Characteristics and outcomes of cancer patients with pre-existing microscopic colitis after exposure to PD-1 and PD-L1 inhibitors.

PURPOSE: Immune checkpoint inhibitors (ICIs) are frequently associated with adverse events, often affecting the gastrointestinal tract. We conducted this study to determine the characteristics and outcomes of cancer patients with pre-existing microscopic colitis (MC) who underwent ICI treatment. METHODS: In this retrospective study, we identified 10 patients with pre-existing MC who received ICIs at our center 01/2010-06/2020. Clinical characteristics and disease outcomes were recorded. RESULTS: Of 124 screened patients with MC before ICI exposure, 10 had sufficient data to be included in the study. Melanoma (40%) and lung cancer (30%) were the most prevalent cancer types, with 70% of stage IV cancer. Patients received either anti-programmed death 1 regimen (8, 80%) or anti-programmed death ligand 1 agent (2, 20%). Six patients (60%) had collagenous colitis, and 4 (40%) had lymphocytic colitis. The median time from MC diagnosis to ICI initiation was 4 years, with 1 patient on budesonide within 2 months of ICI initiation. Eight patients (80%) developed colitis exacerbations after ICI  and required selective immunosuppression. One patient received a compassionate-use fecal transplantation. The median time from ICI to colitis exacerbation was 14 days, with 40% and 50% of patients experiencing grade 3 diarrhea and grade 2 colitis, respectively, leading to hospitalization in 3 patients. Six patients received steroids and vedolizumab with no colitis recurrence. Of 8 patients who had colitis exacerbation, 6 resumed ICI therapy afterward; with 5 receiving concomitant vedolizumab for secondary prophylaxis. CONCLUSION: Our findings suggest that ICI exposure increases the risk of exacerbation of underlying colitis necessitating and responding to potent immunosuppression therapy.

Aquaporin-5 Expression Is Reduced in Lymphocytic Colitis.

OBJECTIVE: Aquaporin-5 (AQP5) is a member of a family of water channel proteins involved in the bidirectional transfer of water across cell membranes. Lymphocytic colitis (LC) and collagenous colitis (CC) are clinically similar diseases characterized by chronic watery diarrhea in patients with usually unremarkable colonic mucosa on colonoscopy. The aim of this study was to determine whether AQP5 expression in colonic epithelium is altered in LC and CC. METHODS: Sections of formalin-fixed and paraffin-embedded colorectal biopsies from three control patients (CTL), 8 patients with chronic non-bloody diarrhea with biopsies negative for active inflammation or significant distortion (CTL-D), 8 patients with LC, and 5 with CC were stained for AQP5 using immunohistochemistry. The staining intensity was scored as 3 (strong), 2 (intermediate), 1 (weak), or 0 (no staining). Statistical analysis was performed using Prism 7 Statistical Soft-ware. RESULTS: AQP5 was strongly expressed (score 3) in the epithelial cells in all three CTL cases and all 8 CTL-D cases. In the 5 cases of CC, 3(60%) had score 3 and 2(40%) had score 2, but none had a score of 1 or 0. Of the 8 LC cases, 2(25%) had score 3, 3 had score 2(37.5%), and 3 had score 1(37.5%) (p=0.0031). In the three cases of LC with markedly reduced AQP5 (score 1), enteric steroid treatment did not lead to significant improvement in diarrhea. CONCLUSIONS: Colorectal AQP5 expression is reduced in most cases of LC. Markedly reduced AQP5 expression in LC may identify a subset of patients with suboptimal response to enteric steroid treatment. Additional larger studies are needed to confirm these findings.This abstract was presented in part at Digestive Diseases Week in San Diego, CA, May 2019.

Intestinal Spirochetosis: Case Series and Review of the Literature.

OBJECTIVE: This study aims to present the clinical, endoscopic, and histopathologic characteristics associated with intestinal spirochetosis (IS). It also serves to heighten awareness among pathologists, since the histologic appearance of spirochetosis could be subtle and easily overlooked. METHODS: Hematoxylin & eosin (H&E) slides and special stains of intestinal biopsies from six patients with a diagnosis of IS at our institution were reviewed. Clinical history, endoscopic, and histopathologic findings were obtained from electronic medical records. RESULTS: The patients presented with diverse clinical symptoms, and only one patient was asymptomatic. The most consistent symptoms were watery diarrhea and abdominal cramps. Two out of five treated patients reported symptomatic improvement after antibiotics therapy. The colonoscopy findings were not specific, ranging from normal mucosa to polyps, to mucosal ulcerations in one patient. On histologic examination, the typical "brush-like" organisms lying perpendicular to the surface epithelium are seen both on H&E stain and special stains. CONCLUSIONS: IS is usually an incidental histologic finding, and the association with symptoms is still unclear. The clinical presentation could be very diverse, hence, a long list of differential diagnosis should be ruled out. Additional clinical testing should be pursued if patients are unresponsive to antibiotic treatment.