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Objective: To assess the efficacy, side effects and progression-free interval of a modified regimen of the combination ofgemcitabine and cisplatin among women with recurrent epithelial ovarian cancer. Methods: Twenty-eight women with recurrent epithelial ovarian, primary peritoneal or fallopian tube cancers were treated withgemcitabine (500 mg/m 2 ) followed by cisplatin (50 mg/m 2 ) on days one and eight every three weeks. Patients’ demographics,response, side effects, and progression-free interval were recorded. Result: The median age of patients was 61 (range 44-74 years). Twenty-three (82.1%) patients had platinum-sensitive and five(17.9%) had platinum-resistant tumors. The median number of prior chemotherapy regimens was two (range 1-4) and ninepatients had > three prior regimens. The median number of cycles was six (range 2-10). Seventeen (60.7%) patients respondedto chemotherapy (11 complete and six partial), six had stable disease and five had progression. The response rate was 69.6%and 20% among women with platinum-sensitive and platinum-resistant tumors, respectively ( P = .024). The median (range)progression-free interval was six (2-12) and nine (4-12) months among all patients and patients who responded to chemotherapy,respectively. Four patients had dose reductions, four had delays and three had their chemotherapy terminated secondary to toxicityor patient desire. There were no chemotherapy-related mortality or hospital admissions. The incidence of grade 3-4 neutropenia,anemia, thrombocytopenia, and nausea or vomiting was 32.1%, 10.7%, 35.7%, and 10.7%, respectively. Conclusion: The combination gemcitabine and cisplatin is highly effective among women with recurrent ovarian cancerincluding those who are heavily pre-treated and is reasonably tolerated. Although, the combination is effective among womenwith plantinum-resistant tumors, these women have a lower response than women with platinum-sensitive tumors.

Objective To assess the feasibility and surgical outcome of laparoscopic surgery among women with large benign ovarian cysts. Methods We conducted a prospective study applying laparoscopic surgery among women with ovarian cysts whose maximum diameter was ≥10 cm and radiologic and laboratory features suggestive of benign disease. Patients' demographics, clinical and ultrasound features, CA-125 values, surgical procedures, operative and post-operative complications, estimated amount of blood loss (EBL), operative time, conversion to laparotomy and the pathologic findings were recorded. Results Thirty-three consecutive patients underwent laparoscopic surgery over 7 years. The mean (range) age and body mass index were 45.2 (17–73 years) and 30 (21–42), respectively. Laparoscopic surgery was successful in 31 (93.9%) patients. The procedure was converted to laparotomy in 2 patients secondary to adhesions. There were no operative or post-operative complications. The mean (range) operative time, EBL and hospital stay were 82 (45–125 min), 89 (20–250 mL) and 0.94 (0–4 days), respectively. Twenty-three (70%) patients were discharged home the day of the surgery. The surgical procedures performed were: unilateral salpingo-oophorectomy (SO) ( n =16), bilateral SO ( n =4), ovarian cystectomy ( n =2) and laparoscopically assisted vaginal hysterectomy and bilateral SO ( n =9). The cysts were extracted after aspiration through the vagina ( n =11), lower quadrant incision ( n =5) or the umbilical incision ( n =15). Pathologic findings included serous cystadenoma ( n =11), mucinous cystadenoma ( n =6), dermoid ( n =6), endometriosis ( n =5), benign epithelial-lined cyst ( n =3) and borderline ovarian tumors ( n =2). Conclusion Laparoscopy is feasible and safe for women with large ovarian cysts with benign features and results in a short hospital stay.

The purpose of our study was to find if uterine manipulation at the time of laparoscopic hysterectomy among women with endometrial carcinoma increases the incidence of malignant cells in the peritoneal washings.We conducted a prospective study including women with clinical stage I endometrioid endometrial carcinoma undergoing laparoscopic surgery between 07/01/2000 and 07/01/2004. Surgery on all patients was conducted by the same surgeon using the same technique and instruments. Two sets of peritoneal washings were obtained, one before and one after the insertion of the Pelosi uterine manipulator. The two sets of washings were blindly reviewed by the same cytopathologist for the presence of malignant cells. Correlation was made between the two sets of washings.Forty-two consecutive women (age 46-90, median: 58) were enrolled in the study. The procedure was converted to laparotomy in 3 (7.6%) patients after obtaining the two sets of washings. The preoperative tumor grades were: G1: 22 (52.4%), G2: 12 (28.6%), and G3: 8 (19.0). The incidence of positive peritoneal washings was 14.3%. All patients underwent laparoscopically assisted vaginal hysterectomy with bilateral salpingo-oophorectomy, 30 patients had bilateral pelvic lymphadenectomy, and 5 patients had bilateral pelvic and para-aortic lymphadenectomy. There was perfect agreement between the two sets of washings in all patients (100%, P.001). No patients had positive washings after the insertion of the uterine manipulator if the washings were negative before the insertion. The surgical stages were: IA: 14 (33.3%), IB: 12 (28.6%), IC: 7 (16.7%), IIA: 1 (2.4%), IIB: 1 (2.4%), IIIA: 4 (9.5%), IIIB: 1 (2.4%), IIIC: 1 (2.4%), and IV: 1 (2.4%). Twenty-nine patients received no postoperative treatment, 2 received chemotherapy, 3 received Megace, and 9 received radiation therapy. Patients were followed-up for 7-56 months (median: 28). Two patients had tumor recurrence, and one patient died secondary to her disease. Two other patients died secondary to other causes.We conclude that uterine manipulation at the time of laparoscopic hysterectomy does not increase the incidence of positive peritoneal cytology among women with endometrial carcinoma.

Purpose The aim of the current study is to compare clear cell ovarian carcinoma (CCOC) and papillary serous ovarian carcinoma (PSOC) with respect to their clinical features and expression of different regulators of cell cycle, apoptosis, and chemoresistance. Experimental Design Women with stage III CCOC (n = 9) and those with stage III, poorly differentiated PSOC (n = 21) seen between 1996 and 2000 and treated with cytoreductive surgery followed by paclitaxel and platinum chemotherapy were compared in their demographic features, tumor marker profile, surgical substage, results of cytoreductive surgery, thromboembolic complications, response to chemotherapy, and tumor recurrence. Tumor samples were compared in their expression of p53, Bcl2, Bclx, Bax, p21, p-glycoprotein (PGP), multi-drug resistance-associated protein (MRP), lung resistance protein (LRP), and glutathione S-transferase (GST) using immunohistochemistry. Results Women with CCOC had significantly lower mean preoperative CA-125 values, lower surgical substage, less expression of p53, and more expression of p21 than women with PSOC (P = 0.037, 0.012, 0.008, and 0.009, respectively). Women with CCOC had less ascites, smaller amount of residual tumor, higher incidence of thromboembolism, chemoresistance, more expression of Bcl2, and less expression of PGP than women with PSOC (P = 0.067, 0.078, 0.108, 0.114, 0.091, and 0.118, respectively). Conclusions Women with CCOC exhibit certain clinical and molecular differences compared to stage- and grade-matched women with PSOC. Women with CCOC have a smaller tumor volume and manifest different expressions of p53, p21, and Bcl2 than women with PSOC. Although further studies with larger number of patients are needed, our findings indicate that chemoresisatnce in CCOC is probably not p53-dependent. J. Surg. Oncol. 2006;93:379–386. © 2006 Wiley-Liss, Inc.

Ovarian cancer is the leading cause of death for all gynecologic malignancies in developed countries, largely owing to the late stage of diagnosis. Despite response to initial surgery and chemotherapy, more than 65% of patients will have recurrent or persistent diseases. Approximately 50% of patients with recurrent ovarian cancer are asymptomatic. Recurrences are often diagnosed using a combination of tests, including cancer antigen 125, computed tomography, magnetic resonance imaging and positron emission tomography scan. The most significant prognostic factor among women with recurrent ovarian cancer is the length of time from initial diagnosis to recurrence. Treatment of recurrent ovarian cancer involves chemotherapy, with or without surgery. In selected patients, secondary cytoreductive surgery might significantly improve survival. Radiotherapy may have a role in the treatment of a small group of patients with localized symptomatic masses. New treatment modalities for women with recurrent ovarian cancer are needed, as none of the available treatments are curative.

Objective. The purpose of our study was to assess the surgical stage, final grade, and survival of women with endometrial carcinoma whose preoperative endometrial biopsy showed well-differentiated (FIGO grade 1) carcinoma. Materials and methods. A retrospective study was conducted including all women treated at the University of Vermont between 1992 and 2004 whose preoperative endometrial biopsy was reviewed by the staff at the Pathology Department and diagnosed as FIGO grade 1 adenocarcinoma and who received peritoneal washings, total abdominal (or laparoscopic) hysterectomy, bilateral salpingo-oophorectomy, and pelvic ± para-aortic lymphadenectomy as part of their surgery. Results. One hundred eighty-two patients (age: 32–91, median: 60) were enrolled. All patients had total hysterectomy, bilateral salpingo-oophorectomy, peritoneal washings, and bilateral pelvic lymphadenectomy. Fifteen (8.2%) patients had para-aortic lymphadenectomy. There were no operative mortalities. Fourteen patients (7.7%) had major operative or postoperative complications. There was disagreement between the pre- and postoperative grade in 30% of the study group. The surgical stages were: IA: 55 (30.2%), IB: 61 (33.5%), IC: 26 (14.3%), IIA: 9 (4.9%), IIB: 8 (4.4%), IIIA: 10 (5.5%), IIIB: 2 (1.1%), IIIC: 8 (4.4%), and IV: 3 (1.6%). Postoperatively, 131 (72%) patients received no additional treatment, 47 (25.8%) received radiation therapy, 3 (1.6%) received chemotherapy, and 1 (0.5%) received Megace. During a median follow-up period of 6 years, 8 (4.4%) patients had recurrence and 6 (3.2%) died from their disease. The 5-year disease-free and overall survival was 95.2% and 96.4%, respectively. Conclusions. Approximately 30% of women with endometrial carcinoma whose preoperative endometrial biopsy shows grade 1 tumors have grade 2 or 3 in the hysterectomy specimen and 12.6% have advanced surgical stage (stage III and IV) disease. Women with preoperative endometrial biopsy showing grade 1 tumors who undergo surgical staging have excellent survival and acceptable operative morbidity.

The aim of the current study is to investigate the clinical and molecular factors associated with cytoreduction among women with advanced stage epithelial ovarian carcinoma EOC.Seventy-two women with FIGO stage III and IV EOC or primary peritoneal carcinoma (PPC) underwent similar attempt at surgical cytoreduction, mostly by the same surgeon. The histologic material of these patients was reviewed and the histologic subtype and grade were assigned. Immunohistochemical tests were performed for expression of molecular regulators of apoptosis (p53, p21, Bcl(2), Bcl(x), Bax) and chemoresistance (PGP, MRP, LRP, GST). The following factors were assessed for their association with complete (no residual tumor) and optimal (residual tumor1 cm) cytoreduction: type of carcinoma (EOC versus PPC), stage, CA-125 values, ascites, histology, tumor grade, and p53, p21, Bcl(2), Bcl(x), Bax, PGP, MRP, LRP, GST expression using the odds ratio and associated 95% confidence intervals. Significant univariate odds ratios were assessed jointly in a multivariate logistic regression model. Receiver operating characteristic curve analysis was performed to determine the CA-125 level with the maximal cytoreduction prognostic power.Twenty-three (31.9%) women had no residual tumor, 35 (48.6%) hador=1 cm residual tumor and 14 (19.4%) had residual tumor1 cm. Factors with significant univariate associations with complete cytoreduction included stage, CA-125 level, ascites, histology, and p53. p53 expression was the only factor which remained significant in the multivariate analysis (odds ratio 7.2, 95% CI 1.5, 34.9). A preoperative CA-125 value ofor=500 IU/ml best determined complete cytoreducibility.Innate tumor characteristics determine cytoreducibility of women with ovarian carcinoma. Pre-operative evaluation of p53 expression may be of value in predicting the outcome of cytoreductive surgery in women with advanced stage EOC.

OBJECTIVE: To examine conventional and liquid-based cervical smears falsely diagnosed as malignant at our institution and to investigate, through cytologic-histologic correlation, factors influence ing false positive diagnoses. STUDY DESIGN: Cervical cytologic diagnoses of malignancy from May 1, 1995, to April 30, 2001, were retrieved through a computer search. A retrospective review of hospital records and pathology reports was performed. Cases identified as false positives were reviewed and correlated with histologic follow-up specimens. RESULTS: A group of 68 patients with malignancy reported on cervical smears and with histologic follow-up was identified. Conventional smears numbered 32 (47%); the remaining 36 (53%) were liquid-based samples. Of the total, 7 false positive cases (10.3%) were identified in 4 conventional and 3 liquid-based preparations. Cytologic diagnosis in these cases was squamous cell carcinoma in 5 and adenocarcinoma in 2. On histologic follow-up, all 7 patients were ultimately found to have high grade squamous intraepithelial lesions (HSILs) without invasion. Review of the original slides confirmed most, or all, of the ' following features in all cases: major cellular pleomorphism, extensive cytoplasmic keratinization, intense nuclear pyknosis, background necrosis and severe atrophy. CONCLUSION: There was no significant difference in rates of false positive diagnoses between conventional (12.5%) and liquid-based (8.3%) samples. The chief reason for overdiagnosis in this series was the capacity of HSIL to exfoliate cells mimicking invasive malignancy, particularly when keratinized and especially in an atrophic milieu. The other cause of false positivity was superimposition of inflammation and atypical reparative change on a background of HSIL, which then suggested invasion.

Objectives The predictive value of cervical Papanicolaou (Pap) smears reported as "positive for malignancy," especially those obtained by the liquid-based method, has not been adequately assessed. The objectives of this study are to determine the positive predictive value of Papanicolaou smears with features of malignancy, to compare the accuracy of Papanicolaou smears obtained by the liquid-based method to those obtained by the conventional technique in this setting, and to study the factors influencing a false-positive cytologic diagnosis of malignancy. Materials and methods Pap smears significant for malignant cytology were identified at Fletcher Allen Health Care Hospital in Burlington, VT, from May 1, 1995, to April 30, 2001. A retrospective review of the hospital records and pathology reports was performed documenting patient characteristics, the collection technique, and the final histology. An independent review of the cytology and histology was performed. The positive predictive value and false-positive rate of malignant cytology were calculated for the liquid-based and conventional Pap smear techniques. Results A total of 472,743 Pap smears were performed during the period specified. One hundred four Pap smears were reported as positive for malignancy, yielding a prevalence rate of 0.02%. A total of 68 patients had paired cytology and histology specimens. Malignant cytology was identified in 36 smears obtained by the liquid-based technique and 32 smears obtained by the conventional technique. A true-positive result, meaning malignant cytology confirmed by the presence of invasive carcinoma on histology, was obtained in 61 of 68 (89.7%) patients. A false-positive result, meaning malignant cytology not confirmed by histology, was obtained in 7 of the 68 (10.3%) patients. The false-positive rate of malignant cytology was 8.4% for the liquid-based technique and 12.5% for the conventional technique. All 7 false-positive smears were diagnosed with high-grade dysplasia by histology. Three of the 7 patients with high-grade dysplasia had previous treatment for dysplasia, one of whom was also pregnant at the time of the smear. Conclusions Malignant cervical Papanicolaou smear cytology has a high positive predictive value in the setting of gynecologic and nongynecologic malignancies. Previous treatment for cervical dysplasia or pregnancy may influence the false-positive rate of malignant cytology.

Background and Objectives Our knowledge regarding the pathologic lymphatic spread pattern of primary peritoneal carcinoma (PPC) is limited. The aim of this study was to compare the incidence and the pathologic patterns of pelvic and para-aortic lymph node metastases among women with PPC and those with papillary serous ovarian carcinoma (PSOC). Methods We conducted a prospective study over the last 4 years among women with FIGO stage III and IV PPC and PSOC who had optimal primary cytoreductive surgery (

Objective. The best treatment modality and factors affecting recurrence among women with vaginal intraepithelial neoplasia (VAIN) are yet to be determined. The aims of the current study were to describe the clinical features, results of treatment, and factors affecting recurrence among patients with VAIN. Methods. We conducted a retrospective review of 121 women with VAIN after confirming the histologic diagnosis. Patient demographics, clinical features, and results of therapy were recorded. Factors affecting recurrence were assessed using the odds ratio and the 95% confidence intervals among patients who were followed up for 7 months or more and had at least one posttreatment Papanicolaou smear. Significant univariate odds ratios were assessed jointly in a multivariate model with a stratified analysis. Results. The mean age of the patients was 35.0 (±17), 41% of the patients smoked, 39% had a history of human papillomavirus infection, 27% had history of sexually transmitted diseases, 22% had history of surgery for cervical intraepithelial neoplasia (CIN), and 23% had total hysterectomy. The upper third of the vagina was the most common site of VAIN and 61% of the lesions were multifocal. Associated cervical and vulvar intraepithelial neoplasia (VIN) were present in 65 and 10%, respectively. Recurrences of VAIN and progression to invasive vaginal cancer occurred in 33 and 2%, respectively. Recurrences following partial vaginectomy, laser, and 5-fluorouracil were 0, 38, and 59%, respectively ( P = 0.0001). Multifocality and method of treatment were significant independent predictors of VAIN recurrences (odds ratio 3.3, 95% CI 1.2, 9.2, P = 0.02, and 22.4, 95% CI 1.3, 393.6, P = 0.001, respectively), with no interaction, based on a stratified analysis. Conclusions. VAIN occurs most often among women with CIN or VIN, commonly involves the upper third of the vagina, and is often multifocal. Partial vaginectomy provides the highest cure rate and multifocality is a risk factor for recurrence.

The use of tamoxifen among women with breast cancer or at high risk of the disease has greatly expanded over the past several decades. Tamoxifen has a complex effect on the female reproductive tract and several tamoxifen-associated changes have been described among tamoxifen users. These include endometrial thickening, cervical and endometrial polyps, endometrial hyperplasia, endometrial adenocarcinoma, uterine sarcoma, increase in the size of uterine leiomyomata, exacerbation of endometriosis and ovarian cysts. The most common uterine change associated with tamoxifen is endometrial polyps. The annual incidence of endometrial cancer among women on tamoxifen is 2 per 1000 and seems to be related to the cumulative tamoxifen dose. It is not clear whether endometrial cancer occurring among women on tamoxifen is of worse prognosis than endometrial cancer occurring among women not receiving tamoxifen. Tamoxifen is associated with several sonographic changes which make the use of ultrasound in surveillance of these patients difficult. There is no indication to implement routine screening for endometrial cancer among all women on tamoxifen. However, endometrial biopsy, preferably via hysteroscopy, should be considered in women with uterine bleeding.

Objective. The best technique for obtaining cytologic specimens necessary for evaluation of diaphragmatic spread among women undergoing surgical staging for ovarian cancer has yet to be determined. The aim of the current study was to compare two methods for obtaining diaphragmatic cytology—wash and scrape—in accuracy, correlation to clinical findings, and smear quality. Methods. We conducted a prospective study among women undergoing surgical staging for ovarian cancer. In each patient diaphragmatic scrape and wash specimens were obtained, then the undersurface of the diaphragm was inspected and palpated. The smears were examined for presence of cancer cells, correlated to clinical findings, and scored for quality (cellularity, preservation, and background). Results. In 46 consecutive patients with stage I–III ovarian cancer, the diaphragm was clinically involved in 12 (26.1%). Malignant cells were demonstrated in 21 (45.7%) of wash and scrape specimens. There was perfect agreement between washes and scrapes and good agreement between clinical evaluation and scrapes or washes (κ = 1.0 and 0.592, respectively). Wash specimens had significantly higher overall smear quality and cellularity scores (6.26 ± 1.26 vs 6.11 ± 1.06, P < 0.02, and 2.20 ± 0.81 vs 1.85 ± 0.76, P < 0.05, respectively). Conclusion. Although diaphragmatic wash specimens provide better-quality smears than scrape specimens, both techniques are equally diagnostic of diaphragmatic involvement in women undergoing surgical staging for ovarian cancer.

Objective: This study was undertaken to determine the accuracy of systematic intraoperative clinical evaluation of lymph nodes in women with gynecologic cancers and to examine the factors affecting such accuracy. Study Design: The characteristics and overall intraoperative clinical impression of lymph node metastases were prospectively recorded for 178 consecutive women undergoing lymphadenectomy. The overall clinical impression and lymph node characteristics (enlargement, firmness, and adherence) were correlated with the final histopathologic diagnosis. Results: The overall clinical impression showed excellent agreement with the final histopathologic diagnosis (κ = 0.753) but had a high false-negative rate (25.8%). The combination of enlargement and firmness had the highest overall accuracy (93.3%). Accuracy of clinical evaluation varied significantly according to the type of cancer, node positivity, and the proportion of positive nodes with respect to the total number of nodes. Conclusion: Although systematic intraoperative clinical evaluation of lymph nodes by a trained surgeon has high overall accuracy and correlates well with the final histopathologic diagnosis, it has a high false-negative rate and cannot substitute for histopathologic examination. (Am J Obstet Gynecol 2001;184:1177-81.)

BACKGROUND The current study was conducted to assess the feasibility of laparoscopy in the treatment of women with early stage endometrial carcinoma and to compare the surgical outcome, cost, and quality of life among these patients with those treated with laparotomy. METHODS A prospective study was conducted over 2 years in which all women with early stage endometrial carcinoma who could tolerate laparoscopic surgery were treated with laparoscopically assisted vaginal hysterectomy (LAVH), bilateral salpingo-oophorectomy (BSO), and lymphadenectomy. Women with a similar disease stage who underwent similar surgical procedures through laparotomy in the previous 2 years were used as the control group. Both groups were compared with regard to their characteristics, surgical outcome, and cost and were interviewed regarding their quality of life. RESULTS Eighty-six of 90 women with endometrial carcinoma underwent LAVH. The procedure was converted to laparotomy in 5 patients (5.8%). Laparoscopic surgery thus was successful in 90% of the women. There were no significant differences noted between those women who underwent LAVH and those who underwent total abdominal hysterectomy (TAH) (n = 57) with regard to patient characteristics, type of surgical procedure, preoperative and postoperative hematocrit, complications, patient recall of postoperative pain, and tumor recurrence. LAVH patients had significantly smaller body mass indices, a longer surgical time, more pelvic lymph nodes, a smaller decrease in postoperative hematocrit, received less pain medication, had a shorter hospital stay, an earlier return to full activity and work, and a higher level of satisfaction with their treatment, although their procedures had a higher cost compared with TAH patients. CONCLUSIONS The majority of women with early stage endometrial carcinoma can be treated with laparoscopy with an excellent surgical outcome, shorter hospitalization, earlier recovery, and improved quality of life, but with a higher financial cost. Cancer 2001;91:378–87. © 2001 American Cancer Society.

Women with ovarian cancer have poor overall survival rates, largely because the disease is so often diagnosed at an advanced, less curable stage. Because women with early ovarian cancer experience good survival rates, there is great interest in the study and detection of early disease. Familial ovarian cancer has been relevant to the study of early ovarian cancer in two different ways. First, women from ovarian cancer families often undergo prophylactic oophorectomy to prevent development of this disease. These ovaries have been studied for pathologic or molecular features that might represent early preinvasive disease. Second, screening tests to detect presymptomatic ovarian cancer have selectively targeted this population because of the increased positive predictive value of these tests in this population. A review of the clinical, pathologic, epidemiologic, and molecular biologic aspects of familial ovarian cancer provides a background to facilitate understanding these issues.

The aim of this study was to investigate the feasibility and safety of laparoscopic management of obese women with early stage endometrial cancer and to compare the surgical outcome, cost, hospital stay, recall of postoperative pain control, time to return to full activity and to work, and overall satisfaction among these women and those managed by laparotomy.We conducted a prospective study over 2 years applying laparoscopic surgery to all women with clinical stage I endometrial cancer and body mass indices (BMIs) between 28.0 and 60.0 who can tolerate such surgery. As a control, we used women with clinical stage I endometrial cancer and similar BMIs who underwent laparotomy in the previous 2 years. Both groups were compared in their characteristics, surgical outcome, cost, and hospital stay, and interviewed regarding time to recovery, recall of postoperative pain control, and overall satisfaction with their management.Forty of 42 obese women who presented with clinical stage I endometrial cancer during the study period were offered laparoscopic surgery. The procedure was converted to laparotomy in 3 (7.5%) patients. Laparoscopic surgery was thus successful in 88.1% of all obese women. There was no significant difference between women who underwent laparoscopy and those who underwent laparotomy in patient characteristics, proportion of women who underwent lymphadenectomy, complications, total cost, patients' recall of postoperative pain, and patients' satisfaction with management. Women who underwent laparoscopy had a significantly longer operative time, more pelvic lymph nodes removed, a smaller drop in postoperative hematocrit, less pain medication, and a shorter hospital stay (194.8 versus 137.7 min, P0.001; 11.3 versus 5.3, P0.001; 3.9 versus 5.4, P = 0.029; 32.3 versus 124.1 mg, P0.001; and 2.5 versus 5.6 days, P0.001, respectively). There was a trend toward earlier resumption of full activity and return to work among women who underwent laparoscopy (23.2 versus 45.0 days, P = 0.073, and 35.3 versus 67.0 days, P = 0.055, respectively).Most obese women with early stage endometrial cancer can be safely managed through laparoscopy with excellent surgical outcome, shorter hospitalization, and less postoperative pain than those managed through laparotomy.

Background and Objectives The extreme drug resistance (EDR) assay is an in vitro chemoresistance assay performed on tumor samples grown in culture and is claimed to predict drugs unlikely to produce response. Its clinical value in patients with epithelial ovarian cancer (EOC) has recently been questioned. The aim of this study is to describe EDR assay results and responses to chemotherapy among women with primary peritoneal adenocarcinoma (PPA) and to compare them with those of women with EOC. Methods Fresh tumor specimens from 20 consecutive women with PPA were tested for EDR to the following drugs: cisplatin, carboplatin, paclitaxel, doxorubicin, cyclophosphamide, ifosfamide, etoposide, hexamethylmelamine, and topotecan. They were then treated with cisplatin-based combination chemotherapy. The results of the EDR assay and response to chemotherapy were compared with those among women with EOC. Results There was no significant difference in the incidence of EDR to cisplatin, carboplatin, paclitaxel, doxorubicin, cyclophosphamide, ifosfamide, etoposide, hexamethylmelamine, and topotecan among patients with PPA and those with EOC. The response rate of PPA patients to chemotherapy was 80.0% and unrelated to EDR to the individual drugs used in combination chemotherapy. Conclusions The EDR profile and response to cisplatin-based chemotherapy among women with PPA were similar to those among women with EOC. These findings support treating both conditions similarly. EDR to individual drugs does not preclude response to combination chemotherapy. J. Surg. Oncol. 2000;73:148–152. © 2000 Wiley-Liss, Inc.

Objective. The aim of this study was to assess the role of first-line chemotherapy with paclitaxel and platinum in the treatment of advanced or recurrent cervix cancer. Methods. Twenty patients with advanced or recurrent cancer of the cervix with no prior chemotherapy and measurable disease were entered in a phase II trial from September 1995 to September 1998. Seventeen patients were treated with paclitaxel at 135 mg/m 2 over 24 h followed by cisplatin at 75 mg/m 2 every 4 weeks. Three patients with impaired renal function were treated with paclitaxel at 135 mg/m 2 over 3 h with carboplatin at 300 mg/m 2 . Results. A clinical response rate of 45% was noted (two complete responses and seven partial responses) with a median duration of 6 months (range: 1.5–9). The median progression-free interval and overall survival in patients with a clinical response was 10.5 and 13 months, respectively, compared to 4 ( P = 0.015) and 6 months in the nonresponders ( P = 0.14). Seven of nine patients (77.8%) with a clinical response are alive. Patients with recurrences outside the radiation field had twice the response rate (60%) than that of those within the radiated field. The chemotherapy was well tolerated; the most significant toxicity was grade 3/4 neutropenia (55%). No patient had discontinuation of chemotherapy due to toxicity. Conclusions. First-line chemotherapy with paclitaxel and platinum for advanced and recurrent cervix cancer is promising and deserves consideration for large phase III trials.

Objective: To assess the feasibility and complications of operative laparoscopy in women with high body mass indices (BMIs). Methods: Forty-seven consecutive patients with BMIs exceeding 30 who underwent operative laparoscopy were compared with 160 consecutive patients with BMIs of 30 or less who underwent the same procedure. Patient characteristics, ultrasound features of adnexal masses, and details of operative procedures were compared. Operative and postoperative complications, the percentage of failed laparoscopies, and length of hospital stay were compared between groups. Results: There were no significant differences between groups in terms of age, parity, menopausal status, history of laparotomy, ultrasound features of adnexal masses, complexity of laparoscopic procedures, and the presence and degree of adhesions at the time of laparoscopy. Estimated blood loss, operative times, operative and major postoperative complications, and lengths of hospital stay also did not differ significantly between women with high BMIs and those with low BMIs (180.3 versus 151.4 mL, P = .41; 150.5 versus 146.5 minutes, P = .78; 2.1 versus 1.9%, P = .90; 2.1 versus 1.9%, P = .91; and 2.3 versus 1.9 days, P = .51, respectively). However, women with BMIs exceeding 30 had a significantly higher incidence of procedure conversion to laparotomy (14.9 versus 5.6%, P = .04). Conclusion: Operative laparoscopy is safe and feasible in women with high BMIs. Although there is an increased chance of procedure conversion to laparotomy in these women, the morbidity and length of hospitalization associated with the procedure are similar to those among women with low BMIs.

Background and Objective The safety of laparoscopic surgery in women with a family history of ovarian cancer predicted to have benign disease has not been established. The objective of this study was to evaluate the feasibility and complications of operative laparoscopy and to describe the pathologic findings in this patient population. Methods Sixty-two consecutive women with a family history of ovarian cancer who elected prophylactic oophorectomy or had predicted benign adnexal disease were offered laparoscopic surgery. Patient characteristics, details of laparoscopic surgery, operative and postoperative complications, and histopathologic findings were recorded. Results Laparoscopy was converted to laparotomy in 2 patients (3.2%); 1 patient (1.6%) had an operative vascular complication, and 1 patient (1.6%) had postoperative bleeding. Median (range) estimated blood loss, operative time, and hospital stay were 50 ml (50–1,500), 120 min (60–290), and 1 day (0–9), respectively. Histopathologic findings included normal ovaries (n = 20), corpus luteum cyst (n = 16), follicular cyst (n = 8), endometriotic cyst (n = 7), serous cystadenoma (n = 5), epithelial hyperplasia (n = 4), dermoid cyst (n = 1), and fibrothecoma (n = 1). Conclusions Laparoscopic surgery is feasible and safe in women with a family history of ovarian cancer predicted to have benign disease and is associated with low blood loss and short hospital stay. Most ovaries removed are either normal or have benign disease. J. Surg. Oncol. 1999;72:9–13. © 1999 Wiley-Liss, Inc.

The aim of this study was to study the relationship between borderline ovarian tumors (BLOT) and epithelial ovarian cancer (EOC) by comparing the epidemiologic features of women with BLOT with those of women with EOC of similar histology.The epidemiologic features of 32 women with serous and mucinous BLOT were compared with those of 273 women with primary serous or mucinous EOC. We included all women with the documented respective histologic diagnoses admitted to Roswell Park Cancer Institute between 1982 and 1996 who returned a self-administered epidemiologic questionnaire which contained 44 items pertaining to reproductive, contraceptive, medical, social, dietary, occupational, and family histories of cancer. Individual variables between both groups were compared using the Student t test, chi2 analysis, the Mantel-Haenszel test, and the Wilcoxon nonparametric test. Two-tailed P0.05 was considered significant.The response rate to the questionnaire was 63% in the BLOT group and 60% in the EOC group. There was no significant difference between the two groups in geographic location, race, education, income, smoking, marital status, age at first pregnancy, age at first birth, history of hysterectomy, history of infertility, history of tubal surgery, use of hormone replacement therapy, or history of diaphragm or intrauterine contraceptive device use. There were no significant differences in family history of malignancy between women with BLOT and those with EOC. Women with BLOT were significantly younger than those with EOC (mean age 47 +/- 14.0 versus 56 +/- 13.7, P0.01). There was an apparent difference in oral contraceptive pill use between both groups. However, when we adjusted for age by stratification this difference was not significant (P = 0.089).The epidemiologic features of women with BLOT are similar to those of women with EOC with the exception of an earlier age of onset. These findings might be consistent with one etiology for both conditions.

The Papanicolaou smear has proven to be an excellent screening test for cervical cancer and has resulted in a significant decrease in mortality from invasive cervical cancer. A relatively high false-negative rate of Pap smears might cause failure to diagnose preinvasive disease, especially when coupled with an increased screening interval. This review focuses on the causes of and methods to reduce the number of false-negative Pap smears. In addition, we address the clinical significance of ambiguous Pap smear diagnoses, such as atypical squamous/glandular cells of undetermined significance, and suggest a scheme for management of patients with these diagnoses. Although efforts to reduce false-negative Pap smears are important, the most effective way of reducing mortality from invasive cervical cancer is universal, organized, population-based screening of all women.

Background and Objectives The clinical picture, response to therapy, and prognosis of women with diffuse malignant peritoneal mesotheliomas (DMPM) are ill defined. The purpose of this study is to report on the clinical picture, response to therapy, and survival of women with DMPM. Methods The study is a retrospective review of 15 women with the confirmed pathologic diagnosis of DMPM treated between 1964 and 1996. Survival curves were constructed according to the Kaplan-Meier method. The effect of different factors on survival was studied using the log-rank test. Two-tailed P values < 0.05 were considered significant. Results Clinical features included abdominal distension (11/15, 73%), abdominal pain (6/15, 40%), ascites (9/15, 60%), abdominal or pelvic masses (14/15, 93%), elevated CA-125 (4/4, 100%), thrombocytosis (4/15, 27%), and thrombo-embolic manifestations (3/15, 20%). The response rate to all first-line chemotherapy regimens was 30%. The response rate to paclitaxel/cisplatin was 66.7% and the toxicity was tolerable. The median survival of all patients was 12.5 months. Patients who underwent cytoreductive surgery survived longer than those who underwent biopsy only (median survival 13.5 vs. 6.0 months, P = 0.24). Patients who received chemotherapy survived significantly longer than those who did not receive chemotherapy (29.0 vs. 1.0 months, P = 0.03). Patients who responded to first-line chemotherapy survived significantly longer than those who did not respond (P = 0.04). Conclusions Cytoreductive surgery and chemotherapy, especially with paclitaxel and cisplatin, might be of benefit in women with DMPM. J. Surg. Oncol. 1999;70:6–12. © 1999 Wiley-Liss, Inc.

To determine the pathological, clinical, and therapeutic factors which had prognostic significance in women with extraovarian primary peritoneal carcinoma (EOPPC).A retrospective, clinicopathologic study was conducted of 75 women diagnosed with EOPPC. Diagnosis and assessment of prognostic pathological factors were based on the Gynecologic Oncology Group (GOG) criteria. Univariate and multivariate analyses were used to assess the following factors for their effect on overall survival: age, parity, presenting symptoms and signs, ascites, CA 125 level, history of oophorectomy, maximum ovarian dimension, histologic type, architectural and nuclear grades, number of mitosis and psammoma bodies, depth of ovarian invasion, estrogen and progesterone receptors (positive, negative), p53 overexpression (present, absent), performance status (GOG criteria), stage (FIGO criteria for ovarian cancer), debulking surgery (optimal versus suboptimal), first-line chemotherapy (platin-based without paclitaxel versus platin/paclitaxel), secondary cytoreduction, and second-line chemotherapy (paclitaxel-based versus no paclitaxel).The median overall survival of all patients was 23.5 months (95% CI 18.6, 39.8 months). The 5-year survival was 26.5% (SE 6.7%). p53 overexpression and estrogen and progesterone receptor positivity were demonstrated in 42.4, 50.0, and 6.3%, respectively. In univariate analysis, performance status, primary debulking surgery, stage, and age were significant on overall survival (P0.001,0. 001, 0.004, and 0.012, respectively). In multivariate analysis, only performance status (P0.001) and primary debulking surgery (P = 0. 03) were independent prognostic factors. Conclusions. Overall survival in women with EOPPC is affected significantly by performance status and primary debulking surgery as independent variables. To improve survival, efforts should be made to achieve optimal tumor cytoreduction at primary surgery.

Objective. The aim of this study was to determine the potential benefit and complications of prolonged salvage and maintenance chemotherapy among patients with recurrent epithelial ovarian cancer who achieve response to salvage chemotherapy. Methods. Patients with recurrent platinum-sensitive epithelial ovarian cancer who were treated between 1982 and 1996 and achieved complete response to platinum-based salvage chemotherapy were offered prolonged (1 year) monthly salvage followed by maintenance (every 8 weeks) chemotherapy. Patients who accepted such treatment ( n = 16) were compared to those who refused and discontinued therapy ( n = 11) with regard to overall survival from time of initial diagnosis and overall and disease-free survival from time of recurrence. Chemotherapy-related toxicity in the study group was recorded. Survival curves were constructed according to the Kaplan and Meier method and survival curves were compared using the log-rank test. Results. Patients in the study and control groups were similar with regard to age, stage, histology, grade, performance status, primary cytoreductive surgery, type of primary and salvage chemotherapy, and method of assessment of tumor response. The study group had a significantly longer disease-free interval from date of recurrence than the control group (median: 35.0 versus 6.0 months, respectively, P = 0.001). The study group had longer overall survival from date of recurrence than the control group. However, the difference did not achieve statistical significance (median: 119 versus 90 months, respectively, P = 0.056). There was no significant difference between the study group and the control group as to survival from date of initial diagnosis (median: 157 versus 124 months, respectively, P = 0.28). Chemotherapy-related toxicity was minimal. Conclusions. Prolonged salvage and maintenance chemotherapy is a safe method of treatment that may extend disease-free interval among patients with platinum-sensitive recurrent epithelial ovarian cancer who achieve response to salvage chemotherapy. These preliminary results need to be confirmed by a larger prospective randomized trial.

The purpose of this study was to determine if tumor estrogen receptor (ER) or progesterone receptor (PR) status were significant prognostic variables of survival and progression-free survival among patients with International Federation of Gynecology and Obstetrics (FIGO) stage III and IV epithelial ovarian cancer. Tumor steroid receptor status was evaluated among 67 consecutive patients who underwent primary surgery from June 1983 through September 1990. Characteristics of receptor-negative and receptor-positive populations were compared by chi-square analysis. Univariate and multivariate analyses were used to identify variables prognostic of survival and progression-free survival. Fifty-one of 67 patients (76.1%) had ER-positive tumors and 31 (46.3%) patients had PR-positive tumors. Significant differences between receptor-positive and receptor-negative populations were not observed. Neither univaritate nor multivariate analysis identified ER or PR status as significant prognostic variables of survival (p = 0.93 and p = 0.06. rcspectively). Progesterone receptor-positive status was a significant prognostic variablc of progression-free survival in both univaritate (p = 0.03) and multivariate (p =0.04) analyses even after adjustment for residual disease and patient age. Estrogen receptor status was not a significant prognostic indicator of progression-free survival in either univariate or multivariate analyses. Progesterone receptor-positive tumor status is shown to be an independent prognostic variable of improved progression-free survival among patients with advanced epithelial ovarian cancer.

To assess the rate of complications of indwelling caval catheter (ICC) use on a gynecologic oncology service and to compare complication rates between subcutaneous ports and external catheters.A retrospective analysis of 185 patients who underwent 216 ICC placements between April 1, 1987 and April 1, 1997, was performed. Patient and catheter characteristics were analyzed as they related to the rate of pneumothorax, bacteremia, and deep neck and thoracic vein thrombosis (DNVT).A total of 216 ICCs were placed including 152 implanted ports and 64 external catheters. Pneumothorax occurred in 2% of ICC insertions. Bacteremia complicated 16% of ICCs. Multivariate analysis demonstrated that external catheters (P0.01) and neutropenia (P0.01) were independent risk factors for bacteremia. DNVT complicated 6% of ICCs and was observed significantly (P0.02) more frequently among 11 catheters placed in patients with clear cell malignancies of the female reproductive tract. Unplanned catheter removal occurred significantly (P0.01) more frequently among patients with external catheters compared to implanted devices.Implantable ICCs appear to offer a significant advantage compared to external devices with regard to the development of bacteremia and unplanned catheter removal. Though catheter type, neutropenia, and TPN are associated with an increased incidence of bacteremia, multivariate analysis does not include TPN as an independent risk factor for ICC-related bacteremia. A significant increase in the rate of DNVT among a small number of patients with clear cell gynecologic malignancies warrants further study.

Objective. The extreme drug resistance (EDR) assay has been correlated with failure of response to chemotherapy in greater than 99% of patients. The goal of this study is to correlate the results of the EDR assay to response to first-line paclitaxel/cisplatin among patients with epithelial ovarian cancer. Methods. Seventy-five of 100 patients with epithelial ovarian cancer for whom EDR assay was performed were treated with weekly induction cisplatin (1 mg/kg body wt) × 4, followed by monthly paclitaxel (135 mg/m 2 ) and cisplatin (75 mg/m 2 ) × 6 and were evaluable for correlation of response to chemotherapy and EDR assay. Specimens for EDR assay were obtained at primary surgery and the EDR assay was performed by Oncotech, Inc. Response to chemotherapy was correlated to EDR assay results regarding paclitaxel and cisplatin. Results. Among 75 evaluable patients, the prevalence of EDR to paclitaxel was 20.0% ( n = 15) and to cisplatin it was 2.7% ( n = 2). Only 1 patient (1.3%) exhibited EDR to both paclitaxel and cisplatin. Surgical assessment of response was performed in 42 patients; 33 patients were clinically evaluable. The overall response rate was 85.3%. The overall response rate for patients whose tumors demonstrated no EDR to either paclitaxel or cisplatin did not differ significantly from that for patients whose tumors demonstrated EDR to at least one of these two drugs (86.4% versus 81.3%, respectively, P = 0.692). Similarly, the complete surgical response rate for both groups did not differ significantly (25.4% versus 12.5%, respectively, P = 0.34). A single patient whose tumor exhibited EDR to both paclitaxel and cisplatin had tumor progression. The sensitivity, specificity, positive predictive value, and negative predictive value of the EDR assay were 79.6, 27.0, 86.0, and 19.0%, respectively. Conclusions. EDR to paclitaxel does not preclude response to the combination of paclitaxel and cisplatin as primary therapy for patients with epithelial ovarian cancer. The role of the EDR assay in the primary management of patients with epithelial ovarian cancer remains to be determined.

Background and Objectives: The incidence and significance of lymph node involvement in patients with primary peritoneal adenocarcinoma (PPA) are unknown. The aim of the current study is to report on the incidence and significance of clinically or surgically detectable lymphadenopathy in women with PPA. Methods The study is a retrospective clinical review of patients with the confirmed diagnosis of PPA treated at Roswell Park Cancer Institute between 1982 and 1996. Patients with clinically or surgically detectable lymphadenopathy confirmed on histologic examination to be secondary to metastases from PPA were identified and compared to patients with negative lymph nodes with regard to clinicopathologic characteristics, treatment, response to treatment, and survival. Results Seventy-two patients with PPA were identified. Pelvic and periaortic lymph node biopsies or sampling were performed in 35% of the patients. In 8/72 patients (11%), lymphadenopathy was one of the presenting clinical or surgical findings. The clinicopathologic features, treatment, response to first-line chemotherapy, and estimated median overall survival were not different in patients with or without lymph node involvement (71.4% vs. 69.7%, P = 1.0, and 21.5 vs. 23.5 months, P = 0.14). Conclusions Lymph node involvement is not an infrequent occurrence in patients with PPA and does not seem to be of adverse prognostic significance. J. Surg. Oncol. 1998;68:144–148. © 1998 Wiley-Liss, Inc.

Objective: To describe the epidemiologic features of women with extraovarian primary peritoneal carcinoma and compare them with those of women with primary epithelial ovarian cancer. Methods: The epidemiologic features of 50 women with extraovarian primary peritoneal carcinoma were compared with those of 503 women with primary epithelial ovarian cancer. We included all women with the respective diagnoses admitted to the Roswell Park Cancer Institute between October 1982 and October 1996 who returned an epidemiologic questionnaire. Epidemiologic features of the study and control groups were extracted from a database compiled from a self-administered questionnaire that has been given to patients as part of the admission process since 1982. Individual variables between the study and control groups were compared using Student t test, χ2 analysis, and Wilcoxon nonparametric test. Two-tailed P < .05 was considered significant. Results: We found few significantly different epidemiologic features between women with extraovarian primary peritoneal carcinoma and those with primary epithelial ovarian cancer. Women with extraovarian primary peritoneal carcinoma were significantly older (mean age 63.8 versus 55.0 years, P < .001), had later menarche (13.3 versus 12.8 years, P = .024), and were less likely to have used perineal talc powder (26.0% versus 48.1%, P = .003). There were no significant differences with respect to reproductive history, contraceptive use, or use of hormone replacement therapy. A larger proportion of ovarian cancer patients reported a family history of breast cancer, but the numbers were too small to reach statistical significance. Conclusion: The epidemiologic features of women with extraovarian primary peritoneal carcinoma compared with women with primary epithelial ovarian cancer show few differences. The observed areas of difference warrant further research to determine whether they suggest the occurrence of distinct disease entities.

Purpose: To assess the efficacy of diagnostic laparoscopy at the time of interstitial brachytherapy in patients with FIGO Stages IIB-IVA cervical carcinoma, who were not candidates for conventional brachytherapy after completion of whole pelvic radiation. Materials and Methods: Six patients with FIGO Stages IIB-IVA cervical carcinoma completed whole pelvic radiation (WPR) and were assessed for the placement of conventional intracavitary brachytherapy. Three patients (Stage IIB) received 50.40 Gy WPR and three (Stage IIIA-VA) received 61.20 Gy WPR. Because distorted vaginal anatomy precluded the placement of standard intracavitary brachytherapy equipment, interstitial therapy was selected. To minimize the risk of source misplacement, needles were placed with laparoscopic guidance. 192 Iridium was utilized as a source of radiation. Results: A total of 98 needles were placed under direct laparoscopic guidance. The median interstitial brachytherapy tumor dose was 20.00 Gy (range 19.00-41.20 Gy). Eleven perforations in the pelvic peritoneum and/or bladder were identified intraoperatively in 5 of the 6 patients, leading to immediate repositioning of needles. No acute or short-term morbidity related to the procedure was appreciated. Conclusion: Interstitial brachytherapy offers an alternative for intracavitary radiation therapy for selected patients, in whom adequate placement of intracavitary afterloading equipment is precluded by abnormal pelvic geometry. Historically, the placement of interstitial sources has been a procedure that was performed without visualization of the pelvic cavity. A major concern is direct injury to pelvic viscera and intestine. The use of diagnostic laparoscopy at the time of placement of interstitial brachytherapy may avert potential complications from misapplication of interstitial sources. Longer follow-up is required to substantiate these results.

Objective. The objective was to study the feasibility and complications of the use of the inferior gluteal flap in the difficult vaginal, perineal, and vulvar reconstruction among women treated for gynecologic cancers. Methods. A prospective pilot study is reported. Between October 1994 and May 1996, seven patients underwent either unilateral ( n = 3) or bilateral ( n = 4) inferior gluteal flaps for primary reconstruction of extensive vulvar, perineal, and vaginal defects. Results. The median age of the patients was 59 years (range, 40–70). The indications for the construction of the flaps were radical resection of recurrent vulvar cancer ( n = 2), radical resection of stage IV vulvar cancer ( n = 2), resection of recurrent Paget's disease of the vulva ( n = 1), resection of perineal recurrence of cancer of the cervix ( n = 1), and resection of enteroperineal fistula following total pelvic exenteration ( n = 1). The median surface area of the vulvar and perineal defect was 113 cm 2 (range, 10.5–448 cm 2 ). The median operative time for both the extirpative and the reconstructive procedures was 270 min (95–685 min) and the median estimated blood loss was 200 mL (50–950 mL). The median postoperative hospital stay was 15 days (9–29). None of the patients experienced complete graft loss. Two patients suffered necrosis of the tip of the flap that resulted in minimal wound dehiscence which healed by secondary intention, and one patient suffered graft separation which required graft revision and reconstruction. The patients were followed for a median of 11 months (3–26 months). No late complications of the reconstructive surgery were recorded. Conclusions. The inferior gluteal flap can be safely used for the reconstruction of the difficult and extensive vulvar, perineal, and vaginal defects with excellent results.

BACKGROUND The clinical significance of p53 overexpression in patients with ovarian carcinoma is uncertain. Previous studies have yielded conflicting results and have been hampered by small patient populations, failure to account for other well-known prognostic variables in multivariate analysis, and failure to account for the grade of p53 overexpression. The aim of this study was to investigate the independent prognostic significance of p53 overexpression in patients with primary ovarian epithelial cancer (POEC). METHODS Tumors obtained from 221 patients with primary ovarian epithelial cancer (POEC) (Stages I-IV) were studied for p53 overexpression semiquantitatively by immunohistochemical techniques. The median duration of follow-up of surviving patients was 7 years. The presence or absence and degree of p53 overexpression were correlated with the clinicopathologic features of the study population and overall survival. Survival curves were constructed according to the Kaplan-Meier method, and differences in survival were assessed with the log rank test. The prognostic significance of p53 overexpression for survival was assessed in a multivariate analysis with the Cox proportional hazards model. RESULTS One hundred seven tumors (48.4%) exhibited p53 overexpression. The overexpression was graded as mild in 16.7% of cases, moderate in 5.9%, and strong in 25.8%. p53 overexpression was associated with advanced stage (P = 0.04), higher grade (P = 0.0003), serous histology (P = 0.0018), and patient age > 61 years (P = 0.013). In univariate analysis, p53 overexpression was a significant prognostic factor (P = 0.049 for any degree of overexpression, P = 0.03 for strong overexpression). However, in multivariate analysis, after adjustment for stage and size of residual tumor following cytoreductive surgery, p53 overexpression did not retain statistical significance. Survival curves for patients with different stages and grades of tumor differentiation did not demonstrate a difference in survival among patients with no p53 overexpression, compared with those who demonstrated any degree of p53 overexpression or compared with those who demonstrated strong p53 overexpression. CONCLUSIONS p53 overexpression is not an independent prognostic factor for patients with primary ovarian epithelial cancer. Cancer 1997; 80:892-8. © 1997 American Cancer Society.

Compliance with estrogen replacement therapy (ERT) following surgical menopause is poor. In women who have a family history of ovarian cancer, fear of the oncogenic potential of estrogen might affect compliance with ERT following oophorectomy. Compliance with ERT in such a select group of women has not been previously reported. The aim of the present study was to report on compliance with and side effects of ERT in women with a family history of ovarian cancer who underwent oophorectomy either prophylactically or for benign disease. Eighty women with a family history of ovarian cancer who underwent oophorectomy at Roswell Park Cancer Institute were followed for a median duration of 4.2 years (range, 5 months to 14 years). Of the 76 women who were given prescriptions for ERT, the rates of commencement and maintenance of ERT at 1, 2, and 5 years were calculated. Side effects related to the different modalities of ERT were recorded. Seventy-one of 76 women (93.4%) who were given prescriptions for ERT initiated treatment. The rate of commencement of ERT was higher in premenopausal than in postmenopausal women (98.3% versus 75%, respectively, P = 0.003). Except for one patient who developed breast cancer after the oophorectomy and was advised to stop estrogen, all patients said they continued to use ERT. The maintenance rates at 1, 2, and 5 years were 100% as per patients' history. The pharmacy records for ERT prescription refills were reviewed for 52 patients who were on ERT for more than 1 year. ERT compliance was confirmed in 42 patients (80.7%). Seven of 30 patients (23.3%) who retained their uterus developed irregular uterine bleeding and 4 underwent endometrial biopsies. The incidence of irregular uterine bleeding was significantly higher after continuous compared to cyclic estrogen and progestogen (37.6 and 7% respectively, P = 0.049). Four patients (5.6%) complained of hot flashes and were managed by changing the dose or formula of estrogen. Compliance with ERT among patients with a family history of ovarian cancer who underwent oophorectomy either prophylactically or for benign disease was excellent. The presence of the uterus and the incidence of irregular uterine bleeding did not affect patients' compliance with ERT.

Primary peritoneal adenocarcinoma is a relatively newly identified disease entity whose clinical behavior is not fully recognized. We report a case of a patient with progressive primary peritoneal adenocarcinoma who developed brain metastases and died shortly afterward. The incidence of central nervous system metastases in 72 patients with documented primary peritoneal adenocarcinoma was 1.4%. The risk factors, clinical behavior, and prognosis of patients with primary peritoneal adenocarcinoma metastatic to the central nervous system seem to be similar to those of patients with epithelial ovarian cancer metastatic to the central nervous system.

Twenty patients with advanced or recurrent cervical cancer were treated with bleomycin 30 U, ifosfamide 5 g/m2, and cisplatin 50 mg/m2 (BIP) every 28 days in a phase II trial. The primary purpose of this study was to compare response rate, survival, and toxicity of this regimen with results obtained in a similar group of patients treated with cisplatin 1 mg/kg per week for six courses followed by cisplatin, 20 mg/m2, plus ifosfamide 1.2 g/m2 daily for 3 days every 28 days. Four of 17 evaluable patients (23.5%) treated with BIP demonstrated a response to therapy (complete response 11.7%; partial response 11.7%). The median duration of response was 8.5+ months (range, 6+ to 24 months). These data do not differ significantly (P = 0.76) from a response rate of 27.5% among patients treated with cisplatin plus ifosfamide (PI). A significant (P = 0.003) increase in myelotoxicity was observed among patients treated with BIP versus those treated with PI. The median survival of patients treated with BIP of 13.5+ months (range, 8+ to 24 months) does not differ significantly from the median survival of 9+ months (3 to 26+ months) among patients treated with PI. The addition of bleomycin and dose-escalated ifosfamide did not significantly improve response rate or survival among patients with advanced or recurrent cervical cancer and resulted in a significant increase in myelotoxicity.

We present the first reported case of cancer-associated retinopathy with uterine sarcoma. A 65-year-old woman presented in August 1990 with loss of vision, photophobia, and visual field restriction. Antiretinal antibodies were elevated. A diagnosis of cancer-associated retinopathy was made, the patient was started on prednisone, and a workup for malignancy was initiated. The patient was found to have uterine sarcoma. She underwent an extrafascial hysterectomy with bilateral salpingo-oophorectomy followed by eight courses of chemotherapy (carboplatin and cyclophosphamide). After that, the patient's vision improved, her visual field stabilized. She was doing well when last seen, in July 1994. The literature regarding cancer-associated retinopathy and paraneoplastic syndromes associated with gynecologic malignancies is reviewed.

To correlate Papanicolaou smear findings with the wet mount and cervical culture results in asymptomatic patients, and to review the value of doing wet mount and/or cervical cultures in these patients at the time of Papanicolaou smear.Asymptomatic women presenting for routine Papanicolaou smears at Sinai Samaritan Medical Center, Milwaukee, Wisconsin, between January 1991 and January 1994 were studied by preparing wet mount (saline and potassium hydroxide preparations) and cervical cultures for Chlamydia trachomatis and Neisseria gonorrhoeae at the same visit. Fisher exact test and Pearson chi 2 statistics were applied.Nine hundred sixty-three patients were studied. Nearly 50% of our asymptomatic young urban women had a vaginal and/or cervical infection. Papanicolaou smears with inflammation were associated with bacterial vaginosis (P.0001), excess white blood cells (P.0001), trichomoniasis (P.0001), abnormal wet mounts in general (P.0001), and positive cervical cultures for C trachomatis and/or N gonorrhoeae (P.001). Papanicolaou smears showing atypical cells of undetermined significance were associated with bacterial vaginosis (P.001) and abnormal wet mounts in general (P.03). Seventy-five percent of patients with positive cervical cultures had abnormal wet mounts. Eighty-three percent of the patients whose initial Papanicolaou smear showed inflammation and whose initial wet mount was abnormal had a normal Papanicolaou smear when the wet mount became normal.Preparing wet mounts at the time of Papanicolaou smear in asymptomatic young urban women will help in the interpretation of minimally abnormal smears and will probably decrease the need for repeat smears and colposcopy. Simultaneous cervical cultures would not add much information for such interpretation.

Background. Synchronicity of renal cell carcinoma and gynecologic malignancies is a rare condition and standardized treatment does not exist. Cases. Three cases of synchronous renal cell carcinoma and gynecologic malignancies are described. All three cases underwent optimal cytoreductive surgery for the gynecologic malignancy and a radical nephrectomy for the renal cell carcinoma. Adjuvant treatment, after surgery, was individualized in each case. Estrogen and progesterone receptors were positive in all the gynecologic tumors but negative in the renal cell tumors. Conclusions. This is apparently the largest report of synchronous renal cell carcinoma and gynecologic malignancies. Despite this rare condition, surgery should still be considered as primary treatment for these patients.

The study was performed to assess response rate, progression-free interval (PFI), and side effects of the combination paclitaxel and carboplatin as second-line therapy among women with platinum-sensitive epithelial ovarian carcinoma (EOC). Thirty women who achieved partial surgical response at second-look surgery (n = 8) or who had recurrence (n = 22) more than 6 months after treatment with platinum-based chemotherapy were treated with paclitaxel (135 mg/m 2 for 3 hours) and carboplatin (area under the concentration-time curve 5) every 3 weeks. Response rate, PFI, and side effects of treatment were recorded. One hundred sixty-seven cycles of treatment (median = 6, range = 2-11) were administered. Among 22 patients with measurable or assessable disease, 14 had complete response and 3 had partial response. Five patients had progressive disease. The overall response rate was 77%. The median PFI was 10 months (range = 1-29). Among 22 patients in whom recurrence or progression developed after second-line therapy, the median interval was 9 months (range = 1-26). The incidence of grade III or IV neutropenia, leukopenia, and thrombocytopenia was 48%, 27%, and 3%, respectively. One patient discontinued treatment secondary to persistent thrombocytopenia. Eight patients died secondary to their disease. It was concluded that the combination paclitaxel and carboplatin has a high success rate, long duration of response, and is well tolerated as a second-line therapy among patients with platinum-sensitive EOC.

BACKGROUND The effect of the laparoscopic surgical approach on the survival of women with endometrial carcinoma remains unclear. The objectives of the current study were to assess the effect of laparoscopic surgery on the survival of women with early-stage endometrial carcinoma and to analyze the factors that affect such survival. METHODS A retrospective review of women presenting with clinical stage I endometrial carcinoma (according to the 1988 International Federation of Gynecology and Obstetrics Staging System) was performed. Women treated with laparoscopy were compared with those treated with laparotomy with regard to their characteristics, surgical procedure, treatment, surgical stage, histology, tumor grade, and recurrence-free and overall survival. Factors affecting survival (surgical approach, histology, grade, and surgical stage) were evaluated using multivariate analysis and survival curves were constructed using Kaplan–Meier analyses. RESULTS One hundred women underwent laparoscopy and 86 underwent laparotomy. Both groups were similar with regard to age, parity, menopausal status, lymphadenectomy, surgical stage, tumor grade, histology, and postoperative radiation therapy. Women who underwent laparoscopy and those who underwent laparotomy had similar 2-year and 5-year estimated recurrence-free survival rates (93% vs. 94% and 90% vs. 92%, respectively), as well as similar 2-year and 5-year overall survival rates (98% vs. 96% and 92% vs. 92%, respectively). There was no apparent difference with regard to the sites of recurrence between both groups. In univariate and multivariate analyses, surgical stage, tumor grade, and histology (but not the surgical approach) were found to have a significant effect on survival. CONCLUSIONS Although longer follow-up is needed, the survival of women with early-stage endometrial carcinoma does not appear to be worsened by laparoscopy. Surgical stage, tumor histology, and tumor grade were found to significantly affect survival regardless of the surgical approach used. Cancer 2002;95:1894–901. © 2002 American Cancer Society. DOI 10.1002/cncr.10928

OBJECTIVE: To determine the prevalence of benign endometrial cells on Papanicolaou smears from postmenopausal women and to compare the prevalence and histologic diagnosis in women who use hormone replacement therapy (HRT) with those who do not. METHODS: Papanicolaou smear diagnoses from postmenopausal women and women over age 50 between April 1995 and December 1998 were retrieved and linked with follow-up smears and biopsies. Hormone status of women with benign endometrial cells smears was obtained from requisition forms or phone conversation with primary care providers. All surgical pathology material as well as Papanicolaou smears from women subsequently diagnosed with endometrial adenocarcinoma were reviewed. Relative prevalence with 95% confidence intervals was determined. RESULTS: A total of 589 of 52,662 Papanicolaou smears from postmenopausal women were diagnosed with benign endometrial cells, a prevalence of 1.1%. Also, HRT was reported in 16,073 (31%), no HRT was reported in 33,170 (63%), and hormone status was unknown in 3379 (6%). Smears from 245 HRT users, 324 nonusers, and 20 with unknown hormone status were diagnosed with benign endometrial cells. There was a significant increased prevalence of benign endometrial cells in women on HRT compared with nonusers (relative prevalence 1.56, 95% confidence interval 1.32, 1.84, P < .001). Among 436 women with known hormonal status and follow-up, 12 (2.7%) had endometrial carcinoma, three (1.5%) in HRT users and nine (3.7%) in nonusers (P = .175). In addition, HRT users had significantly less abnormal endometrial histology than non-HRT users (2.6% versus 7.4%, P = .025). CONCLUSION: We found that HRT is significantly associated with an increased prevalence of benign endometrial cells on Papanicolaou smears. Women on HRT who have benign endometrial cells on their Papanicolaou smears, however, have less abnormal endometrial histology compared with women not using HRT who have benign endometrial cells on their Papanicolaou smears.

Objective. Malignant mixed mullerian tumor (MMMT) of the ovary is a rare tumor with a dismal prognosis. The most effective therapy is unknown. The current study was undertaken to characterize a group of patients treated as if they had aggressive epithelial ovarian tumors, with cytoreductive surgery and combination paclitaxel/platinum chemotherapy. Methods. Retrospective analysis of data obtained from tumor registry and hospital records of cases of malignant mixed mullerian tumor between January 1, 1992 and January 1, 2000 treated at the Massachusetts General Hospital, Brigham and Women's Hospital, and University of Vermont was performed. Only patients treated with combination paclitaxel and platinum therapy were included in the analysis. Data were collected regarding cytoreduction, response to chemotherapy, disease-free interval, and survival. Results. Fifty-five patients were identified with MMMT. Twenty-eight patients with a clearly ovarian primary had received treatment with combination paclitaxel and platinum. Paclitaxel and carboplatin was given as second-line therapy in 2 patients who had chemoresponsive but incurable disease; the remaining patients were treated with paclitaxel and platinum therapy as first-line therapy. These 28 patients had a median (range) age of 66 (46–84 years) and stage was I in 2 patients, II in 3, III in 18, and IV in 5. Treatment was generally well tolerated. Sixteen patients of 26 treated with paclitaxel and platinum as first-line therapy achieved a complete clinical response (55%) and 6 patients achieved partial response for a total response rate of 72%. Optimal cytoreduction was associated with increased time to recurrence ( P = 0.001) but not with survival. Overall median survival for the 28 patients is 27.1 months. Conclusion. Although treatment fails many patients, a minority of patients with MMMT in this highly selected population do unexpectedly well. An aggressive approach with surgery and combination paclitaxel–platinum chemotherapy appears to offer very effective therapy.

We report a case of systemic beta-2 microglobulin amyloidosis (B2M) in which the initial clinical presentation was that of bilateral ovarian masses. A 56-year-old woman who had been on renal dialysis for 12 years because of familial glomerulonephritis underwent a total hysterectomy and bilateral salpingo-oophorectomy for suspected ovarian malignancy. Pathologic findings included extensive amyloid infiltration of both ovaries, fallopian tubes, and focal perivascular deposition in the myometrium. The diagnosis of amyloidosis was confirmed with Congo red stain, B2M immunohistochemistry, and electron microscopy. Systemic amyloidosis in renal dialysis patients commonly presents as bone and/or joint disease, although visceral involvement has been reported. This is the first report in the English language literature to describe amyloidosis presenting as bilateral ovarian masses.

Background and Objectives The difference between the epidemiologic features of women with colorectal cancer and those with ovarian cancer has not been thoroughly studied. The aim of this study is to review the epidemiologic features of women with colorectal cancer and compare them with those of women with ovarian cancer. Methods The epidemiologic features of 705 women with colorectal cancer were compared with those of 503 women with primary epithelial ovarian cancer. Both groups included all women with the confirmed respective histologic diagnoses admitted to Roswell Park Cancer Institute between 1982 and 1996 who returned a voluntary self-administered epidemiologic questionnaire. Results Women with ovarian cancer were significantly younger, had higher education and income, had fewer children, and were more likely to have never been married and nulligravid than those with colorectal cancer. There was a significant difference in the contraceptive history between both groups among women ≥45 years of age. More women with ovarian cancer had a family history of ovarian cancer and more women with colorectal cancer had a family history of colorectal cancer. Conclusions The epidemiologic features of women with colorectal cancer are different from those with ovarian cancer. The difference between both groups might indicate difference in the environmental or genetic etiology of both cancers. J. Surg. Oncol. 2001;76:283–288. © 2001 Wiley-Liss, Inc.

The purpose of this study was to assess the effect of increasing surgeon's experience in the laparoscopic management of women with endometrial cancer on the surgical outcome of these patients.Seventy-five consecutive women with clinical stage I endometrial cancer who underwent laparoscopically assisted vaginal hysterectomy, bilateral salpingo-oophorectomy, and pelvic lymph node sampling by the same surgeon using the same technique and instruments over a period of 2 years were divided into three equal groups based on the date of surgery. The three groups were compared in patient characteristics and surgical outcome using one-way analysis of variance and Pearson chi(2) tests.The three groups were similar in patient characteristics. There was no significant difference in estimated amount of blood loss, rate of conversion to laparotomy, complications, and length of hospital stay among the three groups. There was a significant decrease in operating time (means: 231.0 min for group 1, 175.0 min for group 2, and 167.7 min for group 3, P0.001) and a significant increase in the number of pelvic lymph nodes harvested (7.8 for group 1, 10.6 for group 2, and 11.9 for group 3, P0.05) with increasing surgeon's experience.A learning curve is demonstrated in the laparoscopic management of women with endometrial cancer. With increasing surgeon's experience, there is significant decrease in operating time and increase in the number of pelvic lymph nodes removed.

A 57-year-old woman presented with urinary retention, diarrhea, rectal bleeding, a cystic pelvic mass with thick irregular borders posterior to the vagina displacing the cervix and the bladder, and an intact vaginal mucosa. The patient underwent exploratory laparotomy on the assumption that she had an ovarian neoplasm. The mass originated from the posterior vaginal wall and was consistent with primary squamous cell carcinoma. The patient was treated with surgical cytoreduction followed by external radiation therapy and weekly cisplatin with good response. One year following treatment the patient remains without evidence of disease. Primary vaginal squamous cell carcinoma arising from the posterior vaginal wall can present as a cystic pelvic mass resembling an ovarian neoplasm. Cytoreductive surgery followed by chemoradiation might be of value in some patients with primary vaginal carcinoma.