Folate Receptor Alpha-A Novel Approach to Cancer Therapy.

Folate receptor α (FR) was discovered many decades ago, along with drugs that target intracellular folate metabolism, such as pemetrexed and methotrexate. Folate is taken up by the cell via this receptor, which also targeted by many cancer agents due to the over-expression of the receptor by cancer cells. FR is a membrane-bound glycosyl-phosphatidylinositol (GPI) anchor glycoprotein encoded by the folate receptor 1 (FOLR1) gene. FR plays a significant role in DNA synthesis, cell proliferation, DNA repair, and intracellular signaling, all of which are essential for tumorigenesis. FR is more prevalent in cancer cells compared to normal tissues, which makes it an excellent target for oncologic therapeutics. FRα is found in many cancer types, including ovarian cancer, non-small-cell lung cancer (NSCLC), and colon cancer. FR is widely used in antibody drug conjugates, small-molecule-drug conjugates, and chimeric antigen-receptor T cells. Current oncolytic therapeutics include mirvetuximab soravtansine, and ongoing clinical trials are underway to investigate chimeric antigen receptor T cells (CAR-T cells) and vaccines. Additionally, FRα has been used in a myriad of other applications, including as a tool in the identification of tumor types, and as a prognostic marker, as a surrogate of chemotherapy resistance. As such, FRα identification has become an essential part of precision medicine.

Vanishing Bile Duct Syndrome in a Patient With Recurrent Hodgkin Lymphoma.

Vanishing bile duct syndrome (VBDS) is an acquired syndrome characterized by clinical and laboratory signs of cholestasis with pathologic findings of interlobular bile duct paucity in liver biopsy specimens. VBDS can result from a variety of conditions including infections, autoimmune diseases, adverse drug reactions, and neoplastic processes. Hodgkin lymphoma (HL) is a rare cause of VBDS. The mechanism by which HL leads to VBDS remains unknown. Development of VBDS in patients with HL portends an extremely poor prognosis due to the risk of progression to fulminant hepatic failure. Treatment of the underlying lymphoma has been demonstrated to offer increased probability of recovery from VBDS. The decision to treat and choice of treatment of the underlying lymphoma is often complicated by the hepatic dysfunction characteristic of VBDS. We present the case of a patient who presented with dyspnea and jaundice in the context of recurrent HL and VBDS. We additionally review the literature on HL complicated by VBDS with specific focus on treatment paradigms for management of these patients.

Cirrhosis in intrahepatic cholangiocarcinoma: prognostic importance and impact on survival.

CONTEXT: Cholangiocarcinoma (CCA), a malignancy of the biliary tract epithelium is of increasing importance due to its rising incidence worldwide. There is a lack of data on cirrhosis in intrahepatic CCA (iCCA) and how it affects overall survival and prognosis. OBJECTIVES: The primary objective of this study was to examine if there were differences in survival outcomes between iCCA patients with concomitant cirrhosis and those without cirrhosis. METHODS: The National Cancer Database (NCDB) was used to identify and study patients with iCCA from 2004 to 2017. The presence of cirrhosis was defined using CS Site-Specific Factor 2 where 000 indicated no cirrhosis and 001 indicated the presence of cirrhosis. Descriptive statistics were utilized for patient demographics, disease staging, tumor, and treatment characteristics. Kaplan-Meier (KM) method with log-rank test and a multivariate logistic regression model was used to assess if the presence of cirrhosis in iCCA was associated with survival status and long-term survival (60 or more months after diagnosis). RESULTS: There were 33,160 patients with CCA in NCDB (2004-2017), of which 3644 patients were diagnosed with iCCA. One thousand fifty-two patients (28.9%) had cirrhosis as defined by Ishak Fibrosis score 5-6 on biopsy and 2592 patients (71.1%) did not meet the definition for cirrhosis. Although in univariate analyses using KM/log-rank tests showed a survival advantage for non-cirrhotic patients, there was no statistically significant association found between cirrhosis and survival status (OR = 0.82, p = 0.405) or long-term survival (OR = 0.98, p = 0.933) when multivariate analysis was used. iCCA patients with cirrhosis and Stage 1 tumor had the highest median OS (132 months) vs 73.7 months in the non-cirrhotic arm, while patients with stage IV disease who had cirrhosis had half the survival time of those without. Our data thus indicates that the presence of cirrhosis is not an independent prognostic factor for survival.

Retrospective Analysis of Patients with Gynecological Uterine Sarcomas: Leiomyosarcomas and other Histological Subtypes at a Single Institution from 1996 to 2015.

Uterine sarcomas are a rare group of malignancies that account for less than 10% of all uterine malignancies. They are histologically diverse and fall into two broad groups: mesenchymal and epithelial tumors. The treatment in both these groups is marked by high failure rates and quick progression of disease. Patients with stage I to II with resectable disease benefit from operative cytoreduction. Those with advanced stages, benefit from chemotherapy with or without external beam radiation therapy. Our research in this paper looks at the number of LMS cases at our institution, Wyckoff Heights Medical Center in Brooklyn, NY for a period of 20 years from 1996 until 2015 and assesses our cohort's age at diagnosis and their survival in accordance to grade and stage of diagnosis. Our findings suggest that disease stage is a strong prognostic factor with good survival rates in stage I and II, with higher incidence in African-American women. All LMS patients with distant metastasis died within five years.