Small Cell Carcinoma of the Ovary, Hypercalcemic Type (SCCOHT) beyond SMARCA4 Mutations: A Comprehensive Genomic Analysis.

Small cell carcinoma of the ovary, hypercalcemic type (SCCOHT) is an aggressive malignancy that occurs in young women, is characterized by recurrent loss-of-function mutations in the SMARCA4 gene, and for which effective treatments options are lacking. The aim of this study was to broaden the knowledge on this rare malignancy by reporting a comprehensive molecular analysis of an independent cohort of SCCOHT cases. We conducted Whole Exome Sequencing in six SCCOHT, and RNA-sequencing and array comparative genomic hybridization in eight SCCOHT. Additional immunohistochemical, Sanger sequencing and functional data are also provided. SCCOHTs showed remarkable genomic stability, with diploid profiles and low mutation load (mean, 5.43 mutations/Mb), including in the three chemotherapy-exposed tumors. All but one SCCOHT cases exhibited 19p13.2-3 copy-neutral LOH. SMARCA4 deleterious mutations were recurrent and accompanied by loss of expression of the SMARCA2 paralog. Variants in a few other genes located in 19p13.2-3 (e.g., PLK5) were detected. Putative therapeutic targets, including MAGEA4, AURKB and CLDN6, were found to be overexpressed in SCCOHT by RNA-seq as compared to benign ovarian tissue. Lastly, we provide additional evidence for sensitivity of SCCOHT to HDAC, DNMT and EZH2 inhibitors. Despite their aggressive clinical course, SCCOHT show remarkable inter-tumor homogeneity and display genomic stability, low mutation burden and few somatic copy number alterations. These findings and preliminary functional data support further exploration of epigenetic therapies in this lethal disease

Clinical Impact of Lymphadenectomy after Neoadjuvant Chemotherapy in Advanced Epithelial Ovarian Cancer: A Review of Available Data

Recent robust data allow for omitting lymph node dissection for patients with advanced epithelial ovarian cancer (EOC) and without any suspicion of lymph node metastases, without compromising recurrence-free survival (RFS), nor overall survival (OS), in the setting of primary surgical treatment. Evidence supporting the same postulate for patients undergoing complete cytoreductive surgery after neoadjuvant chemotherapy (NACT) is lacking. Throughout a systematic literature review, the aim of our study was to evaluate the impact of lymph node dissection in patients undergoing surgery for advanced-stage EOC after NACT. A total of 1094 patients, included in six retrospective series, underwent either systematic, selective or no lymph node dissection. Only one study reveals a positive effect of lymphadenectomy on OS, and two on RFS. The four remaining series fail to demonstrate any beneficial effect on survival, neither for RFS nor OS. All of them highlight the higher peri- and post-operative complication rate associated with systematic lymph node dissection. Despite heterogeneity in the design of the studies included, there seems to be a trend showing no improvement on OS for systematic lymph node dissection in node negative patients. A well-conducted prospective trial is mandatory to evaluate this matter

Quilting sutures reduces seroma in mastectomy

Background Drainage duration and seroma formation occurring after mastectomy with or without axillary surgery lengthens hospitalization and delays adjuvant treatment. The aim of the study was to evaluate the effect of quilting in the prevention of seroma after mastectomy for breast cancer. Patients and Methods Eighty-two breast cancer patients about to undergo mastectomy with or without axillary surgery lymphadenectomy were enrolled in the study. We conducted an observational comparison between 41 patients in whom quilting with closed suction drainage was used and 41 patients in whom drainage only was used. Results The mean drained volume was significantly lower in the quilting group compared with the control group on days 1 and 2 (day 1: 107.1 mL vs. 156.5 mL; P =.02; day 2: 108.4 mL vs. 162.8 mL; P =.01). The mean drainage period was shorter in the quilting group (4.6 vs. 5.3 days; P =.046). There were fewer needle aspirations for seroma in the padding group (n = 14, 34.1% vs. n = 24, 58.5%; P =.03). Conclusion The use of padding after mastectomy seems to reduce seroma formation, volume drained, and length of drainage tim

Staging surgery in early-stage ovarian mucinous tumors according to expansile and infiltrative types

The aim of this study is to determine the value of surgical staging for the two histologic types (expansile or infiltrative) of apparent stage I mucinous ovarian carcinoma. We retrospectively analyzed patients treated from 1976 and 2016 for apparent macroscopic stage I ovarian mucinous carcinoma. Extra-ovarian disease and tumors that metastasized to the ovaries were excluded. Two expert pathologists performed pathologic reviews of tumor data, according to 2014 WHO classification criteria. Tumors were typed as expansile or infiltrative and clinical and histologic characteristics were studied. The value of staging procedures (peritoneal and nodal) was based on the rate of microscopic involvement in macroscopically normal specimens. Of 114 cases reviewed, 46 were excluded (26 with macroscopic stage > I; 20 inaccessible for pathologic review). Of 68 patients included, 29 had expansile and 39 had infiltrative types. 27 patients received one-step surgery and 41 received restaging surgery. 52 patients received “complete” peritoneal surgical staging (including cytology, peritoneal biopsies, and an omentectomy or large omental biopsies). 24 underwent appendectomies and 31 underwent lymphadenectomies (8 expansile and 23 infiltrative). Before histologic analyses of staging specimens, 35 had “initial” stage IA and 33 had IC disease. After histologic analyses of lymph nodes, 4 cases (17%, all infiltrative) had nodal involvement, and 2 showed microscopic peritoneal disease (1 omentum and 1 right diaphragm peritoneum). Three patients were upstaged based on isolated positive peritoneal cytology. To conclude, peritoneal staging procedures are required for both types of mucinous ovarian carcinoma. Lymphadenectomy could be omitted in expansile, but required in infiltrative type

Is uterine preservation combined with bilateral salpingo-oophorectomy to promote subsequent fertility safe in infiltrative mucinous ovarian cancer?

According to the latest World Health Organization classification (2014), mucinous ovarian cancers should be classified histologically as being either expansile or infiltrative. Compared to other epithelial cancers, both of these mucinous patterns are diagnosed, in the main, at an early stage, although they can affect relatively young patients. The infiltrative subtype is characterized by a morphologically and clinically more aggressive disease versus the expansile form. Consequently, even in young patients who would prefer fertility sparing management, the removal of both ovaries (even for a unilateral tumor) remains a common recommendation. However case reports describing the preservation of the uterus for a further potential pregnancy (following oocyte donation) have now been described. In this series, we present six patients treated for stage I mucinous infiltrative cancer using bilateral salpingo-oophorectomy with uterine preservation. All but one patient underwent 1-step (n = 1) or 2-step (n = 4) surgery, including peritoneal and nodal (4 patients) procedures. Disease stages were IA (n = 2), IC1 (n = 1), IC2 (n = 2), or IC3 (n = 1). While two patients subsequently became pregnant, two patients also suffered disease recurrence. For one patient, recurrence was at the pelvic peritoneum. For the second patient, an ultimately lethal disease recurrence involved the uterine serosa with nodal involvement. The results of this short series lead us to question the safety of this uterine-preserving strategy