Cytomegalovirus gastritis as a rare adverse event during combined ipilimumab and nivolumab in a patient with melanoma.

Immunotherapy has improved survival outcomes of patients with advanced melanoma. Lower gastrointestinal tract immune-related adverse events (irAEs) are common during treatment; however, gastritis is not frequently observed. Herein, we report a case of severe cytomegalovirus (CMV)-related gastritis in a patient treated with ipilimumab and nivolumab for metastatic melanoma. This report presents a 60-year-old woman with stage IV BRAF wild-type melanoma. After the second course of ipilimumab-nivolumab, the patient reported epigastric discomfort after meals, anorexia, and subsequent nausea, vomiting, epigastric pain, and weight loss. Disease staging with PET/CT scan showed very good partial response and diffuse gastroduodenitis. The patient underwent esophagogastroduodenoscopy, showing severe esophageal candidiasis and diffuse hemorrhagic, edematous, and ulcerative mucosa in the whole gastric wall. Biopsies of the gastric wall were obtained. Before receipt of the final pathology report, the patient was empirically started on corticosteroids based on the clinical suspicion of immune-related gastritis, without improvement of symptoms. The hematoxylin-eosin staining demonstrated active gastritis with diffuse nuclear cytopathic viral inclusions in epithelial and interstitial cells; CMV infection was confirmed with immunohistochemical staining. The patient started ganciclovir and fluconazole, with rapid improvement of symptoms. This case presents a rare instance of CMV gastritis in a patient receiving combined anti-PD1 and anti-CTLA4 , in the absence of immune-suppression to manage an irAE. In the case of suggestive symptoms of irAEs, a high index of clinical suspicion is required to rule out concomitant or isolated infective disease. Guidelines for prophylaxis and treatment of these patients are needed, to optimize treatment results.

Endoscopic characterization of neoplastic and non-neoplastic lesions in inflammatory bowel disease: systematic review in the era of advanced endoscopic imaging.

Background: Current guidelines strongly recommend the use of validated classifications to support optical diagnosis of lesions with advanced endoscopic imaging in the lower gastrointestinal tract. However, the optimal strategy in inflammatory bowel disease (IBD) is still a matter of debate. Objectives: To analyze the accuracy of endoscopic classifications or single predictors for in vivo lesion characterization during endoscopic surveillance of IBD with advanced endoscopic imaging. Design: Systematic review. Data sources and methods: Medline and PubMed were used to extract all studies which focused on lesion characterization of neoplastic and non-neoplastic lesions in IBD. The diagnostic accuracy of endoscopic classifications and single endoscopic predictors for lesion characterization were analyzed according to type of patients, lesions, and technology used. When available, the rates of true and false positives or negatives for neoplasia were pooled and the sensitivity (SE), specificity (SP), positive predictive value, and negative predictive value (NPV) were calculated. Results: We included 35 studies (2789 patients; 5925 lesions - 1149 neoplastic). Advanced endoscopic imaging included dye-based chromoendoscopy, virtual chromoendoscopy (VCE), magnification and high-definition endoscopy, confocal laser endomicroscopy (CLE), endocytoscopy, and autofluorescence imaging. The Kudo classification of pit patterns was most frequently used, with pooled SE 83%, SP 83%, and NPV 95%. The endoscopic criteria with the highest accuracy, with minimum SE ⩾ 90%, SP ⩾ 80%, and NPV ⩾ 90% were: the Kudo-IBD classification used with VCE (Fuji Intelligent Color Enhancement and i-SCAN); combined irregular surface and vascular patterns used with narrow band imaging; the Mainz classification used with CLE. Multiple clinical and technical factors were found to influence the accuracy of optical diagnosis in IBD. Conclusion: No single endoscopic factor has yet shown sufficient accuracy for lesion characterization in IBD surveillance. Conventional classifications developed in the non-IBD setting have lower accuracy in IBD. The use of new classifications adapted for IBD (Kudo-IBD), and new technologies based on in vivo microscopic analysis show promise.

Continuous clinical remission with biologics in ulcerative colitis: the 'AURORA' comparison study.

OBJECTIVES: Comparative trials among biological drugs for the treatment of ulcerative colitis (UC) provided conflicting results. After patent expire of infliximab originator, adalimumab, infliximab biosimilar, golimumab and vedolizumab have been approved in Italy.We compared the efficacy of these four biologics in UC according to the concept of continuous clinical remission (CCR). METHODS: In a retrospective, multicentre study, all UC patients treated with adalimumab, infliximab biosimilar, golimumab or vedolizumab between 2014 and 2019 were included. All drugs were compared to each other according to the 1-year CCR rate, defined as Mayo partial score ≤2, with bleeding subscore = 0, without any relapse or optimization with dose escalation, topical treatments or steroid use after first clinical remission. RESULTS: Four-hundred sixteen patients (adalimumab = 90, infliximab biosimilar = 105, golimumab = 79, vedolizumab = 142) were included. CCR was achieved in similar percentages among the groups (33%, 37%, 28%, 37%, respectively). All drugs were equivalent in biologic-naive patients, while vedolizumab was better than a second anti-TNFα in prior anti-TNFα agent failures. No differences were found according to type of adverse events or severe adverse events. CONCLUSIONS: Based on a strict definition of clinical remission, all biologics appear equally effective at 1 year. Changing to vedolizumab is more effective than switching to another anti-TNFα in TNFα failures.

Evidence-based efficacy of methotrexate in adult Crohn's disease in different intestinal and extraintestinal indications.

Introduction: Methotrexate (MTX) is included in the therapeutic armamentarium of Crohn's disease (CD), although its positioning is currently uncertain in an era in which many effective biological drugs are available. No systematic reviews or meta-analysis have stratified the clinical outcomes of MTX according to the specific clinical scenarios of its use. Methods: Medline, PubMed and Scopus were used to extract eligible studies, from database inception to May 2021. A total of 163 studies were included. A systematic review was performed by stratifying the outcomes of MTX according to formulation, clinical indication and criteria of efficacy. Results: The use of MTX is supported by randomized clinical trials only in steroid-dependent CD, with similar outcomes to thiopurines. The use of MTX in patients with steroid-refractoriness, failure of thiopurines or in combination with biologics is not supported by high levels of evidence. Combination therapy with biologics can optimize the immunogenic profile of the biological drug, but the impact on long-term clinical outcomes is described only in small series with anti-TNFα. Other off-label uses, such as fistulizing disease, mucosal healing, postoperative prevention and extraintestinal manifestations, are described in small uncontrolled series. The best performance in most indications was shown by parenteral MTX, favouring higher doses (25 mg/week) in the induction phase. Discussion: Evidence from high-quality studies in favour of MTX is scarce and limited to the steroid-dependent disease, in which other drugs are the leading players today. Many limitations on study design have been found, such as the prevalence of retrospective underpowered studies and the lack of stratification of outcomes according to specific types of patients and formulations of MTX. Conclusion: MTX is a valid option as steroid-sparing agent in steroid-dependent CD. Numerous other clinical scenarios require well-designed clinical studies in terms of patient profile, drug formulation and dosage, and criteria of efficacy.

Lower incidence of COVID-19 in patients with inflammatory bowel disease treated with non-gut selective biologic therapy.

BACKGROUND AND AIM: Since the outbreak of COVID-19, concerns have been raised as to whether inflammatory bowel disease (IBD) patients under biologic therapy may be more susceptible to the disease. This study aimed to determine the incidence and outcomes of COVID-19 in a large cohort of IBD patients on biologic therapy. METHODS: This observational retrospective multicenter study collected data about COVID-19 in IBD patients on biologic therapy in Italy, between February and May 2020. The main end-points were (i) to assess both the cumulative incidence and clinical outcome of COVID-19, according to different biologic agents and (ii) to compare them with the general population and a cohort IBD patients undergoing non-biologic therapies. RESULTS: Among 1816 IBD patients, the cumulative incidence of COVID-19 was 3.9 per 1000 (7/1816) with a 57% hospitalization rate and a 29% case-fatality rate. The class of biologic agents was the only risk factor of developing COVID-19 (P = 0.01). Non-gut selective agents were associated with a lower incidence of COVID-19 cases, related symptoms, and hospitalization (P < 0.05). Compared with the general population of Lombardy, an overall lower incidence of COVID-19 was observed (3.9 vs 8.5 per 1000, P = 0.03). Compared with 565 IBD patients on non-biologic therapies, a lower rate of COVID-19 symptoms was observed in our cohort (7.5% vs 18%, P < 0.001). CONCLUSIONS: Compared with the general population, IBD patients on biologic therapy are not exposed to a higher risk of COVID-19. Non-gut selective agents are associated with a lower incidence of symptomatic disease, supporting the decision of maintaining the ongoing treatment.

Prospective evaluation of ERCP performance in an Italian regional database study.

BACKGROUND: Prospective studies about endoscopic retrograde cholangio-pancreatography (ERCP) in a community setting are rare. AIM: To assess success and complication rates of routinely-performed ERCP in a regional setting, and the priority quality indicators for ERCP practice. METHODS: Prospective region wide observational study on consecutive patients undergoing ERCP during a 6-month period. A centralized online ERCP questionnaire was built and used for data storage. Primary quality indicators provided by the American Society of Gastrointestinal Endoscopy (ASGE) were considered. RESULTS: 38 endoscopists from 18 centers performed a total of 2388 ERCP. The most common indication for ERCP was choledocholitiasis (54.8%) followed by malignant jaundice (22.6%). Cannulation of the desired duct was obtained in 2293 cases (96%) and ERCP was successful in 2176 cases (91.1%). Success and ERCP difficulty were significantly related to the experience of the operator (p = 0.001 and p < 0.001, respectively). ERCP difficulty was also significantly related to volume centers (p < 0.01). The overall complication rate was 8.4%: post-ERCP pancreatitis (PEP) occurred in 4.1% of procedures, bleeding in 2.9%, infection in 0.8%, perforation in 0.4%. Mortality rate was 0.4%. All the ASGE priority quality indicators for ERCP were confirmed. CONCLUSIONS: The procedural questionnaire proved to be an important tool to assess and verify the quality of routinely-performed ERCP performance in a community setting.