Mesalamine and cholestyramine for immune checkpoint inhibitor-mediated diarrhea and colitis.

PURPOSE: Immune checkpoint inhibitors (ICI) are effective against various malignancies. However, adverse events including diarrhea and colitis can lead to significant morbidity and mortality. Recommendations for the management of ICI mediated diarrhea and colitis include steroids and biologics. Given their associated risks, this study evaluated the role of the non-immunosuppressive agents, mesalamine and or cholestyramine. METHODS: This is a retrospective, descriptive, single-center study of adults who developed ICI diarrhea and colitis between 2010 and 2020 at MD Anderson Cancer Center. Clinical data and outcomes were compared between those treated with the non-immunosuppressive therapies mesalamine and/or cholestyramine alone versus those who received additional immunosuppression with steroids and biologics. RESULTS: Our sample comprised 66 patients wherein, the mean age was 63 years, 71% were males, and 97% had stage III/IV cancers. Fourteen patients were treated successfully with non-immunosuppressive therapy. They had grade 1-3 diarrhea and 1-2 colitis with no difference in the rate of histologic colitis compared to those who received immunosuppressive therapy. They had less CTLA-4 inhibitor-based therapy (36% vs. 73%, p = 0.034), delayed onset of symptoms (159 vs. 64 days, p = 0.011), lower fecal calprotectin levels (56 vs. 234, p = 0.012) and were more likely to resume ICI therapy (64% vs. 25%, p = 0.006). CONCLUSION: Mesalamine and/or cholestyramine may be effective for mild ICI diarrhea and colitis among patients with delayed symptom onset with lower colonic inflammatory burden. Prospective studies randomizing patients with mild colitis between mesalamine/cholestyramine and immunosuppressive treatment are warranted to assess their efficacy and safety.

Clinical Characteristics and Outcomes of Patients with Positive Celiac Serology and Cancer Therapy Exposure.

Objectives: The prevalence of celiac disease (CD) among cancer patients is unknown, yet new cases of CD occur after cancer therapy exposure. The aim of this study was to describe the clinical course and endoscopic features of patients with positive celiac serology (PCS) post-cancer therapy exposure (PCTE) as compared to those with no cancer therapy exposure (NCTE). Methods: A retrospective study of adult patients with PCS at MD Anderson Cancer Center between March 2009 and May 2020. Patients with positive tTG IgA, tTG IgG, and/or EMA IgA were categorized into cases with NCTE and PCTE. Clinical course, endoscopic and histologic features, and treatments were compared between the two groups. Results: Of the 4,345 patients screened for celiac serology, 21 (0.5%) met inclusion criteria. 12 were PCTE, with a median time of 258 days (173-930 days) from initiation of the last cancer therapy. Those PCTE had a higher rate of diarrhea (75% vs 22%, p = 0.030), malnutrition and death. A gluten-free diet was initiated in 82% PCTE vs 89% NCTE, with the majority experiencing symptom resolution. There were no significant differences in endoscopic and histologic features. 17 patients met criteria for CD diagnosis. Conclusions: Our findings suggest that CD may be under-diagnosed in cancer patients. Patients with PCS after cancer therapy may present with diarrhea, nutritional deficiencies, and malnutrition, yet a gluten-free diet may be efficacious in treatment management. Therefore, CD should be considered when treating cancer patients. Given the relative proximity of PCS to cancer therapy exposure, future studies should investigate the association of cancer and cancer therapy with the development of CD.

Case series of cancer patients who developed cholecystitis related to immune checkpoint inhibitor treatment.

BACKGROUND: Immune checkpoint inhibitors (ICIs) represent a promising novel class of cancer therapy, but immune-mediated adverse events can complicate ICI treatment. Acute cholecystitis in patients receiving ICI therapy has not been characterized. We aimed to describe the clinical features of patients who developed ICI-related cholecystitis. METHODS: We evaluated a case series of patients at a tertiary cancer center who received ICI therapy and developed cholecystitis, diagnosed by clinical presentation and diagnostic imaging, during 2010-2018. Patients with a history of chronic cholecystitis or other etiologies of acute cholecystitis, such as cholelithiasis, were excluded. A chi-square test was used to compare the frequency of cholecystitis between ICI regimens. Kaplan-Meier and log rank analyses were used to compare survival between subgroups. RESULTS: Of the 4253 patients who received ICIs in the study period, 25 (0.6%) patients developed suspected ICI-related cholecystitis. Alternatively, of the 31,426 cancer-matched patients who received non-ICI therapy, 72 (0.2%) developed acalculous cholecystitis (P < 0.001). Among the 25 included patients, the median time from ICI initiation to cholecystitis was 6 months (range, 0.1-31 months). Fifteen (60%) patients received an inhibitor of programmed death protein 1 (anti-PD-1) or of its ligand (anti-PD-L1) as a single agent, and 10 (40%) patients received an inhibitor of cytotoxic T-lymphocyte associated protein 4 (anti-CTLA-4) therapy alone or combined with anti-PD-1/L1. Anti-CTLA-4 monotherapy was associated with a higher risk of cholecystitis (P = 0.006). ICI therapy was discontinued in 20 patients, in three (12%) as a result of acute cholecystitis. Two (8%) patients developed sepsis, and four (16%) had perforation of the gallbladder wall. Five (20%) patients underwent surgical cholecystectomy, and eight (32%) underwent percutaneous drainage. Five (20%) patients were treated with steroids; two of them required surgery. Ten (40%) patients were able to restart ICI therapy. Patients who received a combination of anti-CTLA-4 and anti-PD-1/L1 had more complications of cholecystitis than did patients who received either agent alone (P = 0.03). CONCLUSIONS: ICI treatment can result in a clinical condition similar to typical acute cholecystitis in a minority of patients. ICI-related cholecystitis should be managed in a similar fashion to typical cholecystitis. The efficacy of steroids for the treatment of ICI-related cholecystitis is unclear.

A case of successful remission of extensive primary gastric diffuse large B cell lymphoma: radiologic, endoscopic and pathologic evidence.

Though rare amongst stomach neoplasms, primary gastric diffuse large B cell lymphoma is one of the commonest extranodal non-Hodgkin lymphomas. If left untreated, it can have a devastating progression and life-threatening consequences. We present the case of a successfully treated large antral ulcer confirmed to be large B cell lymphoma as evidenced by radiologic, endoscopic and histopathologic findings. A brief discussion about the types of gastric lymphoma, their Helicobacter pylori relation and therapeutic modalities follows.