Quantitative analysis of transforming growth factor beta 1 and 2 in ovarian carcinoma.

Transforming growth factor beta (TGF-beta) is an important family of cytokines that may promote tumor growth in vivo through several mechanisms including interference with antitumor T-cell immune responses, alteration of factors in the stroma and matrix, and the promotion of angiogenesis. TGF-beta isotypes have been detected in malignant and normal ovarian tissues. We have determined by quantitative immunohistochemistry the density of TGF-beta1, TGF-beta2, and human leukocyte antigen (HLA) Class I and Class II antigens on malignant cells in paired primary and metastatic specimens from 10 patients with ovarian carcinoma. Cryostat sections of specimens from the carcinomas and from normal ovaries of three women of similar age without ovarian cancer were stained respectively with specific antibodies to TGF-beta1, TGF-beta2, and HLA Class I and II antigens, and with isotype-matched control antibodies. Antigen density was quantitated blindly as mean absorbance on a SAMBA 4000 image analyzer. TGF-beta1 and TGF-beta2 were overexpressed in both primary and metastatic tumor specimens in comparison with normal ovarian tissue. No statistical correlation was found between the expression of TGF-beta1 or TGF-beta2 and HLA class I or HLA class II, which suggests that TGF-beta isotypes could have effects on the immune system other than down-modulation of these HLA molecules. Furthermore, the lack of association between levels of TGF-beta expression and the reduced expression of HLA molecules could suggest that tumor cells expressing both HLA and TGF-beta may be suitable targets for adaptive immunotherapy. Additional studies are necessary to determine whether TGF-beta expressed by ovarian cancer cells merits evaluation as a therapeutic target.

The effects of a course in cadaver dissection on resident knowledge of pelvic anatomy: an experimental study.

OBJECTIVE: To determine whether a course in cadaver dissection can significantly increase resident knowledge of pelvic anatomy beyond that of current educational practices. METHODS: Thirteen first- and second-year residents were randomly assigned to a cadaver dissection course (seven) or a control group (six). The dissection group performed dissections with instruction, using a dissection guide designed specifically for the course. The control group received study references on pelvic anatomy and protected study time. Each participant took a practical and written examination at the beginning and end of the study. RESULTS: The two groups did not differ statistically in their scores on the pre-test. Both groups improved on the post-test, but the dissection group scored nearly 50% higher on the test than did the controls. The two groups differed significantly on the post-test, adjusted for pre-test performance (P < .01). In their evaluation of the course, participants from the dissection group emphasized its educational value and urged that it be offered to residents as a regular part of their training. CONCLUSION: Dissection of a human cadaver provides a valuable experience, allowing participants to gain a greater understanding of surgical anatomy and surgical procedures in a no-risk, unhurried setting. Residents who participated in a cadaver dissection course designed specifically for their needs showed a statistically significant increase in knowledge compared with those without this experience. Both objectively and subjectively, a cadaver dissection course is an excellent tool for instructing gynecology residents.

Retraction of an intraperitoneal chemotherapy port: a case report and literature review.

Delivery of chemotherapy directly into the peritoneal cavity is becoming part of the standard frontline management of patients with optimally cytoreduced ovarian carcinoma. Traditionally, the peritoneal access devices used for this have had relatively high complication rates including infection, blockage, leakage, and difficulties with port access. In order to reduce the risk of infection, we have been using a Bard 9.6F silastic infusaport that does not have a Dacron cuff to secure it into the tissues of the anterior abdominal wall. It has the added advantage of being more easily removed at the end of treatment. We report a case of spontaneous retraction of such a port out of the peritoneal cavity into the subcutaneous tissues. This complication associated with a silastic cuffless port is presented to raise awareness of this possible complication and suggest ways of preventing it.

Cytoreduction and intraperitoneal heated chemotherapy for the treatment of endometrial carcinoma recurrent within the peritoneal cavity.

Our experience with hyperthermic intraperitoneal chemotherapy (IPHC) in conjunction with surgical resection for endometrial cancer recurrent within the abdominal cavity was reviewed. Eligible patients underwent exploratory laparotomy with the aim of resecting disease to < or =5 mm maximum dimension followed immediately by intraperitoneal perfusion of cisplatin (100 mg/m(2)) heated to 41-43 degrees C (105.8-109.4 degrees F) for 1.5 h. Data for analysis was extracted from retrospective chart review. Five patients underwent surgery and IPHC between September 2002 and January 2005 for abdomino-pelvic recurrence. Original stage and histology were 1A papillary serous (1), 1C endometrioid with clear cell features (1), and 1B endometrioid (3). Mean age was 61 (41-75) years, mean prior laparotomies were 1.4 (1-2), and mean chemotherapy agent exposure was 1.6 (0-4). Mean time from initial treatment to surgery and IPHC was 47 (29-66) months. Mean length of surgery was 9.8 (7-11) h after which three patients had no residual disease and two had < or =5 mm disease. The mean duration of hospital stay was 12.6 (6-20) days. Postoperative surgical complications included wound infection with septicemia in one patient. Mean maximum postoperative serum creatinine was 1.02 (0.6-1.70) mg/dL. There was no ototoxicity or neuropathy and no perioperative mortality. No patients have been lost to follow-up. Two are living disease free at 28 and 32 m and two are living with disease at 12 and 36 m. One patient died at 3 m without evidence of cancer. Two patients who had no residual macroscopic disease at the end of surgery are alive at 32 and 36 m. The combination of IPHC with surgery for recurrent endometrial carcinoma is relatively well tolerated. The unexpectedly long survival seen in this cohort supports a phase II trial of IPHC with cisplatin for recurrent endometrial cancer.

Thiotepa in combination with cisplatin for primary epithelial ovarian cancer: a phase II study.

The objectives of this phase II protocol were: 1) to determine the clinical activity of thiotepa combined with cisplatin in suboptimally debulked advanced epithelial ovarian carcinoma as first-line chemotherapy, 2) to determine by surgery the response after 6 courses of chemotherapy, and 3) to identify the regimen's qualitative and quantitative toxicities. Patients with FIGO stage IIIC or IV epithelial ovarian cancer were eligible to receive cisplatin (50 mg/m2) followed by thiotepa (40 mg/m2) on an every 4-week schedule. Patients showing no evidence of disease after six cycles of chemotherapy underwent surgical reassessment. Thirty-one patients were evaluable for toxicity and response. Myelosuppression was the major toxicity and hematologic toxicities prompted all dose reductions. No growth factor support was given in this trial. Thirty-nine percent of patients (12/31) had a clinical complete response. Of these, 16% (5/31) had complete pathologic response and 19% (6/31) had partial pathologic response. One long-term survivor declined reassessment laparotomy. Including the 16% of patients with a partial response, the overall response rate was 55% (17/31). Five patients are currently alive 8 years after enrollment. Median survival was 16.8 months for all patients, 21.5 months for patients with partial response, and 60.8 months for patients with complete pathologic response. A normalization or >50% decrease in CA125 level occurred in 93% of patients. This study indicates that first-line treatment with thiotepa and cisplatin produces significant long-term responses when tumors are sensitive. Such treatment is a reasonable option when paclitaxel is not available.

Survey of female gynecologic oncologists and fellows: balancing professional and personal life.

OBJECTIVE: The aim of this study was to determine how female gynecologic oncologists have dealt with the challenge of combining childbearing and a career in gynecologic oncology and to identify other issues which need to be addressed to improve job satisfaction. METHODS: This survey of female members of the Society of Gynecologic Oncologists and fellows addressed demographics, timing of childbearing, type and cost of childcare, satisfaction with childcare choices, and mentorship. Those without children were queried about plans and reservations. Open-ended questions investigated how female gynecologic oncologists felt job satisfaction could be improved. RESULTS: A total of 65/110 (59%) attendings and 18/36 (50%) fellows responded. Three-fourths of respondents felt that the ideal time to have children was postfellowship. Timing of childbearing caused moderate to severe stress in the personal relationships of 23% of respondents. Median maternity leave was 6 weeks (1-120 days). Seventy-eight percent of female gynecologic oncologists with children employed a nanny. Over half of the respondents estimated weekly childcare cost at over $400. A successful balance between family and full-time practice was the most commonly cited quality of an ideal mentor. Sixty-six percent of the respondents replied to open-ended questions with narrative answers, revealing three major areas for improvement: childcare issues, increased flexibility in hours and duties (clinical, surgical, and research), and the need for more female mentoring. CONCLUSIONS: This survey highlighted the concerns of female gynecologic oncologists about achieving a successful balance between family and professional duties. It also revealed the ways in which women have responded and identified other issues that may be targeted to improve job satisfaction.

S-Phase fraction, p53, and HER-2/neu status as predictors of nodal metastasis in early vulvar cancer.

OBJECTIVE: Our aim was to determine the value of the S-phase fraction, p53, and HER-2/neu status as predictors of inguinal nodal metastasis in early vulvar cancer. METHODS: The charts of 100 consecutive patients with invasive squamous cell cancer of the vulva were reviewed and a cohort of patients with clinical stage I or II disease treated primarily with radical surgery and inguinal node dissection was identified. Within this cohort, all node-positive patients were matched with node-negative controls by depth of invasion. Tumor from the 13 node-positive patients and 26 controls was then analyzed by flow cytometry and immunohistochemistry. RESULTS: The median value of the S-phase fraction was higher in tumor from patients with inguinal nodal metastasis (median, 18.2; 25th-75th percentile: 13.9-28.3) than in node-negative patients (median, 8.9; 25th-75th percentile: 5.4-15.6) (P = 0.01). The presence of the HER-2/neu immunopositivity was also found to be associated with nodal metastasis (OR 4.05, 95% CI 1.0-16.6), but we found no evidence that DNA index or the presence of p53 immunopositivity was associated with nodal metastasis. CONCLUSION: Early vulvar cancer patients with inguinal node metastasis have a significantly higher S-phase fraction and are more likely to have HER-2/neu immunopositivity when compared to those without nodal metastasis.