Global expression analysis of endometrial cancer cells in response to progesterone identifies new therapeutic targets.

Progesterone prevents development of endometrial cancers through its receptor (PR) although the molecular mechanisms have yet to be fully characterized. In this study, we performed a global analysis of gene regulation by progesterone using human endometrial cancer cells that expressed PR endogenously or exogenously. We found progesterone strongly inhibits multiple components of the platelet derived growth factor receptor (PDGFR), Janus kinase (JAK), signal transducer and activator of transcription (STAT) pathway through PR. The PDGFR/JAK/STAT pathway signals to control numerous downstream targets including AP-1 transcription factors Fos and Jun. Treatment with inhibitors of the PDGFR/JAK/STAT pathway significantly blocked proliferation in multiple novel patient-derived organoid models of endometrial cancer, and activation of this pathway was found to be a poor prognostic signal for the survival of patients with endometrial cancer from The Cancer Genome Atlas. Our study identifies this pathway as central to the growth-limiting effects of progesterone in endometrial cancer and suggests that inhibitors of PDGFR/JAK/STAT should be considered for future therapeutic interventions.

The impact of near-infrared angiography and proctoscopy after rectosigmoid resection and anastomosis performed during surgeries for gynecologic malignancies.

OBJECTIVES: Reducing anastomotic leak rates after rectosigmoid resection and anastomosis is a priority in patients undergoing gynecologic oncology surgery. Therefore, we investigated the implications of performing near-infrared angiography (NIR) via proctoscopy to assess anastomotic perfusion at the time of rectosigmoid resection and anastomosis. METHODS: We identified all patients who underwent rectosigmoid resection and anastomosis for a gynecologic malignancy between January 1, 2013 and December 31, 2018. NIR proctoscopy was assessed via the PINPOINT Endoscopic Imaging System (Stryker). RESULTS: A total of 410 patients were identified, among whom NIR was utilized in 133 (32.4%). There were no statistically significant differences in age, race, BMI, type of malignancy, surgery, histology, FIGO stage, hypertension, diabetes, or preoperative chemotherapy between NIR and non-NIR groups. All cases of rectosigmoid resection underwent stapled anastomosis. The anastomotic leak rate was 2/133 (1.5%) in the NIR cohort compared with 13/277 (4.7%) in the non-NIR cohort (p = 0.16). Diverting ostomy was performed in 9/133 (6.8%) NIR and 53/277 (19.9%) non-NIR patients (p < 0.001). Postoperative abscesses occurred in 8/133 (6.0%) NIR and 44/277 (15.9%) non-NIR patients (p = 0.004). The NIR cohort had significantly fewer post-operative interventional procedures (12/133, 9.0% NIR vs. 55/277, 19.9% non-NIR, p = 0.006) and significantly fewer 30-day readmissions (14/133, 10.5% NIR vs. 61/277, 22% non-NIR, p = 0.004). CONCLUSIONS: NIR proctoscopy is a safe tool for assessing anastomotic rectal perfusion after rectosigmoid resection and anastomosis, with a low anastomotic leak rate of 1.5%. Its potential usefulness should be evaluated in randomized trials in patients undergoing gynecologic cancer surgery.

Low incidence of complications using polyglactin 910 (Vicryl) mesh in breast reconstruction: A systematic review.

BACKGROUND: Mastectomy and breast reconstruction are essential parts of the treatment of breast cancer. Acellular dermal matrices (ADMs) have been used for the reconstruction of the lower pole due to many advantages; however, its cost is seen as a major drawback in this era of concern for the allocation of health-care funds. Recently, polyglactin 910 (Vicryl; Ethicon, Somerville, NJ, USA) mesh has been published as an alternative. We assessed the published literature, in particular investigating for studies that compare Vicryl mesh with ADM. METHODS: We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) methodology. Searched databases included Medline/PubMed, Cochrane Reviews, Embase, Web of Science, ClinicalTrials, and SCOPUS. Search criteria were as follows: (1) reporting of clinical data using Vicryl mesh in breast reconstruction, (2) reporting of original data, and (3) outcome of interest reported. RESULTS: We retrieved 290 de-duplicated articles. After title and abstract screening, we dismissed 258 articles, and thus full text was reviewed for 32 articles; only three retrospective articles met inclusion criteria. The total population included 112 patients and 156 breasts. The reported incidence of complications was as follows: infection 2.6% (confidence interval (CI): 0.7-6.6%), reconstruction failure 3.2% (CI: 1.0-7%), and seroma 1.3% (CI: 0.2-4.6%). A seven- to 12-fold cost difference was reported. Follow-up length ranged from 1.2 to 3.6 years. No studies directly compared Vicryl mesh with ADM. CONCLUSIONS: Although the evidence is limited, polyglactin 910 (Vicryl) mesh for immediate breast reconstruction appears to be a potentially safe, effective, and less expensive alternative to ADM. Prospective studies are needed to further compare mesh with ADM.