Surgical efficacy and quality of wide resection of the pelvic peritoneum in patients with epithelial ovarian cancer.

PURPOSE: The aim of the study was to evaluate the impact of adding an extensive pelvic peritoneal stripping procedure, termed "wide resection of the pelvic peritoneum," (WRPP) to standard surgery for epithelial ovarian cancer on survival effectiveness and to investigate the role of ovarian cancer stem cells (CSCs) in the pelvic peritoneum. METHODS: A total of 166 patients with ovarian cancer undergoing surgical treatment at Kumamoto University Hospital between 2002 and 2018 were retrospectively analyzed. Eligible patients were divided into three groups based on the surgical approach: standard surgery (SS) group (n = 36), WRPP group (standard surgery plus WRPP, n = 100), and rectosigmoidectomy (RS) group (standard surgery plus RS, n = 30). Survival outcomes were compared between the three groups. CD44 variant 6 (CD44v6) and EpCAM expression, as markers of ovarian CSCs, in peritoneal disseminated tumors were evaluated using immunofluorescence staining. RESULTS: With respect to patients with stage IIIA-IVB ovarian cancer, there were significant differences in overall and progression-free survival between the WRPP and SS groups, as revealed by univariate (hazard ratio [HR], 0.35; 95% confidence interval [CI], 0.17-0.69; P = 0.003 and HR, 0.54; 95% CI, 0.31-0.95; P = 0.032, respectively) and multivariate Cox proportional hazards models (HR, 0.35; 95% CI, 0.17-0.70; P = 0.003 and HR, 0.54; 95% CI, 0.31-0.95; P = 0.032, respectively). Further, no significant differences were observed in survival outcomes between the RS group and the SS or WRPP group. Regarding the safety of WRPP, no significant differences in major intraoperative and postoperative complications were found between the three groups. Immunofluorescence analysis revealed a high percentage of CD44v6/EpCAM double-positive ovarian cancer cells in peritoneal disseminated tumors. CONCLUSION: The present study demonstrates that WRPP significantly contributes to improved survival in patients with stage IIIA-IVB ovarian cancer. WRPP could result in eradicating ovarian CSCs and disrupting the CSC niche microenvironment in the pelvic peritoneum.

Long-Term Outcome of Aromatase Inhibitor Therapy With Letrozole in Patients With Advanced Low-Grade Endometrial Stromal Sarcoma.

BACKGROUND: There has been no consensus on the indications for the treatment of advanced low-grade endometrial stromal sarcoma (LGESS), and the possible effects of hormonal treatment including progestins and aromatase inhibitors have been reported. The aim of this study was to investigate the efficacy of aromatase inhibitor therapy with letrozole for patients with residual or recurrent LGESS. METHODS: We retrospectively reviewed the clinical response of patients with advanced LGESS who had been treated with letrozole. We also analyzed the adverse effects after the administration of letrozole. The expression levels of estrogen receptor and aromatase in the tumors were immunohistochemically examined. RESULTS: In 5 patients who had been treated for unresectable LGESS lesions after initial or repeat surgical procedures, residual lesions in 3 patients and recurrence lesions in 2 patients were the indications for hormonal therapy with letrozole. The median duration of letrozole exposure at retrospective analysis was 53 (10-96) months. The clinical outcomes were classified as complete response in 2 patients, partial response in 1 patient, and stable disease in 2 patients. Myalgias, hot flashes, and arthralgias were not observed during the follow-up period in any patients. The median serum levels of estradiol were <5.0 (cutoff value, <0.5-11.8) pg/mL. The median age-matched bone mineral densities were 92% (79%-123%). The LGESS tissues in all 5 patients were positive for estrogen receptor and aromatase expression. CONCLUSIONS: Letrozole as well as progestins could be the first choice of treatment for patients with recurrent or residual LGESS, which is difficult to resect surgically because of its efficacy and minimal adverse effects.

Long-term oncological outcomes of ovarian serous carcinomas with psammoma bodies: a novel insight into the molecular pathogenesis of ovarian epithelial carcinoma.

A two-tier system in which ovarian epithelial carcinomas are subdivided into type I and type II tumors has been proposed on the basis of recent molecular pathogenesis findings. Type I tumors, unrelated to tumor protein p53 (TP53) mutations, show favorable prognosis in a slow step-wise process, whereas type II tumors, related to TP53 mutations, contribute to poor prognosis. Ovarian serous carcinomas with excessive psammoma bodies behave like type I tumors. However, their etiology and prognostic significance remain obscure. The objective of the present study was to evaluate the characteristic features and potential relevance of psammoma bodies to the clinical outcome of 44 patients with serous carcinomas with long-term follow-up. The 5- and 10-year survival rates were significantly different between the serous carcinomas with less than 5% area of psammoma bodies and those at least 5% area (P < 0.01). All tumors with at least 5% area were both diploid and immunohistochemically negative for TP53 mutations. All patients with these tumors, including eight with International Federation of Gynecology and Obstetrics (FIGO) stages III or IV disease, survived more than 5 years and their 10-year survival rate was 76%. In multivariate analysis using clinical parameters, the apparent existence of psammoma bodies was an indication to view serous carcinomas as type I tumors with long-term survival. Our results suggested that the formation of psammoma bodies is associated with increased apoptotic tumor cell death related to normal TP53 function. The pathological findings of psammoma bodies might contribute to the consideration of pathogenesis and to the development of prognostic prediction rules for serous carcinomas.