Final overall survival results of phase III GCIG CALYPSO trial of pegylated liposomal doxorubicin and carboplatin vs paclitaxel and carboplatin in platinum-sensitive ovarian cancer patients.

BACKGROUND: The CALYPSO phase III trial compared CD (carboplatin-pegylated liposomal doxorubicin (PLD)) with CP (carboplatin-paclitaxel) in patients with platinum-sensitive recurrent ovarian cancer (ROC). Overall survival (OS) data are now mature. METHODS: Women with ROC relapsing > 6 months after first- or second-line therapy were randomised to CD or CP for six cycles in this international, open-label, non-inferiority trial. The primary endpoint was progression-free survival. The OS analysis is presented here. RESULTS: A total of 976 patients were randomised (467 to CD and 509 to CP). With a median follow-up of 49 months, no statistically significant difference was observed between arms in OS (hazard ratio = 0.99 (95% confidence interval 0.85, 1.16); log-rank P = 0.94). Median survival times were 30.7 months (CD) and 33.0 months (CP). No statistically significant difference in OS was observed between arms in predetermined subgroups according to age, body mass index, treatment-free interval, measurable disease, number of lines of prior chemotherapy, or performance status. Post-study cross-over was imbalanced between arms, with a greater proportion of patients randomised to CP receiving post-study PLD (68%) than patients randomised to CD receiving post-study paclitaxel (43%; P < 0.001). CONCLUSION: Carboplatin-PLD led to delayed progression and similar OS compared with carboplatin-paclitaxel in platinum-sensitive ROC.

Barriers to prenatal detection of congenital heart disease: a population-based study.

OBJECTIVE: To evaluate the extent and determinants of missed prenatal detection of congenital heart disease (CHD) in a population-based setting. METHODS: This was a retrospective cohort study of cases with CHD, excluding minor defects, identified between 1997 and 2007 by a statewide surveillance program. We examined a comprehensive list of potential risk factors for which data were available in the surveillance database from abstracted medical charts. We analyzed the association of fetal, maternal and encounter factors with 1) whether a prenatal ultrasound was performed and 2) prenatal detection of CHD. RESULTS: CHD was detected prenatally in only 39% of 1474 cases, with no improvement in detection rate over the 10-year period. Among the 97% (n = 1431) of mothers who underwent one or more ultrasound examinations, 35% were interpreted as abnormal; fetal echocardiography was performed in 27% of the entire cohort. Maternal and encounter factors increasing the adjusted odds of prenatal detection included: family history of CHD (OR, 4.3 (95% CI, 1.9-9.9)), presence of extracardiac defects (OR, 2.7 (95% CI, 1.9-3.9)) and ultrasound location i.e. high risk clinic vs clinic (OR, 2.1 (95% CI, 1.3-3.1)). Defects that would be expected to have an abnormal outflow-tract view were missed more often (64%) than were those that would be expected to have an abnormal four-chamber view (42%). CONCLUSION: The majority of CHD cases over the 10-year study period were missed prenatally and detection rates did not increase materially during that time. The failure to detect CHD prenatally was related to encounter characteristics, specifically involving screening ultrasound examinations, which may be targeted for improvement.

Thalamic burst firing propensity: a comparison of the dorsal lateral geniculate and pulvinar nuclei in the tree shrew.

Relay neurons in dorsal thalamic nuclei can fire high-frequency bursts of action potentials that ride the crest of voltage-dependent transient (T-type) calcium currents [low-threshold spike (LTS)]. To explore potential nucleus-specific burst features, we compared the membrane properties of dorsal lateral geniculate nucleus (dLGN) and pulvinar nucleus relay neurons using in vitro whole-cell recording in juvenile and adult tree shrew (Tupaia) tissue slices. We injected current ramps of variable slope into neurons that were sufficiently hyperpolarized to de-inactivate T-type calcium channels. In a small percentage of juvenile pulvinar and dLGN neurons, an LTS could not be evoked. In the remaining juvenile neurons and in all adult dLGN neurons, a single LTS could be evoked by current ramps. However, in the adult pulvinar, current ramps evoked multiple LTSs in >70% of recorded neurons. Using immunohistochemistry, Western blot techniques, unbiased stereology, and confocal and electron microscopy, we found that pulvinar neurons expressed more T-type calcium channels (Ca(v) 3.2) and more small conductance potassium channels (SK2) than dLGN neurons and that the pulvinar nucleus contained a higher glia-to-neuron ratio than the dLGN. Hodgkin-Huxley-type compartmental models revealed that the distinct firing modes could be replicated by manipulating T-type calcium and SK2 channel density, distribution, and kinetics. The intrinsic properties of pulvinar neurons that promote burst firing in the adult may be relevant to the treatment of conditions that involve the adult onset of aberrant thalamocortical interactions.

Phase ii/iii study of intraperitoneal chemotherapy after neoadjuvant chemotherapy for ovarian cancer: ncic ctg ov.21.

Three large randomized clinical trials have shown a survival benefit in women with stage iii epithelial ovarian cancer (eoc) who receive intraperitoneal (IP) chemotherapy after optimal primary debulking surgery. The most recent Gynecologic Oncology Group study, gog 172, showed an improvement in median overall survival of approximately 17 months. That result led to a U.S. National Cancer Institute (nci) clinical announcement recommending that IP chemotherapy be considered for this group of women with eoc. However, IP chemotherapy is associated with increased toxicity, and rates for completion of treatment are low (42% in gog 172). The optimal IP regimen and duration of treatment has yet to be defined. Women undergoing chemotherapy before optimal debulking surgery were not included in the studies or in the nci clinical announcement. The National Cancer Institute of Canada Clinical Trials Group has developed a protocol for a randomized phase ii/iii study which will examine whether IP platinum-taxane-based chemotherapy benefits women who have received neoadjuvant chemotherapy before optimal surgical debulking. To address whether the less systemically toxic carboplatin can be substituted for cisplatin IP, the first phase of the study will have 3 arms: 1 intravenous-only, and 2 IP-containing regimens. At the end of the first stage, and provided that IP therapy is feasible to administer in this patient population, one of the IP regimens, either IP carboplatin or IP cisplatin, will proceed into a phase iii comparison with the intravenous arm. This exciting new study has gathered international support.

Vision improvement in retinal degeneration patients by implantation of retina together with retinal pigment epithelium.

PURPOSE: To demonstrate efficacy and safety of the implantation of neural retinal progenitor cell layers (sheets) with its retinal pigment epithelium (RPE) in retinitis pigmentosa (RP) and dry age-related macular degeneration (AMD) patients with 20/200 or worse vision in the surgery eye. DESIGN: Interventional nonrandomized clinical trial. METHODS: Ten patients (six RP, four AMD) received retinal implants in one eye and were followed in a phase II trial conducted in a clinical practice setting. Early Treatment Diabetic Retinopathy Study (EDTRS) was the primary outcome measure. All implant recipients and nine of 10 tissue donors were deoxyribonucleic acids typed. RESULTS: Seven patients (three RP, four AMD) showed improved EDTRS visual acuity (VA) scores. Three of these patients (one RP, two AMD) showed improvement in both eyes to the same extent. Vision in one RP patient remained the same, while vision in two RP patients decreased. One RP patient has maintained an improvement in vision from 20/800 to 20/200 ETDRS for more than five years; at the six-year examination, it was still maintained at 20/320 while the nonsurgery eye had deteriorated to hand motion vision. This patient also showed a 22.72% increase in light sensitivity at five years compared to microperimetry results at two years; the other patients showed no improved sensitivity. Although no match was found between donors and recipients, no rejection of the implanted tissue was observed clinically. CONCLUSIONS: Seven (70%) of 10 patients showed improved VA. This outcome provides clinical evidence of the safety and beneficial effect of retinal implants and corroborates results in animal models of retinal degeneration.

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.

HIV testing in the workplace: clarifying the meaning of South Africa's Employment Equity Act.

PIP: This article clarifies the meaning of South Africa's Employment Equity Act, which includes HIV testing in the workplace. This historic piece of legislation is intended to promote equality and equal opportunity in the workplace. Among other things, the Act prohibits employers to conduct pre-employment HIV testing unless the Labor Court has given permission. Several interpretations have ensued which was seen as damaging to HIV prevention strategies in the workplace. Employers, likewise, have used these interpretations to justify a threat to withdraw from the Joint UN Program on the HIV/AIDS-Sponsored Greater Involvement of People Living with HIV/AIDS program. Similarly, arguments for HIV testing followed which were based on a fancifully narrow and literal reading of the section. This resulted to the literal interpretation of the Act that eventually made the contested sections unconstitutional and deprived employees of their fundamental rights to freedom and security, and access to health care services. A non-literal interpretation of the Act, on the other hand, does require the prohibition as applying only to ¿employer-initiated¿ HIV testing. One immediate remedy to the confusion would be for the Employment Equity Commission to publish a code of good practice on HIV testing in the workplace.^ieng

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.

Randomised trial of subcuticular suture versus metal clips for wound closure after thyroid and parathyroid surgery.

A randomised trial was conducted to compare the results of neck wound closure using metal (Michel) clips or subcuticular suture. All operations were performed using a standardised technique, which included wound infiltration with 10 ml bupivacaine and adrenaline solution, no strap muscle division and the use of suction drains. All the collar incisions and wound closures were performed by the same surgeon. At the end of each operation patients were randomised to wound closure by either metal clips (n = 38) or a continuous 3/0 prolene subcuticular suture (n = 42). Daily postoperative pain scores and the discomfort caused by clip/suture removal were recorded. The cosmetic appearance of each wound was scored by the patient, the surgeon, and an independent observer using verbal response and linear analogue scales. The two study groups were well matched for age, sex, indication for surgery and operation performed. There were no differences in postoperative pain scores between clips and sutures. Removal of subcuticular sutures was performed more quickly (P < 0.0001) and caused less pain (P < 0.0001, visual analogue scale; P = 0.0042, verbal response scale) than the removal of clips. At the time of discharge, the cosmetic appearance scores generated by the surgeon, patient and independent observer were higher for suture closed wounds than clips. However, by 3 and 6 months follow-up there were no differences in cosmetic appearance between the two methods of closure. Only very short-term cosmetic results are influenced by the type of wound closure in thyroid and parathyroid surgery, but sutures are quicker and less painful to remove than Michel clips.

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.

Rectal endosonography for the visualisation of the anastomosis after anterior resection and its relevance to local recurrence.

Rectal endosonography can be used to detect and localise recurrent rectal carcinoma. Distal and proximal to a rectal anastomosis the separate layers of the bowel wall as seen by rectal endosonography are well defined but at the precise level of the anastomosis separation of the layers is lost and they appear to merge. By studying histological sections of a normal anastomosis we have demonstrated that this loss of definition seen endosonographically correlates with the histological appearances. These appearances of the normal anastomosis provide a baseline image for the identification of recurrences in the region of the anastomosis.