Laparoscopic surgery in endometriosis.

Endometriosis (the presence of endometrial glands and stroma outside of the uterine cavity) is a common gynecologic problem affecting 10% of women in the general population, 40% of women with infertility and 60% of women with chronic pelvic pain. Laparoscopy has revolutionized management of women with endometriosis. Diagnosis of endometriosis depends on visualization of endometriotic lesions and histologic confirmation. Endometriotic implants have a multitude of appearances: powder burns, red, blue-black, yellow, white, clear vesicular and peritoneal windows. Diagnostic laparoscopy is often combined with operative procedures to treat manifestations and symptoms of endometriosis. This often includes removal or laser vaporization of endometriotic implants, lysis of adhesions, restoration of normal anatomy and removal or fulguration of ovarian endometriomas (conservative surgery). Severe incapacitating endometriosis, recurrent endometriosis following conservative surgery and symptomatic endometriosis in women not desiring more children is often treated by laparoscopic unilateral or bilateral salpingo-oophorectomy or laparoscopically-assisted vaginal hysterectomy with bilateral salpingo-oophorectomy (radical surgery). Endometriosis affecting the appendix, ureters, bladder wall and rectosigmoid colon could be treated with laparoscopic appendectomy, excision of endometriotic implants or laparoscopic colectomy and anastomosis, respectively. Hydrodis-section and use of CO2 super pulsed laser aid in removal of adherent endometriotic implants without damage to normal underlying structures. Robotic-assisted laparoscopic surgery promises to provide advantages in the management of women with severe endometriosis secondary to 3-dimensional visualization, decreasing surgeon's fatigue and hand tremors and improving surgical precision.

Effect of menopausal status on insulin-stimulated glucose disposal: comparison of middle-aged premenopausal and early postmenopausal women.

OBJECTIVE: Studies in animal models suggest that ovarian hormone deficiency is associated with the development of insulin resistance. In women, ovarian hormone levels are dramatically reduced after the menopause transition. However, the effect of the menopause transition on insulin sensitivity is unclear. Thus, we examined the effect of menopausal status on insulin sensitivity. RESEARCH DESIGN AND METHODS: Insulin-stimulated glucose disposal was measured in 43 middle-aged premenopausal women (47 +/- 3 years of age) during the luteal phase of the menstrual cycle and 40 early postmenopausal women (51 +/- 4 years; time since menopause, 21 +/- 13 months) using the hyperinsulinemic-euglycemic clamp technique. Body composition was measured by dual-energy X-ray absorptiometry and abdominal fat distribution by computed tomography RESULTS: No difference in fat-free mass (FFM) was found between groups. Total body (P < 0.01), subcutaneous abdominal (P < 0.05), and intra-abdominal (P < 0.01) adiposity were greater in postmenopausal women compared with premenopausal women. No differences in insulin-stimulated glucose disposal were found between premenopausal and postmenopausal women on an absolute basis (pre, 436 +/- 130 vs. post, 446 +/- 120 mg/min), when expressed relative to FFM (pre, 10.7 +/- 3.0 vs. post, 11.5 +/- 3.6 mg x kg(-1) FFM x min(-1)) or when statistically adjusted for FFM (pre, 436 +/- 125 vs. post, 445 +/- 126 mg/min). CONCLUSIONS: These results suggest that menopausal status does not affect insulin sensitivity, as measured by the hyperinsulinemic-euglycemic clamp technique.

What are the physical characteristics associated with a normal metabolic profile despite a high level of obesity in postmenopausal women?

Although obesity is often associated with insulin resistance and a cluster of metabolic disturbances, the existence of a subgroup of healthy but obese individuals has been postulated. It is unclear why some obese individuals fail to show traditional risk factors associated with the insulin resistance syndrome despite having a very high accumulation of body fat. To address this issue, we identified and studied a subgroup of metabolically normal but obese (MNO) postmenopausal women to gain insight into potential physiological factors that may protect them against the development of obesity-related comorbidities. We carefully examined the metabolic characteristics of 43 obese, sedentary postmenopausal women (mean +/- SD, 58.0 +/- 6.0 yr). Subjects were classified as MNO or as metabolically abnormal obese (MAO) based on an accepted cut-point for insulin sensitivity (measured by the hyperinsulinemic/euglycemic clamp technique). Thereafter, we determined 1) body composition (fat mass and lean body mass), 2) body fat distribution (abdominal visceral and sc adipose tissue areas, midthigh sc adipose tissue and muscle attenuation), 3) plasma lipid-lipoprotein levels, 4) plasma glucose and insulin concentrations, 5) resting blood pressure, 6) peak oxygen consumption, 7) physical activity energy expenditure, and 8) age-related onset of obesity with a questionnaire as potential modulators of differences in the risk profile. We identified 17 MNO subjects who displayed high insulin sensitivity (11.2 +/- 2.6 mg/min.kg lean body mass) and 26 MAO subjects with lower insulin sensitivity (5.7 +/- 1.1 mg/min.kg lean body mass). Despite comparable total body fatness between groups (45.2 +/- 5.3% vs. 44.8 +/- 6.6%; P: = NS), MNO individuals had 49% less visceral adipose tissue than MAO subjects (141 +/- 53 vs. 211 +/- 85 cm(2); P: < 0.01). No difference was noted between groups for abdominal sc adipose tissue (453 +/- 126 vs. 442 +/- 144 cm(2); P: = NS), total fat mass (38.1 +/- 10.6 vs. 40.0 +/- 11.8 kg), muscle attenuation (42.2 +/- 2.6 vs. 43.6 +/- 4.8 Houndsfield units), and physical activity energy expenditure (1060 +/- 323 vs. 1045 +/- 331 Cal/day). MNO subjects had lower fasting plasma glucose and insulin concentrations and lower insulin levels during the oral glucose tolerance test (P: values ranging between 0.01-0.001). No difference was observed between groups for 2-h glucose levels and glucose area during the oral glucose tolerance test. MNO subjects showed lower plasma triglycerides and higher high density lipoprotein cholesterol concentrations than MAO individuals (P: < 0.01 in both cases). Results from the questionnaire indicated that 48% of the MNO women presented an early onset of obesity (<20 yr old) compared with 29% of the MAO subjects (P: = 0.09). Stepwise regression analysis showed that visceral adipose tissue and the age-related onset of obesity explained 22% and 13%, respectively, of the variance observed in insulin sensitivity (total r(2) = 0.35; P: < 0.05 in both cases). Our results support the existence of a subgroup of obese but metabolically normal postmenopausal women who display high levels of insulin sensitivity despite having a high accumulation of body fat. This metabolically normal profile is associated with a lower accumulation of visceral adipose tissue and an earlier age-related onset of obesity.

Excellent long-term survival and absence of vaginal recurrences in 332 patients with low-risk stage I endometrial adenocarcinoma treated with hysterectomy and vaginal brachytherapy without formal staging lymph node sampling: report of a prospective trial.

PURPOSE: The value of adjuvant radiation therapy and staging pelvic lymphadenectomy in patients with low-risk, early-stage endometrial cancer is controversial. The aim of this study was to report the long-term survival, rate of recurrences, and complications in patients with Stage I endometrial cancer, Grade 1-2, with <50% myometrial invasion treated with hysterectomy (without formal staging pelvic and periaortic lymph node sampling or lymphadenectomy) and postoperative vaginal brachytherapy. METHODS AND MATERIALS: A total of 303 patients with pathologic Stage I endometrial cancer, Grade 1-2, with <50% myometrial invasion and nonmalignant peritoneal cytology, were treated with total abdominal hysterectomy, bilateral salpingo-oophorectomy, and postoperative vaginal brachytherapy (30 Gy to point 0.5 cm depth) in a prospective study extending from 1958 to 1994. In addition, 29 additional Stage I, Grade 1-2 patients with <50% myometrial invasion and malignant peritoneal cytology were treated with 1 year of progesterone therapy. Patients were followed for 1.2-32 years (median 8.1 y). RESULTS: Six patients had recurrences and died secondary to disease. There were no vaginal recurrences. The 5-, 10-, 20-, and 30-year disease-free survivals of the 303 patients with nonmalignant peritoneal cytology were 98.9%, 97.8%, 96.7%, and 96.7%, respectively. Patients with malignant peritoneal cytology had a 5- and 10-year disease-free survival of 100%. Significant radiation complications occurred in 2.1% of the patients. CONCLUSION: In patients with low-risk, Stage I endometrial cancer, hysterectomy and adjuvant postoperative vaginal brachytherapy provide excellent long-term survival, eliminate vaginal recurrences, and are not associated with significant complications. The addition of 1 year of progesterone therapy to patients with malignant cytology provides 100% long-term survival. Based on these results, patients with low-risk, Stage I endometrial adenocarcinoma do not need formal staging pelvic and periaortic lymphadenectomy.

Laparoscopic-assisted application of interstitial brachytherapy for locally advanced cervical carcinoma: results of a pilot study.

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. 192Iridium 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.

Altered surface and cyst epithelium of ovaries removed prophylactically from women with a family history of ovarian cancer.

Despite intensive investigation, the nature of epithelial ovarian cancer precursors remains controversial. Because women with a strong family history of ovarian cancer have a high probability of developing ovarian cancer themselves, ovaries removed prophylactically from such patients provide an opportunity to identify early neoplastic changes. Ovaries removed from 64 consecutive patients undergoing prophylactic oophorectomy and from 30 women with normal ovaries and no known family history of ovarian cancer were examined by light microscopy for a number of histopathologic features and by image cytometry for abnormalities of the cyst and surface epithelium. All analyses were performed without knowledge of the family history. Seven benign, but no tumors of low malignant potential or malignant epithelial tumors were found in the prophylactic oophorectomy group. There were more cortical inclusion cysts in the prophylactically removed than controls ovaries (P = .016), but no other architectural features differed between the two groups. No abnormalities were found in the surface or cyst epithelium in either group by light microscopy. In contrast, image analysis identified differences in the nuclei between the two groups, indicating that those from the surface epithelium of prophylactically removed ovaries were larger and contained more heterogeneously dense chromatin than those of controls, and that nuclei of the cyst epithelium had more irregular outlines. Ovarian epithelium from prophylactically removed ovaries exhibit abnormalities that are only identified by image analysis, and which might represent early preneoplastic changes. Such ovaries may be useful for identifying early molecular changes in ovarian cancer.

Telomerase in gynecologic cancers.

OBJECTIVE: To provide the obstetrician-gynecologist with the following: 1) basic concepts of telomere shortening and telomerase activation and their relation to cellular immortalization and cancer, 2) an overview of potential uses of telomerase activity in cancer diagnosis, assessment of prognosis, and the development of new anticancer therapeutic approaches, and 3) a review of the literature on telomerase activity in gynecologic cancers. DATA SOURCES: A computerized search for articles published in which telomerase or telomerases were included as a subject heading or a textword was performed using the Ovid Search Software (Ovid Technologies Inc., New York, NY). The search was conducted of the following databases of the National Library of Medicine and the National Cancer Institute: MEDLINE January 1966 to May 1997, HealthSTAR January 1975 to May 1997, AIDSline January 1980 to May 1997, and CancerLit January 1980 to May 1997. Additional sources were identified through cross-referencing. METHODS OF STUDY SELECTION: All sources identified were reviewed with particular attention to human application, specifically in gynecologic cancers. TABULATION, INTEGRATION, AND RESULTS: A total of 304 references was identified. Each reference was reviewed to determine the relevant contribution to the basic understanding of the role of telomerase in cellular immortalization and the development of cancer, potential uses of telomerase measurement in cancer, gynecologic applications, and potential use of telomerase inhibitors in cancer therapy. CONCLUSION: Telomerase activity might be a valuable diagnostic and prognostic tool in gynecologic and other types of cancer, and telomerase inhibition might prove to be a significant therapeutic approach for some types of cancer. Better understanding of the relation between telomerase activation, tumor suppressor genes, and oncogenes might clarify several aspects of early tumorigenesis and result in development of novel approaches to early cancer detection and prevention.

Scrape cytology for intraoperative evaluation of lymph nodes in gynecologic cancer.

OBJECTIVE: To compare scrape cytology with frozen section in accuracy and time required for preparation and interpretation and assess accuracy and surgical effect of scrape cytology as the only method of intraoperative evaluation of lymph nodes from women with gynecologic cancers. METHODS: Between February 1998 and March 1999, 242 lymph nodes removed from 60 women with gynecologic cancers were submitted for scrape cytology alone (34 women, 177 lymph nodes) or with frozen section (26 women, 65 lymph nodes). Results of scrape cytology and time required for preparation and interpretation were compared with those from frozen section. Accuracy and proportion of incorrect surgical decisions based on combined evaluation by scrape cytology and frozen section were compared with those from scrape cytology alone. For statistical analysis, we used Student t test, chi2, and Cohen's kappa statistics. Two-tailed P < .05 was considered significant. RESULTS: There was excellent agreement between scrape cytology and frozen section (kappa = .78 with 95% confidence interval .495, 1.065). Scrape cytology had a higher accuracy than frozen section and required significantly less time (95.8% versus 87.5% and 14 +/- 3.2 versus 25 +/- 5.1 minutes, P < .005). The accuracy and proportion of incorrect surgical decisions based on combined evaluation were similar to those based on cytology alone (91.7% for both and 7.7% versus 8.8%, respectively). CONCLUSION: Scrape cytology is as accurate and faster than frozen section in intraoperative evaluation of lymph nodes from women with gynecologic cancers. Adding frozen section to scrape cytology did not seem to improve accuracy or reduce incorrect surgical decisions.

Epidemiologic differences between women with extraovarian primary peritoneal carcinoma and women with epithelial ovarian cancer.

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, chi2 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.

Value of wet mount and cervical cultures at the time of cervical cytology in asymptomatic women.

OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Remarkable response of primary squamous cell carcinoma of the ovary to paclitaxel and cisplatin.

BACKGROUND: The survival rate of patients with advanced stage primary squamous cell carcinoma of the ovary is dismal and the best treatment is unknown. We describe the response of this tumor to systemic chemotherapy employing paclitaxel and cisplatin. CASE: A 31-year-old white woman diagnosed with International Federation of Gynecology and Obstetrics stage IV primary squamous cell carcinoma of the ovary associated with ovarian endometriosis underwent cytoreductive surgery followed by paclitaxel and cisplatin every 4 weeks for 12 courses. The patient tolerated chemotherapy well, demonstrated a dramatic response with disappearance of hepatic metastases, and remains without evidence of disease 2 years after diagnosis. CONCLUSION: Paclitaxel and cisplatin may be effective in treating primary squamous cell carcinoma of the ovary.

Laparoscopic surgery in obese women.

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.

Immunoreactive beta-endorphin in human ovaries.

Beta-endorphin (beta-EP) immunostainable cells were demonstrated in human ovarian tissue using a non-cross-reacting anti-beta-EP serum and the avidin-biotin-peroxidase detection technique. In ovaries from ovulating and premenopausal women, beta-EP immunoreactivity was localized in the luteinized cells of theca interna of maturing follicles with almost negligible staining in granulosa cells; cells of primary follicles did not stain. In corpora lutea, luteinized cells in both theca interna and granulosa, layers were equally positive. In postmenopausal ovaries, staining was detectable only in scattered luteinized stromal cells. This is the first report on the presence of immunoreactive beta-EP in human ovaries, in which beta-EP seems to be produced by the same sex cord cells engaged in active steroidogenesis and may be under gonadotropin central regulation. The significance of this finding is discussed.

Extraovarian primary peritoneal carcinoma.

Extraovarian primary peritoneal carcinoma (EOPPC), a relatively newly defined disease that develops only in women, accounts for approximately 10% of cases with a presumed diagnosis of ovarian cancer. Characterized by abdominal carcinomatosis, uninvolved or minimally involved ovaries, and no identifiable primary, EOPPC has been reported following bilateral oophorectomy performed for benign disease or prophylaxis. Most cases are of serous histology; however, nonserous tumors have been observed. Although EOPPC is similar to serous ovarian carcinoma with respect to clinical presentation, histologic appearance, and response to chemotherapy, molecular and epidemiologic studies have indicated that it may be a separate entity. This review explores the clinical presentation, management, prognosis, and survival of EOPPC.

Tamoxifen and the female reproductive tract.

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.

Current treatment for ovarian cancer.

Ovarian cancer is the most lethal gynaecologic malignancy. Epithelial ovarian cancer (EOC) constitutes approximately 90% of cases of ovarian cancer and 70% of the patients with EOC present in advanced stage. Treatment of EOC usually consists of cytoreductive surgery which includes total abdominal hysterectomy (TAH), bilateral salpingo-oophorectomy (BSO), omentectomy and lymphadenectomy followed by adjuvant chemotherapy. Current adjuvant chemotherapy includes paclitaxel and either cisplatin or carboplatin given every 3 weeks for six cycles. The combination paclitaxel and platinum chemotherapy achieves clinical response in approximately 80% of patients. However, most patients will have tumour recurrence within 3 years following treatment. Patients with platinum-sensitive tumours can be re-treated with platinum and/or paclitaxel. Those with platinum-resistant tumours have poor prognosis and treatment is palliative. Options of treatment in these patients include topotecan, doxil, gemcitabine, etoposide, or enrolment in clinical trials. Future research needs to focus on the role of cytoreductive surgery, second-look surgery, consolidation chemotherapy, development of new chemotherapeutic agents, chemoresistance modulators, as well as new approaches to the treatment of women with ovarian cancer.

The addition of bleomycin and dose-escalated ifosfamide to the combination of cisplatin plus ifosfamide does not improve survival in advanced or recurrent cervical carcinoma.

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.

Stage I adenocarcinoma of the cervix: does lesion size affect treatment options and prognosis?

A retrospective analysis of 93 patients with International Federation of Gynecology and Obstetrics stage I adenocarcinoma of the cervix was performed to determine the significance of tumor size, patient age, tumor grade, lymph node status, and primary treatment modality as prognostic variables of 5-year survival and 5-year progression-free survival (PFS). Multivariate analysis demonstrated that patient age and tumor grade were significant variables prognostic of survival (p < 0.01 and p = 0.01, respectively). Tumor size was a significant (p < 0.01) prognostic variable of PFS in a multivariate model that included tumor size and patient age. An important advantage in survival and PFS for patients with lesions smaller than 3 cm compared with those patients with lesions 3 cm or more was observed (92% vs. 76% and 89% vs. 67%, respectively). Among surgically treated patients, survival and PFS among patients with lesions smaller than 3 cm were significantly improved compared with patients with tumors 3 cm or more (97% vs. 77% [p = 0.03] and 90% vs. 69% [p = 0.03], respectively). Significant improvement in survival and PFS was observed among patients with lesions smaller than 3 cm who were treated with surgery compared with those who received radiation therapy (97% vs. 77% [p = 0.03] and 90% vs. 77% [p = 0.048], respectively).

Progesterone receptor status is a significant prognostic variable of progression-free survival in advanced epithelial ovarian cancer.

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 univariate nor multivariate analysis identified ER or PR status as significant prognostic variables of survival (p = 0.93 and p = 0.06, respectively). Progesterone receptor-positive status was a significant prognostic variable of progression-free survival in both univariate (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.

c-erbB-2 Immunohistochemistry in Paraffin Tumors.

Immunohistochemistry is the study of the intracellular distribution of antigens based on the formation of an immune complex. The concept is based on the application of a specific antibody to the antigen to be detected and visualization of the antigen-antibody reaction with a staining procedure. Immunohistochemical staining allows direct observation of antigenic expression at the cellular level.