Background: Regulatory agencies have concluded that sodium glucose cotransporter 2 (SGLT2) inhibitors lead to ketoacidosis, but published literature on this point remains controversial.Methods: We searched the FDA Adverse Event Reporting System (FAERS) for reports of acidosis in patients treated with canagliflozin, dapagliflozin, or empagliflozin (from the date of each drug's FDA approval until May 15, 2015). We compared the number of SGLT2 inhibitor‐related reports to reports of acidosis in patients treated with the 2 most commonly used DPP4 inhibitors: sitagliptin and saxagliptin. We estimated relative risks of acidosis by relating the number of reports to cumulative drug sales (a surrogate for patient exposure).Results: FAERS contained 259 reports of acidosis (including 192 reports of ketoacidosis) for SGLT2 inhibitors compared with 477 reports of acidosis for DPP4 inhibitors (including 71 reports of ketoacidosis). Based on estimated patient exposure, the overall risk of developing acidosis was ~14‐fold higher for SGLT2 inhibitors. Among 51 SGLT2 inhibitor‐related reports with quantifiable metabolic information, 20 cases occurred in patients with type 1 diabetes (T1D), 25 in type 2 diabetes (T2D), and 6 in patients with unspecified type of diabetes. After excluding patients with T1D and focusing on patients identified as having T2D, we estimate that SGLT2 inhibitors were associated with ~7‐fold increase in developing acidosis. Seventy‐one percent had euglycemic ketoacidosis.Conclusions: Our results support the FDA's warning that SGLT2 inhibitors lead to ketoacidosis, as evidenced by an increased reporting rate for acidosis above that in a comparator population treated with DPP4 inhibitors.

Pancreatic cancer is the third most common cause of cancer deaths in the United States. Surgical resection with negative margins still constitutes the cornerstone of potentially curative therapy, but is possible only in 15–20% of patients at the time of initial diagnosis. Accumulating evidence suggests that the neoadjuvant approach may improve R0 resection rate in localized resectable and borderline resectable diseases, and potentially downstage locally advanced disease to achieve surgical resection, though the impact on survival is to be determined. Despite advancements in the last decade in developing effective combinational chemo-radio therapeutic options, preoperative treatment strategies, and better peri-operative care, pancreatic cancer continues to carry a dismal prognosis in the majority. Prodigious efforts are currently being made in optimizing the neoadjuvant therapy with a better toxicity profile, developing novel agents, imaging techniques, and identification of biomarkers for the disease. Advancement in our understanding of the tumor microenvironment and molecular pathology is urgently needed to facilitate the development of novel targeted and immunotherapies for this setting. In this review, we detail the current literature on contemporary management of resectable, borderline resectable and locally advanced pancreatic cancer with a focus on future directions in the field.

Context Adrenocortical Carcinoma (ACC) is rare and knowledge on the prognostic factors and survival outcomes is limited. Objective To describe predictors of survival and overall survival (OS) outcomes of ACC. Design Retrospective review of ACC patients from National Cancer Database (NCDB) Setting Nationwide cancer registry based study. Patients Pathologically confirmed 3185 ACC patients identified from NCDB between 2004 and 2015. Main Outcome Measures Baseline description, survival outcomes, and predictors of survival were evaluated in patients with ACC. Results Median age at diagnosis of ACC was 55 (range:18-90) years and did not differ by sex or stage of disease at diagnosis. On multivariate analysis, increasing age (p < 0.0001), higher Charlson comorbidity index (p < 0.0001), high tumor grade (p < 0.0001), stage IV disease (p=0.002), no surgical therapy (p < 0.0001), and performance of lymphadenectomy during surgery (p=0.02) were associated with poor prognosis. In stage I-III disease, patients treated with surgical resection had significantly better median OS (63 vs 8 months, p <0.001). In stage IV disease, patients treated with surgery (19 vs 6 months, p < 0.001), and post-surgical radiation (29 vs 10 months, p < 0.001) or chemotherapy (22 vs 13 months, p=0.004) had a better median OS. Conclusions OS of ACC varied with increasing age, higher comorbidity index, grade and stage of the disease at presentation. In addition, we noted improved survival with surgical resection of primary tumor, irrespective of the stage of the disease though, post-surgical chemo or radiation benefitted only in stage IV disease.

Medullary thyroid carcinoma (MTC), arising from the parafollicular C cells of the thyroid, accounts for 1–2% of thyroid cancers. MTC is frequently aggressive and metastasizes to cervical and mediastinal lymph nodes, lungs, liver, and bones. Although a number of new imaging modalities for directing the management of oncologic patients evolved over the last two decades, the clinical application of these novel techniques is limited in MTC. In this article, we review the biology and molecular aspects of MTC as an important background for the use of current imaging modalities and approaches for this tumor. We discuss the modern and currently available imaging techniques—advanced magnetic resonance imaging (MRI)-based techniques such as whole-body MRI, dynamic contrast-enhanced (DCE) technique, diffusion-weighted imaging (DWI), positron emission tomography/computed tomography (PET/CT) with 18F-FDOPA and 18F-FDG, and integrated positron emission tomography/magnetic resonance (PET/MR) hybrid imaging—for primary as well as metastatic MTC tumor, including its metastatic spread to lymph nodes and the most common sites of distant metastases: lungs, liver, and bones.

Introduction: Surgical resection remains the mainstay of potentially curative treatment in the early stages of cholangiocarcinoma, whereas for the advanced-stage, systemic chemotherapeutics and experimental targeted therapies are the primary treatment options. The molecular heterogeneity of the tumor is based on location, liver dysfunction and relative rarity of the disease and confers challenges for clinical trial enrollment. The advancements in the understanding of molecular pathogenesis of cholangiocarcinoma have led to the development of targeted therapies that are currently being evaluated in the clinical trials. Areas covered: This review summarizes the current understanding and future directions of targeted therapeutic options in the management of advanced cholangiocarcinoma. Expert opinion: Advanced cholangiocarcinoma has a dismal prognosis; improved understanding of the molecular pathogenesis and advancements in development of targeted therapy offers hope that we may improve outcomes in this rare, but highly lethal cancer. Among the newly discovered molecular alterations, targeting FGFR2 fusions, IDH1/2 mutations and HER2 receptors hold great promise for improving the future management of cholangiocarcinoma. Immunotherapy in combination with targeted agents and chemotherapy may improve outcomes. In addition, drugs targeting the MEK, EGFR, KRAS, BRAF and ROS1 pathways and neo-angiogenesis may also provide new horizons in the management of cholangiocarcinoma.