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Objectives: To determine if nutritional status effects response to immunotherapy in women with gynecologic malignancies., Methods: A retrospective chart review was conducted on gynecologic cancer patients who received immunotherapy at a single institution between 2015 and 2022. Immunotherapy included checkpoint inhibitors and tumor vaccines. The prognostic nutritional index (PNI) was calculated from serum albumin levels and total lymphocyte count. PNI values were determined at the beginning of treatment for each patient and assessed for their association with immunotherapy response. Disease control response (DCR) as an outcome of immunotherapy was defined as complete response, partial response, or stable disease., Results: One hundred and ninety-eight patients received immunotherapy (IT) between 2015 and 2022. The gynecological cancers treated were uterine (38%), cervix (32%), ovarian (25%), and vulvar or vaginal (4%) cancers. The mean PNI for responders was higher than the non-responder group (p < 0.05). The AUC value for PNI as a predictor of response was 49. A PNI value of 49 was 43% sensitive and 85% specific for predicting a DCR. In Cox proportional hazards analysis, after adjusting for ECOG score and the number of prior chemotherapy lines, severe malnutrition was associated with progression-free survival (PFS) (HR = 1.85, p = 0.08) and overall survival (OS) (HR = 3.82, p < 0.001). Patients with PNI < 49 were at a higher risk of IT failure (HR = 2.24, p = 0.0001) and subsequent death (HR = 2.84, p = 9 × 10 -5 )., Conclusions: PNI can be a prognostic marker to predict response rates of patients with gynecologic cancers treated with immunotherapy. Additional studies needed to understand the mechanistic role of malnutrition in immunotherapy response., Competing Interests: Declaration of competing interest The authors declare no potential conflicts of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Disorders of sexual development (DSDs) represent a spectrum of conditions characterized by atypical gonadal and/or genital development. The incidence is 1 in 5,000 live births. Patients with DSD may be at increased risk for developing gonadal and reproductive tract tumors. This report summarizes the current knowledge on the risks of gonadal tumors in patients with DSD. Specifically, we focus on ovotesticular DSD (OT-DSD), which accounts for 5% of DSD cases and is defined by the presence of both ovarian and testicular tissues in the same individual. We present a rare case of a phenotypically male XY patient with OT-DSD who was diagnosed with aggressive peritoneal cancer at the age of 71., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors. Published by Elsevier Inc.)

Background: A pure ovarian dysgerminoma in a postmenopausal female is a rare phenomenon., Case: A 65-year-old female presented with a large pelvic mass. Following surgical debulking, the patient was diagnosed with FIGO Stage IIB ovarian dysgerminoma. She was treated with three cycles of etoposide and cisplatin and has been disease-free for 12 months., Conclusion: Dysgerminomas in postmenopausal females are uncommon. Gynecologic oncologists should be familiar with the pathological diagnosis and treatment recommendations to achieve optimal outcomes., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Authors.)

Background: Use of immune checkpoint inhibitors in treatment of gynecologic malignancies is increasing. Rare, but potentially fatal, immune-related neurologic adverse events may occur as a result of treatment., Case: A 72 year old female with recurrent metastatic uterine adenocarcinoma received pembrolizumab and lenvatinib combination therapy. Following her second dose of pembrolizumab, the patient developed multiple neurologic symptoms. She was ultimately diagnosed with Guillain-Barre Syndrome based on neurologic evaluation with imaging, serum studies, and cerebrospinal fluid analysis. The patient was successfully treated with high-dose intravenous corticosteroids and intravenous immunoglobulin., Conclusion: Neurologic complications related to immune checkpoint inhibitor therapy are rare. It is imperative for gynecologic oncologists to be familiar with potentially fatal hazards of therapy to allow for rapid diagnosis and treatment., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2021 The Authors.)

Study Objective: To compare outcomes of advanced ovarian cancer patients who had minimally invasive surgery (MIS) with outcomes of advanced ovarian cancer patients who had laparotomy for interval cytoreduction after neoadjuvant chemotherapy (NACT)., Design: Retrospective cohort study (Canadian Task Force classification II-2)., Setting: One large teaching hospital with a tertiary referral function for gynecologic oncology and MIS., Patients: All consecutive patients with stages III to IV epithelial ovarian, tubal, or peritoneal cancer who underwent MIS or laparotomy for interval cytoreduction after at least 1 NACT cycle from 2006 to 2017 at 1 institution., Interventions: Patients underwent either MIS or laparotomy for interval cytoreduction after at least 1 cycle of NACT., Measurements and Main Results: Medical records were reviewed and data abstracted and analyzed. Survival was estimated by the Kaplan-Meier method, and outcomes were compared with Fisher's exact test, Student's t test, Wilcoxon rank sum test, and the log-rank test. In total, 157 assessable patients underwent interval cytoreductive surgery through MIS (n = 53) or laparotomy (n = 104). MIS was completed without conversion in 44 of 53 patients (83%), of whom 20 required a hand port and/or mini-laparotomy. R-zero and optimal resections were achieved in 60.4% and 96.3% of MIS patients respectively, compared with 42.3% and 82.7% of laparotomy patients (p = .02). MIS patients had lower estimated blood loss (EBL; 156 vs 278 mL, p <.001), fewer intraoperative transfusions (2% vs 17%, p = .006), and shorter hospital stay (3.0 vs 5.7 days, p < .001). Operative time was longer (171 vs 150 minutes, p = .007), but complications, intensive care unit stay, readmission, median progression-free survival (27 vs 29 months, p = .45), and median overall survival (37 vs 35 months, p = .74) were similar., Conclusion: MIS is feasible and effective for interval cytoreduction after NACT in advanced ovarian cancer patients. MIS is associated with less EBL, lower transfusion rate, and shorter length of hospital stay with no difference in patient outcomes., (Copyright © 2018 AAGL. Published by Elsevier Inc. All rights reserved.)

Objectives: To compare the outcomes after intraperitoneal (IP) chemotherapy in patients with and without pathogenic BRCA mutations., Methods: Patients with high grade ovarian cancer who were treated with adjuvant IP chemotherapy in the initial setting between 2005 and 2016 were identified. Outcomes were compared between patients with pathogenic mutations in BRCA (BRCA+) and those who tested negative or were unknown (BRCA-)., Results: A total of 100 eligible patients were identified. The median follow-up was 47.0 months (range, 6.6-144.1 months). Of these 100 patients, 77 patients underwent BRCA testing; 25 patients (32%) were BRCA+ (23 germline, 2 somatic). No differences were noted between groups with respect to number of IP cycles, stage, or residual disease after surgery. The median progression-free survival (PFS) was longer in the BRCA+ group; median PFS was not reached in the BRCA+ group compared to 17.3 months in the BRCA- group (HR = 0.38; 95% CI 0.20-0.73, P = 0.003). Median overall survival (OS) was longer in the BRCA+ group at 110.4 months versus 67.1 months (HR = 0.28, 95% CI 0.11-0.73, P = 0.009)., Conclusions: Pathogenic BRCA mutations are more common than expected in optimally resected ovarian cancer patients selected for IP therapy. IP therapy was associated with a dramatic improvement in PFS and OS in BRCA+ patients compared with BRCA- patients. This improvement is greater than has been reported for BRCA+ patients with IV chemotherapy. The magnitude of this benefit suggests that patients with pathogenic mutations in BRCA may benefit from IP therapy., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Objectives: The aim of this study was to demonstrate the utility of a comprehensive program involving management-based evidence, telemedicine, and patient navigation to provide genetic counseling services for patients with ovarian and breast cancer across a geographically large health care system., Methods: We identified all patients with newly diagnosed ovarian and breast cancer in our health care system from January 2013 to December 2015 through the cancer registry. Referral characteristics and testing outcomes were recorded for each year and compared using the χ or Fisher exact test., Results: Because the implementation of this program, the number of new ovarian cancer cases remained constant (109-112 cases/year) but patients referred for genetic counseling increased annually from 37% to 43% to 96% (P < 0.05). The percentage of ovarian cancer patients who underwent genetic testing increased annually from 24% to 27% to 53% (P < 0.05). The number of new breast cancer patients was constant (1543-1638 cases/year). The percentage of patients with triple negative breast cancer referred for genetic counseling rose from 69% in 2013 to 91% in 2015; the percentage of patients who underwent testing increased annually from 59% to 86% (P < 0.05). Of women with breast cancer diagnosed at less than 45 years of age, 78% to 85% were referred for genetic counseling across this period; the percentage of patients who underwent testing increased annually from 66% to 82% (P < 0.05). Patient navigation was initiated and was available to all patients in the system during this period. Telemedicine consults were performed in 118 breast/ovarian patients (6%) during this period., Conclusions: A comprehensive program may improve access to effective genetic counseling services in patients with ovarian and breast cancer despite geographic barriers.

Background: Brivanib is an oral, tyrosine kinase inhibitor against vascular endothelial growth factor (VEGF) and fibroblast growth factor receptor (FGFR). We studied its efficacy and tolerability in persistent or recurrent cervical cancer patients., Methods: Eligible patients had at least one prior cytotoxic regimen for recurrence and with measurable disease. Brivanib 800mg was administered orally every day (1cycle=28days) until disease progression or prohibitive toxicity. Primary endpoints were progression-free survival (PFS) >6months and objective tumor response., Results: Of 28 eligible and evaluable women enrolled, 11 (39%) had primary surgery and 25 (89%) had prior radiation. Eighteen (64%) received one prior cytotoxic treatment and 10 (36%) had 2 prior regimens. Twelve (43%) had >2cycles of brivanib with 4 (14%) receiving >10cycles (range: 1-20). Seven (25%) patients had PFS >6months (90% CI: 7.3%-33.9%). Two (7%) (90% CI: 1.3%-20.8%) patients had partial tumor response with duration of 8 and 22months and 12 (43%) had stable disease. The median PFS was 3.2months (90% CI: 2.1-4.4). The median overall survival was 7.9months (90% CI: 6.1-11.7). More common grade 3 adverse events were hypertension, anemia, hyponatremia, hyperglycemia, elevated liver enzymes, nausea, headache, and colon hemorrhage. Grade 4 adverse events included sepsis and hypertension., Conclusions: Based on early results of this phase II trial, brivanib was well tolerated and demonstrated sufficient activity after first stage but trial was stopped due to lack of drug availability., (Copyright © 2017. Published by Elsevier Inc.)

Purpose: A simple measure to predict chemotherapy tolerance in elderly patients would be useful. We prospectively tested the association of baseline Instrumental Activities of Daily Living (IADL) score with ability to complete 4 cycles of first line chemotherapy without dose reductions or >7days delay in elderly ovarian cancer patients., Patients and Methods: Patients' age ≥70 along with their physicians chose between two regimens: CP (Carboplatin AUC 5, Paclitaxel 135mg/m 2 ) or C (Carboplatin AUC 5), both given every 3weeks either after primary surgery or as neoadjuvant chemotherapy (NACT) with IADL and quality of life assessments performed at baseline, pre-cycle 3, and post-cycle 4., Results: Two-hundred-twelve women were enrolled, 152 selecting CP and 60 selecting C. Those who selected CP had higher baseline IADL scores (p<0.001). After adjusting for age and PS, baseline IADL was independently associated with the choice of regimen (p=0.035). The baseline IADL score was not found to be associated with completion of 4 cycles of chemotherapy without dose reduction or delays (p=0.21), but was associated with completion of 4 cycles of chemotherapy regardless of dose reduction and delay (p=0.008) and toxicity, with the odds ratio (OR) of grade 3+ toxicity decreasing 17% (OR: 0.83; 95%CI: 0.72-0.96; p=0.013) for each additional activity in which the patient was independent. After adjustment for chemotherapy regimen, IADL was also associated with overall survival (p=0.019) for patients receiving CP., Conclusion: Patients with a higher baseline IADL score (more independent) were more likely to complete 4 cycles of chemotherapy and less likely to experience grade 3 or higher toxicity., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: While performance feedback and assessment are hallmarks of surgical training, they abruptly cease after training is completed. In their absence, performance may stagnate and poor habits persist. Our aim was to develop a coaching mechanism for practicing surgeons with feedback provision based on objective performance assessment., Methods: Technical and nontechnical intraoperative video recordings from laparoscopic or robotic cholecystectomies, colectomies, and hysterectomies were assessed by a blinded surgeon and a human factors expert, respectively. Aspects of performance in need of improvement were noted, and a coaching session was developed for feedback provision to participating surgeons. This 4-hour coaching session consisted of a didactic lecture with video review and hands-on practice using procedural and mannequin-based simulation., Results: Thirty-two practicing surgeons (18 general; 14 gynecologists) from 6 different hospitals were assessed, and 9 of them participated in coaching. Technical aspects identified for performance improvement included suboptimal trocar placement, inadequate critical view achievement during laparoscopic cholecystectomies, poor visualization of the operating field, bimanual dexterity, and dissection techniques, while nontechnical aspects included inappropriate handling of distractions and interruptions, poor ergonomic positioning and situational awareness, and inadequate mitigation of delays. Most surgeons appropriately accomplished some of the objectives of the distraction scenario, but none was able to achieve expert levels on Fundamentals of Laparoscopy tasks. Participants perceived the coaching sessions as highly valuable., Conclusion: Our study identified several technical and nontechnical skill sets of practicing surgeons in need of improvement and provided support for the implementation of coaching programs for surgeons on an ongoing basis., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Objective: To identify potential cost savings in gynecologic oncology care without sacrificing quality., Methods: Members of the Clinical Practice Committee of the Society of Gynecologic Oncology were asked to review current practice patterns in gynecologic oncology and assess the potential for cost savings founded on evidence-based medicine and current guidelines., Results: Five clinical practices were identified including the following: vaginal cytology for endometrial cancer survivors; colposcopy for low grade cytologic abnormalities for cervical cancer survivors; routine imaging studies for gynecologic cancer survivors; screening for ovarian cancer with serum biomarkers and ultrasound; and improving palliative care for gynecologic cancer patients. Review of the published literature and guidelines were performed to make evidence-based recommendations for cost effective quality gynecologic oncology care., Recommendations: • Do not perform Pap tests of the vaginal cuff in patients with a history of endometrial cancer. • Do not perform colposcopy for low grade Pap tests in women with a history of cervical cancer. • Avoid routine imaging for cancer surveillance in asymptomatic women with gynecologic cancer, specifically ovarian, endometrial, cervical, vulvar and vaginal cancer. • Do not screen women at low risk for ovarian cancer with ultrasound or CA-125 or other biomarkers. • Do not delay basic level palliative care for women with advanced or relapsed gynecologic cancer, do refer to a palliative care specialist when needed, and avoid unnecessary treatments at life's end., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: The aim of this randomized clinical trial was to evaluate the efficacy and safety of combination (cDC) and sequential (sDC) weekly docetaxel and carboplatin in women with recurrent platinum-sensitive epithelial ovarian cancer (EOC)., Methods: Participants were randomized to either weekly docetaxel 30 mg/m(2) on days 1 and 8 and carboplatin area under the curve (AUC) = 6 on day 1, every 3 weeks or docetaxel 30 mg/m(2) on days 1 and 8, every 3 weeks for 6 cycles followed by carboplatin AUC = 6 on day 1, every 3 weeks for 6 cycles or until disease progression. The primary endpoint was measurable progression-free survival (PFS)., Results: Between January 2004 and March 2007, 150 participants were enrolled. The response rate was 55.4% and 43.2% for those treated with cDC and sDC, respectively. The median PFS was 13.7 months (95% confidence interval [CI], 9.9-16.8) for cDC and 8.4 months (95% CI, 7.1-11.0) for sDC. On the basis of an exploratory analysis, patients treated with sDC were at a 62% increased risk of disease progression compared to those treated with cDC (hazard ratio = 1.62; 95% CI, 1.08-2.45; P = .02). The median overall survival time was similar in both groups (33.2 and 30.1 months, P = .2). The incidence of grade 2 or 3 neurotoxicity and grade 3 or 4 neutropenia was higher with cDC than with sDC (11.7% vs 8.5%; 36.8% vs 11.3%). The sDC group demonstrated significant improvements in the Functional Assessment for Cancer Therapy-Ovarian, Quality of Life Trial Outcome Index scores compared with the combination cohort (P = .013)., Conclusions: Both cDC and sDC regimens have activity in recurrent platinum-sensitive EOC with acceptable toxicity profiles. The cDC regimen may provide a PFS advantage over sDC., (Copyright © 2011 American Cancer Society.)

Background: In a randomized controlled trial (RCT) of patients with recurrent, platinum-sensitive ovarian cancer, the combination weekly docetaxel and carboplatin was associated a with progression-free survival (PFS) of 13.7 months compared with 8.4 months for sequential, single-agent docetaxel followed by carboplatin. The objective of the current study was to construct a cost-utility model to compare these 2 regimens with the incorporation of prospectively collected quality-of-life (QoL) data., Methods: An RCT of concurrent docetaxel and carboplatin (cDC) versus docetaxel followed by carboplatin (sequential docetaxel and carboplatin [sDC]) was the basis for a Markov decision model, and the primary effectiveness outcome was PFS. Costs were estimated using US dollars based on Medicare reimbursements for chemotherapy regimens, bone marrow support, and management of adverse events. QoL data obtained using the Functional Assessment of Cancer Therapy-General questionnaire were converted to utilities. Costs and incremental cost-effectiveness ratios (ICERs) were reported in US dollars per quality-adjusted life year (QALY). Extensive 1-way sensitivity analyses and a Monte Carlo probabilistic sensitivity analysis were performed., Results: The least expensive strategy was sDC, which cost an average of $20,381, compared with cDC, which cost an average of $25,122. cDC had an ICER of $25,239 per QALY compared with sDC. cDC remained cost-effective, with an ICER <$50,000 per QALY, over a range of costs and estimates. In Monte Carlo sensitivity analysis using a $50,000 per QALY willingness-to-pay threshold, cDC was either dominant or cost-effective with an ICER <$50,000 per QALY in 83% of simulations., Conclusions: Combined weekly cDC appeared to be cost-effective compared with sDC as treatment strategy for patients with platinum-sensitive ovarian cancer, even when accounting for slightly lower QoL during treatment., (Copyright © 2011 American Cancer Society.)

Objectives: A phase II clinical trial compared docetaxel in combination with carboplatin to sequential single agent docetaxel followed by carboplatin for treatment of recurrent platinum-sensitive ovarian, peritoneal, or tubal cancer. This manuscript reports prospectively collected health-related quality of life (HRQL)., Methods: Participants were randomized to either weekly docetaxel 30 mg/m(2)/days 1 and 8 and carboplatin AUC 6/day 1 every 3 weeks (cDC) or docetaxel 30 mg/m(2)/days 1 and 8, repeated every 3 weeks for 6 cycles followed by carboplatin AUC 6/day 1 every 3 weeks for 6 cycles or until disease progression (sDC). The primary HRQL endpoint was the trial outcome index (TOI) score of the Functional Assessment of Cancer Therapy-Ovarian (FACT-O) instrument, and was assessed as an intent-to-treat analysis. The secondary HRQL endpoints included the FACT-O total score, the FACT-General, and several domain scores of the FACT-O instrument (physical well-being (PWB), social/family well-being (SWB), emotional well-being (EWB), functional well-being (FWB), and the ovarian cancer specific (OCS) module). The FACT-O was administered at randomization, prior to each of 6 cycles of treatment, and at study endpoint., Results: One hundred forty-eight participants were randomized to each group. Sequential docetaxel followed by carboplatin (sDC) was associated with significant improvements in the FACT-O TOI (p=0.013), FACT-O total score (p=0.033), and OCS (p=0.029) compared to the combination docetaxel and carboplatin group (cDC)., Conclusions: Sequential single agent docetaxel followed by carboplatin is associated with improved HRQL when compared to cDC. The improved progression-free survival observed with cDC should be weighed against lower quality of life during treatment., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Objective: To determine the presenting symptoms, gynecologic manifestations, and optimal intraoperative management of women with primary appendiceal cancer., Methods: A multi-institutional investigation was performed to identify female patients with primary appendiceal cancer who were treated from 1990 to present., Results: Forty-eight women with primary appendiceal cancer were identified from the tumor registries of participating institutions. The most common symptoms were abdominal pain (40%) and bloating (23%), but only 8% experienced rectal bleeding. Serum CEA was elevated (>2.5 U/ml) in 67% of patients, and serum Ca-125 was elevated (>35 U/ml) in 50% of patients. Thirty-one patients (65%) presented with a right adnexal or right lower quadrant mass and were operated on initially by a gynecologic oncologist. Ovarian involvement by metastatic appendiceal cancer was documented in 18 patients (38%). All of these patients underwent total abdominal hysterectomy, bilateral salpingo-oophorectomy, and staging, but only 8 had a right hemicolectomy at the time of initial surgery. Forty-one patients (85%) presented with advanced stage appendiceal cancer (Stage III or IV) and 19 patients (46%) received postoperative chemotherapy, most commonly with a combination of 5-FU/Leukovorin. Following surgery, 22 patients (46%) experienced disease progression or recurrence, and 14 have died of disease. The most common sites of recurrence were abdominal or pelvic peritoneum (18), colon (2), and ovary (2). Patient survival was 70% at 2 years, and 60% at 5 years., Conclusion: Women with primary appendiceal cancer frequently present with ovarian metastases, and initial surgical intervention is often performed by a gynecologic oncologist. All patients with mucinous epithelial ovarian cancer should undergo appendectomy at the time of surgical staging. The appendix should be examined intraoperatively, and if appendiceal carcinoma is identified, a right hemicolectomy and appropriate surgical staging should be considered.

Ovarian cancer is the fourth leading cause of gynecological cancer death among women in the United States. Early detection is a critical prerequisite to initiating effective cancer therapy. Gene microarray technology and proteomics have provided much of the biomarkers with potential use for diagnosis. However, more research is needed to fully understand disease onset and progression. To this end, we have performed microarray analysis with the goal of identifying molecular interaction networks defining tumor growth. Microarray analysis was performed on a limited set of ovarian tissues with various pathological diagnoses using Human Genome Focus Array (HGFA) for the detection of approximately 8500 human transcripts. Hierarchical clustering identified groups of ovarian tissues reflective of low malignant potential/early cancer onset and possible pre-cancerous stages involving small molecule, cytokine and/or hormone-dependent feed-back responses specific to the pelvic reproductive system and a priori initiated tumor suppression mechanisms. ANOVA followed by post hoc Scheffe confirmed our hypotheses. Moreover, we established a protein/protein interaction database associated with HGFA probe sets. This database was used to build and visualize molecular networks integrating small but significant changes in gene expression. In conclusion, we were able for the first time to delineate an intersecting genetic pattern linking ovarian tissues reflective of low potential malignancy/early cancer onset stages via long distance signaling between tissues of gynecological origin.

Objective: To determine the efficacy of adjuvant platinum-based chemotherapy in Stage I uterine papillary serous carcinoma (UPSC)., Methods: A retrospective multi-institutional investigation was performed to identify surgically staged patients with Stage I UPSC who were (1) treated after surgery with 3-6 courses of platinum-based chemotherapy without radiation from 1990-2003, and (2) followed for a minimum of 12 months, or until recurrence., Results: Six patients (IA-2, IB-3, IC-1) were treated with carboplatin (AUC 6) or cisplatin (50 mg/m2) alone. One patient recurred to the vagina, was treated with chemo-radiation, and is alive and well at 122 months. One patient recurred to the lung, liver, and brain, and died of disease at 24 months. The remaining 4 patients are alive with no evidence of disease 15-124 months (mean 62 months) after treatment. Two patients (IB-1, IC-1) were treated with cisplatin (50 mg/m2) and cyclophosphamide (1000 mg/m2), and both are alive and well with no evidence of disease 75 and 168 months after treatment. Twenty-one patients (IA-5, IB-13, IC-3) were treated with a combination of carboplatin (AUC 6) and paclitaxel (135 mg/m2-175 mg/m2). One patient recurred to the vagina after 3 cycles of carboplatin/paclitaxel, and was treated with chemo-radiation. She is now without evidence of disease 10 months after treatment. At present, all 21 patients with Stage I UPSC treated following surgical staging with carboplatin/paclitaxel chemotherapy are alive and well with no evidence of disease 10-138 months (mean 41 months) after treatment., Conclusion: Combination carboplatin/paclitaxel chemotherapy following surgery is effective in the treatment of Stage I UPSC.

Objectives: The objectives were to determine the acute toxicities of concurrent carboplatin and radiation therapy in the primary treatment of cervix cancer and to ascertain the antitumor activity of this regimen., Methods: Patients with stage IB-1 to IVA untreated primary cervix cancers were eligible for enrollment into this study. Carboplatin was administered on a weekly basis with external radiation therapy (ERT). Low-dose brachytherapy was given after completion of ERT. Acute toxicities and response to treatment were assessed., Results: Thirty-one evaluable patients were enrolled. The majority of patients had early stage disease. Carboplatin was successfully administered in 175 out of 186 (94%) planned treatments. All patients completed the prescribed course of radiation therapy. The mean treatment time was 50 days (36-73). There were no treatment delays for neutropenia or gastrointestinal toxicity. No patient was hospitalized for treatment related toxicities. Gastrointestinal toxicity equivalent to grade 3 or 4 was not reported. The objective tumor response based on physical exam findings and computed tomography measurements was 90%., Conclusion: Patients with cervix cancer can be treated on schedule with concurrent carboplatin and pelvic radiation therapy. This regimen is well tolerated and produces excellent response rates.

Objective: The goal of this study was to determine the clinical implications of a progressively rising serum CA-125 level in the normal (< 35 U/ml) range in ovarian cancer patients with complete response to therapy., Methods: A multi-institutional investigation was undertaken to identify patients with CA-125-producing epithelial ovarian cancers who experienced progressively rising antigen levels in the normal (<35 U/ml) range after completion of therapy. All patients had (1) histologic documentation of epithelial ovarian cancer and (2) complete clinical remission (CR) as defined by negative imaging studies, normal clinical examination, and a normal (<35 U/ml) serum CA-125 value. All patients had serum CA-125 determinations at 1- to 3-month intervals after treatment. A rising serum CA-125 level was defined as a progressive increase in at least three CA-125 values above the coefficient of variation (CV) for the assay. No patient had a known episode of pelvic or gastrointestinal inflammatory disease during the period when the progressive rise in serum CA-125 took place., Results: Eleven patients with rising serum CA-125 levels in the normal range were identified. Original stage of disease was as follows: stage IIA, 1; stage IIIC, 10. Cell type was as follows: endometrioid adenocarcinoma, 4; serous adenocarcinoma, 6; clear cell carcinoma, 1. Of the 11 patients identified, all developed recurrent ovarian cancer. Tumor recurrence was documented either by new lesions appearing on imaging studies (6/11) or by histologic confirmation (5/11). The mean time from CR to recurrence was 21 months (median = 22, range = 12-33). The mean time from the third early rising serum CA 125 value to clinical or radiographic confirmation of recurrence was 189 days (range = 84-518). All recurrences were intraabdominal with the exception of one axillary recurrence., Conclusion: In patients with a history of ovarian cancer, three progressively rising serum CA-125 values in the normal range (< 35 U/ml) at 1- to 3-month intervals are associated with a high likelihood of tumor recurrence. Patients with such a pattern should undergo immediate investigation to rule out and/or identify recurrent cancer.

Objectives: The purpose of this study was to determine the recurrence rate, survival, and pregnancy outcome in patients with Stage IA and Stage IC invasive epithelial ovarian cancer treated with unilateral adnexectomy., Methods: A multi-institutional retrospective investigation was undertaken to identify patients with Stage IA and IC epithelial ovarian cancer who were treated with fertility-sparing surgery. All patients with ovarian tumors of borderline malignancy were excluded. Long-term follow-up was obtained through tumor registries and telephone interviews. The time and sites of tumor recurrence, patient survival, and pregnancy outcomes were recorded for every patient., Results: Fifty two patients with Stage I epithelial ovarian cancer treated from 1965 to 2000 at 8 participating institutions were identified. Forty-two patients had Stage IA disease, and 10 had Stage IC cancers. Cell type was distributed as follows: mucinous, 25; serous, 10; endometrioid, 10; clear cell, 5; and mixed, 2. Histologic differentiation was as follows: grade 1, 38; grade 2, 9; and grade 3, 5. Twenty patients received adjuvant chemotherapy (mean 6 courses, range 3-12 courses). Patients received the following chemotherapeutic agents: cisplatin/taxol or carboplatin/taxol, 11; melphalan, 5; cisplatin and cyclophosphamide, 3; and single-agent cisplatin, 1. Eight patients had second-look laparotomies and all were negative. Duration of follow-up ranged from 6 to 426 months (median 68 months). Five patients developed tumor recurrence 8-78 months after initial surgery. Sites of recurrence were as follows: contralateral ovary, 3; peritoneum, 1; and lung, 1. Nine patients underwent subsequent hysterectomy and contralateral oophorectomy for benign disease. At present, 50 patients are alive without evidence of disease and 2 have died of disease 13 and 97 months after initial treatment. The estimated survival was 98% at 5 years and 93% at 10 years.Twenty-four patients attempted pregnancy and 17 (71%) conceived. These 17 patients had 26 term deliveries (no congenital anomalies noted) and 5 spontaneous abortions., Conclusion: The long-term survival of patients with Stage IA and IC epithelial ovarian cancer treated with unilateral adnexectomy is excellent. Fertility-sparing surgery should be considered as a treatment option in women with Stage I epithelial ovarian cancer who desire further childbearing.

Objectives: The aims of the study were to determine whether a Gram stain of cervical mucus can accurately rule out infection with Neisseria gonorrhoeae or Chlamydia trachomatis and to compare a diagnostic test that is based on the polymerase chain reaction with a deoxyribonucleic acid probe in the detection of these organisms., Study Design: Gravid patients were screened for N gonorrhoeae and C trachomatis with a deoxyribonucleic acid probe, Gram stain, and analysis with the polymerase chain reaction. A normal, noninfected sample was defined by <10 polymorphonuclear leukocytes per high-power field on the Gram stain. Standard statistical methods were used to compare results of the Gram stain and the deoxyribonucleic acid probe, as well as to compare results of deoxyribonucleic acid probe hybridization and polymerase chain reaction analysis. A P value of <.05 was considered statistically significant., Results: Patient enrollment totaled 519. The prevalence of infection as determined by deoxyribonucleic acid probe hybridization was 1.4% for N gonorrhoeae (7/518) and 6.8% for C trachomatis (35/518). The cervical Gram stain predicted the absence of infection in 17% (90/518) of patients, with a negative predictive value of 99% for N gonorrhoeae and 97% for C trachomatis. African American race, age <20 years, and unmarried status were all predictors of the presence of C trachomatis or N gonorrhoeae cervicitis. For the patients who lacked these risk factors (n = 74), the Gram stain had 100% negative predictive value. Analysis with the polymerase chain reaction detected 8 additional patients with C trachomatis and 105 additional patients with N gonorrhoeae, in comparison with deoxyribonucleic acid probe hybridization., Conclusion: The cervical Gram stain can accurately predict the absence of N gonorrhoeae and C trachomatis in gravid women. Analysis with the polymerase chain reaction indicates that N gonorrhoeae and C trachomatis are significantly more prevalent in this population than previously reported.

Objective: This is a pilot study to evaluate sexual dysfunction in women after vulvectomy., Methods: An 88-question survey was used to assess body image and the DSM IV criteria for sexual dysfunction on women who had undergone vulvectomy., Results: Forty-seven women agreed to participate in the study and 41 women (87%) returned the survey. There was a significant alteration of body image in these women after vulvectomy (P = 0.004). Sexual frequency significantly decreased after surgery (P = 0.001) and there was significant sexual dysfunction in the categories of sexual aversion disorder (P = 0.01), arousal disorder (P = 0.02), and hypoactive sexual disorder (P = 0. 001). The extent of surgery did not correlate with degree of sexual dysfunction in any category. Women who were depressed at the time of survey (as determined by the PRIME-MD scale) were more likely to suffer sexual aversion disorder (P = 0.05) and tended to have more body image disturbance (P = 0.1) and global sexual dysfunction (P = 0.06)., Conclusions: Women experience significant sexual dysfunction after vulvectomy and the extent of surgery or type of vulvectomy did not correlate with degree of sexual dysfunction. There is a significant need to address sexual problems with all women after any vulvectomy. Age, depression, worsening GOG performance status, and preoperative hypoactive sexual dysfunction were risk factors for sexual dysfunction after vulvar surgery. Appropriate counseling and treatment of depression may be of benefit to this patient population., (Copyright 2000 Academic Press.)

To identify potential prognostic indicators of ovarian cancer and identify targets for therapeutic strategies, mRNA differential display was used to analyze gene expression differences in normal, benign, and cancerous ovarian tissue. One cDNA isolated by this technique, Op18/stathmin, is a highly conserved gene that is reported to have many different functions within a cell, including signal transduction, control of the cell cycle, and the regulation of microtubules. Quantitative Northern blot analysis of 12 malignant ovarian samples, 8 benign ovarian tumors, and 10 normal ovarian tissue samples demonstrated overexpression of Op18/stathmin mRNA in the malignant cancers. Immunohistochemistry showed an apparent overexpression of Op18/stathmin protein level and an association with proliferating cells.

Objective: The objective of this study was to determine whether the toxicities associated with chemotherapy are age related in women treated for ovarian cancer., Methods: Patients with stage II-IV epithelial ovarian cancer underwent cytoreductive surgery. Adjunctive therapy was given to each patient consisting of intravenous (IV) paclitaxel 175 mg/m(2) over 3 h with a subsequent 30-min IV infusion of carboplatin. Carboplatin dose was calculated to achieve a targeted area under the curve (AUC) of 5.0-7.5. Treatment was repeated at 21- to 28-day intervals for six cycles. Toxicities were graded after each dose of chemotherapy. Results were analyzed using the Wilcoxon rank sum test and log likelihood ratio to compare toxicities in women age <60 years old to women >/=60 years old., Results: Fifty-three women, 22 of whom were >/=60 years old, were treated with 309 cycles of chemotherapy. Forty-eight patients (92%) completed all six cycles. AUC dosing of carboplatin was equivalent for both groups. Carboplatin dose reduction occurred in 75% of patients for grade 4 neutropenia or thrombocytopenia. No patient required a reduction in the paclitaxel dose. Neutropenia was less frequent in women >/=60 years old than in women <60 years old (P = 0.02). There was no difference between women <60 years old and women >/=60 years old in the incidence of anemia, thrombocytopenia, or the use of growth factors. A 68% complete clinical response rate was observed in women >/=60 years old compared to a 74% complete response rate for women under age 60 (P = 0.22)., Conclusion: Age is not a barrier to the aggressive treatment of ovarian cancer with this regimen of paclitaxel and carboplatin., (Copyright 1999 Academic Press.)

Unlabelled: OBJECTIVES. The aim of this study was to determine the attitudes of the members of the Society of Gynecologic Oncologists with respect to the use of adjuvant radiation therapy in women with endometrial cancer., Methods: An anonymous survey concerning the use of adjuvant radiation therapy in endometrial cancer was mailed to all members of the Society of Gynecologic Oncologists listed in the 1998 directory., Results: Of the 767 listed members, 325 (42%) returned completed surveys. Less than 20% of respondents recommended adjuvant radiation therapy in stage IA grade 1 or 2 and stage IB grade 1 endometrial cancer. Adjuvant radiation is recommended by 40 to 50% of respondents in women with stage IA grade 3 and IB grade 2 tumors. Most recommend adjuvant radiation for all women with >50% myometrial invasion or grade 3 tumors with any myometrial invasion. Lymph node sampling is attempted in all cases by 48% of respondents. For those familiar with Gynecologic Oncology Group (GOG) Study No. 99, 20% stated that they were more likely to recommend adjuvant radiation and 27% stated that they were less likely to recommend adjuvant radiation based on the preliminary results. Except in stage IA grade 1 tumors, the chance of recommending further therapy in women with all stages and grades was significantly less if a complete staging procedure including lymph node dissection had been performed., Conclusions: Complete staging appears to decrease the chance that postoperative therapy will be recommended. The use of adjuvant radiation therapy seem to have declined slightly as a result of GOG Study No. 99. Future studies in women with endometrial cancer that do not require lymph node sampling should evaluate the frequency of adjuvant therapy in the absence of complete staging., (Copyright 1999 Academic Press.)

Objective: The purpose of this study was to compare cytologic findings of fluid from ovarian cysts with ovarian histologic findings., Study Design: Ovaries submitted for pathologic examination were grossly examined for ovarian cysts. Fluid was removed by needle aspiration from intact ovarian cysts and prepared for cytologic examination. The cytologic findings were categorized as benign, malignant, indeterminate, and nondiagnostic. Histologic classification was assigned using the guidelines established by the World Health Organization. A single pathologist evaluated each cytologic specimen and was blinded to the gross appearance and histologic findings of each ovary. Cytologic diagnoses were compared with the histologic diagnoses., Results: The study material consisted of 105 ovaries from 98 women. A comparison of the ovarian histologic findings with the cytologic diagnosis was performed in 89 of 105 cases. Histologic examination of the ovaries revealed 89 benign ovarian tumors and 13 ovarian carcinomas. The sensitivity of ovarian cyst cytologic evaluation was 25%, and the specificity was 90%. The false-positive rate for ovarian cytologic evaluation was 73%, and the false-negative rate was 12%., Conclusions: Cytologic examination of aspirated ovarian cyst fluid does not accurately predict ovarian histologic findings.

Objective: Our purpose was to determine whether prenatal colposcopy is beneficial in pregnant women with squamous atypia, atypical squamous cells of undetermined significance, or low-grade squamous intraepithelial lesions on an initial screening Papanicolaou smear., Study Design: A retrospective chart review identified a cohort of pregnant patients referred to the colposcopy clinic at Carolinas Medical Center between October 1991 and December 1994 with squamous atypia, atypical squamous cells of undetermined significance, or low-grade squamous intraepithelial lesions. Results of the colposcopic examination, cervical biopsy specimens, postpartum evaluation, and postpartum treatment were recorded. Descriptive statistics were used to tabulate numbers and percentages for all variables with 95% confidence intervals to determine disease progression., Results: Prenatal colposcopy was performed on 253 women during the study period. The colposcopic impression was normal or consistent with low-grade squamous intraepithelial lesions in 235 (93%) of the women. Of the 67 women who had a cervical biopsy, 6 had a histologic diagnosis of high-grade squamous intraepithelial lesions. Postpartum Papanicolaou smears were obtained in 224 patients; 71 (32%) were normal, 145 (65%) were unchanged, and 8 (3%) showed high-grade squamous intraepithelial lesions. Of the 69 patients who had a postpartum cervical biopsy, 4 were found to have high-grade squamous intraepithelial lesions. Eight of the 10 women with biopsy-proved high-grade squamous intraepithelial lesions were compliant with treatment after delivery. Histologic examination of the cervix with tissue obtained by either loop conization or cold knife conization showed no evidence of invasive carcinoma., Conclusion: Squamous atypia, atypical squamous, cells of undetermined significance, or low-grade squamous intraepithelial lesions on a Papanicolaou smear in a pregnant patient does not require colposcopic evaluation during pregnancy. Progression of low-grade dysplasia to carcinoma during pregnancy is unusual, and no patient in this study was found to have invasive cancer.

Objective: Our purpose was to determine the extent of primary care delivered by obstetrician-gynecologists and compare practice patterns with published primary care and preventive service guidelines., Study Design: All 277 active fellows of The South Atlantic Association of Obstetricians and Gynecologists were mailed a self-administered questionnaire. The type of primary care offered by these physicians and their attitudes about the training of residents in obstetrics and gynecology were surveyed. Physicians were categorized as generalists or specialists on the basis of the completion of a fellowship program. Descriptive statistics and chi 2 analysis were used for statistical analysis., Results: Completed surveys were returned by 82% of the fellows. The majority of the respondents perceived their practice as specialty care for women. Generalists offered recommended screening services to women of all ages with greater frequency than the specialists did (p = 0.05). Both groups did not provide care for the chronic medical illnesses most commonly seen in a primary care practice. The respondents favored more residency training in those common acute illnesses frequently encountered in a primary care setting., Conclusions: Obstetrician-gynecologists in The South Atlantic Association of Obstetricians and Gynecologists selectively practice primary care. These physicians did not support caring for chronic medical problems frequently treated in an ambulatory care practice.

Radiation myelopathy is a severe consequence of radiation to the spinal cord which rarely occurs with standard doses of radiation. This entity commonly results in different degrees of sensory and motor deficits. Diagnosis of radiation myelopathy in women with gynecologic malignancies may increase with the concomitant use of chemotherapy and radiation therapy. This paper reports the effect of this combination therapy in a 60-year-old woman with fallopian tube carcinoma.

Objective: The optimal management of cervical intraepithelial neoplasia after cold knife conization remains controversial. Reliable predictors of residual dysplasia in the cervix after cold knife conization have not been consistently identified. This study was initiated to examine the accuracy of the traditional factors used to predict residual dysplasia in hysterectomy specimens after cold knife conization., Study Design: A retrospective 10-year chart review identified a cohort of 1272 patients who underwent cold knife conization, of whom 311 had a subsequent hysterectomy within 1 year of conization. Residual disease was defined as cervical intraepithelial neoplasia or cancer in the hysterectomy specimen. All cone specimens were completely submitted for pathologic examination, and the following factors were analyzed for their predictive value: degree of dysplasia, margin involvement, endocervical gland involvement, and status of the endocervical curettage. The predictive value of age, race, gravidity, parity, socioeconomic status, cigarette smoking, and marital status were also examined. The chi 2 test, t test, and logistic regression were used for statistical analysis., Results: Dysplasia or cancer were identified in 1066 (84%) of the 1272 patients who underwent cold knife conization. Of the 311 patients having a subsequent hysterectomy, 106 (34%) had residual disease in their hysterectomy specimen. By multivariate analysis only increasing age and degree of dysplasia were predictive of residual disease. The odds ratio of residual disease in the hysterectomy specimen for a 25-year-old woman was 2.7 (95% confidence interval 1.6 to 4.4) compared with a 40-year-old woman whose odds ratio was 4.9 (95% confidence interval 2.2 to 10.8). The presence of dysplasia in the cold knife conization specimen conferred an odds ratio of 12.1 (95% confidence interval 2.7 to 54.5) of identifying residual disease. Dysplasia involving the ectocervical margin, endocervical margin, and endocervical glands was not predictive of disease in the hysterectomy specimens. Endocervical curettage was not performed in 44% of the patients, preventing reliable statistical evaluation. Further analysis indicated that residual disease was found in 32% of the hysterectomy specimens with negative margins, in 31% with no endocervical gland involvement, and in 23% with a negative endocervical curettage sample., Conclusions: The presence or absence of dysplasia in the cold knife conization ectocervical margin, endocervical margin, and endocervical glands was not predictive of residual dysplasia in post-cold knife conization hysterectomy specimens. Increasing age and severity of disease in the cone specimen were the only factors that accurately predicted residual dysplasia. The traditional factors used to justify hysterectomy after cold knife conization may not be valid on the basis of these results.

Splenosis is the autotransposition of splenic tissue and is rarely encountered by the gynecologist. Most patients with splenosis are asymptomatic but may present with gynecologic symptoms. There are few reports in the gynecologic literature describing the management of pelvic splenosis. This paper reports the first case of laparoscopic management of pelvic splenosis.

Large loop excision of the transformation zone (LLETZ) provides a pathologic specimen similar to a cold-knife cone (CKC) biopsy of the cervix. One hundred twenty women with indications for a cone biopsy were evaluated with LLETZ to determine if this procedure is an acceptable alternative to traditional cold-knife conization of the cervix. All patients had LLETZ performed in the clinic under local anesthesia. An average of 2.1 slices was required to remove the transformation zone. Coagulation artifact interfered with histologic diagnosis in only 1.8% of specimens. The number of slices taken during the LLETZ procedure significantly correlated with the amount of heat artifact in the pathology specimen (P = 0.02) and interfered with the ability of the pathologist to determine complete excision of dysplasia (P = 0.03). LLETZ is an acceptable alternative to diagnostic CKC and can offer a substantial cost savings. To facilitate histopathologic interpretation, every effort should be made to minimize the number of slices and to maintain orientation of the LLETZ specimen. Endocervical curettage performed after LLETZ can identify a group of patients who are at high risk for CIN recurrence.

Objective: To examine the efficacy of the different modalities used to evaluate an initial abnormal Papanicolaou smear., Methods: The study population comprised 214 nonpregnant women referred with a Papanicolaou smear diagnosis of cervical intraepithelial neoplasia. Each patient was evaluated by a repeat Papanicolaou smear, colposcopy, and colposcopically directed cervical biopsies. Immediate loop excision was performed to remove the entire transformation zone in all patients. Kappa statistics were calculated to determine agreement among the modalities, and logistic regression was used for determining relative risks (RR)., Results: There was 53% agreement between the initial and repeat Papanicolaou smears. When low-grade squamous intraepithelial lesion (SIL) was diagnosed by Papanicolaou smear, there was 89% agreement with the colposcopic impression. However, a colposcopic impression of high-grade SIL was found in only one-third of the women diagnosed with high-grade SIL by Papanicolaou smear. A comparison of the histology of the cervical biopsy and the loop specimen revealed 57% agreement. Univariate analysis indicated that each modality was able to predict the RR of high-grade dysplasia in the loop specimen at a statistical significance level of .05. A colposcopic impression of high-grade dysplasia conferred an RR of 7.43 (95% confidence interval [CI] 2.17-25.49) for high-grade dysplasia in the loop specimen. An initial Papanicolaou smear diagnosis of high-grade SIL did not contribute to the multivariate model for calculating the risk of high-grade dysplasia, as the RR was 1.6 (95% CI 0.68-3.81)., Conclusion: Patients with an initial Papanicolaou smear showing low-grade SIL would benefit from a repeat Papanicolaou smear and colposcopically directed biopsies before proceeding with loop diathermy. In contrast, patients with a colposcopic impression of high-grade dysplasia combined with high-grade SIL on Papanicolaou smear appear to be candidates for immediate loop excision.

Three hundred seventy-five patients with CIN on referral Pap and with a distinct cervical lesion on colposcopy were prospectively randomized to treatment with LLETZ or to standard colposcopic evaluation with directed cervical biopsies, endocervical curettage, and laser ablation of the transformation zone for biopsy proven CIN. Of the 195 patients that randomized to treatment with LLETZ, 32.5% had no evidence of dysplasia, 26.5% had CIN 1, 17.3% had CIN 2, 22.7% had CIN 3, and 0.5% had microinvasive carcinoma on final histologic evaluation. Of the 180 patients randomized to laser ablation, initial cervical biopsies demonstrated no evidence of dysplasia in 52.8% of patients, CIN 1 in 22.0%, CIN 2 in 18.3%, and CIN 3 in 5.7%. Only 114 (63.3%) of the women in the laser group required therapy. Complications were comparable for each treatment arm. Only 6.7% of patients randomized to LLETZ and 4.4% with laser ablation had persistent CIN on follow-up Pap. LLETZ appears to be effective, well tolerated, and less expensive, but the cost savings advantage of LLETZ over laser ablation may not apply to patients with CIN 1 on referral Pap smear since many do not require treatment.

Second-look laparotomy is performed to evaluate response to chemotherapy and to determine the need for additional treatment. The relationship between absolute levels of serum CA 125 less than 35 u/ml and disease status at second-look operation was evaluated in 95 patients with advanced-stage epithelial ovarian cancer. Eighty-six patients had Stage III disease and nine patients had Stage IV cancer. Residual tumor was documented at second-look laparotomy in 52 (55%) of the patients studied. Forty-nine percent of the 82 patients with serum CA 125 values less than 20 u/ml had residual disease. In contrast, 12 of 13 (92%) patients with serum CA 125 values of 20-35 u/ml had residual tumor at second-look laparotomy. All patients with serous cystadenocarcinomas and serum CA 125 values of 20-35 u/ml had residual tumor, and two-thirds of these cases had grossly visible disease. The positive predictive value of a serum CA 125 level of 20-35 u/ml was 0.92. These data suggest that second-look laparotomy should be deferred in patients with advanced-stage ovarian cancer until serum CA 125 values are less than 20 u/ml.

Seventy-four patients with Stage II endometrial cancer were treated by a combination of preoperative radiation therapy followed by extrafascial hysterectomy, bilateral salpingo-oophorectomy, and paraaortic lymph node sampling at the University of Kentucky Medical Center from 1967 to 1988. All patients had histologically confirmed endometrial cancer with involvement of the endocervix. The cell types and numbers of the tumors treated were as follows: adenocarcinoma, 58; adenoacanthoma, six; adenosquamous carcinoma, nine; and clear cell carcinoma, one. Preoperative radiation consisted of 4500 cGy external therapy followed by one intracavitary implant providing an additional 2000 cGy to point A. Surgery was done 4 to 6 weeks after completion of radiation therapy. Five patients (7.1%) had paraaortic lymph node metastases. Four were treated with extended-field radiation therapy and one with platinum-based combination chemotherapy. After treatment, the patients were followed at regular intervals from 2 to 22 years (mean, 5.4 years). Eleven patients (15%) had recurrent cancer, with the vagina and upper abdomen being the most common sites of spread. The estimated 5-year and 10-year disease-free survival rates of these patients are 88% and 76%, respectively. Cell type, depth of myometrial invasion, and lymph node status were the most important prognostic variables in the patients evaluated. These data confirm that the combination of preoperative radiation therapy and surgery produces excellent long-term survival in patients with Stage II endometrial cancer.

Ultrasound examination of ovarian size and morphology has been proposed as a screening method for ovarian carcinoma. A screening test must give consistent results when performed by different examiners to reliably determine the sensitivity and specificity of the test. This study was designed to evaluate interobserver variation in ovarian size measurements using transvaginal sonography. Two examiners independently measured 86 ovaries in three planes and ovarian volumes were calculated using the prolate ellipsoid formula. The correlation coefficient between the ovarian volume measurements made by each examiner was 0.960. These results indicate that interobserver variation in ovarian volume measurements is extremely low as determined by transvaginal sonography.

From November 1987 to April 1989, 1000 women 40 years or older underwent screening vaginal sonography at the University of Kentucky Medical Center (Lexington, KY). Patients included in this investigation were all asymptomatic and had no known pelvic abnormalities. Each ovary was measured in three planes and ovarian volume was calculated using the prolate ellipsoid formula. The upper limit of normal for ovarian volume was 18 cm3 in premenopausal women and 8 cm3 in postmenopausal women. In patients with normal scans, mean ovarian volumes decreased from 6.8 cm3 to 3.0 cm3 with menopause. Thirty-one patients (3.1%) had abnormal vaginal sonograms and 24 underwent exploratory laparotomy. All patients undergoing surgery had ovarian or fallopian tube tumors with dimensions identical to those predicted by ultrasound. Histologic diagnoses of these tumors included the following: adenocarcinoma, one, serous cystadenoma, eight; endometrioma, six; and cystic teratomas, two. Vaginal sonography was performed easily and without complications, and was well accepted by patients. All patients with normal sonograms have been rescreened annually and none have subsequently developed ovarian cancer. Further clinical trials to determine the efficacy of vaginal sonography as a screening method for ovarian cancer are indicated.

The efficacy of carbon dioxide laser therapy in the treatment of cervical intraepithelial neoplasia (CIN) was evaluated in 253 patients treated at the University of Kentucky Medical Center from 1984 to 1987. All patients had histologically confirmed CIN and were treated in an outpatient setting. Parameters examined included severity of neoplasia, presence of koilocytosis on biopsy, depth of laser ablation, and the number of cervical quadrants involved by CIN. Following therapy, patients were examined at 3-month intervals from 12 to 48 months (mean 18 months). Eighty-nine per cent of patients were successfully treated with one laser ablation and all patients were cured of disease with two treatments. Over 70% of patients initially failing therapy had CIN III or greater than or equal to 3 quadrant disease. The most significant predictor of failure was lesion size. Only 74% of women with 3 or 4 quadrant disease were successfully treated with one treatment. No patient experienced postoperative infection or bleeding requiring treatment. These data confirm that carbon dioxide laser therapy is a safe and highly effective treatment method for all forms of CIN.

From November 1, 1987, to July 1, 1988, 506 asymptomatic patients 40 years or older underwent screening vaginal sonography at the University of Kentucky Medical Center. Eligibility requirements included no known pelvic symptoms or clinical abnormalities, no history of pelvic radiation, and no history of ovarian cancer. Each ovary was measured in three planes and ovarian volume was calculated using the prolate ellipsoid formula. Ovarian morphology was classified as uniformly hypoechogenic, cystic, solid, or complex. The upper limit of normal for ovarian volume was 18 cm3 in premenopausal women and 8 cm3 in post-menopausal women. With respect to these criteria, 12 patients (2.4%) were noted to have abnormal sonograms, and 10 agreed to surgery. All 10 patients had ovarian tumors with dimensions equal to those predicted by ultrasound. These tumors included four serous cystadenomas, three endometriomas, two cystic teratomas, and one adenocarcinoma. Vaginal sonography is a relatively simple test that can detect subtle changes in ovarian size and morphology. Further evaluation of this test as a screening method for ovarian cancer should be performed in the setting of controlled clinical trials that emphasize cost control and strict patient follow-up.

From 1973 to 1987, 16 patients with International Federation of Gynecology and Obstetrics (FIGO) Stage I serous papillary endometrial carcinoma were evaluated and treated at the University of Kentucky Medical Center (Lexington, KY). All patients were 60 years of age or older, and all were postmenopausal. Patients were treated with total abdominal hysterectomy, bilateral salpingo-oophorectomy, and paraaortic lymph node sampling, and 38% were noted to have more extensive disease than appreciated clinically. Nine patients were given adjuvant postoperative radiation. Seven patients (44%) developed recurrent cancer with liver, lung, and upper abdomen being the most common sites of spread. Prognosis was most directly related to the presence of lymph vascular space invasion and the depth of myometrial penetration. No patient with serous papillary carcinoma confined to the endometrium developed recurrent cancer. In contrast, the recurrence rate of patients having myometrial invasion was 70% (P less than 0.03). Hormonal therapy was of limited value in the treatment of recurrent disease. This data suggests the need for adjuvant systemic therapy in the treatment of patients with Stage I serous papillary carcinoma of the endometrium who have myometrial invasion.

From November 1973 to May 1986, 50 patients with Stage I epithelial ovarian cancer were treated at the University of Kentucky Medical Center (Lexington, KY) with oral Alkeran (melphalan) chemotherapy after primary surgery. Twenty-two patients had Grade 1 tumors, 23 patients had Grade 2 tumors, and five patients had Grade 3 tumors. Patients with ovarian tumors of borderline malignancy were excluded from this study. Twenty-eight patients received from six to 11 courses of chemotherapy and 22 patients completed 12 courses of chemotherapy. Chemotherapy was well tolerated and no patient died of chemotherapy-related complications. Thirty-eight patients underwent second-look laparotomy died of disease 41 months after diagnosis and one patient died with no evidence of disease 6 months after treatment. The actuarial survival of the total group of patients was 98% at 2 years and 94% at 5 years. Fewer than 12 months of chemotherapy may be necessary to obtain long-term survival in these patients.

From 1962 to 1985, 2201 patients with invasive cervical cancer were staged, evaluated, and treated at the University of Kentucky Medical Center. After a thorough evaluation, 25 cases (1.1%) fulfilled the histologic criteria for small cell cancer defined by Reagan and coworkers. These patients were computer-matched for age, disease stage, and lesion size to 25 patients with large cell nonkeratinizing cancer and 25 patients with keratinizing squamous cell cancer. Morphometric analyses of nuclear size and maximum nuclear diameter were performed on all cases without knowledge of cell type. Small cell cancers were characterized by a nuclear area of 160 mu 2 or less and a maximum nuclear diameter of 16.2 mu, which was significantly lower than that for large cell tumors. Thirty-three percent of the small cell carcinomas stained positively for the neuroendocrine markers (neuron-specific enolase [NSE] and chromogranin [CGR]), whereas the remainder contained only epithelial markers such as cytokeratin (CYK) and epithelial membrane antigen (EMA). Small cell cancers were associated with a high frequency of lymph-vascular space invasion and a diminished lymphoplasmacytic response. Patients with small cell cancer had a significantly higher recurrence rate, particularly to extrapelvic sites, than the matched patients with large cell cancers, and their survival was lower. Clinical trials to determine the efficacy of adjuvant chemotherapy in the treatment of small cell cervical cancer are needed.

Prognostic parameters were evaluated in 22 patients with small (less than or equal to 2 cm) superficially invasive (less than 5 mm) squamous cell carcinoma of the vulva. Primary surgery included radical vulvectomy with bilateral superficial and deep inguinal lymph node dissection in 11 patients, and wide local excision with ipsilateral superficial inguinal lymph node dissection in 11 patients. Of the 22 patients studied, only 2 (9%) had lymph node metastases. Both patients had a single positive ipsilateral superficial inguinal node. Perineural invasion was strongly associated with lymph node metastases (P less than 0.01). In this group of patients, grade, depth of invasion, lymph-vascular space invasion, and lymphoplasmacytic infiltration were not predictive of lymph node metastases (P greater than 0.05). Two patients initially treated with wide local excision and ipsilateral superficial inguinal lymph node dissection developed recurrent vulvar neoplasia on the contralateral vulva, and both were successfully retreated by wide local excision. All patients are presently alive and well with no evidence of disease. None of the histomorphologic parameters studied were predictive of tumor recurrence. These data suggest that wide local excision with ipsilateral superficial inguinal lymphadenectomy is effective in the treatment of patients with small, superficially invasive carcinomas of the vulva.

Primary hyperparathyroidism in pregnancy is an uncommon event, with approximately 100 reported cases in the literature. Two cases illustrate the common problems in diagnosing this disease in pregnancy and indicate that surgery should be considered the primary modality of treatment. These two are the 24th and 25th cases of surgery for primary hyperparathyroidism in pregnancy reported in the literature.

A case of poor prognosis metastatic trophoblastic disease resistant to chemotherapy with methotrexate, dactinomycin, and cyclophosphamide is presented. The patient responded promptly to etoposide-based combination chemotherapy and has remained in complete remission since completion of therapy.