Assessing the impact of mailing self-sampling kits for human papillomavirus testing to unscreened non-responder women in Manitoba.

Background: CervixCheck, Manitoba's cervical cancer screening program, conducted a pilot study to assess whether screening participation could be improved in unscreened women by offering a mailed self-sampling kit for human papillomavirus (hpv) testing instead of a Pap test. Methods: In a prospective cohort study design, a sample of unscreened women (n = 1052) who had been sent an invitation letter from CervixCheck in the past but who did not respond were randomized to either an intervention group or a control group. The intervention group received a mailed hpv self-sampling kit; the control group received no additional communication. Returned hpv self-sampling swabs were analyzed by a provincial laboratory. After 6 months, screening participation in the two study groups was compared using a logistic regression model adjusted for age and area of residence (urban or rural). Secondary outcomes included hpv positivity, specimen inadequacy, compliance with follow-up, and time to colposcopy. Results: Screening participation was significantly higher in the intervention group than in the control group (n = 51, 9.6%, vs. n = 13, 2.5%; odds ratio: 4.7; 95% confidence interval: 2.56 to 8.77). Geographic area of residence (urban or rural) and age were not statistically significant. Conclusions: The study demonstrated that hpv self-sampling kits can enhance screening participation in unscreened non-responder women in the setting of an organized screening program. Next steps should include additional research to determine the best implementation strategy for hpv self-sampling in Manitoba.

Measuring colposcopy quality in Canada: development of population-based indicators.

Background: Colposcopy is a key part of cervical cancer control. As cervical cancer screening and prevention strategies evolve, monitoring colposcopy performance will become even more critical. In the present paper, we describe population-based colposcopy quality indicators that are recommended for ongoing measurement by cervical cancer screening programs in Canada. Methods: The Pan-Canadian Cervical Cancer Screening Network established a multidisciplinary expert working group to identify population-based colposcopy quality indicators. A systematic literature review was conducted to ascertain existing population and program-level colposcopy quality indicators. A systems-level cervical cancer screening pathway describing each step from an abnormal screening test, to colposcopy, and back to screening was developed. Indicators from the literature were assigned a place on the pathway to ensure that all steps were measured. A prioritization matrix scoring system was used to score each indicator based on predetermined criteria. Proposed colposcopy quality indicators were shared with provincial and territorial screening programs and subsequently revised. Results: The 10 population-based colposcopy quality indicators identified as priorities were colposcopy uptake, histologic investigation (biopsy) rate, colposcopy referral rate, failure to attend colposcopy, treatment frequency in women 18-24 years of age, re-treatment proportion, colposcopy exit-test proportion, histologic investigation (biopsy) frequency after low-grade Pap test results, length of colposcopy episode of care, and operating room treatment rate. Two descriptive indicators were also identified: colposcopist volume and number of colposcopists per capita. Summary: High-quality colposcopy services are an essential component of provincial cervical cancer screening programs. The proposed quality and descriptive indicators will permit colposcopy outcomes to be compared between provinces and across Canada so as to identify opportunities for improving colposcopy services.

Malignant transformation of mature cystic teratoma of the ovary: 30-year experience of a single tertiary care center.

OBJECTIVE: To review the authors' experience with this rare disease and describe their management modality and the outcome. MATERIAL AND METHODS: From January 1983 to December 2013, 13 patients with malignant transformation arising in ovarian MCT were treated at the Division of Gynecologic Oncology in the University of Manitoba. Demographic characteristics, symptoms, signs, stage, mode of therapy, and results of follow-up were reviewed retrospectively. RESULTS: Median age at diagnosis was 53 years (range 25-65). The most common presenting symptom was a palpable mass in nine cases. Squamous cell carcinoma (SCC) was found in 38% (five cases), adenocarcinoma in 15% (two cases), anaplastic carcinoma in 8% (one case), and papillary thyroid carcinoma in 38% (five cases). Eight cases were Stage I, two cases were Stage II, and three cases were Stage III. All patients underwent surgery. Five patients received adjuvant treatment with platinum-based chemotherapy + pelvic radiation. Four patients had recurrent disease (two SCC and two adenocarcinoma). Three patients died of disease after recurrence. The median follow up period of the entire patient population was 60 months, with a three-year overall survival of 76%. CONCLUSION: Malignant transformation of MCT is large ovarian tumors that mainly occur in patients in their fifth and sixth decades of life. They often present as incidental pathologic findings after surgery for MCT. SCC has traditionally been the most common pathology, however in the present series, the authors found that papillary thyroid carcinoma was equally common. Platinum-based chemotherapy with pelvic radiation in early stage (including Stage IA) and locally recurrent dis- ease should be offered. Advanced stages and mucinous adenocarcinoma represent a poorer prognosis despite adjuvant treatment. In patients with papillary thyroid carcinoma, conservative surveillance in early stage and adjuvant total thyroidectomy with radioactive iodine treatment in advanced stage disease appears to be an effective treatment.

Changes in cervical cancer screening behavior for women attending Pap Test Week clinics.

OBJECTIVE: This retrospective study of all women who accessed the 2006 Manitoba Pap Test Week clinics was designed to determine factors associated with inadequate cervical cancer screening and changes in cervical cancer screening behavior. METHODS: Data were acquired using the CervixCheck Manitoba registry and an ancillary database of demographic information collected from clinic attendees. RESULTS: The study included 1124 women. Of these, 53% (n = 598) were under-screened (no Pap test in the previous 2 years) prior to accessing the clinics. Logistic regression analyses demonstrated that older age (odds ratio [OR] = 1.02, 95% confidence interval [CI] 1.01-1.03), no doctor (OR = 1.4, 95% CI 1.05-1.54), and living in Canada < 1 year (OR = 5.5, 95% CI 2.73-11.12) were associated with being under-screened prior to accessing the Pap Test Week clinics. Thirty-seven percent (n = 223) of under-screened women demonstrated improved screening status subsequent to the 2006 Pap Test Week (had a subsequent Papanicolaou [Pap] test performed within 2 years) and these women were more likely to live in an urban setting (P = 0.003), be younger (P < 0.001), originate outside Canada (P = 0.006), have lived in Canada for less than 1 year (P = 0.006), and have had an abnormal Pap test result in 2006 (P < 0.001). Previously under-screened women were less likely to become adequately-screened subsequent to 2006 if they had a Pap test performed at a Pap Test Week clinic compared to having a Pap test performed elsewhere (37% versus 60%, P < 0.001). CONCLUSION: This study identified a subset of under-screened women accessing Pap Test Week clinics whose screening status might be most modifiable.

Distribution of human papillomavirus types, cervical cancer screening history, and risk factors for infection in Manitoba.

OBJECTIVES: We conducted a study to investigate the prevalence of human papillomavirus (HPV) infections in an opportunistic sample of women in Manitoba, Canada. We inquired about risk factors associated with HPV infections and linked the HPV typing results with the cervical cancer screening history of the participants. METHODS: The study population included 592 women attending Papanicolaou (Pap) test clinics. After signing a consent form, participants were given a self-administered questionnaire on risk factors and received a conventional Pap test. Residual cells from the Pap tests were collected and sent for HPV typing. RESULTS: The mean age of the population was 43 years. A total of 115 participants (19.4%) had an HPV infection, 89 of whom had a normal Pap test. Of those who were HPV-positive, 61 (10.3%) had high-risk (Group 1) HPV. HPV-16 was the most prevalent type (15/115: 13.0% of infections). The most consistent risk factors for HPV infection were young age, Aboriginal ethnicity, higher lifetime number of sexual partners and higher number of sexual partners in the previous year. CONCLUSION: The prevalence of HPV types in Manitoba is consistent with the distributions reported in other jurisdictions. These data provide baseline information on type-specific HPV prevalence in an unvaccinated population and can be useful in evaluating the effectiveness of the HPV immunization program. An added benefit is in the validation of a proof of concept which links a population-based Pap registry to laboratory test results and a risk behaviour survey to assess early and late outcomes of HPV infection. This methodology could be applied to other jurisdictions across Canada where such capacities exist.

Early ovarian cancer: what is the staging impact of retroperitoneal node sampling?

BACKGROUND: Comprehensive surgical staging of apparent early-stage epithelial ovarian cancer includes peritoneal washings, biopsies, and retroperitoneal lymph node dissection. Unresolved is the relative frequency or importance of the lymph node dissection. OBJECTIVES: (1) To determine the site(s) of microscopic metastatic disease in women undergoing a comprehensive staging for apparent early-stage cancer of the ovary; (2) to identify those women with metastases in the retroperitoneal lymph nodes alone. METHODS: Between 1985 and 2000, we reviewed all records of women at cancer centres in Winnipeg, Ottawa, and Saskatoon who had undergone a "staging laparotomy" for an apparent early-stage IA epithelial cancer of the ovary. Histology, tumour grade, initial and final surgical stage, and the site(s) of metastatic disease were recorded for all cases. RESULTS: Forty-three of the 128 women (34%) had a final surgical stage of II or III. Sixteen women had positive pelvic biopsies, while 19 had microscopic upper abdominal disease. Eight women had positive retroperitoneal nodes, and in only 2 of these women, disease was found in the retroperitoneal nodes alone. In the 8 women with nodal disease, 5 had grade 3 tumours and 6 had serous histology tumours. CONCLUSION: Comprehensive staging is important to identify women with metastatic disease. Solitary nodal metastases are predominantly found in grade 3 and serous tumours.

The benefits of comprehensive surgical staging in the management of early-stage epithelial ovarian carcinoma.

OBJECTIVE: The management of understaged patients with apparent clinically early ovarian cancer is difficult. Options include offering chemotherapy based on histopathologic factors or reoperation to obtain the necessary information needed to assign an accurate surgical stage. This study aims to compare these two approaches and to define the role of staging surgery in this common patient population. METHODS: Retrospective chart reviews were carried out at the Universities of Manitoba and Saskatchewan over the period 1975 to 1999. Demographic data and surgical findings were abstracted and entered into a computerized database for analysis. Patients not having surgical staging procedures were offered platinum-based chemotherapy based on high tumor grades, dense adhesions, and presence of surface excrescences or large necrotic areas. Patients with surgically proven stage I disease were treated with no further therapy regardless of histopathologic factors. Descriptive statistics are used to summarize the data. Logistic and Cox regression models are used to identify significant predicting factors for recurrences and progression-free intervals. RESULTS: One hundred and thirty-eight patients presented with tumor macroscopically confined to the ovary at the time of laparotomy. The median age at presentation is 56.5 (18-90). The histology distribution was serous tumor in 28.3%, mucinous in 26.1%, endometrioid in 23.2%, clear cell in 14.5%, anaplastic in 2.2%, and mixed types in 5.8%. The grade distribution was 47.1% grade 1, 27.5% Grade 2, and 25.4% Grade 3. Sixty-eight percent of the patients had a comprehensive surgical staging procedure initially. Thirty-six percent of these patients were found to have extraovarian metastases and were subsequently treated with adjuvant chemotherapy. Forty-three percent of those not having staging laparotomy were offered chemotherapy based on high risk factors only. At a median follow-up of 58 months. 77% of patients remained disease-free and 23% had recurrent disease. Of 60 patients with surgically proven stage I treated expectantly, 6 (10%) recurred, whereas of 25 unstaged patients treated expectantly due to lack of risk factors 7 (28%) recurred (P = 0.036). In patients treated expectantly, a significant survival advantage was noted in the staged group. Logistic regression showed age (OR 1.032, P = 0.043), high grade (OR 4.16, P = 0.003), and lack of a proper staging surgery (OR 2.62, P = 0.032) to be important factors predicting recurrence. In terms of progression-free interval, only age (OR 1.027, P = 0.048) and tumor grade (OR 3.62, P = 0.05) are significant predictors. CONCLUSION: Absence of surgical pathologic high-risk factors is inferior to comprehensive staging laparotomy findings in guiding recommendations for subsequent adjuvant therapy. Patients who have not been properly staged stand a significant risk of recurrent disease despite more frequent use of chemotherapy. All clinically early-stage ovarian cancer patients should be considered for comprehensive staging surgery prior to further treatment recommendations.

Antiestrogens affect both pathways of killer cell-mediated oncolysis.

BACKGROUND: Our previous studies indicate that antiestrogenic drugs tamoxifen (TX) and toremifene (TO) augment immune oncolysis induced by various killer cells. The underlying mechanism(s), however, have not been fully elucidated. MATERIALS AND METHODS: Ovarian carcinoma cells freshly isolated from cancer patients and the human erythroleukemia cell line, K562 were used as targets for killer cells and/or the anti-Fas monoclonal antibody, CH-11 in 51Cr release assays. In a number of experiments, extracellular Ca++ was chelated by EGTA/MgCl2 to distinguish Ca(++)-dependent perforin/granzyme pathway from Fas/FasL pathway. Fas expression was studied by flow cytometry. RESULTS: Ovarian carcinoma cells were sensitized by antiestrogens towards enhanced cytolysis mediated by autologous cytotoxic lymphocytes. Antiestrogens also significantly augmented the killing of ovarian carcinoma cells triggered by anti-Fas monoclonal antibody. Flow cytometry analyses showed an upregulation of Fas (CD 95/Apo-1) upon TX or TO treatment in a number of cases. By contrast, antiestrogen treatment did not induce Fas expression in the Fas-negative K562 cells; yet, natural killer cell-mediated cytotoxicity against K562 was augmented by antiestrogens and maximal lysis was achieved when both target and effector cells were treated. The presence of Ca++ chelator (EGTA/MgCl2) in the assay abrogated killing of K562 and its antiestrogen--mediated augmentation. This indicates the involvement of the perforin/granzyme pathway. CONCLUSION: Antiestrogens can influence both Fas/FasL and perforin/granzyme pathways of killer cell--mediated oncolysis.

Antiestrogens sensitize human ovarian and lung carcinomas for lysis by autologous killer cells.

BACKGROUND: The antiestrogens tamoxifen (TX) and toremifene (TO) were shown previously to enhance the lysis of target cells by natural killer cells (NK), lymphokine activated killer (LAK) cells, and by cytotoxic T lymphocytes (CTL). MATERIALS AND METHODS: CTL were cultured from lung cancer tissue and from ascites fluid of ovarian carcinoma patients with the aid of human recombinant interleukin-2 (hrIL-2). The target, effector or both cell populations were pretreated by TX, TO and/or with human recombinant interferon-alpha (IFN-alpha). RESULTS: Significant enhancement of cytotoxicity occurred when the tumor targets or both the target and effector cells were treated with TX, TO or when these drugs were used in combination with IFN-alpha. The lytic activity of CTL cultured from draining lymph nodes of lung cancer patients, was also observed after similar treatment. The lytic effect of autologous LAK cells derived from peripheral blood was increased to a lesser extent, which could be amplified by additional treatment with IFN-alpha. CONCLUSIONS: The antiestrogens TX and TO and IFN-alpha enhance the lysis of autologous tumor cells by CTL and LAK effectors.

Clinically apparent early stage invasive epithelial ovarian carcinoma: should all be treated similarly?

OBJECTIVES: The role of adjuvant therapy in patients with early stage ovarian carcinoma has not been clearly defined. Most randomized trials examining this issue have not used the vigorous staging exploration accepted as today's standard. This report examines the natural history of patients after surgically documented stage 1 ovarian carcinoma followed expectantly. METHODS: A retrospective chart review was carried out using strict criteria to include only patients who had an adequate staging procedure performed by gynecologic oncologists following a fixed protocol from 1987 to 1997. Patients' demographic data as well as current disease status were abstracted and analyzed. RESULTS: A total of 80 comprehensive surgical staging procedures were carried out over a 10-year period for apparent stage 1 ovarian cancer at the time of exploratory laparotomy. Fifty cases were true surgicopathological stage 1. It was found that serous and anaplastic tumors were more likely than other subtypes to be upstaged by the procedure. Further follow-up confirmed the excellent prognosis of early stage serous, endometrioid, and mucinous tumor with only one recurrence noted in an extraabdominal location in a patient with serous histology with no postoperative adjuvant therapy. Clear cell histology stands out as a significant recurrence risk (33%) despite an initially negative surgical assessment. CONCLUSION: Careful surgical exploration can identify a group of patients with early stage epithelial ovarian carcinoma who will benefit little from further adjuvant therapy. Patients with clear cell histology prove to be at a high risk for recurrence even at an early stage such that chemotherapy should be considered.

Does debulking surgery improve survival in biologically aggressive ovarian carcinoma?

Aggressive tumor reduction surgery has been widely used in patients with advanced stage epithelial ovarian carcinoma before initiation of cytotoxic chemotherapy. No randomized controlled trial has been carried out to confirm the benefits of such procedures. To examine the role of cytoreductive surgery in the management of stage 2 and 3 patients with epithelial ovarian carcinoma treated with postoperative adjuvant platinum-based chemotherapy, survival analysis was carried out on patients with initial microscopic disease documented on staging laparotomies, patients with large volume of disease at time of exploration and tumor reduced to microscopic residuals, and patients who were suboptimally debulked with more than 2-cm residual disease. Twenty-four, 81, and 191 patients were identified from a computerized data base, respectively. Kaplan-Meier survival estimates showed that 62% with initial microscopic residual are alive with no evidence of disease at 5 years and 56% of patients left with microscopic residuals after tumor reduction are alive and well at 5 years. There was no statistical significant difference between these two groups. The groups are equivalent with respect to known adverse prognostic factors. In contrast, 5-year survival in the suboptimal debulked group was significantly lower at 15%. Debulking surgery to achieve microscopic residual disease improved the prognosis in patients with initial large volume of disease. Survival was similar to survival in patients with microscopic disease at time of exploration. The beneficial effect may be attributed to the removal of chemoresistant clones in bulky tumors. Tumor reduction surgery remains important in the management of advanced stage epithelial ovarian carcinoma.

Malignant mixed mesodermal ovarian tumor treatment and prognosis: a 20-year experience.

Mixed mesodermal sarcoma of the ovary is a rare clinical entity. To review the epidemiology, prognostic factors, and treatment results related to primary ovarian sarcoma at our center, a retrospective chart review of all patients referred for ovarian cancer was carried out from 1974 to 1994. Cases with confirmed pathologic diagnosis of primary mixed mesodermal ovarian sarcomas were selected, forming the present study group. Thirty-six charts were identified. The median age at presentation was 67.5 years. Findings at laparotomy demonstrated extraovarian metastasis in 33/35 patients. Total abdominal hysterectomy and bilateral salpingo-oophorectomy +/- omentectomy were performed in 34 patients, with 22 patients left with macroscopic residual disease after surgery. Follow-up adjuvant chemotherapy consisting of cisplatin and doxorubicin was administered to 29/36 patients. Follow-ups ranged from 1 to 11 years with a median of 2 years. As with epithelial ovarian cancer, residual disease after initial surgery is an important prognostic factor. Thirteen patients had a second-look laparotomy. Five patients were positive for disease. Eight patients, one of whom recurred, were histologically negative. The patients with positive second-look findings, as well as all those who recurred clinically, subsequently died within 12 months despite trials with different second-line chemotherapeutic agents. Survival analysis showed a median survival of 3 years among patients treated with combination cytotoxic chemotherapy. Primary ovarian sarcomas make up about 2-3% of all ovarian cancer cases seen in our center. These are often very aggressive tumors with widespread metastasis at the time of presentation, making optimal tumor debulking difficult. The combination of cisplatin and doxorubicin appears to have activity resulting in a survival of 35% at 5 years. Second-look surgery offers little helpful information on the management of these tumors.

Early ovarian cancer: value of a negative staging laparotomy.

OBJECTIVE: To assess the risk of recurrence in patients with stage I (negative cytology) epithelial ovarian cancer receiving no adjuvant therapy. METHODS: Between 1976 and 1991, 51 patients with apparent stage I ovarian cancer underwent a comprehensive surgical staging that included: peritoneal cytology, omentectomy, pelvic and para-aortic lumphadenectomy, peritoneal biopsies and either unilateral salpingo-oophorectomy or TAH and BSO. RESULTS: Eleven of 51 patients (22%) were found to have stage II or III disease based on a positive staging laparotomy. Thirty-seven of 40 patients with stage I disease received no further therapy. There was one recurrence (stage 1C - grade 1) in patients with surgical stage 1C while there were no recurrences in patients with either stage 1A or 1B disease. CONCLUSION: This study concludes that surgical staging in apparent early stage ovarian cancer can identify a group of patients that require surgical therapy alone.

Peritoneovenous shunt for palliation of gynecologic malignant ascites.

BACKGROUND: Ascites is a common sequela of advanced or recurrent gynecologic malignancies, such as carcinoma of the ovary, fallopian tube, or endometrium. Symptomatic treatment with repeated paracentesis is the initial management after failure of chemotherapy. STUDY DESIGN: This study was done to evaluate the safety and effectiveness of a peritoneovenous shunt (PVS) in the palliation of these patients with recurrent ascites. A retrospective review of 25 patients having a PVS between 1982 and 1992 was performed. RESULTS: The 25 patients consisted of 21 patients with carcinoma of the ovary, two with primary carcinoma of the peritoneum, one with carcinoma of the endometrium, and one patient with carcinoma of the fallopian tube. The mean weight and abdominal girth decreased after shunt insertion (p < 0.001). Gastrointestinal dysfunction and dyspnea also improved with PVS insertion. There was no change in mean Karnofsky score after placement of a PVS. Two patients died within ten days postoperatively. The median survival period was 80 days and shunt occlusion occurred in four patients. CONCLUSIONS: The insertion of a PVS is effective in relieving refractory malignant ascites in gynecologic malignancies. The impact on quality of life requires further study.

Should selective paraaortic lymphadenectomy be part of surgical staging for endometrial cancer?

Surgical staging of adenocarcinoma of the endometrium attempts to identify the true distribution of disease. The survival value of paraaortic lymphadenectomy selectively performed in patients with histologic risk factors is unproven. The objective of this study was to determine if a staging procedure that did not include paraaortic lymphadenectomy predicted recurrence-free survival in disease surgically confined to the uterus. Between 1978 and 1990, 273 patients underwent surgical staging. Two hundred and sixty-nine were clinical stage I and 4 were stage II. The staging procedure included peritoneal cytology, TAH and BSO, and pelvic lymphadenectomy. Postoperative therapy, if any, consisted of whole pelvis and vault radiotherapy in disease confined to the uterus and systemic chemotherapy in patients with extrauterine disease. Surgical staging resulted in 220 (81%) stage I, 20 (7%) stage II, 27 (10%) stage III, and 6 (2%) stage IV. Eighty-eight patients in stages I and II had deep myometrial invasion or a grade 3 tumor. There were 12 recurrences, 8 in stage I and 4 in stage II, in patients with disease confined to the uterus. Four patients (1.7%) recurred outside the pelvis. Had paraaortic lymphadenectomy been performed in patients with risk factors, this would have mandated 88 dissections to potentially benefit 4 patients. We conclude that paraaortic lymphadenectomy would have been of small benefit to these surgically staged patients.

Primary ovarian cancer: prospective comparison of contrast-enhanced CT and pre-and postcontrast, fat-suppressed MR imaging, with histologic correlation.

Sixteen patients with clinically suspected malignant ovarian disease underwent contrast agent-enhanced computed tomography (CT) and magnetic resonance (MR) imaging in a prospective comparative study. MR imaging included fat-suppressed spin-echo and breath-hold FLASH (fast low-angle shot) before and after intravenous injection of gadopentetate dimeglumine. Histologic confirmation was obtained at laparotomy (n = 13) and biopsy (n = 3). Thirteen patients had histologically proven primary ovarian cancer. MR images showed the internal architecture of ovarian tumors better than CT in nine patients and equivalently in seven. MR images showed the relationship between ovarian tumors and adjacent pelvic structures (uterus [n = 9], sigmoid colon [n = 7], bladder [n = 7], and rectum [n = 3]) better than CT in nine patients and equivalently in seven. Intraabdominal extent of disease was better defined on MR than on CT images in nine patients, equivalently in six, and worse in one. Peritoneal metastases 1-2 cm in diameter were detected on MR images and missed on CT scans in six patients. In only one case did this result in a staging error with CT. The results suggest that MR imaging is at least equivalent and may be superior to CT in the evaluation of ovarian malignancy.

Glassy cell carcinoma of the cervix: a bimodal treatment strategy.

Glassy cell carcinoma of the cervix is a distinct clinicopathologic entity. This infrequent pathologic subtype is an aggressive biologic tumor associated with a rapid clinical course and poor outcome with conventional treatment modalities in the majority of cases. In a 12-year period from July 1976 to June 1988, 32 cases of glassy cell carcinoma of the cervix were identified. This accounted for 5.3% of all cervical carcinomas. The mean age was 10 years younger than that of other histologic subtypes. A disproportional number of patients with glassy cell carcinoma had malignancies of early clinical stages. The 5-year survival of patients with Stage IB glassy cell carcinoma of the cervix was 45% when treated with primary radical surgery in contrast to 90% for squamous cell and 78% for adenocarcinoma. When bimodal therapy with radical surgery and radical radiotherapy was used, the survival of patients with Stage IB glassy cell carcinoma improved to 87%. Survival of patients with Stage II glassy cell carcinoma of the cervix improved from 50% to 85% with combined radical surgery and radiotherapy. Despite a combination of radical surgery and radiotherapy, complications were minimal.

Treatment of recurrent and metastatic adenocarcinoma of the endometrium with cisplatin, doxorubicin, cyclophosphamide, and medroxyprogesterone acetate.

We conducted a retrospective review of 44 patients with metastatic or recurrent endometrial carcinoma treated with cisplatin, doxorubicin, cyclophosphamide, and medroxyprogesterone acetate. Thirty-six women had metastatic disease; eight had recurrent disease. In the metastatic group, 12 women had positive peritoneal cytology as the only criterion for metastatic disease. Grade 1 tumors represented 25%, grade 2, 47.7%, and grade 3, 27.3%. The series was divided into four groups based on disease volume before chemotherapy: positive peritoneal cytology only (N = 12), microscopic (N = 11), macroscopic less than 2 cm (N = 6), and macroscopic greater than 2 cm (N = 15). Fifteen patients had measurable disease and eight (53%) had an objective response. The median survival was 31 months for the whole group. Median survivals were not reached for the positive peritoneal cytology only and the microscopic groups. Median survival for the macroscopic less than 2 cm and greater than 2 cm groups were 15 and 10 months, respectively (P less than .0001). The volume of disease was the most important factor in determining survival as well as the time to progression (P less than .0001). The distribution of grade was similar in all groups (P = .88), and grade did not predict survival (P = .80) or recurrence (P = .87). The significant number of low-grade lesions in our series as well as the importance of positive cytology as a predictor of survival underscore the need for surgical pathologic staging in an effort to identify those patients in need of adjuvant therapy.

Tubular Krukenberg tumor in pregnancy with virilization.

A case of tubular Krukenberg tumor in pregnancy with virilization is presented. The pathology is reviewed. This rare tumor must be distinguished from a Sertoli-Leydig tumor. The index case adds to the previously recorded eight cases. All nine cases reviewed presented with progressive virilization between the third and eighth month of gestation, which regressed after surgery. The fetal outcomes of seven cases have been recorded. The fetuses were all female and of these five were virilized. A gastric primary was found in five cases. A primary breast carcinoma was postulated in another. In the remaining cases either no autopsy was performed or no primary tumor was found.

Factor analysis of false-negative second-look laparotomy.

From January 1976 through December 1987, 155 patients with ovarian epithelial malignancy underwent a second-look laparotomy. Seventy-seven (50%) had a negative second-look. Recurrence after negative second-look occurred in 15 patients (19.5%). Of the factors analyzed, serous histology and residual disease after initial laparotomy were found to be of significance. Grade of tumor, stage, and ascites were not found to be of significance.