmenopausal women enrolled to date in an ongoing randomized trial of cancer screening with data on the established risk factors for ovarian cancer obtained from self-administered questionnaires. We distinguished cysts with the suggestive characteristic(s) of a septum, a solid component, or an irregular or thick wall (complex cysts) from simple sonolucent cysts with none of those features.
Conclusions : Although a very small proportion of the clinically silent ovarian abnormalities found on ultrasonography are determined to be ovarian cancers, the remaining complex cysts and other clinically suspicious abnormalities do not appear to be the immediate precursors of ovarian cancer. The eventual identification of such precursors will yield opportunities for earlier diagnosis, screening of high-risk groups, and better understanding of the cause of this often lethal malignancy.
Comment : Complex cysts were less prevalent in women of high parity, but age, oral contraceptive use, and family cancer history were unrelated to prevalence. Indeed, although one or more types of abnormality were weakly related to one or more of the established risk factors, no group of abnormalities resembled ovarian cancer in its epidemiologic profile.
Longitudinal data from successive screening may reveal whether the presence of new cysts or a change in existing cysts constitutes a cancer precursor. In addition, as the genetic markers of premalignancy are elucidated, it may be possible to locate precursors by combining the risk profile approach taken here with other data comparing morphologic features seen on ultransonography to genetic markers in tissue taken from the visualized ovaries. In addition, observational studies of ovaries from women at high risk and of very early ovarian cancers may disclose precursors.
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.