Influence of bevacizumab on vaginal cuff evisceration eight months after ovarian cancer cytoreduction surgery: A case report.

•44 year old woman treated with bevacizumab for metastatic epithelial ovarian cancer•The patient experienced vaginal cuff dehiscence and evisceration at 8 months post-operatively.•Metastasis at the surgical site and chronic inflammation implicated

Metformin as a Therapeutic Target in Endometrial Cancers.

Endometrial cancer is the most common gynecologic malignancy in developed countries. Its increasing incidence is thought to be related in part to the rise of metabolic syndrome, which has been shown to be a risk factor for the development of hyperestrogenic and hyperinsulinemic states. This has consequently lead to an increase in other hormone-responsive cancers as well e.g., breast and ovarian cancer. The correlation between obesity, hyperglycemia, and endometrial cancer has highlighted the important role of metabolism in cancer establishment and persistence. Tumor-mediated reprogramming of the microenvironment and macroenvironment can range from induction of cytokines and growth factors to stimulation of surrounding stromal cells to produce energy-rich catabolites, fueling the growth, and survival of cancer cells. Such mechanisms raise the prospect of the metabolic microenvironment itself as a viable target for treatment of malignancies. Metformin is a biguanide drug that is a first-line treatment for type 2 diabetes that has beneficial effects on various markers of the metabolic syndrome. Many studies suggest that metformin shows potential as an adjuvant treatment for uterine and other cancers. Here, we review the evidence for metformin as a treatment for cancers of the endometrium. We discuss the available clinical data and the molecular mechanisms by which it may exert its effects, with a focus on how it may alter the tumor microenvironment. The pleiotropic effects of metformin on cellular energy production and usage as well as intercellular and hormone-based interactions make it a promising candidate for reprogramming of the cancer ecosystem. This, along with other treatments aimed at targeting tumor metabolic pathways, may lead to novel treatment strategies for endometrial cancer

Utilization of a multimodal preoperative pain regimen prior to gynecologic oncology exploratory laparotomies

Objective: The aim of this study was to evaluate the use of a combination of non-opioid preoperative pain medications including Tylenol, Lyrica, and Celecoxib (TLC) in patients undergoing gynecologic oncologic exploratory laparotomies. We evaluated postoperative narcotic use in morphine equvalents (ME) as well as pain scores, anti-emetic use, and length of stay.https://jdc.jefferson.edu/patientsafetyposters/1055/thumbnail.jp

Microcystic, Elongated, and Fragmented (MELF) Pattern Invasion in Ovarian Endometrioid Carcinoma: Immunohistochemical Profile and Prognostic Implications

BACKGROUND •Microcystic, Elongated and Fragmented (MELF) is a well-recognized pattern of uterine endometrioid carcinoma (UEC) associated with lymphovascular space invasion and occult lymph node metastasis •MELF in UEC may be seen with Lynch Syndrome •MELF in UEC is hypothesized to be histologic evidence of an epithelial mesenchymal transition •MELF pattern invasion in ovarian endometrioid carcinoma (OEC) was first described at USCAP 2015 • Current study evaluates MELF in OEC for •Prognostic implications •Immunohistochemical (IHC) profile related to •Lynch Syndrome •Epithelial mesenchymal transition DESIGN •42 consecutive cases of OEC without concurrent UEC (1996-2014) evaluated by 2 pathologists •MELF defined as at least three glands fulfilling histologic criteria •32 cases had blocks available for staining •MLH1, PMS2, MSH2 and MSH6 for mismatch repair (MMR) protein expression •Graded as “retained” or “lost” •β-catenin, e-cadherin, CK19 and cyclin D1 for evidence of epithelial mesenchymal transition •Graded as “rare” (75% cells stain) •Retrospective chart review of clinical and demographic features and overall survival •Data analyzed using Fisher exact test analysis •Survival analyzed using Kaplan-Meier metho

Surgical Resection of a Rare Primary Retroperitoneal Mucinous Borderline Tumor of Müllerian Origin: A Case Report

•Primary retroperitoneal mucinous tumors (PRMTs) are a rare group of cystic neoplasms consisting of three subtypes.•PRMTs are histologically similar to ovarian mucinous tumors but lack true ovarian tissue.•PRMTs should be considered in the differential diagnosis when encountering retroperitoneal cystic lesions.•During surgical resection tumor disruption should be avoided.•Surgical resection alone provides durable disease control for mucinous borderline tumors of low malignant potential

Rare occurrence of pseudomyxoma peritonei (PMP) syndrome arising from a malignant transformed ovarian primary mature cystic teratoma treated by cytoreductive surgery and HIPEC: a case report

Background: Pseudomyxoma peritonei (PMP) syndrome is a disease process that typically occurs from ruptured appendiceal mucocele neoplasms. PMP syndrome arising from malignant transformation of an ovarian primary mature cystic teratoma (MCT) is a pathogenesis rarely encountered. Case presentation: Herein, we report a 28-year-old patient evaluated and treated for a right ovarian mass and large volume symptomatic abdominopelvic mucinous ascites. Molecular profiling and genetic analysis revealed mutations in ATM, GNAS, and KRAS proteins while IHC demonstrated gastrointestinal-specific staining for CK20, CDX2, CK7, and SATB2. Peritoneal cytology showed paucicellular mucin. Diffuse peritoneal adenomucinosis (DPAM) variant of PMP arising from a ruptured ovarian primary MCT after malignant transformation to a low-grade appendiceal-like mucinous neoplasm was ultimately confirmed. Treatment included staged therapeutic tumor debulking and right salpingo-oophorectomy followed by cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC). Conclusions: Our report builds upon the existing literature supporting this aggressive treatment option reserved for advanced abdominal malignancies utilized in this patient with a rare clinical entity

Vitamin D status is inversely associated with markers of risk for type 2 diabetes: A population based study in Victoria, Australia

A growing body of evidence suggests a protective role of Vitamin D on the risk of type 2 diabetes mellitus (T2DM). We investigated this relationship in a population sample from one Australian state. The data of 3,393 Australian adults aged 18±75 years who participated in the 2009±2010 Victorian Health Monitor survey was analyzed. Socio-demographic information, biomedical variables, and dietary intakes were collected and fasting blood samples were analyzed for 25, hydroxycholecalciferol (25OHD), HbA1c, fasting plasma glucose (FPG), and lipid profiles. Logistic regression analyses were used to evaluate the association between tertiles of serum 25OHD and categories of FPG (<5.6 mmol/L vs. 5.6±6.9 mmol/L), and HbA1c (<5.7% vs. 5.7±6.4%). After adjusting for social, dietary, biomedical and metabolic syndrome (MetS) components (waist circumference, HDL cholesterol, triglycerides, and blood pressure), every 10 nmol/L increment in serum 25OHD significantly reduced the adjusted odds ratio (AOR) of a higher FPG [AOR 0.91, (0.86, 0.97); p = 0.002] and a higher HbA1c [AOR 0.94, (0.90, 0.98); p = 0.009]. Analysis by tertiles of 25OHD indicated that after adjustment for socio-demographic and dietary variables, those with high 25OHD (65±204 nmol/L) had reduced odds of a higher FPG [AOR 0.60, (0.43, 0.83); p = 0.008] as well as higher HbA1c [AOR 0.67, (0.53, 0.85); p = 0.005] compared to the lowest 25OHD (10±44 nmol/L) tertile. On final adjustment for other components of MetS, those in the highest tertile of 25OHD had significantly reduced odds of higher FPG [AOR 0.61, (0.44, 0.84); p = 0.011] and of higher HbA1c [AOR 0.74, (0.58, 0.93); p = 0.041] vs. low 25OHD tertile. Overall, the data support a direct, protective effect of higher 25OHD on FPG and HbA1c; two criteria for assessment of risk of T2DM

Challenges Facing Physician Scientist Trainees: a Survey of Trainees in Canada’s Largest Undergraduate and Postgraduate Programs in a Single Centre

Purpose: A number of indicators suggest that the physician scientist career track is threatened. As such, it is an opportune time to evaluate current training models. Perspectives on physician scientist education and career path were surveyed in trainees at the University of Toronto, home to Canada’s longest standing physician scientist training programs. Methods: Trainees from the Clinician Investigator Program (CIP) and MD/PhD Program at the University of Toronto were surveyed. Liekert-style closed-ended questions were used to assess future career goals, present and future perspectives and concerns about and beliefs on training. Demographic information was collected regarding year of study, graduate degree program and focus of clinical and health research. Statistical analysis included non-parametric tests for sub-group comparisons. Results: Both groups of trainees were motivated to pursue a career as a physician scientist. While confident in their decision to begin and complete physician scientist training, they expressed concerns about the level of integration between clinical and research training in the current programs. They also expressed concerns about career outlook, including the ability to find stable and sustainable careers in academic medicine. Trainees highlighted a number of factors, including career mentorship, as essential for career success. Conclusion: These findings indicate that while trainees at different stages consistently express career motivation, they identified concerns that are program- and training stage-specific. These concerns mirror those highlighted in the medical education literature regarding threats to the physician scientist career path. Understanding these different and changing perspectives and exploring those differences could form an important basis for trainee program improvements both nationally and internationally

Hepatocyte Growth Factor-Mediated Renal Epithelial Branching Morphogenesis Is Regulated by Glypican-4 Expression

The glypican (Gpc) family of cell surface heparan sulfate proteoglycans are expressed in a tissue-specific and developmentally regulated fashion. To determine if individual Gpcs can modulate heparin-binding growth factor signaling, we examined hepatocyte growth factor (HGF)-stimulated mitogenic, motogenic, and morphogenic responses of renal tubular cells expressing different Gpcs. Adult inner medullary collecting duct (IMCD) cells were found to express primarily Gpc4 and to proliferate, migrate, and form tubules with HGF, correlating with sustained extracellular signal-regulated kinase (ERK) activation. Embryonic IMCD cells expressing predominantly Gpc3 proliferated and migrated in response to HGF but activated ERK only transiently and failed to form tubules. Overexpressing Gpc-4 but not Gpc-3 or Gpc-1 led to sustained HGF-stimulated ERK activation and rescued the tubulogenic response in these cells. These results demonstrate that both signaling and phenotypic responses to HGF can be regulated by specific Gpc expression patterns