Ronald S. Leuchter

Association between BRCA1 and BRCA2 mutations and survival in women with invasive epithelial ovarian cancer

CONTEXT Approximately 10% of women with invasive epithelial ovarian cancer (EOC) carry deleterious germline mutations in BRCA1 or BRCA2. A recent article suggested that BRCA2-related EOC was associated with an improved prognosis, but the effect of BRCA1 remains unclear. OBJECTIVE To characterize the survival of BRCA carriers with EOC compared with noncarriers and to determine whether BRCA1 and BRCA2 carriers show similar survival patterns. DESIGN, SETTING, AND PARTICIPANTS A pooled analysis of 26 observational studies on the survival of women with ovarian cancer, which included data from 1213 EOC cases with pathogenic germline mutations in BRCA1 (n = 909) or BRCA2 (n = 304) and from 2666 noncarriers recruited and followed up at variable times between 1987 and 2010 (the median year of diagnosis was 1998). MAIN OUTCOME MEASURE Five-year overall mortality. RESULTS The 5-year overall survival was 36% (95% CI, 34%-38%) for noncarriers, 44% (95% CI, 40%-48%) for BRCA1 carriers, and 52% (95% CI, 46%-58%) for BRCA2 carriers. After adjusting for study and year of diagnosis, BRCA1 and BRCA2 mutation carriers showed a more favorable survival than noncarriers (for BRCA1: hazard ratio [HR], 0.78; 95% CI, 0.68-0.89; P < .001; and for BRCA2: HR, 0.61; 95% CI, 0.50-0.76; P < .001). These survival differences remained after additional adjustment for stage, grade, histology, and age at diagnosis (for BRCA1: HR, 0.73; 95% CI, 0.64-0.84; P < .001; and for BRCA2: HR, 0.49; 95% CI, 0.39-0.61; P < .001). The BRCA1 HR estimate was significantly different from the HR estimated in the adjusted model (P for heterogeneity = .003). CONCLUSION Among patients with invasive EOC, having a germline mutation in BRCA1 or BRCA2 was associated with improved 5-year overall survival. BRCA2 carriers had the best prognosis.

Management of Regional Lymph Nodes and their Prognostic Influence on Vulvar Cancer

One hundred thirteen patients with invasive carcinoma of the vulva underwent radical vulvectomy and bilateral inguinal-femoral lymphadenectomy between 1957 and 1978. Eighteen had unilateral pelvic lymphadenectomy. Thirty-one patients (27.4%) had positive lymph nodes. The corrected actuarial five-year survival for patients with negative nodes was 96%, whereas it was 94% for patients with one positive node, 80% for those with two positive nodes, and 12% for those with three or more positive nodes. All patients with positive pelvic nodes or pelvic recurrence had three or more positive unilateral groin nodes, and all had palpably suspicious groin nodes preoperatively. Groin and systemic recurrences occurred in 2.9 and 3.8%, respectively, of patients with fewer than three positive unilateral inguinalfemoral nodes, as compared to 33 and 66%, respectively, of patients with three or more positive nodes. These data do not support routine pelvic lymphadenectomy in patients who have no clinically suspicious groin nodes and fewer than three positive nodes on histologic examination.

Effect of obesity on survival in epithelial ovarian cancer

Epidemiologic studies suggest that obese women are more likely to die of ovarian cancer than those of ideal body weight, but it is not known whether increased incidence, comorbidities common to obese women, or altered tumor biology is responsible for this difference. The current study attempted to determine the influence of excess body weight on ovarian cancer survival, disease progression, and clinicopathologic factors.

Hormone receptor expression in uterine sarcomas: Prognostic and therapeutic roles

OBJECTIVES.: The utility of hormone therapy in the management of uterine sarcomas is poorly defined. We hypothesize that estrogen receptor (ER) expression is common in uterine sarcomas, and carries prognostic significance. Further, we hypothesize that ER-positive uterine sarcomas respond to hormone therapy. METHODS.: We retrospectively reviewed charts of patients with uterine sarcomas. Stepwise Cox proportional hazards regression model was used to evaluate variables related to the risk of death: age, histology, stage, use of pelvic radiotherapy, and ER expression. In addition, we examined clinical outcomes in patients treated with aromatase inhibitors, megestrol acetate, depot medroxyprogesterone acetate, and tamoxifen. RESULTS.: Fifty-four patients underwent immunohistochemical staining, and 34 (63%) were ER-positive. Kaplan-Meier survival analysis and log-rank test indicated that patients with ER-positive sarcomas demonstrated improved overall survival when compared with ER-negative patients (median OS 36 vs. 16 months, p=0.004). Upon multivariate analysis, ER positivity retained significance as an independent predictor of survival (HR=0.32, CI 0.12-0.89, p=0.03). Four patients received hormonal treatment in the adjuvant setting and remained in remission (range of follow up: 18-68 months). Eighteen patients received hormone therapy in the setting of recurrent or progressive disease: fourteen (78%) demonstrated stable disease or complete or partial response (range of follow up: 6-124 months). CONCLUSIONS.: ER expression is common and is associated with improved overall survival in uterine sarcomas. Conducting immunohistochemical staining to ascertain ER status may aid with prognostication in this disease. Hormone therapy should be considered in patients with primary and recurrent ER-positive uterine sarcomas.

Neuroendocrine features in poorly differentiated and undifferentiated carcinomas of the cervix

Neuroendocrine or argyrophil cell carinoma of the cervix has recently been accepted as a distinct clinical‐pathological entity. The histologic pattern of these carcinomas is usually poorly differentiated or undifferentiated. Twenty patients with a histologic diagnosis of small cell carcinoma, undifferentiated carcinoma, poorly differentiated adenocarcinoma, or poorly differentiated, adenosquamous carcinoma of the cervix were evaluated for neuroendocrine features. The results of studies to detect neurosecretory granules were positive in seven of the 20 cases. Not only small cell carcinomas, but also tumors classified as undifferentiated carcinoma and poorly differentiated, adenosquamous carcinoma contained cytoplasmic granules consistent with neuroendocrine carcinoma of the cervix. The prognosis for survival appears poorer for patients having tumors with neurosecretory granules after controlling for stage and histologic grade of the neoplasm.

Treatment of vulvar carcinoma in situ with the CO2 laser

Between January 1960 and December 1982, 142 patients with carcinoma in situ of the vulva were treated at Cedars-Sinai Medical Center and UCLA Medical Center. Primary treatment consisted of wide excision in 45 patients; vulvectomy in 23 patients; topical chemotherapy in 9 patients; and CO2 laser therapy in 42 patients. Twenty-three patients were also treated with the CO2 laser for recurrent disease. Multifocal disease was present in 59% of the cases. Lesions involving the posterior vulva recurred most commonly, for both initial and recurrent disease. Results utilizing the CO2 are compared with the other methods of treating carcinoma in situ of the vulva. The CO2 laser is well suited for treatment of both multifocal and unifocal vulvar lesions, as it allows for maximal retention of vulvar integrity with no decrease in therapeutic efficacy.

Lower urinary tract resection as part of cytoreductive surgery for ovarian cancer

Abstract Twenty-four patients underwent lower urinary tract resection as part of cytoreductive surgery for ovarian epithelial malignancy from 1960 to 1979. Eight patients had partial cystectomies, two of which had reimplantation of the ureters, and 16 had partial ureteral resection. Optimal cytoreduction was associated with a longer mean survival. Patients who presented without ureteral obstruction also survived significantly longer than those with obstruction. Morbidity from surgery involving the urinary tract was not excessive in this series. Partial lower urinary tract resection appears justified as part of a primary cytoreductive effort.

Estrogen and progesterone receptors in ovarian neoplasms

The cytoplasmic receptors for 17 beta-estradiol (ER) and progesterone (PR) were measured in 39 malignant and 15 benign ovarian neoplasms. All eight endometroid carcinomas had positive ER sites, one-half contained PR. The number of ER binding sites decreased as tumor grade increased. Conversely, none of the 11 mucinous tumors contained either ER or PR receptors. One-half of the well-differentiated serous tumors had ER (57 +/- 23 fmole/mg protein) while none of the poorly differentiated tumors had measurable binding. In serous carcinomas, PR was only detected in well-differentiated lesions (447 +/- 240 fmole/mg protein). Only one of 15 benign neoplasms contained ER and PR receptors. Correlation of tumor grade and type may help to plan hormonal therapies in advanced ovarian malignancies.

Management of postexenteration perineal hernias by myocutaneous axial flaps

Abstract Two cases of perineal hernias following pelvic exenteration are presented. Each was treated by means of myocutaneous axial flaps, the type used being dependent on the nature of the defect. A bulbocavernosus axial flap was used in one patient and a gracilis myocutaneous axial flap in the other. Factors contributing to perineal hernias are discussed. Satisfactory results can be obtained using axial flaps for treatment of this uncommon condition.

A pilot study of lorazepam-induced amnesia with cis-platinum-containing chemotherapy

Eighteen patients with advanced epithelial ovarian cancer were given 36 courses of cis-platinum-containing chemotherapy at Cedars-Sinai Medical Center. Patients were given lorazepam (Ativan) prior to chemotherapy. Amnesia for the day of chemotherapy was reported in 29 courses. Lack of recall for the chemotherapy infusion and the subsequent 8 hr or greater was reported in 33 of the 36 courses. In two courses, no amnesia effects were noted. No serious side effects of lorazepam therapy occurred and all patients believed that the amnesic effect was beneficial during chemotherapy. Lorazepam (Ativan) appears to be a safe medication to induce amnesia for cis-platinum chemotherapy and deserves further study to determine its effect on anticipatory vomiting, nausea and vomiting, and patient compliance with continued chemotherapy.