Blockade of various immune targets such as cytotoxic T-lymphocyte antigen-4 and Programmed cell death leads to immune-mediated tumor regression and immune-related adverse events, predominantly gastrointestinal events including diarrhea and colitis. The current review is done to understand the underlying mechanism of action and to identify potential biomarkers that could help in the prediction and management of gastrointestinal immune-related adverse events. Histological assessment of bowel biopsies and assessment of serologic markers of inflammatory bowel disease and colitis secondary to immune mediated antibodies are reviewed. Ipilimumab causes dysregulation of gastrointestinal mucosal immunity, which can be evidenced by altered antibody levels to enteric flora and inflammatory cell infiltration into gastrointestinal mucosa associated with diarrhea and clinical evidence of colitis. The pattern of drug induced antibody titers to microbial flora and the histological features and location of the inflammation were distinct from classic inflammatory bowel disease. Although classic inflammatory bowel disease and immune mediated antibodies related gastrointestinal toxicity are both immune mediated, the pattern of biomarkers and histological features suggests that the later may be a distinct clinicopathologic entity.

INTRODUCTION: Acute lower gastrointestinal (GI) bleeding is uncommonly due to medication induced-colitis, reported in less than 6% of all lower GI bleeds. Identifying medications that may cause GI bleeding is particularly important in chronically ill patients at high risk for morbidity and mortality. A commonly used medication in patients with advanced renal disease is sevelamer, a phosphate binder in renal failure patients. CASE DESCRIPTION/METHODS: A 53-year-old female with end-stage renal disease presented with hematochezia for 2 days. She notes dark black stools for two weeks followed by rectal bleeding. Her past history is notable for a renal transplantation in 2008 with graft failure requiring hemodialysis. She has no history of NSAID use and her prior screening colonoscopy showed no evidence of colitis. Her medication list was extensive and included sevelamer and cinacalcet. The patient was hemodynamically stable. Initial labs showed a hemoglobin of 6.0 g/dl, baseline was 8.0-9.0 g/dl. She was resuscitated with intravenous fluids and received 2 units of blood. Next, the patient’s upper endoscopy showed gastric erythema only with no stigmata of recent bleeding. Her colonoscopy showed a macroscopically normal appearing colon however random biopsies revealed expansion of the lamina propria with significant population of increased eosinophils. Several crystals were embedded within the colonic mucosa and submucosa resembling sevelamer crystals. Based on the pathology, she was diagnosed with sevelamer-induced colitis and this medication was discontinued. Follow-up at 3 months showed the patient remained asymptomatic without further GI bleeding. DISCUSSION: Sevelamer is a common medication used in renal failure patients. It is a resin that binds and prevents absorption of phosphate within the GI tract and has been shown to cause GI issues such as nausea, vomiting and diarrhea. Rarely it can crystalize, become embedded in the GI tract and ulcerate and cause bleeding. A few case reports have described rectosigmoid ulceration and pseudotumor presentation of sevelamer induced colitis.1,2 Understanding and recognizing the potential for sevelamer-induced colitis is important with such a widely used medication.

Esophageal obstructions are a medical emergency, due to inability to control secretions and risk of perforation. Epidemiology of esophageal foreign-body impaction has evolved to include increasing incidence of non-meat food causes as well as increasing underlying prevalence of pathologies including eosinophilic esophagitis. Chia seeds, a staple known for health benefits, have an uncanny ability to absorb large quantities of water leading to a hydrated gel-like substance which can cause an obstruction. We report the first case of chia seed impaction in a patient with likely eosinophilic esophagitis.

INTRODUCTION: Crohn's Disease (CD) diagnosis is usually based on the presence of gastrointestinal symptoms and findings. Extra-intestinal manifestations (EIMs) occur in up to 50% of patients with CD. We present two cases of rare renal EIM associated with CD activity. CASE DESCRIPTION/METHODS: Case 1: 31 yo white male w/ ileal-colonic CD diagnosed in 2014 presents with 6 weeks of diarrhea, abdominal pain, fatigue, and frothy urine. 3 years prior he developed biopsy proven acute interstitial nephritis from mesalamine which resolved with cessation and steroid taper. He is not on any medications. Laboratory analysis reveals: BUN 40 mg/dL, Cr 6.06 mg/dL, GFR of 13 mL/min, CRP 4 mg/dL, urinalysis with 25 RBCs and no leukocytes, urine protein/creatinine ratio (Pr/Cr) of 1.6, and negative serologies for HIV, HCV, HBV, ANA, ANCA. Complement levels were normal. Renal biopsy shows tubular interstitial nephritis (TIN) with lymphocytic T-cell infiltrate with interstitial fibrosis and tubular atrophy. Random colon biopsies show mild active pan-colitis with non-necrotizing granulomas and normal terminal ileum. He is treated with a slow prednisone taper and adalimumab, but does not have renal recovery resulting in a kidney transplant. Immunosuppression includes tacrolimus, mycophenolate mofetil, and prednisone. Follow-up CD monitoring reveals no symptoms and negative fecal calprotectin. Case 2: 21 yo healthy white female presents with 3 months of watery diarrhea, abdominal pain, and fevers up to 103 F. She is on no medications. Laboratory analysis reveals: Hgb 8.4 g/dL, normal BUN, and a Cr of 1.8 rising to 2.6 mg/dL. Urinalysis with 4 RBCs, 39 leukocytes with negative culture, positive urine eosinophils, Pr/Cr 0.36, CRP of 17 mg/dL, and negative serologies as in case 1. Colonoscopy reveals moderate pan-colitis with non-necrotizing granulomas. Renal biopsy reveals granulomatous interstitial nephritis. She improves with a prolonged steroid taper but has persistent but mild colitis on evaluation. She has no renal recovery but does not require dialysis. DISCUSSION: Renal EIMs of CD are rare. Most commonly they include nephrolithiasis in 28% CD, medication adverse effects, amyloidosis, as well as CD activity correlated TIN and glomerulonephritis. There is no standard treatment for TIN, but a prolonged steroid taper, MMF, cyclosporine, and anti-TNF therapy may be attempted for CD and renal recovery. Both cases reveal renal recovery may not occur with significant immunosuppression and transplant may be required.

INTRODUCTION: Since the 1960’s, the incidence of esophageal cancer has increased steadily by 8% annually in the U.S, and has an overall 5-year survival for early stage adenocarcinoma < 15%. Combined modality of endoscopy, CT and/or CT/PET imaging, and endoscopic ultrasound (EUS) are often utilized to diagnose and stage according TNM classification. If no distant metastases are found, EUS can be used to stage regional lymph nodes and tumor depth. Historically, esophagectomy was the therapeutic mainstay, but is associated with 10% mortality and > 50% morbidity. Endoscopic therapy is now utilized in patients with Tis or T1a tumors with improved survival. We examined the likelihood of clinical symptomatology predicting esophageal carcinoma TNM stage at the time of EUS. METHODS: Our IRB approved retrospective study from January 2007 to July 2017 included 300 medical records of patients over 18 years old obtained through ICD 9&10 codes. 100 patients were randomly chosen for analysis. Patients were excluded for the following: insufficient records, caustic or hazardous exposures, acute trauma, perforation, or surgery, radiation or chemotherapy, HIV, eosinophilic esophagitis, or those undergoing Barret’s esophagus surveillance screening. Data analysis included student t-test to determine significance. RESULTS: Mean age at time of diagnosis was 64, with 77% male. Eighty-one percent of lesions were in the distal third of the esophagus. Adenocarcinoma was the predominant tumor at 81% followed by squamous cell carcinoma. Of these cancer diagnoses, 78 patients experienced either solid food or progressive dysphagia prior to endoscopy. 83% of dysphagia patients were T3 or greater by EUS [Figure 1]. There was no correlation between dysphagia symptoms and lymphadenopathy on either CT (P = 0.21) or EUS (P = 0.34). CONCLUSION: Our results show a strong association of dysphagia as a presenting symptom with advanced TNM stage at the time of EUS (P = 0.03). CT imaging techniques alone may be sufficient in individuals with dysphagia and exophytic lesion by ruling out distant metastasis. Evidence gained by EUS and the associated added costs may not add clinical information to assist in management decisions with neoadjunvant therapy or esophagectomy candidacy. Further prospective study is needed to determine if EUS is warranted in individuals with dysphagia and an exophytic mass at the time of EGD, who have undergone CT staging to rule out distant metastasis.