M.Steven Piver

Primary peritoneal carcinoma after prophylactic oophorectomy in women with a family history of ovarian cancer. A report of the Gilda Radner Familial Ovarian Cancer Registry.

Background. According to previous reports, primary peritoneal carcinoma indistinguishable from primary ovarian adenocarcinoma had developed in five women with a history of familial ovarian cancer who had undergone prophylactic oophorectomy.

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

PURPOSEnThe 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.nnnMETHODS AND MATERIALSnA 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).nnnRESULTSnSix 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.nnnCONCLUSIONnIn 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.

Clinical picture, response to therapy, and survival of women with diffuse malignant peritoneal mesothelioma.

The clinical picture, response to therapy, and prognosis of women with diffuse malignant peritoneal mesotheliomas (DMPM) are ill defined. The purpose of this study is to report on the clinical picture, response to therapy, and survival of women with DMPM.

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.

Laparoscopic surgery in obese women

Abstract 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.

Lack of improved survival plus increase in thromboembolic complications in patients with clear cell carcinoma of the ovary treated with platinum versus nonplatinum‐based chemotherapy

This study was conducted to evaluate survival rates for patients with clear cell ovarian carcinoma who had platinum‐based chemotherapy versus nonplatinum‐based chemotherapy and the risk of thromboembolic complications.

SEVERE RADIATION MORBIDITY IN CARCINOMA OF THE CERVIX: IMPACT OF PRETHERAPY SURGICAL STAGING AND PREVIOUS SURGERY

PURPOSEnThe purpose of this study is to delineate the factors which (a) contribute to an increase in the severe, radiation induced complication rate and (b) have a significant effect on survival in patients with International Federation of Gynecologists and Obstetricians (FIGO) Stage I-IVA cervical cancer undergoing pretherapy surgical staging.nnnMETHODS AND MATERIALSnFrom 1971-1991, 189 patients underwent pretherapy surgical staging via a retroperitoneal approach (67) or transperitoneal approach (122). Seventy-nine patients had previously experienced a laparotomy. Patients subsequently received a median of 85 Gy to point A. In patients receiving paraaortic radiation, a median of 45 Gy was administered. One hundred and thirty-two (69.8%) patients received hydroxyurea as a radiation sensitizer.nnnRESULTSnPretherapy surgical evaluation revealed that 21 of 89 (23.6%) Stage II patients and 32 of 85 (37.6%) Stage III patients had paraaortic lymph node metastases. Multivariate logistic regression analysis detailed the significant factors favorably influencing the radiation-induced complication rate to be a retroperitoneal approach of pretherapy surgical staging and no previous laparotomy. Survival was significantly prolonged in patients receiving hydroxyurea, evaluated via a retroperitoneal incision, with negative paraaortic lymph nodes, and with an early stage of disease.nnnCONCLUSIONnA retroperitoneal approach to pretherapy surgical staging and absence of previous surgery reduced the incidence of subsequent radiation-induced complications. Despite improvements in the detection of occult disease, prolonged survival is impaired when the therapeutic measures currently available are used.

Improvements in pelvic exenteration: Factors responsible for reducing morbidity and mortality

AbstractBackground: Since pelvic exenteration for the treatment of recurrent gynecologic malignancy first was described, reported rates of morbidity and mortality have declined steadily. However, the factors responsible for this decline have never been clearly delineated.nMethods: We reviewed the charts of 154 patients who underwent pelvic exenteration for gynecologic malignancy between 1954 and 1994. Charts were abstracted for details of the surgical procedure, pathologic findings, postoperative management, short- and long-term complications, time to recurrence, and overall survival.nResults: Seventy-two patients (47%) experienced 95 identifiable postoperative complications, resulting in death in 22 patients (14%). The rate of infectious complications declined to a statistically significant degree between the first two decades and latter two decades of the study (odds ratio [OR] 0.28, 95% CI 0.11–0.69). The use of routine prophylactic antibiotics was associated with this decline in infectious complications (OR 0.25, 95% CI 0.07–0.83). The use of preoperative subcutaneous heparin was associated with a reduction in thrombotic complications from 5 of 100 patients to 0 of 54 patients (P=.11), as well as a significant reduction in overall risk of complications (OR 0.53, 95% CI 0.33–0.85) and risk of postoperative mortality (OR 0.19, 95% CI 0.05–0.80). There was a significant reduction in overall risk of postoperative complications with both intensive care unit monitoring postoperatively (OR 0.65, 95% CI 0.43–0.99) and routine postoperative monitoring with a pulmonary artery catheter (OR 0.61, 95% CI 0.38–0.98).nConclusions: Routine use of prophylactic antibiotics, prophylactic subcutaneous heparin, and intensive postoperative monitoring appear to have reduced morbidity from pelvic exenteration.

Mutations in BRCA1 from Fixed, Paraffin-Embedded Tissue Can Be Artifacts of Preservation

DNA isolated from paraffin-embedded tissues has been used for analysis of DNA alterations in disease states. Use of archival tissue can expedite the gathering of large numbers of specimens from rare disease subtypes that would take years to accumulate prospectively. Therefore, archival tissues from 70 ovarian cancer cases diagnosed before or at age 40 were retrieved for analysis of BRCA1 mutations. DNA was isolated from paraffin-embedded tissue of 70 ovarian cancer cases diagnosed before or at age 40. BRCA1 mutation analysis was conducted by single-strand conformation polymorphism analysis and DNA sequencing. Fifty-eight BRCA1 mutations were found in 34 of the 70 ovarian cancer cases. Twenty-two cases had one mutation each and 12 cases had multiple mutations. Multiple mutations found in histologically normal tissue of 2 cases were not present in matched tumor tissue. For another case, DNA from two separate blocks of normal tissue contained different mutations. These observations were anomalous and suggested that mutations detected in fixed tissues may be artifacts of tissue preservation and not present in the original unfixed tissues. To test this suggestion, blood was obtained from 2 patients for whom mutations were found in fixed, normal tissue. DNA from their unfixed lymphocytes did not contain the mutations found in fixed normal tissue. Thus, mutations found in fixed, paraffin-embedded tissues can be artifacts of tissue preservation. The reliability of DNA sequence data derived from such tissues must be questioned in the absence of corroborating data from unfixed tissues. This severely limits the use of fixed tissues as a source of DNA for retrospective research and for clinical genetic testing in families for which a disease-affected member is not alive.

Prognostic significance of the extent of cervical involvement by endometrial cancer

The prognostic significance of the extent of cervical involvement by endometrial cancer is impossible to determine from the literature because previous reports have included fractional dilatation and curettage for staging, preoperative radiotherapy, and surgical stage III and IV disease. Therefore, we reviewed and restaged according to the new FIGO system all patients with endometrial cancer from January 1981 to December 1989. Of 180 patients undergoing hysterectomy for endometrial cancer, 20 had surgical stage II disease. No patient received preoperative radiotherapy. None of 12 patients (0%) with stage IIA disease developed recurrence, while 5 of 8 (63%) with stage IIB disease recurred (P less than 0.01). All 5 recurrences were in extrapelvic sites. Endocervical stroma invasion appears to import a statistically significant worse prognosis than endometrial glandular involvement.