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Tang W, Lv Y, Yang X, Gan K, Feng G, Li J, Ni L, Bai Y, Du X, Gao F. Sintilimab‑induced acute erosive hemorrhagic gastritis as an adverse reaction of third‑line therapy in a nasopharyngeal carcinoma patient: A case report. Oncol Lett 2025; 30:326. [PMID: 40370643 PMCID: PMC12076053 DOI: 10.3892/ol.2025.15072] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/20/2024] [Accepted: 04/02/2025] [Indexed: 05/16/2025] Open
Abstract
Immune checkpoint inhibitors (ICIs) have become an important treatment option for patients with nasopharyngeal carcinoma. With the increasing use of such agents, immune-related adverse events (irAEs) have become a concern. Identifying and managing the toxicity and side effects of ICIs is crucial, since it not only has implications for their safety but also the intensity and efficacy of subsequent use by patients. The present case report documents a 40-year-old male patient with acute erosive hemorrhagic gastritis associated with sintilimab treatment. In particular, the clinical manifestations, treatment, side effects and prognosis of this case was focused upon. The patient was diagnosed with locally advanced nasopharyngeal carcinoma (cT4N3M0 stage IVa) and developed bone metastases after 1 year of standard radiotherapy and adjuvant chemotherapy. After the first- and second-line treatments, pulmonary metastases occurred and sintilimab monotherapy was used as the third-line therapy. During the course of treatment, the optimal outcome for this patient was partial response according to the Response Evaluation Criteria in Solid Tumors (version 1.1). However, after 14 cycles of sintilimab the patient developed melena and epigastric pain and was diagnosed with acute erosive hemorrhagic gastritis, which was treated with methylprednisolone therapy. Progression-free survival with the third-line treatment was 542 days. Sintilimab-associated hemorrhagic gastritis is not fully recognized as an irAE. Therefore, early identification, diagnosis and management of irAEs are critical for subsequent therapy and progression-free survival of patients.
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Affiliation(s)
- Wenqiang Tang
- Department of Oncology, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan 637002, P.R. China
| | - Yun Lv
- Departmant of Oncology, Mianyang Central Hospital, Mianyang, Sichuan 621000, P.R. China
| | - Xiyue Yang
- Departmant of Oncology, Mianyang Central Hospital, Mianyang, Sichuan 621000, P.R. China
| | - Kunyuan Gan
- Department of Oncology, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan 637002, P.R. China
| | - Gang Feng
- Departmant of Oncology, Mianyang Central Hospital, Mianyang, Sichuan 621000, P.R. China
| | - Jie Li
- Departmant of Oncology, Mianyang Central Hospital, Mianyang, Sichuan 621000, P.R. China
| | - Lu Ni
- Departmant of Oncology, Mianyang Central Hospital, Mianyang, Sichuan 621000, P.R. China
| | - Yuxi Bai
- Departmant of Oncology, Mianyang Central Hospital, Mianyang, Sichuan 621000, P.R. China
| | - Xiaobo Du
- Departmant of Oncology, Mianyang Central Hospital, Mianyang, Sichuan 621000, P.R. China
- Sichuan Clinical Research Center for Radiation and Therapy, Mianyang Central Hospital, Mianyang, Sichuan 621000, P.R. China
| | - Feng Gao
- Departmant of Oncology, Mianyang Central Hospital, Mianyang, Sichuan 621000, P.R. China
- Sichuan Clinical Research Center for Radiation and Therapy, Mianyang Central Hospital, Mianyang, Sichuan 621000, P.R. China
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Nakajima M, Iwao Y, Okabayashi K, Kanai Y, Shimoda M. Pathological characteristics of inflammatory bowel diseases. J Med Ultrason (2001) 2025; 52:187-196. [PMID: 40025407 DOI: 10.1007/s10396-025-01520-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2024] [Accepted: 12/24/2024] [Indexed: 03/04/2025]
Abstract
Inflammatory bowel disease (IBD) is an inflammatory disorder in which intestinal homeostasis is disrupted for some reason. Among them, ulcerative colitis (UC) and Crohn's disease (CD) are frequently referred to as IBD in the narrow sense, characterized by relapse episodes and remission periods. The differential diagnosis of IBD involves a broad spectrum of inflammatory or infectious diseases that mimic UC and/or CD, as well as others that may complicate existing IBD. Accordingly, these differential diseases and modifying factors should be considered in their pathological diagnosis, and a careful diagnosis should be made in close collaboration with clinicians. Here, we provide a pathological overview of UC, CD, and their differential diseases, as well as IBD-associated cancers, demonstrating their typical gross and histological features. Further, we introduce a pathological scoring system for biopsy specimens to diagnose IBD that may potentially be integrated into clinical practice.
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Affiliation(s)
- Makoto Nakajima
- Department of Pathology, The Jikei University School of Medicine, 3-25-8 Nishi-Shimbashi, Minato-ku, Tokyo, 105-8461, Japan
- Department of Pathology, Keio University School of Medicine, Tokyo, Japan
| | - Yasushi Iwao
- Center for Preventive Medicine, Keio University School of Medicine, Tokyo, Japan
| | - Koji Okabayashi
- Department of Surgery, Keio University School of Medicine, Tokyo, Japan
| | - Yae Kanai
- Department of Pathology, Keio University School of Medicine, Tokyo, Japan
| | - Masayuki Shimoda
- Department of Pathology, The Jikei University School of Medicine, 3-25-8 Nishi-Shimbashi, Minato-ku, Tokyo, 105-8461, Japan.
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Deng YF, Cui XS, Wang L. Reconceptualization of immune checkpoint inhibitor-associated gastritis. World J Gastroenterol 2024; 30:4031-4035. [PMID: 39351252 PMCID: PMC11439116 DOI: 10.3748/wjg.v30.i36.4031] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/24/2024] [Revised: 08/28/2024] [Accepted: 09/09/2024] [Indexed: 09/20/2024] Open
Abstract
In recent years, with the extensive application of immunotherapy in clinical practice, it has achieved encouraging therapeutic effects. While enhancing clinical efficacy, however, it can also cause autoimmune damage, triggering immune-related adverse events (irAEs). Reports of immunotherapy-induced gastritis have been increasing annually, but due to its atypical clinical symptoms, early diag-nosis poses a certain challenge. Furthermore, it can lead to severe complications such as gastric bleeding, elevating the risk of adverse outcomes for solid tumor patients if immunotherapy is interrupted. Therefore, gaining a thorough under-standing of the pathogenesis, clinical manifestations, diagnostic criteria, and treatment of immune-related gastritis is of utmost importance for early identification, diagnosis, and treatment. Additionally, the treatment of immune-related gastritis should be personalized according to the specific condition of each patient. For patients with grade 2-3 irAEs, restarting immune checkpoint inhibitors (ICIs) therapy may be considered when symptoms subside to grade 0-1. When restarting ICIs therapy, it is often recommended to use different types of ICIs. For grade 4 irAEs, permanent discontinuation of the medication is necessary.
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Affiliation(s)
- Ying-Fang Deng
- Department of Oncology, Affiliated Hospital of Qinghai University, Xining 810000, Qinghai Province, China
- Ying-Fang Deng and Xian-Shu Cui
| | - Xian-Shu Cui
- Department of Oncology, Affiliated Hospital of Qinghai University, Xining 810000, Qinghai Province, China
- Ying-Fang Deng and Xian-Shu Cui
| | - Liang Wang
- Department of Gastrointestinal Oncology Surgery, Affiliated Hospital of Qinghai University, Xining 810000, Qinghai Province, China
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Lei H, Sun W, Liu X, Wang C. Clinical Characteristics and Outcomes of Pembrolizumab Induced Gastritis: A Systematic Review of the Literature. J Gastrointest Cancer 2024; 55:1-8. [PMID: 38787493 DOI: 10.1007/s12029-024-01067-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 05/05/2024] [Indexed: 05/25/2024]
Abstract
BACKGROUND Pembrolizumab is associated with the development of gastritis, but its clinical features have not been characterized. To explore the clinical features of pembrolizumab induced gastritis and provide reference for the prevention and treatment of gastritis. METHODS Case reports and case series related to pembrolizumab induced gastritis were retrospectively analyzed by searching the database from inception to September 30, 2023. RESULTS Thirty-nine patients with gastritis entered the study with a median age of 63 years (range 34, 81). The median time to gastritis was 11.1 months (range 0.3, 60) and 7 cycles (range 1, 27) after administration. Epigastric pain (24 cases, 61.5%), nausea (17 cases, 43.6%), and vomiting (16 cases, 41.0%) were the most frequently complained symptoms. Esophagogastroduodenoscopy mainly showed erythematous (16 cases, 41.0%), hemorrhage (14 cases, 35.9%) and erosions (11 cases, 28.2%). Gastric mucosal biopsy shows chronic active gastritis with lymphocytic infiltration. These patients' symptoms and gastric mucosa improved or recovered after receiving systemic steroid and proton pump inhibitor therapy regardless of whether pembrolizumab was discontinued. These patients' symptoms and gastric mucosa improved or recovered after treatment with systemic steroids, proton pump inhibitors, and biological agents. CONCLUSIONS Gastritis is an extremely rare adverse effect of pembrolizumab. When patients receiving pembrolizumab complain of abdominal symptoms, endoscopy, tissue biopsy, and immunohistochemical staining should be actively performed for early identification and diagnosis of gastritis.
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Affiliation(s)
- Haibo Lei
- Department of Clinical Pharmacy, Xiangtan Central Hospital, No. 120 Heping Road, Yuhu District, Xiangtan, 411100, Hunan, China
| | - Wei Sun
- Department of Pharmacy, The Third Xiangya Hospital, Central South University, No. 138 Tongzipo Road, YueLu District, Changsha, 410013, Hunan, China
| | - Xiang Liu
- Department of Clinical Pharmacy, Xiangtan Central Hospital, No. 120 Heping Road, Yuhu District, Xiangtan, 411100, Hunan, China.
| | - Chunjiang Wang
- Department of Pharmacy, The Third Xiangya Hospital, Central South University, No. 138 Tongzipo Road, YueLu District, Changsha, 410013, Hunan, China.
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Lopez-Olivo MA, Kachira JJ, Abdel-Wahab N, Pundole X, Aldrich JD, Carey P, Khan M, Geng Y, Pratt G, Suarez-Almazor ME. A systematic review and meta-analysis of observational studies and uncontrolled trials reporting on the use of checkpoint blockers in patients with cancer and pre-existing autoimmune disease. Eur J Cancer 2024; 207:114148. [PMID: 38834015 PMCID: PMC11331889 DOI: 10.1016/j.ejca.2024.114148] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2024] [Revised: 05/01/2024] [Accepted: 05/29/2024] [Indexed: 06/06/2024]
Abstract
BACKGROUND Cancer patients with autoimmune disease have been excluded from randomized trials of immune checkpoint blockers (ICBs). We conducted a systematic review of observational studies and uncontrolled trials including cancer patients with pre-existing autoimmune disease who received ICBs. METHODS We searched 5 electronic databases through November 2023. Study selection, data collection, and quality assessment were performed independently by 2 investigators. We performed a meta-analysis to pool incidence of immune-related adverse events (irAEs), including de novo events and flares of existing autoimmune disease, hospitalizations due to irAEs, as well as deaths. RESULTS A total of 95 studies were included (23,897 patients with cancer and preexisting autoimmune disease). The most common cancer evaluated was lung cancer (30.7 %) followed by skin cancer (15.7 %). Patients with autoimmune disease were more likely to report irAEs compared to patients without autoimmune disease (relative risk 1.3, 95 % CI 1.0 to 1.6). The pooled occurrence rate of any irAEs (flares or de novo) was 61 % (95 % CI 54 % to 68 %); that of flares was 36 % (95 % CI 30 % to 43 %), and that of de novo irAEs was 23 % (95 % CI 16 % to 30 %). Flares were mild (grade <3) in half of cases and more commonly reported in patients with psoriasis/psoriatic arthritis (39 %), inflammatory bowel disease (37 %), and rheumatoid arthritis (36 %). 32 % of the patients with irAEs required hospitalization and treatment of irAEs included corticosteroids in 72 % of the cases. The irAEs mortality rate was 0.07 %. There were no statistically significant differences in cancer response to ICBs between patients with and without autoimmune disease. CONCLUSIONS Although more patients with pre-existing autoimmune disease had irAEs, these were mild and managed with corticosteroids in most cases, with no impact on cancer response. These results suggest that ICBs can be used in these patients, but careful monitoring is required, as over a third of the patients will experience a flare of their autoimmune disease and/or require hospitalization. These findings provide a crucial foundation for oncologists to refine their monitoring and management strategies, ensuring that the benefits of ICB therapy are maximized while minimizing its risks.
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Affiliation(s)
- Maria A Lopez-Olivo
- Department of Health Services Research, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
| | - Johncy J Kachira
- Department of Health Services Research, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Noha Abdel-Wahab
- Section of Rheumatology and Clinical Immunology, Department of General Internal Medicine, and Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA; Rheumatology and Rehabilitation Department, Assiut University Hospitals, Faculty of Medicine, Assiut, Egypt
| | - Xerxes Pundole
- Center for Observational Research, Amgen Inc., Thousand Oaks, CA, USA
| | - Jeffrey D Aldrich
- Department of Medicine, Division of Oncology, University of North Carolina School of Medicine, Chapel Hill, NC, USA
| | - Paul Carey
- Department of Health Services Research, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Muhammad Khan
- Section of Rheumatology and Clinical Immunology, Department of General Internal Medicine, and Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Yimin Geng
- Research Medical Library, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Gregory Pratt
- Research Medical Library, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Maria E Suarez-Almazor
- Department of Health Services Research, The University of Texas MD Anderson Cancer Center, Houston, TX, USA; Section of Rheumatology and Clinical Immunology, Department of General Internal Medicine, and Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
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Del Gaudio A, Di Vincenzo F, Petito V, Giustiniani MC, Gasbarrini A, Scaldaferri F, Lopetuso LR. Focus on Immune Checkpoint Inhibitors-related Intestinal Inflammation: From Pathogenesis to Therapeutical Approach. Inflamm Bowel Dis 2024; 30:1018-1031. [PMID: 37801695 PMCID: PMC11144981 DOI: 10.1093/ibd/izad229] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/25/2023] [Indexed: 10/08/2023]
Abstract
Recently, antitumor immunotherapies have witnessed a breakthrough with the emergence of immune checkpoint inhibitors (ICIs) including programmed cell death-1 (PD-1), programmed cell death-ligand 1 (PD-L1), and cytotoxic T lymphocyte antigen 4 (CTLA-4) inhibitors. Unfortunately, the use of ICIs has also led to the advent of a novel class of adverse events that differ from those of classic chemotherapeutics and are more reminiscent of autoimmune diseases, the immune-related adverse events (IRAEs). Herein, we performed an insight of the main IRAEs associated with ICIs, focusing on gastroenterological IRAEs and specifically on checkpoint inhibitor colitis, which represents the most widely reported IRAE to date. We comprehensively dissected the current evidence regarding pathogenesis, diagnosis, and management of ICIs-induced colitis, touching upon also on innovative therapies.
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Affiliation(s)
- Angelo Del Gaudio
- UOS Malattie Infiammatorie Croniche Intestinali, Centro di Malattie dell’Apparato Digerente (CEMAD), Fondazione Policlinico Universitario A. Gemelli IRCCS, Università Cattolica del Sacro Cuore, Roma, 00168, Italy
- UOC di Medicina Interna e Gastroenterologia, Dipartimento di Scienze Mediche e Chirurgiche, Fondazione Policlinico Universitario A. Gemelli IRCCS, Università Cattolica del Sacro Cuore, Roma, 00168, Italy
| | - Federica Di Vincenzo
- UOS Malattie Infiammatorie Croniche Intestinali, Centro di Malattie dell’Apparato Digerente (CEMAD), Fondazione Policlinico Universitario A. Gemelli IRCCS, Università Cattolica del Sacro Cuore, Roma, 00168, Italy
- UOC di Medicina Interna e Gastroenterologia, Dipartimento di Scienze Mediche e Chirurgiche, Fondazione Policlinico Universitario A. Gemelli IRCCS, Università Cattolica del Sacro Cuore, Roma, 00168, Italy
| | - Valentina Petito
- UOS Malattie Infiammatorie Croniche Intestinali, Centro di Malattie dell’Apparato Digerente (CEMAD), Fondazione Policlinico Universitario A. Gemelli IRCCS, Università Cattolica del Sacro Cuore, Roma, 00168, Italy
- UOC di Medicina Interna e Gastroenterologia, Dipartimento di Scienze Mediche e Chirurgiche, Fondazione Policlinico Universitario A. Gemelli IRCCS, Università Cattolica del Sacro Cuore, Roma, 00168, Italy
| | | | - Antonio Gasbarrini
- UOS Malattie Infiammatorie Croniche Intestinali, Centro di Malattie dell’Apparato Digerente (CEMAD), Fondazione Policlinico Universitario A. Gemelli IRCCS, Università Cattolica del Sacro Cuore, Roma, 00168, Italy
- UOC di Medicina Interna e Gastroenterologia, Dipartimento di Scienze Mediche e Chirurgiche, Fondazione Policlinico Universitario A. Gemelli IRCCS, Università Cattolica del Sacro Cuore, Roma, 00168, Italy
| | - Franco Scaldaferri
- UOS Malattie Infiammatorie Croniche Intestinali, Centro di Malattie dell’Apparato Digerente (CEMAD), Fondazione Policlinico Universitario A. Gemelli IRCCS, Università Cattolica del Sacro Cuore, Roma, 00168, Italy
- UOC di Medicina Interna e Gastroenterologia, Dipartimento di Scienze Mediche e Chirurgiche, Fondazione Policlinico Universitario A. Gemelli IRCCS, Università Cattolica del Sacro Cuore, Roma, 00168, Italy
| | - Loris Riccardo Lopetuso
- UOS Malattie Infiammatorie Croniche Intestinali, Centro di Malattie dell’Apparato Digerente (CEMAD), Fondazione Policlinico Universitario A. Gemelli IRCCS, Università Cattolica del Sacro Cuore, Roma, 00168, Italy
- UOC di Medicina Interna e Gastroenterologia, Dipartimento di Scienze Mediche e Chirurgiche, Fondazione Policlinico Universitario A. Gemelli IRCCS, Università Cattolica del Sacro Cuore, Roma, 00168, Italy
- Department of Medicine and Ageing Sciences, G. d’Annunzio University of Chieti-Pescara, Chieti, 66100, Italy
- Center for Advanced Studies and Technology (CAST), “G. d’Annunzio” University of Chieti-Pescara, Chieti, 66100, Italy
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Townsend MJ, Benque IJ, Li M, Grover S. Review article: Contemporary management of gastrointestinal, pancreatic and hepatic toxicities of immune checkpoint inhibitors. Aliment Pharmacol Ther 2024; 59:1350-1365. [PMID: 38590108 DOI: 10.1111/apt.17980] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/04/2023] [Revised: 11/13/2023] [Accepted: 03/21/2024] [Indexed: 04/10/2024]
Abstract
BACKGROUND Immune checkpoint inhibitors (ICIs) are effective oncologic agents which frequently cause immune-related adverse events (irAEs) which can impact multiple organ systems. Onco-Gastroenterology is a novel and emerging subspecialty within gastroenterology focused on cancer treatment-related complications. Gastroenterologists must be prepared to identify and manage diverse immune-mediated toxicities including enterocolitis, hepatitis, pancreatitis and other ICI-induced toxicities. AIM To provide a narrative review of the epidemiology, diagnostic evaluation and management of checkpoint inhibitor-induced gastrointestinal and hepatic toxicities. METHODS We searched Cochrane and PubMed databases for articles published through August 2023. RESULTS Gastrointestinal and hepatic irAEs include most commonly enterocolitis and hepatitis, but also pancreatitis, oesophagitis, gastritis, motility disorders (gastroparesis) and other rarer toxicities. Guidelines from the National Comprehensive Cancer Network, American Society of Clinical Oncology and European Society for Medical Oncology, in combination with emerging cohort and clinical trial data, offer strategies for management of ICI toxicities. Evaluation of irAEs severity by formal classification and clinical stability, and a thorough workup for alternative etiologies which may clinically mimic irAEs underlie initial management. Treatments include corticosteroids, biologics and other immunosuppressive agents plus supportive care; decisions on dosing, timing and choice of steroid adjuncts and potential for subsequent checkpoint inhibitor dosing are nuanced and toxicity-specific. CONCLUSIONS Expanding clinical trial and cohort data have clarified the epidemiology and clinical characteristics of gastrointestinal, pancreatic and hepatic toxicities of ICIs. Guidelines, though valuable, remain based principally on retrospective cohort data. Quality prospective, controlled studies may refine algorithms for treatment and potential immunotherapy rechallenge.
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Affiliation(s)
- Matthew J Townsend
- Department of Medicine, Duke University Hospital, Durham, North Carolina, USA
| | - Isaac J Benque
- University of California San Francisco School of Medicine, San Francisco, California, USA
| | - Michael Li
- University of California San Francisco School of Medicine, San Francisco, California, USA
- Division of Gastroenterology, University of California San Francisco Medical Center, San Francisco, California, USA
| | - Shilpa Grover
- Division of Gastroenterology, Hepatology, and Endoscopy, Brigham and Women's Hospital, Boston, Massachusetts, USA
- Harvard Medical School, Boston, Massachusetts, USA
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Riveiro-Barciela M, Carballal S, Díaz-González Á, Mañosa M, Gallego-Plazas J, Cubiella J, Jiménez-Fonseca P, Varela M, Menchén L, Sangro B, Fernández-Montes A, Mesonero F, Rodríguez-Gandía MÁ, Rivera F, Londoño MC. Management of liver and gastrointestinal toxicity induced by immune checkpoint inhibitors: Position statement of the AEEH-AEG-SEPD-SEOM-GETECCU. GASTROENTEROLOGIA Y HEPATOLOGIA 2024; 47:401-432. [PMID: 38228461 DOI: 10.1016/j.gastrohep.2023.10.009] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/12/2023] [Revised: 09/28/2023] [Accepted: 10/19/2023] [Indexed: 01/18/2024]
Abstract
The development of the immune checkpoint inhibitors (ICI) is one of the most remarkable achievements in cancer therapy in recent years. However, their exponential use has led to an increase in immune-related adverse events (irAEs). Gastrointestinal and liver events encompass hepatitis, colitis and upper digestive tract symptoms accounting for the most common irAEs, with incidence rates varying from 2% to 40%, the latter in patients undergoing combined ICIs therapy. Based on the current scientific evidence derived from both randomized clinical trials and real-world studies, this statement document provides recommendations on the diagnosis, treatment and prognosis of the gastrointestinal and hepatic ICI-induced adverse events.
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Affiliation(s)
- Mar Riveiro-Barciela
- Liver Unit, Internal Medicine Department, Hospital Universitari Vall d'Hebron, Vall d'Hebron Barcelona Hospital Campus, Barcelona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid, Spain; Universitat Autònoma de Barcelona (UAB), Department of Medicine, Spain.
| | - Sabela Carballal
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid, Spain; Gastroenterology Department, Hospital Clinic de Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Spain; Universitat de Barcelona, Spain
| | - Álvaro Díaz-González
- Gastroenterology Department, Grupo de Investigación Clínica y Traslacional en Enfermedades Digestivas, Instituto de Investigación Valdecilla (IDIVAL), Hospital Universitario Marqués de Valdecilla, Santander, Spain
| | - Míriam Mañosa
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid, Spain; Gastroenterology Department, Hospital Universitari Germans Trias i Pujol, Badalona, Spain
| | | | - Joaquín Cubiella
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid, Spain; Gastroenterology Department, Hospital Universitario de Ourense, Grupo de Investigación en Oncología Digestiva-Ourense, Spain
| | - Paula Jiménez-Fonseca
- Medical Oncology Department, Hospital Universitario Central de Asturias, ISPA, Oviedo, Spain
| | - María Varela
- Gastroenterology Department, Hospital Universitario Central de Asturias, IUOPA, ISPA, FINBA, University of Oviedo, Oviedo, Spain
| | - Luis Menchén
- Servicio de Aparato Digestivo - CEIMI, Instituto de Investigación Sanitaria Gregorio, Marañón, Spain; Departamento de Medicina, Universidad Complutense, Madrid, Spain
| | - Bruno Sangro
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid, Spain; Liver Unit, Cancer Center Clinica Universidad de Navarra, Pamplona-Madrid, Spain
| | - Ana Fernández-Montes
- Medical Oncology Department, Complexo Hospitalario Universitario de Ourense, Ourense, Spain
| | - Francisco Mesonero
- Gastroenterology and Hepatology Department, Hospital Universitario Ramón y Cajal, Madrid, Spain; Universidad de Alcalá de Henares, Spain
| | - Miguel Ángel Rodríguez-Gandía
- Gastroenterology and Hepatology Department, Hospital Universitario Ramón y Cajal, Madrid, Spain; Instituto Ramón y Cajal de Investigación Sanitaria (IRyCIS), Madrid, Spain
| | - Fernando Rivera
- Medical Oncology Department, Hospital Universitario Marqués de Valdecilla, IDIVAL, Santander, Spain
| | - María-Carlota Londoño
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid, Spain; Universitat de Barcelona, Spain; Liver Unit, Hospital Clínic Barcelona, Fundació de Recerca Clínic Barcelona-Institut d'Investigacions Biomèdiques August Pi i Sunyer, European Reference Network on Hepatological Diseases (ERN RARE-LIVER), Spain
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Rugge M, Genta RM, Malfertheiner P, Dinis-Ribeiro M, El-Serag H, Graham DY, Kuipers EJ, Leung WK, Park JY, Rokkas T, Schulz C, El-Omar EM. RE.GA.IN.: the Real-world Gastritis Initiative-updating the updates. Gut 2024; 73:407-441. [PMID: 38383142 DOI: 10.1136/gutjnl-2023-331164] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/18/2023] [Accepted: 12/18/2023] [Indexed: 02/23/2024]
Abstract
At the end of the last century, a far-sighted 'working party' held in Sydney, Australia addressed the clinicopathological issues related to gastric inflammatory diseases. A few years later, an international conference held in Houston, Texas, USA critically updated the seminal Sydney classification. In line with these initiatives, Kyoto Global Consensus Report, flanked by the Maastricht-Florence conferences, added new clinical evidence to the gastritis clinicopathological puzzle.The most relevant topics related to the gastric inflammatory diseases have been addressed by the Real-world Gastritis Initiative (RE.GA.IN.), from disease definitions to the clinical diagnosis and prognosis. This paper reports the conclusions of the RE.GA.IN. consensus process, which culminated in Venice in November 2022 after more than 8 months of intense global scientific deliberations. A forum of gastritis scholars from five continents participated in the multidisciplinary RE.GA.IN. consensus. After lively debates on the most controversial aspects of the gastritis spectrum, the RE.GA.IN. Faculty amalgamated complementary knowledge to distil patient-centred, evidence-based statements to assist health professionals in their real-world clinical practice. The sections of this report focus on: the epidemiology of gastritis; Helicobacter pylori as dominant aetiology of environmental gastritis and as the most important determinant of the gastric oncogenetic field; the evolving knowledge on gastric autoimmunity; the clinicopathological relevance of gastric microbiota; the new diagnostic horizons of endoscopy; and the clinical priority of histologically reporting gastritis in terms of staging. The ultimate goal of RE.GA.IN. was and remains the promotion of further improvement in the clinical management of patients with gastritis.
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Affiliation(s)
- Massimo Rugge
- Department of Medicine-DIMED, University of Padova, Padua, Italy
- Azienda Zero, Veneto Tumour Registry, Padua, Italy
| | - Robert M Genta
- Gastrointestinal Pathology, Inform Diagnostics Research Institute, Dallas, Texas, USA
- Pathology, Baylor College of Medicine, Houston, Texas, USA
| | - Peter Malfertheiner
- Medizinische Klinik und Poliklinik II, Ludwig Maximilian Universität Klinikum München, Munich, Germany
- Klinik für Gastroenterologie, Hepatologie und Infektiologie, Otto-von-Guericke Universität Magdeburg, Magdeburg, Germany
| | - Mario Dinis-Ribeiro
- Porto Comprehensive Cancer Center & RISE@CI-IPO, University of Porto, Porto, Portugal
- Gastroenterology Department, Portuguese Institute of Oncology of Porto, Porto, Portugal
| | - Hashem El-Serag
- Gastroenterology and Hepatology, Baylor College of Medicine, Houston, Texas, USA
- Houston VA Health Services Research & Development Center of Excellence, Michael E DeBakey Veterans Affairs Medical Center, Houston, Texas, USA
| | - David Y Graham
- Department of Medicine, Michael E DeBakey Veterans Affairs Medical Center, Houston, Texas, USA
| | - Ernst J Kuipers
- Erasmus University Medical Center, Rotterdam, The Netherlands
| | | | - Jin Young Park
- International Agency for Research on Cancer, Lyon, France
| | - Theodore Rokkas
- Gastroenterology, Henry Dunant Hospital Center, Athens, Greece
| | | | - Emad M El-Omar
- Microbiome Research Centre, University of New South Wales, Sydney, New South Wales, Australia
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10
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Riveiro-Barciela M, Carballal S, Díaz-González Á, Mañosa M, Gallgo-Plazas J, Cubiella J, Jiménez-Fonseca P, Varela M, Menchén L, Sangro B, Fernández-Montes A, Mesonero F, Rodríguez-Gandía MÁ, Rivera F, Londoño MC. Management of liver and gastrointestinal toxicity induced by immune checkpoint inhibitors: Position statement of the AEEH-AEG-SEPD-SEOM-GETECCU. REVISTA ESPANOLA DE ENFERMEDADES DIGESTIVAS 2024; 116:83-113. [PMID: 38226597 DOI: 10.17235/reed.2024.10250/2024] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/17/2024]
Abstract
The development of the immune checkpoint inhibitors (ICI) is one of the most remarkable achievements in cancer therapy in recent years. However, their exponential use has led to an increase in immune-related adverse events (irAEs). Gastrointestinal and liver events encompass hepatitis, colitis and upper digestive tract symptoms accounting for the most common irAEs, with incidence rates varying from 2 % to 40 %, the latter in patients undergoing combined ICIs therapy. Based on the current scientific evidence derived from both randomized clinical trials and real-world studies, this statement document provides recommendations on the diagnosis, treatment and prognosis of the gastrointestinal and hepatic ICI-induced adverse events.
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Affiliation(s)
| | | | | | - Miriam Mañosa
- Gastroenterology, Hospital Universitari Germans Trias i Pujol
| | | | | | | | - María Varela
- Gastroenterology, Hospital Universitario Central de Asturias
| | - Luis Menchén
- Digestive Diseases, Instituto de Investigación Sanitaria Gregorio Marañón
| | | | | | | | | | - Fernando Rivera
- Hospital Universitario Marqués de Valdecilla, Medical Oncology
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11
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Haryal A, Townsend MJ, Baskaran V, Srivoleti P, Giobbie-Hurder A, Sack JS, Isidro RA, LeBoeuf NR, Buchbinder EI, Hodi FS, Grover S. Immune checkpoint inhibitor gastritis is often associated with concomitant enterocolitis, which impacts the clinical course. Cancer 2023; 129:367-375. [PMID: 36377339 DOI: 10.1002/cncr.34543] [Citation(s) in RCA: 12] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/04/2022] [Revised: 10/06/2022] [Accepted: 10/07/2022] [Indexed: 11/16/2022]
Abstract
BACKGROUND Gastrointestinal immune-related adverse events are frequently caused by immune checkpoint inhibitors (ICIs) and often require interruption of cancer treatment. Compared with ICI colitis and enteritis, limited information exists about ICI gastritis. This study characterized clinical features and treatment outcomes of ICI gastritis. METHODS Consecutive cancer patients who received ICIs and underwent endoscopy with gastric biopsies while on ICIs from 2011 to 2021 were retrospectively assessed. Specific histopathologic features identified ICI gastritis. RESULTS Of 6450 ICI-treated patients, 162 (2.5%) underwent endoscopy with gastric biopsies. ICI gastritis was identified in 54 (33%) biopsied patients; 38 (70%) had concurrent ICI enteritis/colitis and 16 (30%) had isolated ICI gastritis. Dyspepsia (38%) and bloating (25%) were the most frequent symptoms of isolated ICI gastritis. Compared with patients with concomitant enteritis/colitis, patients with isolated gastritis were less likely to have diarrhea (13% vs 68%; p < .001) or abdominal pain (19% vs 47%; p = .07). Patients with isolated ICI gastritis less frequently required glucocorticoids (69% vs 92%; p = .04) and had lower incidence of ICI hold/withdrawal (13% vs 42%; p = .06). There was no association between severity or extent of luminal inflammation and antitumor response (p = .85 and p = .44, respectively). Endoscopically, gastric mucosa appeared normal in 11 (20%) patients with biopsy-proven ICI gastritis. CONCLUSION ICI gastritis may present alone or more commonly with concurrent enteritis/colitis, which may differentiate its clinical course. Gastric biopsies are required to diagnose a substantial minority of endoscopically normal, clinically significant cases. Most patients with isolated gastritis can continue ICI therapy uninterrupted, but a notable proportion require glucocorticoids. PLAIN LANGUAGE SUMMARY Immune checkpoint inhibitors are effective anticancer treatments, but can cause inflammatory toxicities, including of the stomach (gastritis), intestine, and colon. Limited information is available on gastritis triggered by these agents. Adult patients with cancer who were treated with immune checkpoint inhibitors and had an upper gastrointestinal endoscopy with biopsies of the stomach were examined. More than two-thirds (70%) of people with checkpoint inhibitor gastritis also had inflammatory changes of the small intestine and/or colon. Compared with patients with isolated checkpoint gastritis, the subgroup with concomitant enteritis/colitis more frequently had abdominal pain, diarrhea, needed steroids, and/or needed to pause or stop antitumor therapy.
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Affiliation(s)
- Aneesha Haryal
- Division of Gastroenterology, Hepatology, and Endoscopy, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA
| | - Matthew J Townsend
- Department of Medicine, Duke University Hospital, Durham, North Carolina, USA
| | - Vinitha Baskaran
- Division of Gastroenterology, Hepatology, and Endoscopy, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA
| | - Padmavathi Srivoleti
- Division of Gastroenterology, Hepatology, and Endoscopy, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA
| | - Anita Giobbie-Hurder
- Division of Biostatistics, Department of Data Science, Dana-Farber Cancer Institute, Boston, Massachusetts, USA
| | - Jordan S Sack
- Division of Gastroenterology, Hepatology, and Endoscopy, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA.,Harvard Medical School, Boston, Massachusetts, USA
| | - Raymond A Isidro
- Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts, USA
| | - Nicole R LeBoeuf
- Harvard Medical School, Boston, Massachusetts, USA.,Department of Dermatology, Center for Cutaneous Oncology, Dana-Farber/Brigham and Women's Cancer Center, Boston, Massachusetts, USA
| | - Elizabeth I Buchbinder
- Harvard Medical School, Boston, Massachusetts, USA.,Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA
| | - F Stephen Hodi
- Harvard Medical School, Boston, Massachusetts, USA.,Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA
| | - Shilpa Grover
- Division of Gastroenterology, Hepatology, and Endoscopy, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA.,Harvard Medical School, Boston, Massachusetts, USA
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12
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Fuji T, Arai J, Otoyama Y, Nio Y, Sugiura I, Nakajima Y, Kajiwara A, Ichikawa Y, Uozumi S, Shimozuma Y, Uchikoshi M, Sakaki M, Nozawa H, Momo K, Sasaki T, Yoshida H. A Case of Hepatocellular Carcinoma Successfully Resumed Atezolizumab and Bevacizumab After Associated Grade 3 Diarrhea and Grade 2 Colitis: Case Report and Literature Review. Onco Targets Ther 2022; 15:1281-1288. [PMID: 36303951 PMCID: PMC9594877 DOI: 10.2147/ott.s383769] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2022] [Accepted: 09/10/2022] [Indexed: 11/16/2022] Open
Abstract
Systemic chemotherapy has shown a significant survival benefit in patients with hepatocellular carcinoma (HCC). However, it is associated with various immune-related adverse events (irAEs). We report a case with grade 3 diarrhea and grade 2 colitis following systemic chemotherapy, successfully treated with prednisolone. An 89-year-old man was incidentally detected with a 140-mm hypervascular intrahepatic nodule on contrast-enhanced computed tomography (CECT). Washout of the contrast medium was also detected, and protein induced by vitamin K deficiency or antagonists-II (PIVKA-II) was elevated. Since the Albumin-Bilirubin (ALBI) grade was 2a without any distant metastasis, transarterial chemoembolization (TACE) was performed to treat the HCC, but several intrahepatic nodules were seen in both lobes. Therefore, the patient was treated with lenvatinib for 1 year and 4 months. A complete response according to modified Response Evaluation Criteria in Solid Tumors (mRECIST) criteria was achieved in 2 months; however, multiple hypervascular nodules were detected again. Since the ALBI grade was 1, a second round of chemotherapy with atezolizumab and bevacizumab was initiated. Although a complete response was achieved, the therapy was discontinued due to grade 3 diarrhea and grade 2 colitis after the sixth course. Based on the stool analysis and culture, CECT, and colonoscopy, the diagnosis was atezolizumab-associated colitis. Diarrhea was controlled following the oral administration of 0.5 mg/kg/day of prednisolone, and atezolizumab-bevacizumab therapy was successfully reinitiated without recurrence of colitis. The management of irAEs is important for a significant survival benefit. Systemic chemotherapy with atezolizumab and bevacizumab can be resumed despite a grade 3 irAE due to atezolizumab.
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Affiliation(s)
- Takahiro Fuji
- Department of Medicine, Division of Gastroenterology, Showa University School of Medicine, Tokyo, Japan
| | - Jun Arai
- Department of Medicine, Division of Gastroenterology, Showa University School of Medicine, Tokyo, Japan,Correspondence: Jun Arai, Department of Medicine, Division of Gastroenterology, Showa University School of Medicine, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo, 142-8666, Japan, Tel +81-3-3784-8535, Fax +81-3-3784-7553, Email
| | - Yumi Otoyama
- Department of Medicine, Division of Gastroenterology, Showa University School of Medicine, Tokyo, Japan
| | - Yuta Nio
- Department of Hospital Pharmaceutics, School of Pharmacy, Showa University Hospital, Tokyo, Japan,Department of Pharmacy, Showa University Hospital, Tokyo, Japan
| | - Ikuya Sugiura
- Department of Medicine, Division of Gastroenterology, Showa University School of Medicine, Tokyo, Japan
| | - Yoko Nakajima
- Department of Medicine, Division of Gastroenterology, Showa University School of Medicine, Tokyo, Japan
| | - Atsushi Kajiwara
- Department of Medicine, Division of Gastroenterology, Showa University School of Medicine, Tokyo, Japan
| | - Yuki Ichikawa
- Department of Medicine, Division of Gastroenterology, Showa University School of Medicine, Tokyo, Japan
| | - Shojiro Uozumi
- Department of Medicine, Division of Gastroenterology, Showa University School of Medicine, Tokyo, Japan
| | - Yuu Shimozuma
- Department of Medicine, Division of Gastroenterology, Showa University School of Medicine, Tokyo, Japan
| | - Manabu Uchikoshi
- Department of Medicine, Division of Gastroenterology, Showa University School of Medicine, Tokyo, Japan
| | - Masashi Sakaki
- Department of Medicine, Division of Gastroenterology, Showa University School of Medicine, Tokyo, Japan
| | - Hisako Nozawa
- Department of Medicine, Division of Gastroenterology, Showa University School of Medicine, Tokyo, Japan
| | - Kenji Momo
- Department of Hospital Pharmaceutics, School of Pharmacy, Showa University Hospital, Tokyo, Japan
| | - Tadanori Sasaki
- Department of Pharmacy, Showa University Hospital, Tokyo, Japan
| | - Hitoshi Yoshida
- Department of Medicine, Division of Gastroenterology, Showa University School of Medicine, Tokyo, Japan
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13
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Obeidat A, Silangcruz K, Kozai L, Wien E, Fujiwara Y, Nishimura Y. Clinical Characteristics and Outcomes of Gastritis Associated With Immune Checkpoint Inhibitors: Scoping Review. J Immunother 2022; 45:363-369. [PMID: 35972801 DOI: 10.1097/cji.0000000000000435] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/12/2022] [Accepted: 06/30/2022] [Indexed: 11/25/2022]
Abstract
Among immune-related adverse events associated with immune checkpoint inhibitors, immune-mediated gastritis (IMG) has been rarely described in the literature and has not yet been well characterized. This scoping review aimed to characterize IMG in terms of precipitating agents, clinical presentations, and prognosis. After the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews, we searched MEDLINE and EMBASE for all peer-reviewed articles using keywords including "gastritis," "immune checkpoint inhibitor," and "immune-related adverse event" from their inception to December 28, 2021. Twenty-two articles, including 5 observational studies and 17 case reports and case series, were included. Nivolumab, pembrolizumab, and combination therapy with those and cytotoxic T-lymphocyte-associated antigen-4 inhibitor (ipilimumab) were commonly used in those with IMG. 59.8% had epigastric pain, and 50% had erosive gastritis. 87.5% had Common Terminology Criteria for Adverse Events (CTCAE) grade 3 gastritis, and 91.2% received corticosteroids. Recurrence was noted in 16.7%, and only 1 expiration was noted. 4.3% had positive helicobacter pylori and cytomegalovirus from the gastric specimen. Similar to immune-related colitis, patients with IMG may have a favorable prognosis with a better response to immune checkpoint inhibitors if treated appropriately. The diagnosis of IMG is made by exclusion, and a thorough workup is necessary to rule out concurrent helicobacter pylori and cytomegalovirus involvement. Further studies are critical for a better understanding of this complication.
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Affiliation(s)
- Adham Obeidat
- Department of Medicine, John A. Burns School of Medicine, University of Hawai'i, Honolulu, HI
| | - Krixie Silangcruz
- Department of Medicine, John A. Burns School of Medicine, University of Hawai'i, Honolulu, HI
| | - Landon Kozai
- Department of Medicine, John A. Burns School of Medicine, University of Hawai'i, Honolulu, HI
| | - Eric Wien
- Department of Medicine, John A. Burns School of Medicine, University of Hawai'i, Honolulu, HI
| | - Yu Fujiwara
- Department of Medicine, Icahn School of Medicine at Mount Sinai, Mount Sinai Beth Israel, New York, NY
| | - Yoshito Nishimura
- Department of Medicine, John A. Burns School of Medicine, University of Hawai'i, Honolulu, HI
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14
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Immune checkpoint Inhibitor–Induced diarrhea and Colitis: Incidence and Management. A systematic review and Meta-analysis. Cancer Treat Rev 2022; 109:102440. [PMID: 35917654 DOI: 10.1016/j.ctrv.2022.102440] [Citation(s) in RCA: 50] [Impact Index Per Article: 16.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2022] [Revised: 07/19/2022] [Accepted: 07/22/2022] [Indexed: 11/22/2022]
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15
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Immunotherapy-induced Colitis: A Comprehensive Review of Epidemiology, Clinical Presentation, Diagnostic Workup, and Management Plan. J Clin Gastroenterol 2022; 56:555-564. [PMID: 35470301 DOI: 10.1097/mcg.0000000000001705] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
Immune checkpoint inhibitors (ICIs) have revolutionized the treatment of a variety of malignancies including advanced melanoma, non-small cell lung cancer, renal cell carcinoma, head and neck cancers among others. Since their introduction, there has been significant improvement in survival and prognosis in patients with advanced malignancies. Unfortunately, improved outcomes have come at a price of significant immune-related adverse events, with those of the gastrointestinal tract being the most common. Gastrointestinal immune-related adverse events frequently present as diarrhea and colitis, the severity of which can range from mild diarrhea to fulminant colitis with intestinal perforation. Currently, management of ICI-induced colitis is primarily guided by retrospective studies and expert opinion. A significant number of ICI-induced colitis responds to high-dose corticosteroids; however, some patients require further therapy with biologics. There is limited information on the factors which may predispose patients to ICI-induced colitis. Future research elucidating these risk factors along with development of a scoring system could allow for risk-stratification of patients before initiation of ICI therapy. Such a system may help clinicians and patients keep a high index of suspicion regarding ICI-induced colitis and could hopefully reduce the incidence of severe cases. Similarly, future studies should investigate protective factors against ICI-induced colitis, which could potentially allow more patients to safely benefit from ICI therapy.
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16
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Sugiyama Y, Tanabe H, Matsuya T, Kobayashi Y, Murakami Y, Sasaki T, Kunogi T, Takahashi K, Ando K, Ueno N, Kashima S, Moriichi K, Tanino M, Mizukami Y, Fujiya M, Okumura T. Severe immune checkpoint inhibitor-associated gastritis: A case series and literature review. Endosc Int Open 2022; 10:E982-E989. [PMID: 35845030 PMCID: PMC9286772 DOI: 10.1055/a-1839-4303] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/05/2022] [Accepted: 04/28/2022] [Indexed: 02/07/2023] Open
Abstract
Background and study aims Recent advances in cancer treatment have involved the clinical application of immune checkpoint inhibitors (ICIs) for various type of cancers. The adverse events associated with ICIs are generally referred to as immune-related adverse events (irAEs). Gastrointestinal irAEs are a major disorder, but gastritis is not frequently observed. The aims of this study were to elucidate the clinical, endoscopic, and histological characteristics of irAE gastritis. Patients and methods Information on patients treated with ICIs were collected from a single institute over 3 years. IrAE gastritis was identified based on the clinical course and endoscopic and histopathological findings. Of the 359 patients treated with ICIs, four cases of irAE gastritis were identified in clinical records from the endoscopy unit. The endoscopic and histopathological findings were analyzed, and further immunohistochemical studies with immune subtype markers and programmed cell death ligand-1 (PD-L1) antibody were conducted. Results Among four patients with irAE gastritis, the remarkable endoscopic characteristics were network-pattern erosion, erythematous and edematous mucosa with thick purulent discharge, and fragile mucosa. Corresponding histological features were fibrinopurulent exudate, severe inflammatory cell infiltration, and epithalaxia, respectively. The PD-L1 expression rate was ≥ 1 % in the gastric tissue of all patients with gastritis. These patients were treated with prednisolone (PSL) and their symptoms improved within a few days to 2 weeks. Conclusions IrAE gastritis were characterized by specific endoscopic findings. The appropriate endoscopic diagnosis may lead to effective treatment with PSL.
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Affiliation(s)
- Yuya Sugiyama
- Division of Metabolism and Biosystemic Science, Gastroenterology, and Hematology/Oncology, Department of Medicine, Asahikawa Medical University, Asahikawa, Hokkaido, Japan
| | - Hiroki Tanabe
- Division of Metabolism and Biosystemic Science, Gastroenterology, and Hematology/Oncology, Department of Medicine, Asahikawa Medical University, Asahikawa, Hokkaido, Japan
| | - Taisuke Matsuya
- Department of Dermatology, Asahikawa Medical University, Asahikawa, Hokkaido, Japan
| | - Yu Kobayashi
- Division of Metabolism and Biosystemic Science, Gastroenterology, and Hematology/Oncology, Department of Medicine, Asahikawa Medical University, Asahikawa, Hokkaido, Japan
| | - Yuki Murakami
- Division of Metabolism and Biosystemic Science, Gastroenterology, and Hematology/Oncology, Department of Medicine, Asahikawa Medical University, Asahikawa, Hokkaido, Japan
| | - Takahiro Sasaki
- Division of Metabolism and Biosystemic Science, Gastroenterology, and Hematology/Oncology, Department of Medicine, Asahikawa Medical University, Asahikawa, Hokkaido, Japan
| | - Takehito Kunogi
- Division of Metabolism and Biosystemic Science, Gastroenterology, and Hematology/Oncology, Department of Medicine, Asahikawa Medical University, Asahikawa, Hokkaido, Japan
| | - Keitaro Takahashi
- Division of Metabolism and Biosystemic Science, Gastroenterology, and Hematology/Oncology, Department of Medicine, Asahikawa Medical University, Asahikawa, Hokkaido, Japan
| | - Katsuyoshi Ando
- Division of Metabolism and Biosystemic Science, Gastroenterology, and Hematology/Oncology, Department of Medicine, Asahikawa Medical University, Asahikawa, Hokkaido, Japan
| | - Nobuhiro Ueno
- Division of Metabolism and Biosystemic Science, Gastroenterology, and Hematology/Oncology, Department of Medicine, Asahikawa Medical University, Asahikawa, Hokkaido, Japan
| | - Shin Kashima
- Division of Metabolism and Biosystemic Science, Gastroenterology, and Hematology/Oncology, Department of Medicine, Asahikawa Medical University, Asahikawa, Hokkaido, Japan
| | - Kentaro Moriichi
- Division of Metabolism and Biosystemic Science, Gastroenterology, and Hematology/Oncology, Department of Medicine, Asahikawa Medical University, Asahikawa, Hokkaido, Japan
| | - Mishie Tanino
- Department of Diagnostic Pathology, Asahikawa Medical University Hospital, Asahikawa Medical University, Asahikawa, Hokkaido, Japan
| | - Yusuke Mizukami
- Division of Metabolism and Biosystemic Science, Gastroenterology, and Hematology/Oncology, Department of Medicine, Asahikawa Medical University, Asahikawa, Hokkaido, Japan
| | - Mikihiro Fujiya
- Division of Metabolism and Biosystemic Science, Gastroenterology, and Hematology/Oncology, Department of Medicine, Asahikawa Medical University, Asahikawa, Hokkaido, Japan
| | - Toshikatsu Okumura
- Division of Metabolism and Biosystemic Science, Gastroenterology, and Hematology/Oncology, Department of Medicine, Asahikawa Medical University, Asahikawa, Hokkaido, Japan
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17
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Saito K, Nagumo H, Iwasaki M, Nishiwaki T, Ozono D, Inoue S, Yoshimura S, Kishita H, Nakachi K, Harasawa H, Kawamitsu N, Yoshimura S, Shiratori T, Nakaji S, Ito H. A case of severe acute hemorrhagic duodenitis after administration of immune checkpoint inhibitor. DEN OPEN 2022; 2:e19. [PMID: 35310734 PMCID: PMC8828217 DOI: 10.1002/deo2.19] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/01/2021] [Revised: 04/04/2021] [Accepted: 04/07/2021] [Indexed: 11/18/2022]
Abstract
Case: A 66-year-old man started carboplatin + etoposide + atezolizumab therapy for advanced small cell lung cancer. Seventeen days after the start of treatment, the patient presented with hematemesis and underwent emergency endoscopy, which revealed multiple erosions and ulcers in the duodenum. Some ulcers showed pulsating bleeding, which was stopped by clipping and cauterization using hemostats. Biopsy of the mucosal peri-ulcer showed lymphocyte, eosinophil, and plasma cell infiltration. The patient was suggested to have acute hemorrhagic duodenitis, which was associated with immune checkpoint inhibitors (ICIs), and conservative treatment with blood transfusion and antacids was continued. However, 11 days after hemostasis, bleeding from a new ulcer was observed. Hemostasis was achieved by coagulation and clipping again, but the general condition of the patient deteriorated owing to the rapid progression of the primary disease, and he died 8 weeks after the start of treatment. Discussion: Although there have been several reports of colitis and other adverse events caused by ICIs, there have been very few reports of duodenitis. Endoscopic findings include diffuse erythema, erosions/ulcerations, and villous atrophy, and pathological findings include eosinophilic infiltration and increased levels of CD8-positive T cells. However, there have been no reports of duodenal mucosal damage caused after administration of atezolizumab nor of severe cases of massive bleeding requiring endoscopic hemostasis and blood transfusion, as in this case.
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Affiliation(s)
- Keita Saito
- Department of GastroenterologyKameda General HospitalChibaJapan
| | - Hironobu Nagumo
- Department of GastroenterologyKameda General HospitalChibaJapan
| | - Miyuki Iwasaki
- Department of GastroenterologyKameda General HospitalChibaJapan
| | | | - Daiki Ozono
- Department of GastroenterologyKameda General HospitalChibaJapan
| | - Shin Inoue
- Department of GastroenterologyKameda General HospitalChibaJapan
| | | | | | | | - Hisato Harasawa
- Department of GastroenterologyKameda General HospitalChibaJapan
| | | | | | | | - So Nakaji
- Department of GastroenterologyKameda General HospitalChibaJapan
| | - Hiroyuki Ito
- Department of Respiratory MedicineKameda General HospitalChibaJapan
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18
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Feakins R, Torres J, Borralho-Nunes P, Burisch J, Cúrdia Gonçalves T, De Ridder L, Driessen A, Lobatón T, Menchén L, Mookhoek A, Noor N, Svrcek M, Villanacci V, Zidar N, Tripathi M. ECCO Topical Review on Clinicopathological Spectrum and Differential Diagnosis of Inflammatory Bowel Disease. J Crohns Colitis 2022; 16:343-368. [PMID: 34346490 DOI: 10.1093/ecco-jcc/jjab141] [Citation(s) in RCA: 18] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
INTRODUCTION Many diseases can imitate inflammatory bowel disease [IBD] clinically and pathologically. This review outlines the differential diagnosis of IBD and discusses morphological pointers and ancillary techniques that assist with the distinction between IBD and its mimics. METHODS European Crohn's and Colitis Organisation [ECCO] Topical Reviews are the result of an expert consensus. For this review, ECCO announced an open call to its members and formed three working groups [WGs] to study clinical aspects, pathological considerations, and the value of ancillary techniques. All WGs performed a systematic literature search. RESULTS Each WG produced a draft text and drew up provisional Current Practice Position [CPP] statements that highlighted the most important conclusions. Discussions and a preliminary voting round took place, with subsequent revision of CPP statements and text and a further meeting to agree on final statements. CONCLUSIONS Clinicians and pathologists encounter a wide variety of mimics of IBD, including infection, drug-induced disease, vascular disorders, diverticular disease, diversion proctocolitis, radiation damage, and immune disorders. Reliable distinction requires a multidisciplinary approach.
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Affiliation(s)
- Roger Feakins
- Department of Cellular Pathology, Royal Free Hospital, London, and University College London, UK
| | - Joana Torres
- Department of Gastroenterology, Hospital Beatriz Ângelo, Loures, Portugal
| | - Paula Borralho-Nunes
- Department of Pathology, Hospital Cuf Descobertas, Lisboa and Faculdade de Medicina da Universidade de Lisboa, Lisbon, Portugal
| | - Johan Burisch
- Gastrounit, Medical Division, Hvidovre Hospital, University of Copenhagen, Denmark
| | - Tiago Cúrdia Gonçalves
- Department of Gastroenterology, Hospital da Senhora da Oliveira, Guimarães, Portugal.,School of Medicine, University of Minho, Braga/Guimarães, Portugal.,ICVS/3B's-PT Government Associate Laboratory, Braga/Guimarães, Portugal
| | - Lissy De Ridder
- Department of Paediatric Gastroenterology, Erasmus MC Sophia Children's Hospital, University Medical Center Rotterdam, The Netherlands
| | - Ann Driessen
- Department of Pathology, University Hospital Antwerp, University Antwerp, Edegem, Belgium
| | - Triana Lobatón
- Department of Gastroenterology, Ghent University Hospital, Ghent, Belgium
| | - Luis Menchén
- Department of Digestive System Medicine, Hospital General Universitario-Insitituto de Investigación Sanitaria Gregorio Marañón, Madrid, Spain.,Department of Medicine, Universidad Complutense, Madrid, Spain.,Centro de Investigación Biomédica En Red de Enfermedades Hepáticas y Digestivas [CIBEREHD], Madrid, Spain
| | - Aart Mookhoek
- Department of Pathology, Amsterdam UMC, Amsterdam, The Netherlands
| | - Nurulamin Noor
- Department of Gastroenterology, Addenbrooke's Hospital, Cambridge University Hospitals NHS Trust, Cambridge, UK
| | - Magali Svrcek
- Department of Pathology, Sorbonne Université, AP-HP, Saint-Antoine Hospital, Paris, France
| | - Vincenzo Villanacci
- Department of Histopathology, Spedali Civili and University of Brescia, Brescia, Italy
| | - Nina Zidar
- Institute of Pathology, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia
| | - Monika Tripathi
- Department of Histopathology, Cambridge Biomedical Campus, Addenbrooke's Hospital, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK
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19
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Del Sordo R, Volta U, Lougaris V, Parente P, Sidoni A, Facchetti M, Bassotti G, Carosi I, Clemente C, Villanacci V. Histological Features of Celiac-Disease-like Conditions Related to Immune Checkpoint Inhibitors Therapy: A Signal to Keep in Mind for Pathologists. Diagnostics (Basel) 2022; 12:395. [PMID: 35204486 PMCID: PMC8871268 DOI: 10.3390/diagnostics12020395] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2021] [Revised: 01/19/2022] [Accepted: 02/02/2022] [Indexed: 11/17/2022] Open
Abstract
Immune checkpoint inhibitors (ICIs) targeting cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4), programmed cell death protein (PD-1), and its ligand PDL-1, are finding increasing application in the treatment of malignant neoplasms. The widespread clinical use of these drugs, however, resulted in the discovery of side effects. The occurrence of celiac disease (CD) after ICIs therapy has been reported in the literature, but its incidence remains unknown and the role of ICIs in its onset is not yet clear. In this review, we examine the published data on this topic in order to better understand and define this entity from a histological point of view. We performed an electronic literature search to identify original reports in which CD or pathological CD-like conditions were documented histologically in patients treated with ICIs. We identified ten papers. A total of twenty-five patients were included in these publications, eleven of them receiving a serologic and histological diagnosis of CD, and four a histological diagnosis of CD-like conditions, in which pathogenesis appears to be multifactorial. ICIs can cause a CD-like enteropathy and biopsies with clinical integration are crucial to diagnose this condition. CD rarely has been observed during treatment with ICIs and its morphological aspects are similar to ICIs-CD enteropathy. Moreover, the onset of ICIs-CD may have a distinct immune mechanism compared to classical CD. Thus, the pathologists must make a histological diagnosis of CD with caution and only in adequate clinical and serological context.
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Affiliation(s)
- Rachele Del Sordo
- Department of Medicine and Surgery, Section of Anatomic Pathology and Histology, Medical School, University of Perugia, 06132 Perugia, Italy; (R.D.S.); (A.S.)
| | - Umberto Volta
- Department of Medical and Surgical Sciences, University of Bologna, 40126 Bologna, Italy;
| | - Vassilios Lougaris
- Pediatrics Clinic, Department of Clinical and Experimental Sciences, University of Brescia and Children’s Hospital, ASST-Spedali Civili, 25123 Brescia, Italy;
| | - Paola Parente
- Pathology Unit, Fondazione IRCCS Ospedale Casa Sollievo della Sofferenza, 71013 San Giovanni Rotondo, FG, Italy; (I.C.); (C.C.)
| | - Angelo Sidoni
- Department of Medicine and Surgery, Section of Anatomic Pathology and Histology, Medical School, University of Perugia, 06132 Perugia, Italy; (R.D.S.); (A.S.)
| | - Mattia Facchetti
- Institute of Pathology, ASST-Spedali Civili Brescia, 25123 Brescia, Italy;
| | - Gabrio Bassotti
- Gastroenterology & Hepatology Section, Department of Medicine and Surgery, University of Perugia, 06132 Perugia, Italy;
| | - Illuminato Carosi
- Pathology Unit, Fondazione IRCCS Ospedale Casa Sollievo della Sofferenza, 71013 San Giovanni Rotondo, FG, Italy; (I.C.); (C.C.)
| | - Celeste Clemente
- Pathology Unit, Fondazione IRCCS Ospedale Casa Sollievo della Sofferenza, 71013 San Giovanni Rotondo, FG, Italy; (I.C.); (C.C.)
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20
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Saito K, Ozono D, Nagumo H, Yoshimura M, Masuzawa Y. Temporal observation of endoscopic and histological findings of gastritis after administration of an immune checkpoint inhibitor: a case report. Clin J Gastroenterol 2022; 15:368-373. [PMID: 34985687 PMCID: PMC8956546 DOI: 10.1007/s12328-021-01582-5] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/29/2021] [Accepted: 12/22/2021] [Indexed: 11/04/2022]
Abstract
A 71-year-old Japanese man was treated with 200 mg of pembrolizumab for lung adenocarcinoma with multiple bone metastases at the Department of Respiratory Medicine of Kameda General Hospital. After 19 treatment courses, he complained of epigastric pain before meals. Upper gastrointestinal endoscopy showed multiple erosions in the gastric antrum, and antacids were administered at follow-up. After 27 treatment courses, the patient underwent another endoscopy because of anorexia. The erosions were enlarged and had increased from the gastric antrum to the greater curvature of the body. Histological biopsy showed lymphocytic infiltration with a predominance of CD8-positive T cells. The patient had previously been treated for Helicobacter pylori infection, and we suspected drug-induced gastritis due to the administration of immune checkpoint inhibitors in the course of the disease. Pembrolizumab was discontinued, and the patient’s symptoms gradually improved. Endoscopic examinations were performed 2, 5, and 9 months after discontinuation of pembrolizumab, and improvement in mucosal findings and decreased lymphocyte infiltration were confirmed each time. The patient has remained without any relapse of symptoms for more than 1 year after discontinuing treatment.
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Affiliation(s)
- Keita Saito
- Department of Gastroenterology, Kameda General Hospital, 929, Higashi-cho, Kamogawa, Chiba, 296-8602, Japan.
| | - Daiki Ozono
- Department of Gastroenterology, Kameda General Hospital, 929, Higashi-cho, Kamogawa, Chiba, 296-8602, Japan
| | - Hironobu Nagumo
- Department of Gastroenterology, Kameda General Hospital, 929, Higashi-cho, Kamogawa, Chiba, 296-8602, Japan
| | - Masayo Yoshimura
- Department of Anatomic Pathology, Kameda General Hospital, Chiba, Japan
| | - Yoko Masuzawa
- Department of Anatomic Pathology, Kameda General Hospital, Chiba, Japan
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21
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Mor A, Strazza M. Bridging the Gap: Connecting the Mechanisms of Immune-Related Adverse Events and Autoimmunity Through PD-1. Front Cell Dev Biol 2022; 9:790386. [PMID: 35047501 PMCID: PMC8762228 DOI: 10.3389/fcell.2021.790386] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/06/2021] [Accepted: 11/30/2021] [Indexed: 12/19/2022] Open
Abstract
The emergence of anti-cytotoxic T-lymphocyte antigen 4 (anti-CTLA-4), anti-programmed cell death 1 ligand (anti-PD-1), and anti-PD-L1 antibodies as immune checkpoint inhibitors (ICIs) revolutionized the treatment of numerous types of tumors. These antibodies, both alone and in combination, provide great clinical efficacy as evidenced by tumor regression and increased overall patients' survival. However, with this success comes multiple challenges. First, while patients who respond to ICIs have outstanding outcomes, there remains a large proportion of patients who do not respond at all. This all-or-none response has led to looking downstream of programmed cell death 1 (PD-1) for additional therapeutic targets and for new combination therapies. Second, a majority of patients who receive ICIs go on to develop immune-related adverse events (irAEs) characterized by end-organ inflammation with T-cell infiltrates. The hallmarks of these clinically observed irAEs share many similarities with primary autoimmune diseases. The contribution of PD-1 to peripheral tolerance is a major mechanism for protection against expansion of self-reactive T-cell clones and autoimmune disease. In this review, we aim to bridge the gaps between our cellular and molecular knowledge of PD-1 signaling in T cells, ICI-induced irAEs, and autoimmune diseases. We will highlight shared mechanisms and the potential for new therapeutic strategies.
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Affiliation(s)
- Adam Mor
- Columbia Center for Translational Immunology, Columbia University Medical Center, New York, NY, United States
- Division of Rheumatology, Department of Medicine, Columbia University Medical Center, New York, NY, United States
| | - Marianne Strazza
- Columbia Center for Translational Immunology, Columbia University Medical Center, New York, NY, United States
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22
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Tang L, Wang J, Lin N, Zhou Y, He W, Liu J, Ma X. Immune Checkpoint Inhibitor-Associated Colitis: From Mechanism to Management. Front Immunol 2021; 12:800879. [PMID: 34992611 PMCID: PMC8724248 DOI: 10.3389/fimmu.2021.800879] [Citation(s) in RCA: 76] [Impact Index Per Article: 19.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/24/2021] [Accepted: 11/29/2021] [Indexed: 02/05/2023] Open
Abstract
Immune checkpoint inhibitors (ICIs), as one of the innovative types of immunotherapies, including programmed cell death-1 (PD-1), programmed cell death-ligand 1 (PD-L1), and cytotoxic T lymphocyte antigen 4 (CTLA-4) inhibitors, have obtained unprecedented benefit in multiple malignancies. However, the immune response activation in the body organs could arise immune-related adverse events (irAEs). Checkpoint inhibitor colitis (CIC) is the most widely reported irAEs. However, some obscure problems, such as the mechanism concerning gut microbiota, the confusing differential diagnosis with inflammatory bowel disease (IBD), the optimal steroid schedule, the reintroduction of ICIs, and the controversial prognosis features, influence the deep understanding and precise diagnosis and management of CIC. Herein, we based on these problems and comprehensively summarized the relevant studies of CIC in patients with NSCLC, further discussing the future research direction of this specific pattern of irAEs.
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Affiliation(s)
- Liansha Tang
- Department of Biotherapy, Cancer Center, West China Hospital, Sichuan University, Chengdu, China
| | - Jialing Wang
- Department of Biotherapy, Cancer Center, West China Hospital, Sichuan University, Chengdu, China
| | - Nan Lin
- Department of Biotherapy, Cancer Center, West China Hospital, Sichuan University, Chengdu, China
| | - Yuwen Zhou
- Department of Biotherapy, Cancer Center, West China Hospital, Sichuan University, Chengdu, China
| | - Wenbo He
- Department of Neurosurgery, West China Hospital, Sichuan University, Chengdu, China
| | - Jiyan Liu
- Department of Biotherapy, Cancer Center, West China Hospital, Sichuan University, Chengdu, China
| | - Xuelei Ma
- Department of Biotherapy, Cancer Center, West China Hospital, Sichuan University, Chengdu, China
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23
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Sugiyama Y, Tanabe H, Fujiya M. Immune checkpoint inhibitor-related gastritis in a patient with metastatic melanoma. JGH Open 2021; 5:1218-1219. [PMID: 34622012 PMCID: PMC8485404 DOI: 10.1002/jgh3.12657] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2021] [Accepted: 09/10/2021] [Indexed: 11/24/2022]
Abstract
Endoscopic finding of immune checkpoint inhibitor-related gastritis is characterized as shallow network-like erosion, which is termed spiderwebs-like appearance.
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Affiliation(s)
- Yuya Sugiyama
- Division of Metabolism and Biosystemic Science, Gastroenterology, and Hematology/Oncology, Department of MedicineAsahikawa Medical UniversityAsahikawaJapan
| | - Hiroki Tanabe
- Division of Metabolism and Biosystemic Science, Gastroenterology, and Hematology/Oncology, Department of MedicineAsahikawa Medical UniversityAsahikawaJapan
| | - Mikihiro Fujiya
- Division of Metabolism and Biosystemic Science, Gastroenterology, and Hematology/Oncology, Department of MedicineAsahikawa Medical UniversityAsahikawaJapan
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24
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Weingarden AR, Rubin SJS, Gubatan J. Immune checkpoint inhibitor-mediated colitis in gastrointestinal malignancies and inflammatory bowel disease. World J Gastrointest Oncol 2021; 13:772-798. [PMID: 34457186 PMCID: PMC8371513 DOI: 10.4251/wjgo.v13.i8.772] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/08/2021] [Revised: 04/09/2021] [Accepted: 07/09/2021] [Indexed: 02/06/2023] Open
Abstract
Immune checkpoint inhibitors (ICI) have markedly changed the landscape of cancer therapy. By re-invigorating the immune system against tumors, ICI provide novel therapeutic options for a broad variety of malignancies, including many gastrointestinal (GI) cancers. However, these therapies can also induce autoimmune-like side effects in healthy tissue across the body. One of the most common of these side effects is ICI-mediated colitis and diarrhea (IMC). Here, we review the incidence and risk of IMC in ICI therapy, with a focus on what is known regarding IMC in patients with GI malignancies. We also discuss data available on the use of ICI and risk of IMC in patients with pre-existing inflammatory bowel disease, as these patients may have increased risk of IMC due to their underlying intestinal pathology.
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Affiliation(s)
- Alexa R Weingarden
- Division of Gastroenterology and Hepatology, Department of Medicine, Stanford University, Redwood City, CA 94063, United States
| | - Samuel J S Rubin
- Stanford University School of Medicine, Stanford University, Redwood City, CA 94063, United States
| | - John Gubatan
- Division of Gastroenterology and Hepatology, Department of Medicine, Stanford University, Redwood City, CA 94063, United States
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25
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Omotehara S, Nishida M, Yamanashi K, Sakurai K, Katsurada T, Komatsu Y, Shimizu A, Shibuya H, Shinagawa N, Sugita J, Teshima T. A case of immune checkpoint inhibitor-associated gastroenteritis detected by ultrasonography. JOURNAL OF CLINICAL ULTRASOUND : JCU 2021; 49:605-609. [PMID: 33580597 DOI: 10.1002/jcu.22975] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/16/2020] [Revised: 12/15/2020] [Accepted: 01/06/2021] [Indexed: 06/12/2023]
Abstract
While immune checkpoint inhibitors (ICIs) have antitumor effects, they also have characteristic side effects, including colitis. However, gastritis has rarely been reported. We report a case of a patient with lung adenocarcinoma who presented with epigastric pain and diarrhea following pembrolizumab administration. Sonography of the abdomen demonstrated diffuse, although mild, gastric wall thickening (mainly in the submucosa), as well as a slight decrease in echogenicity throughout the gastric wall. While the mucosal surface was relatively smooth, color Doppler examination showed increased vascularity. Esophagogastroduodenoscopy and pathological examination confirmed the diagnosis of ICI-related gastroenteritis.
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Affiliation(s)
- Satomi Omotehara
- Division of Laboratory and Transfusion Medicine, Hokkaido University Hospital, Sapporo, Japan
- Diagnostic Center for Sonography, Hokkaido University Hospital, Sapporo, Japan
| | - Mutsumi Nishida
- Division of Laboratory and Transfusion Medicine, Hokkaido University Hospital, Sapporo, Japan
- Diagnostic Center for Sonography, Hokkaido University Hospital, Sapporo, Japan
| | - Kana Yamanashi
- Department of Gastroenterology and Hepatology, Hokkaido University Hospital, Sapporo, Japan
| | - Kensuke Sakurai
- Department of Gastroenterology and Hepatology, Hokkaido University Hospital, Sapporo, Japan
| | | | | | - Ai Shimizu
- Department of Surgical Pathology, Hokkaido University Hospital, Sapporo, Japan
| | - Hitoshi Shibuya
- Diagnostic Center for Sonography, Hokkaido University Hospital, Sapporo, Japan
| | - Naofumi Shinagawa
- Department of Respiratory Medicine, Graduate School of Medicine, Hokkaido University, Sapporo, Japan
| | - Junichi Sugita
- Division of Laboratory and Transfusion Medicine, Hokkaido University Hospital, Sapporo, Japan
- Department of Hematology, Graduate School of Medicine, Hokkaido University, Sapporo, Japan
| | - Takanori Teshima
- Division of Laboratory and Transfusion Medicine, Hokkaido University Hospital, Sapporo, Japan
- Department of Hematology, Graduate School of Medicine, Hokkaido University, Sapporo, Japan
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26
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Checkpoint Inhibitor-Induced Colitis-A Clinical Overview of Incidence, Prognostic Implications and Extension of Current Treatment Options. Pharmaceuticals (Basel) 2021; 14:ph14040367. [PMID: 33923423 PMCID: PMC8074139 DOI: 10.3390/ph14040367] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2021] [Revised: 04/09/2021] [Accepted: 04/14/2021] [Indexed: 12/19/2022] Open
Abstract
In recent years, anti-tumor immunotherapies have witnessed a major breakthrough with the emergence of immune checkpoint inhibitors (ICIs). However, the use of ICIs has also brought an era of a certain class of adverse events that differ from those of classical chemotherapies and are more reminiscent of autoimmune diseases. This article focuses exclusively on colitis as an irAE with emphasis on vulnerable patient groups, the prognostic significance of colitis, treatment, and new therapeutic approaches that may be applicable. Colitis itself is associated with a favorable oncological outcome of the underlying disease but is as well the most common irAE leading to discontinuation of therapy. Especially in vulnerable patient groups such as IBD patients and elderly patients, colitis occurs more frequently as a side effect. It is precisely in these two patient groups that side effects more often lead to discontinuation of therapy. Therefore, in addition to the current therapy of colitis through immunosuppression, the focus should also be on new forms of therapy of severe colitis, such as fecal transplantation or ileostomy creation.
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27
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Shimozaki K, Hirata K, Horie S, Chida A, Tsugaru K, Hayashi Y, Kawasaki K, Miyanaga R, Hayashi H, Mizuno R, Funakoshi T, Hosoe N, Hamamoto Y, Kanai T. The Entire Intestinal Tract Surveillance Using Capsule Endoscopy after Immune Checkpoint Inhibitor Administration: A Prospective Observational Study. Diagnostics (Basel) 2021; 11:543. [PMID: 33803735 PMCID: PMC8003297 DOI: 10.3390/diagnostics11030543] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2021] [Revised: 03/15/2021] [Accepted: 03/16/2021] [Indexed: 12/19/2022] Open
Abstract
BACKGROUND Despite the proven efficacy of immune checkpoint inhibitors (ICIs) against various types of malignancies, they have been found to induce immune-related adverse events, such as enterocolitis; however, the clinical features of ICI-induced enterocolitis remain to be sufficiently elucidated, which is significant, considering the importance of early detection in the appropriate management and treatment of ICI-induced enterocolitis. Therefore, the current study aimed to determine the utility of capsule endoscopy as a screening tool for ICI-induced enterocolitis. METHODS This single-center, prospective, observational study was conducted on patients with malignancy who received any ICI between April 2016 and July 2020 at Keio University Hospital. Next, second-generation capsule endoscopy (CCE-2) was performed on day 60 after ICI initiation to explore the entire gastrointestinal tract. RESULTS Among the 30 patients enrolled herein, 23 underwent CCE-2. Accordingly, a total of 23 findings were observed in 14 (60.8%) patients at any portion of the gastrointestinal tract (7 patients in the colon, 4 patients in the small intestine, 2 patients in both the colon and the small intestine, and 1 patient in the stomach). After capsule endoscopy, 2 patients (8.7%) developed ICI-induced enterocolitis: both had significantly higher Capsule Scoring of Ulcerative Colitis than those who had not developed ICI-induced enterocolitis (p = 0.0455). No adverse events related to CCE-2 were observed. CONCLUSIONS CCE-2 might be a safe and useful entire intestinal tract screening method for the early detection of ICI-induced enterocolitis in patients with malignancies.
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Affiliation(s)
- Keitaro Shimozaki
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo 160-8582, Japan; (K.S.); (S.H.); (A.C.); (K.T.); (Y.H.); (K.K.); (R.M.); (T.K.)
| | - Kenro Hirata
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo 160-8582, Japan; (K.S.); (S.H.); (A.C.); (K.T.); (Y.H.); (K.K.); (R.M.); (T.K.)
| | - Sara Horie
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo 160-8582, Japan; (K.S.); (S.H.); (A.C.); (K.T.); (Y.H.); (K.K.); (R.M.); (T.K.)
| | - Akihiko Chida
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo 160-8582, Japan; (K.S.); (S.H.); (A.C.); (K.T.); (Y.H.); (K.K.); (R.M.); (T.K.)
| | - Kai Tsugaru
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo 160-8582, Japan; (K.S.); (S.H.); (A.C.); (K.T.); (Y.H.); (K.K.); (R.M.); (T.K.)
| | - Yukie Hayashi
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo 160-8582, Japan; (K.S.); (S.H.); (A.C.); (K.T.); (Y.H.); (K.K.); (R.M.); (T.K.)
| | - Kenta Kawasaki
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo 160-8582, Japan; (K.S.); (S.H.); (A.C.); (K.T.); (Y.H.); (K.K.); (R.M.); (T.K.)
| | - Ryoichi Miyanaga
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo 160-8582, Japan; (K.S.); (S.H.); (A.C.); (K.T.); (Y.H.); (K.K.); (R.M.); (T.K.)
| | - Hideyuki Hayashi
- Keio Cancer Center, Keio University School of Medicine, Tokyo 160-8582, Japan; (H.H.); (Y.H.)
| | - Ryuichi Mizuno
- Department of Urology, Keio University School of Medicine, Tokyo 160-8582, Japan;
| | - Takeru Funakoshi
- Department of Dermatology, Keio University School of Medicine, Tokyo 160-8582, Japan;
| | - Naoki Hosoe
- Center for Diagnostic and Therapeutic Endoscopy, Keio University School of Medicine, Tokyo 160-8582, Japan;
| | - Yasuo Hamamoto
- Keio Cancer Center, Keio University School of Medicine, Tokyo 160-8582, Japan; (H.H.); (Y.H.)
| | - Takanori Kanai
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo 160-8582, Japan; (K.S.); (S.H.); (A.C.); (K.T.); (Y.H.); (K.K.); (R.M.); (T.K.)
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