Flexible sigmoidoscopy may be sufficient for initial evaluation of suspected immunotherapy‐mediated colitis: A cross‐sectional study

Abstract

Background and Aim: Immune checkpoint inhibitors (ICIs) have shown promise in treating a variety of cancers. Their increased use coincides with increased incidence of immunotherapy-mediated colitis (IMC), a common adverse effect. Optimal strategy for endoscopic evaluation of IMC (full colonoscopy or flexible sigmoidoscopy) is not welldefined. Methods: Retrospective review of all patients at City of Hope referred to gastroenterology for evaluation of IMC due to gastrointestinal symptoms was performed. Patients with an existing histologic diagnosis of IMC established at an outside hospital or a diagnosis of infectious or chronic colitis were excluded. Results: We identified 51 symptomatic patients on ICIs prompting evaluation for IMC with colonoscopy (47/51) or flexible sigmoidoscopy (4/51). All distal rectosigmoid biopsies during flexible sigmoidoscopy demonstrated histologic evidence of IMC. In full colonoscopy, IMC was either present in all segments of colon simultaneously (35/47) or absent from all segments (12/47). No isolated proximal colonic biopsies demonstrated IMC. Endoscopically normal mucosa demonstrated histologic evidence of IMC up to 68.6% of the time. Endoscopically abnormal right, transverse, and left colon had low sensitivity (35.3%, 34.3%, and 41.7%, respectively) and high specificity (100.0%, 100.0%, and 91.7%, respectively) for histological presence of IMC. Conclusions: Distal colon biopsies in patients on ICI therapy with diarrhea and suspected IMC were sufficient for diagnosing IMC in our cohort. Further, we found histologic evidence of IMC in biopsies taken from normal-appearing mucosa in a number of patients, suggesting that a normal endoscopic appearance does not preclude the presence of IMC and biopsies should be taken from both normal and abnormal-appearing mucosa.

An updated review of gastrointestinal toxicity induced by PD-1 inhibitors: from mechanisms to management

“…Approximately 95% of patients have ICI-induced inflammation in the left colon on biopsy (52). Recently, a cross-sectional study organized by De Silva et al uncovered 93.8% of left-sided colon (defined as distal 25 cm of the colon, rectosigmoid colon) biopsies with an abnormal endoscopic appearance and, to the surprise, up to 68.6% of normal-appearing mucosal biopsies with histological evidence of colitis (53). They finalize by noting that extensive biopsies of left-sided normal and abnormal segmental mucosa for evaluation of immune-mediated colitis with flexible sigmoidoscopy hold promise as a simplified alternative to full colonoscopy, although poor sensitive but extremely specific and is often sufficient for early initial diagnosis or follow-up review to guide treatment strategy.…”

“…Pre-treatment preparation Detection of intestinal inflammatory markers like fecal lactoferrin and calprotectin; Screening for Clostridium difficile and CMV infections in feces; Determination of celiac disease by tTG-IgA; Early use of flexible sigmoidoscopy or colonoscopy with biopsy (53).…”

Check this out: treatment paradigms in immune-checkpoint inhibitor colitis

“…At times, there is a discrepancy between endoscopic and histological findings. Thus, biopsies from normal mucosa are necessary even when there is no macroscopic evidence of inflammation [17 ▪ ].…”