Microscopic colitis (MC) is a disease characterized by chronic watery diarrhea secondary to colonic inflammation. Endoscopically, the mucosa is usually normal but biopsies show characteristic histologic findings.1.

Question: A 71-year-old man with paroxysmal atrial fibrillation and prostate cancer requiring transurethral resection presented with progressively severe diffuse abdominal pain, bloating, abdominal distention, nausea, and intractable vomiting of 2 days duration. Four days before presentation, he underwent successful radiofrequency ablation of the right and left pulmonary vein inlet tract; 35 W radiofrequency ablation was delivered around both sides of the pulmonary veins in a wide circumferential fashion by extending the circumferential lesion over the posterior walls bilaterally and carina area of the left-side pulmonary veins per protocol. His medications on admission included 100 mg flecainide twice daily, 40 mg pantoprazole daily, 20 mg rivaroxaban daily, and 20 mg simvastatin daily. Physical examination in the emergency room revealed him to be in moderate distress with temperature of 98.6°F, blood pressure 118/68 mm Hg, heart rate 58 beats/min, regular respiratory rate of 18 breaths/min, and O2 saturation 100%. Abdominal examination revealed significant distention, scattered bowel sounds, and diffuse tenderness without peritoneal signs. Laboratory studies revealed white blood cell count 6.2 × 109/L (reference range 4.5–11.0 × 109/L), hemoglobin 14 g/dL (reference range 3.8–17.2 g/dL), and normal serum chemistry panel and lipase. Initial cross-sectional imaging is depicted in Figures A, B, and C. What is the diagnosis? See the Gastroenterology website (www.gastrojournal.org) for more information on submitting to Gastro Curbside Consult. Figure A is an anterior coronal computed tomographic view showing marked gastric and small bowel dilation to the level of the distal ileum. Figure B is a posterior coronal view revealing extensive retained food in the stomach. Figure C reveals widely patent celiac and superior mesenteric artery trunks. Within 72 hours of pulmonary vein ablative therapy for atrial fibrillation, patients with vagal nerve injury may experience severe gastroparesis or ileus leading to bloating, abdominal distension, nausea, vomiting, satiation, epigastric pain, and constipation.1Kuwahara T. Takahashi A. Takahashi Y. et al.Clinical characteristics and management of periesophageal vagal nerve injury complicating left atrial ablation of atrial fibrillation: lessons from eleven cases.J Cardiovasc Electrophysiol. 2013; 24: 847-851Crossref PubMed Scopus (53) Google Scholar Peri-esophageal vagal nerve injury due to thermal energy is a rare but serious complication of ablative therapy for atrial fibrillation. A patient experiencing gastrointestinal symptoms shortly after ablation for cardiac dysrhythmias should also have serious complications such as esophageal ulceration, perforation, and atrio-esophageal fistula considered.3Saha S. Trohman R. Periesophageal vagal nerve injury following catheter ablation of atrial fibrillation: a case report and review of the literature.HeartRhythm Case Rep. 2015; 1: 252-256Abstract Full Text Full Text PDF PubMed Scopus (7) Google Scholar The vagus nerve originates in the medulla oblongata of the brainstem and controls foregut peristalsis and plays a major role in gastric and enteric motility.2Jacobs V. May H. Crandall B. et al.Vagus nerve injury symptoms after catheter ablation for atrial fibrillation.Pacing Clin Electrophysiol. 2018; 41: 389-395Crossref PubMed Scopus (4) Google Scholar Thermal energy is likely the mechanism behind periesophageal vagal nerve injury.1Kuwahara T. Takahashi A. Takahashi Y. et al.Clinical characteristics and management of periesophageal vagal nerve injury complicating left atrial ablation of atrial fibrillation: lessons from eleven cases.J Cardiovasc Electrophysiol. 2013; 24: 847-851Crossref PubMed Scopus (53) Google Scholar Periprocedural esophageal temperature near the ablation site can be monitored to reduce complications.2Jacobs V. May H. Crandall B. et al.Vagus nerve injury symptoms after catheter ablation for atrial fibrillation.Pacing Clin Electrophysiol. 2018; 41: 389-395Crossref PubMed Scopus (4) Google Scholar One series found that 2.5% of patients who did not receive such monitoring developed vagal nerve injury, vs 0.2% with protocol monitoring.1Kuwahara T. Takahashi A. Takahashi Y. et al.Clinical characteristics and management of periesophageal vagal nerve injury complicating left atrial ablation of atrial fibrillation: lessons from eleven cases.J Cardiovasc Electrophysiol. 2013; 24: 847-851Crossref PubMed Scopus (53) Google Scholar Post-procedural nausea and vomiting that is un-responsive to antiemetics should be further evaluated for vagal nerve injury.3Saha S. Trohman R. Periesophageal vagal nerve injury following catheter ablation of atrial fibrillation: a case report and review of the literature.HeartRhythm Case Rep. 2015; 1: 252-256Abstract Full Text Full Text PDF PubMed Scopus (7) Google Scholar With an embolic event excluded and vagal nerve injury suspected, conservative management including nasogastric decompression was initiated and is successful in most patients.1Kuwahara T. Takahashi A. Takahashi Y. et al.Clinical characteristics and management of periesophageal vagal nerve injury complicating left atrial ablation of atrial fibrillation: lessons from eleven cases.J Cardiovasc Electrophysiol. 2013; 24: 847-851Crossref PubMed Scopus (53) Google Scholar However, recurrent abdominal distention, vomiting, and radiographic ileus with nasogastric clamping through hospital day 5 led to institution of 20 mg bethanechol 4 times daily. The rationale for this was based on its parasympathomimetic stimulation of muscarinic receptors without affecting nicotinic ones. Unlike acetylcholine, it is not hydrolyzed by cholinesterase and therefore has a longer duration of action. A motilin agonist such as intravenous erythromycin and complete bowel rest for 2 to 14 days are often beneficial and part of conservative management. However, institution of the cholinergic agonist bethanechol led to rapid resolution of abdominal distention and vomiting. Bethanechol was discontinued after 2 weeks and the patient remained asymptomatic over the ensuing 5 years. Most reported cases have demonstrated similar symptom resolution within 3 weeks.3Saha S. Trohman R. Periesophageal vagal nerve injury following catheter ablation of atrial fibrillation: a case report and review of the literature.HeartRhythm Case Rep. 2015; 1: 252-256Abstract Full Text Full Text PDF PubMed Scopus (7) Google Scholar

Introduction: Zollinger-Ellison syndrome (ZES) is a rare condition caused by a gastrin-releasing neuroendocrine tumor (NET), a gastrinoma, that is characterized by hypergastrinemia, gastric acid hypersecretion, chronic diarrhea, and recurrent peptic ulcer disease (PUD). Severe complications of ZES are uncommon. Cardiac arrest from a gastrinoma-related bleeding ulcer with hemorrhagic shock has not been previously reported. Case Description/Methods: A 47-year-old man with recurrent alcoholic pancreatitis and recently diagnosed PUD presented to the ED with epigastric abdominal pain, chronic diarrhea, and melena. He reported frequent NSAID use and PPI nonadherence since his PUD diagnosis. Abdominal CT scan noted prominent gastric folds but no active GI bleeding. Repeat EGD found LA grade D esophagitis, a large distal esophageal ulcer, and multiple duodenal ulcers without stigmata of recent bleeding. Esophageal biopsy showed fibrino-inflammatory exudate, necrotic stroma, and no neoplasia; gastric biopsy was negative for H. pylori. He was diagnosed with NSAID-related PUD and discharged home with high-dose PPI. Four days later he returned with hematemesis, severe anemia, and shock resulting in cardiac arrest but with successful resuscitation. Abdominal CT showed a large distal esophageal pseudoaneurysm with active intra-gastric hemorrhage. Angiography identified extravasation from left and right gastric artery branches which were successfully embolized. Review of prior admission CT showed 2 enhancing duodenal bulb lesions suspicious for a NET. Serum gastrin level resulted at >4,500 pg/mL. An EUS was unrevealing, but a Gallium-68 DOTATATE PET/CT revealed two areas of somatostatin enhancement posterior to the pylorus. He ultimately improved with 80mg PPI TID and was discharged with follow up for gastrinoma resection and genetics evaluation (Figure 1). Discussion: The most common symptoms of ZES are abdominal pain, chronic diarrhea, and heartburn (up to 78%, 75%, and 42% of cases, respectively); chronic diarrhea may be the single presenting symptom in 3-10% of cases. PUD has been identified via EGD in 75% of cases. Severe complications of ZES, sequela of gastric acid hypersecretion and mucosal ulceration, are uncommon (e.g., bleeding 27%, pyloric / duodenal scarring 10%, esophageal stricture 4%). Pseudoaneurysm, hemorrhagic shock, and cardiac arrest have not been previously reported with ZES. The presence of chronic diarrhea and atypical PUD should raise suspicion for ZES, even in the setting of more common culprits of PUD.Figure 1.: Images of the case A and B: Abdominal CT images highlighting prominently enlarged gastric folds (arrows) from hospital admission prior to the patient's cardiac arrest (A), and the distal esophageal pseudoaneurysm with active-intragastric hemorrhage (arrow) immediately following cardiac arrest (B). C: Angiography image capturing the distal esophageal pseudoaneurysm (circle) along with foci of active hemorrhage (arrows). D: PET CT DOTATATE image depicting two duodenal lesions with somatostatin enhancement consistent with gastrinomas.

Introduction: Intraductal papillary mucinous neoplasms (IPMNs) are a common, premalignant form of pancreatic cystic neoplasm. Pseudomyxoma Peritonei (PMP) is a rare clinical syndrome characterized by diffuse peritoneal spread of a gelatinous mucinous material derived from an epithelial neoplasm, typically appendiceal or ovarian. PMP arising from a pancreatic IPMN is exceptionally rare and limited to a few case reports. Case Description/Methods: A 58-year-old female with a history of hemorrhagic pancreatitis status post pancreatic debridement underwent distal pancreatectomy for tissue with high grade dysplasia (HGD). Four years post-operatively, surveillance abdominal CT scan found a new 1.2cm hypodensity of the pancreatic body. Subsequent endoscopic ultrasound (EUS) with fine needle aspiration (FNA) was consistent with a side branch IPMN with high-risk features. Resection of the pancreatic body was performed showing IPMN with HGD on pathology. Surveillance imaging later revealed near-complete replacement of the remnant pancreatic head with multilocular cystic lesions suggestive of recurrent multifocal IPMN. EUS with FNA again confirmed a side branch IPMN with high-risk features. Total pancreatectomy was then completed. Multi-institution review of the surgical pathology revealed extensive HGD without malignancy or lymphatic involvement. Three years later, surveillance imaging showed a new multi-cystic lesion in the prior pancreatic head region with multiple enlarged intra-abdominal lymph nodes, also confirmed by EUS. Weeks later she experienced acute RUQ pain, and subsequent MRCP highlighted new dense mucinous material along the liver periphery suggesting spontaneous cyst rupture and resultant PMP. Percutaneous biopsy of a perihepatic deposit confirmed a mucinous epithelial neoplasm consistent with PMP. The patient was ultimately referred for cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (Figure 1). Discussion: Branch duct (BD) IPMNs carry an overall malignant potential of 20% at 10 years. Surgical resection is recommended for BD-IPMNs with multiple high-risk radiographic features for malignancy. Post-resection development of new IPMNs in residual pancreatic tissue may occur in up to 12.5% of cases. Peritoneal carcinomatosis arises from malignant metastatic peritoneal tumor deposits, whereas the mucin in PMP is often histologically benign. This case highlights the importance of IPMN and pancreatic remnant surveillance due to their risk of malignant conversion and IPMN recurrence, respectively.Figure 1.: Abdominal computed tomography scan images after total pancreatectomy. A and B: Multifocal mucinous pancreatic lesion (arrows) prior to spontaneous lesion rupture; C and D: Multifocal mucinous pancreatic lesion (arrows) after spontaneous lesion rupture, with (D) highlighting multiloculated perihepatic mucin deposits indicative of pseudomyxoma peritonei (stars).

1Resident, Internal Medicine Residency Program, University of Alabama at Birmingham, Birmingham, AL 2Division of Gastroenterology, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL aCorresponding Author: Thomas Ruli, M.D. Resident, Internal Medicine Residency Program, University of Alabama at Birmingham, Birmingham, AL [email protected]

Introduction: Ulcerative colitis is characterized by inflammation of the colon presenting with gastrointestinal symptoms and can also present with extraintestinal manifestations. One such manifestation that is prevalent in inflammatory bowel disease (IBD) cases is eosinophilia, but blood eosinophils seldom reach levels over 1500 cells/𝜇L1. We present a case of ulcerative colitis with a very high eosinophil count presenting as a hematologic extraintestinal manifestation. Case Description/Methods: A 34-year-old Saudi Arabian man presented for a colonoscopy with complaints of bloody stool and bilateral lower quadrant pain starting approximately 5 months prior. During this procedure, inflammation, friability and granularity were noted in the descending colon, sigmoid colon and rectum. His CBC revealed elevated eosinophil count with levels reaching 4,340 cells/𝜇L, and a differential of 28%. Biopsy of the descending colon showed no presence of eosinophils but did show cryptitis and architectural distortion consistent with IBD. Subsequent ova and parasite testing and review including histology for schistosomiasis and amebiasis were negative. Additional testing was performed including an ANA that was negative and calprotectin levels were very high consistent with ulcerative colitis. Liver function tests were normal as well. As a result of the combination of findings, the diagnosis of ulcerative colitis was made. Initial treatment with mesalamine was ineffective. However, upon treatment with vedolizumab he showed definitive clinical and endoscopic response, and his total eosinophil count normalized (Figure 1). Discussion: Worldwide, inflammatory bowel disease’s incidence has seen nearly a 50% increase over the last 30 years; however, reports of significant eosinophilia at the onset of symptoms remain relatively rare, especially with cell counts greater than 1500 cells/𝜇L1. Additionally, literature regarding treatment of such cases is limited. Although infrequent, eosinophilia can be a presenting sign of IBD. Thus, both Crohn's disease and ulcerative colitis should be included in the differential diagnosis in cases with gastrointestinal symptoms and elevated eosinophil levels, especially when parasitic infection has been ruled out. Reference 1. Barrie, Arthur et al. Recurrent blood eosinophilia in ulcerative colitis is associated with severe disease and primary sclerosing cholangitis. Digestive diseases and sciences vol. 58, 1 (2013): 222-8. doi:10.1007/s10620-012-2329-7Figure 1.: Benign ulcerated colonic mucosa with cryptitis and architectural distortion, taken from the descending colon.

Background: Capsule endoscopy (CE) is an emerging tool in the diagnosis and management of occult bleeding and overt obscure gastrointestinal bleeding (OOGIB). Maximizing the efficiency of CE can lead to rapid bleeding localization and shorter time to therapy. We investigated whether a trained registered nurse (RN) can accurately interpret bleeding by observing the CE findings in real time by measuring inter-observer agreement between RN and physician interpretation. Methods: We conducted a prospective study of patients admitted for OOGIB who underwent live-view capsule endoscopy (LVCE) between December 2016 and November 2017. A matched control group who underwent standard CE was obtained through retrospective review. An RN received a 2-day training program for CE interpretation. RN bedside interpretation for bleeding was followed by interpretation by 2 gastrointestinal physicians blinded to LVCE findings. Outcomes were compared between groups using t-tests and chi(2) tests. Cohen's kappa measured the agreement between the physicians and the RN. Results: Ten subjects were in the LVCE group, and 12 subjects were in the standard-ofcare group. The agreement between the physicians and the RN was 9/10 (90%), with a kappa of 0.73 (95% CI: 0.26-1.00; p = 0.016). Patients in the LVCE group had shorter duration to physician interpretation (0.6 vs. 0.7 days [p = 0.50]), shorter duration to endoscopy (1.8 days vs. 3 days [p = 0.240]), and shorter length of stay (8.1 vs. 11.4 days [p = 0.26]) compared to the standard-of-care group. Conclusion: This study utilizing an RN for LVCE interpretation found inter-observer agreement between RN and physician findings. Larger studies are needed to assess whether this RN-physician team approach can translate to improved outcomes. (c) 2022 S. Karger AG, Basel

Question: A 72-year-old woman with a medical history of gastroesophageal reflux disease, obesity, acquired hypothyroidism, diabetes mellitus, hypertension, and diverticulosis presented with proton pump inhibitor–refractory dyspepsia. Esophagogastroduodenoscopy demonstrated a normal esophagus and stomach, but an unusual 20 × 18 mm glandular Paris IIa lesion was found in the duodenal bulb with a normal second portion of the duodenum. Endoscopic and histologic findings are shown in Figures A and B. What was the most likely diagnosis? Look on page 195 for the answer and see the Gastroenterology website (www.gastrojournal.org) for more information on submitting to Gastro Curbside Consult. Gastric heterotopia (GH) is a rare congenital condition where gastric tissue is found at a location outside the stomach. It may be found anywhere in the GI tract from mouth to anus and is found in the duodenal bulb in 0.5%-2% of individuals, where it most commonly appears as single or multiple asymptomatic polypoid lesions.1Khan S. Niaz S. Khan M. et al.A case of heterotopic gastric tissue in duodenal bulb: an interesting endoscopic finding.Cureus. 2022; 14e24271Google Scholar Large lesions may ulcerate (secondary to acid secretion), bleed, intussuscept, or obstruct, but that is uncommon. Histologically, GH shows aggregates of oxyntic glands composed of chief and parietal cells, and the overlying surface often exhibits gastric foveolar mucinous epithelium (apical mucin cap),2Maione F. Chini A. Gennarelli N. et al.Endoscopic resection of a large polypoid gastric heterotopia of duodenum: a case report.Clin Case Rep. 2021; 9e04633Crossref Google Scholar as demonstrated in the left portion of Figure B. The right portion of Figure B demonstrates normal duodenal mucosa (villi lined by goblet cells, absorptive epithelium, and rare Brunner’s glands). It is important to distinguish GH from the more common acquired condition gastric metaplasia (GM). GM involves the villous surface epithelium of the duodenum, and the metaplastic cells contain small apical vacuoles, similar to gastric foveolar cells, also known as gastric foveolar metaplasia. GM is a reactive process, often associated with duodenal mucosal injury/inflammation, which may or may not be due to Helicobacter pylori (HP) infection. In contrast, GH is not associated with HP, it shows normal duodenal mucosa in the background, and has an association with fundic gland polyps, possibly due to an indirect association through PPI therapy enhancing the endoscopic prominence of GH.3Narang Natasha et al.Gastric tissue in the duodenal bulb: heterotopia or metaplasia?.Am J Gastroenterol. 2020; 115: S1446Crossref Google Scholar Importantly, oxyntic glands characteristic of GH are not identified in GM. Finally, GH often manifests as nodular mucosa endoscopically, whereas GM is detected microscopically. It has been suggested that GH may have neoplastic potential.3Narang Natasha et al.Gastric tissue in the duodenal bulb: heterotopia or metaplasia?.Am J Gastroenterol. 2020; 115: S1446Crossref Google Scholar Therefore, accurate endoscopic and pathologic identification may be important, although it will require further investigation to determine if endoscopic surveillance is warranted.

Introduction: Recurrent malignant anastomotic strictures, especially close to the rectum, are challenging to treat. Lumen-apposing metal stents (LAMS) have been increasingly used for benign strictures. Data in malignant strictures is limited. We report a case successfully treated by non-cautery enhanced LAMS. Case Description/Methods: A 54-year-old man with a history of rectosigmoid adenocarcinoma post low anterior resection, adjuvant chemoradiation, and local recurrence with progression to peritoneal carcinomatosis presented with the complaints of intermittent nausea, vomiting, and abdominal distention. A small bowel follow-through did not show an obstruction but a Gastrograffin enema revealed a rectosigmoid anastomotic stricture. Sigmoidoscopy confirmed a high-grade stricture, 0.4 cm (diameter) x < 1 cm (length) at an end-to-end colo-colonic anastomosis, 10 cm from the anus. This was balloon dilated to 16.5 mm using an over-the-wire technique and traversed showing severe upstream colonic dilation. Stricture biopsies showed evidence of at least high-grade dysplasia. Symptoms improved for a month after which they recurred. Interval positron emission tomography scan revealed hypermetabolic recurrent rectosigmoid tumor. After a multidisciplinary discussion, he was deemed a high-surgical risk candidate. Due to proximity to the anus and long-term life expectancy, a LAMS placement was planned. Stricturogram on repeat colonoscopy using a dual-channel gastroscope confirmed < 1 cm length stricture. A 20 x 10 mm LAMS system was exchanged over-the-wire. Using a non-cautery technique both flanges were deployed across the stricture, followed by balloon dilation to 18 mm with improvement in luminal narrowing and decompression of the upstream colon. At 5-month follow-up, the patient continues to do well with the resolution of obstructive symptoms. Discussion: Malignant recurrence at post-surgical anastomotic sites is difficult to manage surgically, especially with peritoneal involvement. Palliative endoscopic options are limited to dilation or uncovered self-expanding metal stents (uSEMS). Due to their longer length, the role of uSEMS is limited in strictures close to the anus (< 10 cm) due to the occurrence of pain and tenesmus. LAMS with their short length and fully covered nature can provide a longer-lasting alternative with the avoidance of adverse effects. To our knowledge, this is the first report using LAMS for a distal colonic malignant post-surgical anastomotic stricture. Watch the video at https://tinyurl.com/ACGAbstractS373

Question: A 19-year-old woman with a history of lactose intolerance, nephrolithiasis, gastroesophageal reflux, irritable bowel syndrome, and multiple colonic polyps presented with intermittent diffuse abdominal pain associated with passage of loose stool over the past several years. Her only medications included a vitamin D supplement and omeprazole. She had a family history of colorectal cancer in her paternal great grandfather and paternal great uncle.

Common variable immunodeficiency (CVID) is a disorder of typically adult-onset hypogammaglobulinemia in the absence of other known causes. Noninfectious gastrointestinal tract manifestations are common, and a subset of patients with CVID present with a severe enteropathy manifesting as severe malabsorption, weight loss, and diarrhea. A 63-year-old man presented with CVID and severe enteropathy who failed to improve with cytomegalovirus therapy, multiple empiric therapies, and corticosteroids. Vedolizumab infusions were initiated with a dramatic, rapid, and durable complete clinical response.

INTRODUCTION: Gastroparesis (GP) is a debilitating disorder that is often refractory to medical therapy. Gastric electrical stimulation (GES) has been suggested as an effective therapy for medically refractory patients and is believed to exert its effect via activation of vagal afferent pathways influencing centrally mediated nausea signals and gastric visceral sensitivity to distention. We report our prospective tertiary center experience using GES in patients with gastroparesis. METHODS: 46 patients underwent GES placement at our institution from 2014 through 2020 of which 34 had preoperative PAGI-SYM and adequate postoperative comparative PAGI-SYM data for analysis. Standardized questionnaire data was prospectively collected postoperatively at standardized intervals over 5 years. GES algorithmic adjustments to settings were performed postoperatively as clinically necessary. The primary outcome for analysis was total symptom score improvement compared with baseline. Secondary outcomes included individual interval symptom score improvement for nausea, vomiting, early satiety, postprandial bloating/distention, and postprandial abdominal pain as determined by a 0-5 point Likert scale assessment. RESULTS: The preoperative mean total symptom score of 40.1(SD 7.9) declined to 23.5(SD 10.9) at 1-3 months postoperatively (P < 0.001) and remained statistically significantly improved at all subsequent time intervals out to 5 years (Table 1). Improvement appeared maximal by 1-3 months when compared to subsequent time intervals. Individual symptom scores are depicted graphically in Figure A and individually for nausea and vomiting Likert scores in Table 2. Individual symptom scores for nausea improved >1 point in 27 (90%) of patients at 1-3 months (P < 0.0001) and remained statistically significantly improved at all subsequent time intervals to 5 years. Individual symptom scores for vomiting improved >1 point in 25 patients (83.3%) at 1-3 months (P < 0.0001) and remained statistically significantly improved at all-time intervals to 5 years. Individual symptom scores for other symptoms were not significantly improved postoperatively at all time intervals. CONCLUSION: GES placement in a group of predominant diabetic GP is effective, exerts a maximal therapeutic effect by 1-3 months and this effect is durable out to 5 years. This benefit is mainly on the symptoms of nausea and vomiting. Larger studies for longer duration are indicated for this chronic usually lifelong disorder.Figure 1.: Figure A.Table 1.: Total PAGI-SYM scoreTable 2.: Individual symptoms score for nausea and vomiting

INTRODUCTION: This case highlights a rare, important and reversible diagnostic consideration for eosinophilia in gastrointestinal and liver disease. CASE DESCRIPTION/METHODS: A 27 year old female of Asian Indian descent with no significant medical history and on no medications was referred for 2 months of bloody diarrhea associated with lower abdominal cramping and 10-lb weight loss. Clinical exam was unremarkable. Laboratory studies demonstrated an alkaline phosphatase (AP) of 221 U/L, ALT of 55 U/L, AST of 41 U/L, normal bilirubin, leukocyte count 28 × 103/cmm (34% eosinophils)and elevated fecal leukocytes, ESR and CRP. Colonoscopy and biopsies were consistent with chronic active ulcerative pancolitis with no increased tissue eosinophilia. After lack of response to mesalamine and budesonide, she had a complete clinical, endoscopic, and histologic response to vedolizumab but the eosinophilic leukocytosis worsened reaching a peak WBC of 40 × 103/cmm (46% eosinophils) and cholestatic liver function tests worsened with peak AP 500, AST 135, ALT 290, with normal bilirubin. Extensive infectious and parasitic investigations were negative. Flow cytometry of blood and bone marrow along with a bone marrow biopsy showed increased eosinophils but no evidence of a malignant process. MRCP was notable for subtle beading of the right and left intrahepatic biliary ducts suggestive of small duct PSC (Figure A). Liver biopsy (Figure B) showed moderately active lobular inflammation with prominent eosinophilic infiltrates and mild ductal injury. The patient was started on prednisone and had normalization of eosinophilic leukocytosis and liver function tests confirming the diagnosis of eosinophilic cholangitis (EC). DISCUSSION: Approaches to diagnosis and management of EC are limited to case reports typically noting the following diagnostic findings: biliary obstruction or ductal thickening, histopathological eosinophilic infiltration, and biliary abnormalities that resolve without intervention or following corticosteroid therapy. Our case is the first to describe a possible association between EC and UC given the concomitant presentations temporally. EC is a rare but reversible condition, without a known cause, that can mimic PSC and is an important consideration for patients with evidence of biliary abnormalities associated with peripheral eosinophilia.Figure 1.: MRCP image with mild beading of the left hepatic duct.Figure 2.: Moderately active hepatitis with prominent eosinophilic infiltrate and mild duct injury.

INTRODUCTION: Microscopic colitis (MC) is characterized by chronic watery diarrhea, histologic inflammatory or collagenous abnormalities and a lack of endoscopic findings. Clinical response to bile acid sequestrants and/or budesonide is typical and corticosteroid failures occur very infrequently. We report the largest prospective study in the United States evaluating clinical response to vedolizumab in corticosteroid-refractory or intolerant patients with MC. METHODS: Adult patients with refractory MC treated with vedolizumab at a tertiary care center in the southeastern United States were included. Refractory MC was defined as persistent symptoms despite trials of current approved therapies. Vedolizumab IV induction infusions were given at 0, 2 and 6 weeks followed by maintenance dosing every 8 weeks. Clinical response to therapy was closely monitored during induction to assess time to clinical response (>50% improvement in stool frequency) and clinical remission (3 or less bowel movements per day with improved consistency). RESULTS: Eight patients (6 female, median age 53 yrs) with refractory MC (2 collagenous, 3 lymphocytic, 1 collagenous and lymphocytic, 2 MC incomplete) and median symptom duration prior to vedolizumab treatment of 7.5 years were included in the case series. In addition to budesonide (n = 8), failed therapies included bile acid sequestrants (n = 8), mesalamine (n = 2), prednisone (n = 2), bismuth (n = 1), adalimumab (n = 1) and 6-mercaptopurine (n = 2). Clinical response with vedolizumab induction was observed in 7 (87.5%) patients. Time to clinical response after initial induction infusion initiation was week 1 (n = 3), week 3 (n = 2) and week 7 (n = 2). Clinical remission was attained in 6 (75%) patients. One patient lost response after transitioning to maintenance and one had insufficient response to induction therapy. CONCLUSION: This is the first United States prospective case series and the world’s largest single center series reported to date of vedolizumab therapy in patients with refractory MC. Vedolizumab led to sustained clinical improvement in the majority of patients. Clinical response appears to be rapid and durable in the short term in most patients with a well-established safety profile. This case series significantly advances the existing limited literature regarding treatment of refractory MC. Vedolizumab shows great promise as therapy for refractory MC, but further randomized controlled trials which include histologic reassessment and long-term durability of response are needed.Table 1