Granulomatous and Sarcoid-like Immune-Related Adverse Events following CTLA4 and PD1 Blockade Adjuvant Therapy of Melanoma: A Combined Analysis of ECOG-ACRIN E1609 and SWOG S1404 Phase III Trials and a Literature Review.

BACKGROUND: Treatment with immune checkpoint inhibitors (ICIs) has been linked to granulomatous and sarcoid-like lesions (GSLs) affecting different organs. This study sought to evaluate GSL incidence in patients with high-risk melanoma treated with cytotoxic T-lymphocyte antigen 4 (CTLA4) or programmed cell death 1 (PD1) blockade adjuvant therapy in two clinical trials: ECOG-ACRIN E1609 and SWOG S1404. Descriptions and GSL severity ratings were recorded. METHODS: Data were collected from ECOG-ACRIN E1609 and SWOG S1404. Descriptive statistics along with GSL severity grades were reported. Additionally, a literature review for such cases was summarized. RESULTS: A total of 11 GSL cases were reported among 2878 patients treated with either ICI or with High-Dose Interferon Alfa-2b (HDI) in ECOG-ACRIN E1609 and SWOG S1404 trials. Cases were numerically more commonly reported with ipi10, followed by pembrolizumab, ipi3, and HDI, respectively. Most of the cases were grade III. Further, organs involved included lung, mediastinal lymph nodes, skin and subcutaneous tissue, and eye. Furthermore, a summary of 62 reports in the literature was described. CONCLUSIONS: GSLs following anti-CTLA4 and anti-PD1 antibody therapy in patients with melanoma were reported unusually. Reported cases ranged in grade from I to III and appeared manageable. Careful attention to these events and their reporting will be essential to better guide practice and management guidelines.

International, multicenter retrospective trial comparing the efficacy and safety of bi-flanged versus lumen-apposing metal stents for endoscopic drainage of walled-off pancreatic necrosis.

BACKGROUND: To compare fully covered bi-flanged metal stents (BFMS) and lumen-apposing metal stents (LAMS) for endoscopic ultrasound (EUS)-guided drainage/debridement of pancreatic walled-off necrosis (WON). METHODS: Patients with WON managed by EUS-guided therapy were divided into those who underwent: 1) drainage using BFMS; and 2) drainage using LAMS and scheduled direct endoscopic necrosectomy (DEN). Clinical success (resolution of the WON), technical success (successful stent placement), and adverse events (AEs) were evaluated. RESULTS: 387 patients underwent WON endoscopic drainage, 205 using BFMS and 182 using LAMS. The clinical success in the BFMS or LAMS groups were similar (197 [96.1%] vs. 174 [95.6%]; P=0.81). Median number of procedures required for WON resolution was significantly lower in BFMS compared to LAMS (2 vs. 3, P<0.001). Technical success for stent placement was similar in BFMS and LAMS groups (203 [99%] vs. 180 [99%], P=0.90). Procedure-related AEs were similar in the BFMS and LAMS groups (19 [9.3%] vs. 20 [10.9%], P=0.61). Stent dysfunction with occluding debris was higher in the BFMS group compared to LAMS group (21 [10.2 %] vs. 11 [5.9%], P=0.04). The migration rate was higher in the BFMS group than in the LAMS group (15 [7.3%] vs. 3 [1.6%]; P<0.001). DEN was required in 23 [11.2%] patients in the BFMS group after lack of WON resolution by conservative means. CONCLUSION: BFMS with a "step-up approach" and LAMS with scheduled DEN are both safe and effective for EUS-guided drainage/debridement of WON.

A Challenging Case of Recurrent Eosinophilic Peritonitis.

Eosinophilic peritonitis is a rare presentation of eosinophilic gastroenteritis and is characterized by eosinophil-rich inflammation in any part of the gastrointestinal tract in the absence of secondary causes of eosinophilia. We report a case of a 48-year-old female who had recurrent hospital admissions due to abdominal pain and distension secondary to relapsing eosinophilic peritonitis.

Unilateral versus bilateral hilar stents for the treatment of cholangiocarcinoma: a multicenter international study.

BACKGROUND: Endoscopic placement of hilar stents is an accepted palliative therapy for patients with advanced, unresectable cholangiocarcinoma. However, whether unilateral versus bilateral stent placement provides optimal relief continues to be a subject of debate. The aim of this study was to compare the technical and clinical outcomes in patients with inoperable cholangiocarcinoma who received unilateral or bilateral self-expanding metal stents (SEMS). METHODS: We conducted a multicenter, international retrospective study of 187 patients with cholangiocarcinoma who received unilateral or bilateral SEMS. Outcomes included, but were not limited to, technical success, clinical success, adverse events, stent occlusion, and survival time. Results were further stratified based on the Bismuth classification. RESULTS: Fifty patients received unilateral stents and 137 patients received bilateral stents. All patients achieved technical success. The clinical success rates were 86% for unilateral stents and 82.5% for bilateral stents (P>0.99). Clinical success was not statistically different for either group when stratified by the Bismuth classification (P=0.62 and P=0.72 respectively). There were significantly more adverse events in the bilateral stents group (11.7% vs. 0%, P=0.007). There was no greater risk of stent occlusion when bilateral stents were used (unadjusted P=0.71, adjusted P=0.81). There was a greater risk of death for patients who received bilateral SEMS (hazard ratio 1.78, 95% confidence interval 1.09-2.89; P=0.02). CONCLUSIONS: Unilateral and bilateral drainage had similar technical and clinical success rates. However, bilateral stents had a higher risk of death and more adverse events. Therefore, unilateral SEMS placement is sufficient for relief of biliary obstruction secondary to cholangiocarcinoma.

Chordoma: A Case Report and Review of Literature.

BACKGROUND Chordoma is a rare, but aggressive bone tumor, primarily affecting the axial skeleton. Systemic chemotherapies are not effective against the tumor, and treatment primarily consists of surgical resection and radiation. Despite these treatment modalities, recurrence is common. Our case highlights the role of afatinib as an effective treatment option in such cases. CASE REPORT We present case of 68-year-old female with chordoma, who underwent multiple surgical resections, radiotherapy session, and had course complication by disease progression on imatinib and local recurrence. She was eventually placed on afatinib with good effect. CONCLUSIONS This article discusses the effectiveness of afatanib as a treatment modality, along with diagnosis, histopathological features, associated genetic aberrations, currently available and upcoming treatment options. Special emphasis is placed on molecular targeted therapy, emerging immunotherapies and use of vaccination in this field.

Breast Cancer Metastasis Masquerading as Primary Colon and Gastric Cancer: A Case Report.

BACKGROUND Breast cancer is the most common malignancy in women worldwide. Despite treatment, recurrence and metastasis are common. Lobular breast cancer most commonly metastasizes to the lungs, liver, lymph nodes, and sites in the brain. Metastasis to the gastrointestinal tract is rare, with few cases reported to date. CASE REPORT This report describes a patient with late colon and gastric metastases from lobular breast cancer mimicking primary colon and gastric cancers. CONCLUSIONS Immunohistochemical methods can help differentiate metastatic breast disease to the gastrointestinal tract from primary gastrointestinal malignancy.

Incidentally Diagnosed Anomalous Right Coronary Artery with an Interarterial Course Presenting as Chest Pain.

The frequency of advanced cardiopulmonary imaging has increased the incidence of diagnosis of coronary artery anomalies, but this poses an interesting management dilemma of what to do with them once these anomalies are found. We present the case of a 57-year-old female with a past medical history of postpartum cardiomyopathy, recovered heart failure with reduced ejection fraction (EF), and alcohol use disorder who presented with chest pain, shortness of breath, nausea, vomiting, and palpitations. A CT angiogram was performed to rule out pulmonary embolism. No pulmonary embolism was found; however, the CT scan revealed an anomalous right coronary artery originating from the left coronary cusp, which had a malignant interarterial course (ARCA-LCC-IA) with a right dominant pattern of myocardial circulation. Subsequent nuclear stress testing did not show evidence of ischemia. Echocardiogram revealed a recurrently reduced EF of 40%. Our patient poses a management dilemma since she presented with possible angina and was found to have an anomalous right coronary artery (ARCA) with a malignant course, but subsequently she had a negative exercise stress test with nuclear perfusion imaging. We will review the literature on ARCA-LCC-IA and its clinical manifestations both generally and with its connection to this case as well as its management. We discuss the incidence, diagnosis, and management of ARCA-LCC-IA, with a focus on incidentally found lesions.

Reversible Ocular Toxicity of Oxaliplatin: A Case Report.

Oxaliplatin, a platinum-based chemotherapy agent, is commonly used in the treatment of various malignancies. Common adverse effects involve neurological, hematological, gastrointestinal system, and hypersensitivity, and rarely ocular changes have also been reported. We describe the case of a 71-year-old male, who developed reversible ocular toxicity after receiving oxaliplatin for treatment for pancreatic cancer.

Secondary Immune Thrombocytopenic Purpura in Renal Cell Cancer: A Paraneoplastic Syndrome.

Secondary immune thrombocytopenic purpura (ITP) as a paraneoplastic syndrome has been reported in literature. It is commonly associated with chronic lymphocytic leukemia (CLL) and hodgkins lymphoma. Its association with solid malignancies, especially renal cell cancer is rare, with only a few documented case reports. Treatment usually consisted of targeting the underlying malignancy or utilization of steroid and intravenous immunoglobulin (IVIG) to improve thrombocytopenia. Here, we describe a case of a 75-year-old man with renal cell cancer (RCC), who presented with secondary thrombocytopenia treated with steroid and IVIG. It is important to keep RCC in differential diagnosis for causes for secondary ITP as this impacts treatment.

Discontinuation of proton pump inhibitor use reduces the number of endoscopic procedures required for resolution of walled-off pancreatic necrosis.

BACKGROUND AND OBJECTIVES: Endoscopic drainage/debridement of symptomatic walled off necrosis (WON) using lumen-apposing metal stents (LAMS) is both safe and effective. While endoscopic management of WON is the standard approach to treatment, the ideal concomitant medical therapy remains unclear. The purpose of this study was to further elucidate the effect of proton pump inhibitor (PPIs) therapy on the technical and clinical success of endoscopic treatment of WON. METHODS: Two hundred and seventy-two patients in 8 centers with WON managed by endoscopic drainage using LAMS were evaluated. Patients were followed for at least 6 months following treatment. The patients were divided into two groups: Those that used PPIs continuously during the therapy and those not on PPIs continuously during the interval of therapy. Outcomes included but were not limited to technical success, clinical success, number of procedures performed, and adverse events. RESULTS: From 2013 to 2016, 272 patients underwent WON drainage with successful transmural LAMS placement. The two groups were split evenly into PPI users and non-PPI users, and matched in regards to demographics, etiology of pancreatitis, WON size, and location. There was no difference in the technical success between the two groups (100% vs. 98.8%, P = 1), or in clinical success rates (78.7% vs. 77.9%). There was a significant difference in the required number of direct endoscopic necrosectomies to achieve clinical success in the PPI vs. non-PPI group (3.2 vs. 4.6 respectively, P < 0.01). There were significantly more cases of stent occlusion in the non-PPI group vs. PPI group (9.5% vs. 20.1% P = 0.012), but all other documented adverse events were not significantly different. CONCLUSION: Discontinuing PPIs during endoscopic drainage and necrosectomy of symptomatic WON appears to reduce the number of endoscopic procedures required to achieve resolution. Continuous PPI results in higher rates of early stent occlusion.

Three-way comparative study of endoscopic ultrasound-guided transmural gallbladder drainage using lumen-apposing metal stents versus endoscopic transpapillary drainage versus percutaneous cholecystostomy for gallbladder drainage in high-risk surgical patients with acute cholecystitis: clinical outcomes and success in an International, Multicenter Study.

BACKGROUND: Percutaneous cholecystostomy tube (PTGBD), endoscopic retrograde cholangiopancreatography with transpapillary gallbladder drainage (TP), and endoscopic ultrasound-guided transmural gallbladder drainage (EGBD) using lumen-apposing metal stents (LAMS) have been offered for gallbladder decompression for acute cholecystitis in high-risk surgical patients. Yet, there are limited data comparing these therapies. Our aim was to compare the safety and efficacy of EGBD to TP and PTGBD for gallbladder drainage. METHODS: We retrospectively collected high-risk surgical patients from six centers with acute cholecystitis who underwent gallbladder drainage by EGBD, TP, or PTGBD. Data included technical success (gallbladder drainage), clinical success (acute cholecystitis resolution), adverse events (AE), and follow-up. RESULTS: From 2010 to 2016, 372 patients underwent gallbladder drainage, with 146 by PTGBD, 124 by TP, and 102 drained by EGBD. Technical (98% vs. 88% vs. 94%; p = 0.004) and Clinical (97% vs. 90% vs. 80%; p < 0.001) success rates were significantly higher with PTGBD and EGBD compared to TP. PTGBD group had statistically significantly higher number of complications as compared to EGBD and TP groups (2 0% vs. 2% vs. 5%; p = 0.01). Mean hospital stay in the EGBD group was significantly less than TP and PTGBD (16 vs. 18 vs. 19 days; p = 0.01), while additional surgical intervention was significantly higher in the PTGBD group compared to the EGBD and TP groups (49% vs. 4% vs. 11%; p < 0.0001). CONCLUSIONS: EGBD with LAMS is an effective and safer alternative to TP and PTGBD for treatment of patients with acute cholecystitis who cannot undergo surgery. EGBD with LAMS has significantly lower overall AEs, hospital stay, and unplanned admissions compared to PTGBD. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01522573.

Takotsubo cardiomyopathy in cancer patients.

BACKGROUND: Cancer is a chronic condition that induces significant emotional and physical stress, which may increase the risk for developing Takotsubo cardiomyopathy (TCM). MAIN BODY: Takotsubo cardiomyopathy, also known as stress cardiomyopathy, is a clinical syndrome that generally presents as chest pain mimicking acute coronary syndrome or as an acute heart failure characterized by severe left ventricular systolic dysfunction in response to emotional, physical, or medical stress. The potential triggers for Takotsubo syndrome in cancer patients include the emotional turmoil of a cancer diagnosis, the inflammatory state of the cancer itself, and the physical stress of cancer surgery, systemic anti-neoplastic therapy, and radiation treatment. TCM is becoming increasingly recognized among patients with cancer and has been associated with adverse outcomes in this patient population. In this study, we searched the Pubmed database using keywords "Takotsubo cardiomyopathy", "cancer", and "anti-neoplastic therapy" to review case reports of Takotsubo syndrome occurring in oncologic patients after systemic anti-neoplastic therapy. Clinical presentation, electrocardiogram, laboratory data, transthoracic echocardiogram and coronary angiogram results, and patient outcomes were collected and analyzed. CONCLUSION: Patients with cancer are at an elevated risk for developing stress cardiomyopathy, and it is important to know which cancer drugs have been associated with the development of the Takotsubo syndrome.

Hepatitis caused by herpes viruses: A review.

Herpes virus hepatitis varies in presentation, ranging from asymptomatic to acute liver failure, in both immunocompetent and immunocompromised individuals. Hepatitis caused by the Herpesviridae family is uncommon and usually results in mild disease. It is also often self-limiting, although in certain populations especially immunosuppressed patients, it can cause severe infections, leading to acute to fulminant hepatic failure. In addition, some isolated cases of fulminant disease in immunocompetent individuals have been reported. As the presentation is frequently non-specific, it is important to maintain a high level of suspicion for these viral etiologies and start empiric therapy with antiviral agents as soon as possible. Liver transplantation is the last resort. Mortality remains high in fulminant hepatic failure caused by Herpesviridae without liver transplantation. Here we review the literatures on hepatitis caused by three members of the Herpesviridae family, cytomegalovirus, Epstein-Barr virus and herpes simplex virus to discuss the epidemiology, diagnostic methods, clinical features and current management, and also to determine which aspects need to be investigated in further detail. Herpesviridae-mediated acute liver failure is rare but is associated with a poor prognosis, even after early treatment.

Efficacy, Safety, and Outcomes of Endoscopic Retrograde Cholangiopancreatography With Per-Oral Pancreatoscopy: A Multicenter Experience.

INTRODUCTION: Per-oral pancreatoscopy can be used for both evaluation and treatment of pancreatic duct stones during endoscopic retrograde cholangiopancreatography, evaluating and treating pancreatic duct strictures of indeterminate etiology, and visual inspection and direct biopsy of pancreatic duct mucosa for diagnosis of intraductal papillary mucinous neoplasm (IPMN). We aim to describe the efficacy, safety, and outcomes of pancreatoscopy in a large, multicenter series of patients. MATERIALS AND METHODS: A multicenter retrospective review was conducted of all patients who underwent per-oral pancreatoscopy at 2 large tertiary-care medical centers. Review of relevant medical records, laboratory data, imaging studies, endoscopic procedure notes, telephone follow-up notes, and progress notes was performed. RESULTS: Thirty-three patients underwent 41 pancreatoscopy procedures. Indications included: 20 (48.8%) for diagnosis and treatment of pancreatic duct stones, 16 (39%) for investigation of IPMN, and 5 (12.2%) for evaluation of pancreatic duct strictures.In 20 procedures performed for stone disease, complete pancreatic duct clearance was achieved in 17 of 20 (85%) cases. Strictures were successfully dilated in 5 of 5 (100%) procedures. Direct visualization and biopsy demonstrated IPMN in 11 of 11 (100%) cases. Adverse events occurred in 3 of 41 (7.3%) of procedures, all of which were mild. CONCLUSIONS: In this large series, we demonstrate that in patients with difficult to manage stone disease, strictures and possible malignant ductal pathology, pancreatoscopy is an effective and safe tool that can facilitate both diagnosis and effective therapy. Adverse events in our study were mild and within acceptable limits, further demonstrating that this is a safe procedure that should be offered to appropriate patients.

The Role of Neighborhood Environment in Promoting Risk Factors of Cardiovascular Disease among Young Adults: Data from Middle to High Income Population in an Asian Megacity.

BACKGROUND: Modifiable risk factors of cardiovascular diseases (CVD) have their triggers in the neighborhood environments of communities. Studying the environmental triggers for CVD risk factors is important to understand the situation in a broader perspective. Young adults are influenced the most by the environment profile around them hence it is important to study this subset of the population. METHODS: This was a descriptive study conducted using the EPOCH research tool designed by the authors of the PURE study. The study population consisted of young adults aged 18-25 in two areas of Karachi. The study setting was busy shopping malls frequented by young adults in the particular community being studied. RESULTS: Our total sample size was 120 individuals, who consented to be interviewed by our interviewers. Less than 50% of the population recognized some form of restriction regarding smoking in their communities. The largest contributor to tobacco advertising was actors smoking in movies and TV shows with 89% responses from both communities. Only 11.9% of the individuals disapproved of smoking cigarettes among men with wide acceptance of 'sheesha' across all age groups. Advertising for smoking and junk food was more frequent as compared to smoking cessation, healthy diet and exercise in both the areas. Unhealthy food items were more easily available in contrast to healthier options. The cost of healthy snack food options including vegetables and fruits was higher than sugary drinks and foods. CONCLUSION: This assessment showed that both communities were exposed to environments that promote risk factors for cardiovascular diseases.