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World Journal of Clinical Cases 2022年第6期10卷 1787-1794页

作者： Samuel J S Rubin Tatiana Balabanis john gubatan Aida Habtezion Division of Gastroenterology and Hepatology Department of MedicineStanford University School of MedicineStanfordCA 94305United States

BACKGROUND Colitis is a known potential toxicity of immune checkpoint inhibitors(ICIs).Studies evaluating the risk of disease exacerbation following ICI treatment in patients with pre-existing inflammatory bowel disease(IBD)are *** To assess the clinical characteristics of IBD patients treated with ICIs and determine prevalence of subsequent IBD *** We conducted a retrospective cohort study of all patients in the Stanford Research Repository database with pre-existing IBD who were exposed to *** The prevalence of IBD exacerbation following ICI was 36.8% amongst 19 patients meeting inclusion *** with exacerbations had more gastrointestinalrelated hospitalizations(4 of 7)than patients without exacerbations(0 of 12;P=0.0090).CONCLUSION The prevalence of IBD exacerbations following ICI was higher than reported rates of ICI-induced colitis and diarrhea in the general population and was associated with hospitalization.

关键词： Inflammatory bowel disease Immune checkpoint inhibitors Immunotherapy Malignancy

Small bowel adenocarcinoma in neoterminal ileum in setting of stricturing Crohn’s disease:A case report and review of literature

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World Journal of Clinical Cases 2023年第9期11卷 2021-2028页

作者： Shruthi Karthikeyan Jeanne Shen Kian Keyashian john gubatan Department of Medicine Division of Gastroenterology and HepatologyStanford University School of MedicineStanfordCA 94306United States Department of Pathology Stanford University School of MedicineStanfordCA 94306United States

BACKGROUND Small bowel adenocarcinomas(SBA) are rare malignancies with exceedingly low survival rates, with different presentation in Crohn’s disease(CD). CD-induced SBA poses diagnostic challenges given overlapping presentation with stricturing CD and lack of diagnostics for early detection. Moreover, guidance is lacking on the impact of recently approved therapeutics in CD on SBA management. Here, we aim to highlight the future of CD-induced SBA management and discuss the potential merit of balloon enteroscopy and genetic testing for earlier *** SUMMARY We report the case of a 60-year-old female with longstanding Crohn’s ileitis, presenting with acute obstructive symptoms attributed to stricturing phenotype. Her obstructive symptoms were refractory to intravenous(Ⅳ) steroids, with further investigation via computed tomography enterography not providing additional diagnostic yield. Ultimately, surgical resection revealed SBA in the neoterminal ileum, with oncologic therapy plan created. However, this therapy plan could not be initiated due to continued obstructive symptoms attributed to active CD. Ultimately, infused biologic therapy was initiated, but her obstructive symptoms continued to remain dependent on Ⅳ corticosteroids. Review of diagnostics by a multidisciplinary care team suggested metastatic disease in the peritoneum, lending to a shift in the goals of care to *** With the diagnostic and therapeutic challenges of concurrent SBA and CD, multidisciplinary care and algorithmic management can optimize outcomes.

关键词： Crohn’s disease Small bowel adenocarcinoma Management Diagnosis Case report

Immune checkpoint inhibitor-mediated colitis is associated with cancer overall survival

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World Journal of Gastroenterology 2022年第39期28卷 5750-5763页

作者： Alexa R Weingarden john gubatan Sundeep Singh Tatiana Clorice Balabanis Akshar Patel Arpita Sharma Aida Habtezion Medicine Division of Gastroenterology and HepatologyStanford University School of MedicineStanfordCA 94305United States

BACKGROUND Immune checkpoint inhibitor-mediated colitis(IMC)is a common adverse event following immune checkpoint inhibitor(ICI)therapy for *** has been associated with improved overall survival(OS)and progression-free survival(PFS),but data are limited to a single site and predominantly for melanoma *** To determine the association of IMC with OS and PFS and identify clinical predictors of *** We performed a retrospective case-control study including 64 ICI users who developed IMC matched according to age,sex,ICI class,and malignancy to a cohort of ICI users without IMC,from May 2011 to May *** univariate and multivariate logistic regression,we determined association of presence of IMC on OS,PFS,and clinical predictors of ***-Meier curves were gen-erated to compare OS and PFS between ICI users with and without *** IMC was significantly associated with a higher OS(mean 24.3 mo vs 17.7 mo,P=0.05)but not PFS(mean 13.7 mo vs 11.9 mo,P=0.524).IMC was significantly associated with OS greater than 12 mo[Odds ratio(OR)2.81,95%confidence interval(CI)1.17-6.77].Vitamin D supplementation was significantly associated with increased risk of IMC(OR 2.48,95%CI 1.01-6.07).CONCLUSION IMC was significantly associated with OS greater than 12 *** contrast to prior work,we found that vitamin D use may be a risk factor for IMC.

关键词： Immune checkpoint inhibitors Immune checkpoint inhibitor-mediated colitis Immune-related adverse events

Immune checkpoint inhibitor-mediated colitis in gastrointestinal malignancies and inflammatory bowel disease

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World Journal of Gastrointestinal Oncology 2021年第8期13卷 772-798页

作者： Alexa R Weingarden Samuel J S Rubin john gubatan Division of Gastroenterology and Hepatology Department of MedicineStanford UniversityRedwood CityCA 94063United States Stanford University School of Medicine Stanford UniversityRedwood CityCA 94063United States

Immune checkpoint inhibitors(ICI)have markedly changed the landscape of cancer *** re-invigorating the immune system against tumors,ICI provide novel therapeutic options for a broad variety of malignancies,including many gastrointestinal(GI)***,these therapies can also induce autoimmune-like side effects in healthy tissue across the *** 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 *** 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.

关键词： Immune checkpoint inhibitors Cytotoxic T-lymphocyte antigen 4 Programmed cell death protein-1 Inflammatory bowel disease Gastrointestinal cancer

Artificial intelligence applications in inflammatory bowel disease:Emerging technologies and future directions

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World Journal of Gastroenterology 2021年第17期27卷 1920-1935页

作者： john gubatan Steven Levitte Akshar Patel Tatiana Balabanis Mike T Wei Sidhartha R Sinha Division of Gastroenterology and Hepatology Stanford University School of MedicineRedwood CityCA 94063United States

Inflammatory bowel disease(IBD)is a complex and multifaceted disorder of the gastrointestinal tract that is increasing in incidence worldwide and associated with significant *** rapid accumulation of large datasets from electronic health records,high-definition multi-omics(including genomics,proteomics,transcriptomics,and metagenomics),and imaging modalities(endoscopy and endomicroscopy)have provided powerful tools to unravel novel mechanistic insights and help address unmet clinical needs in *** the application of artificial intelligence(AI)methods has facilitated the analysis,integration,and interpretation of large datasets in IBD,significant heterogeneity in AI methods,datasets,and clinical outcomes and the need for unbiased prospective validations studies are current barriers to incorporation of AI into clinical *** purpose of this review is to summarize the most recent advances in the application of AI and machine learning technologies in the diagnosis and risk prediction,assessment of disease severity,and prediction of clinical outcomes in patients with IBD.

关键词： Artificial intelligence Machine learning Inflammatory bowel disease Crohn’s disease Ulcerative colitis Clinical outcomes

Antimicrobial peptides and the gut microbiome in inflammatory bowel disease

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World Journal of Gastroenterology 2021年第43期27卷 7402-7422页

作者： john gubatan Derek R Holman Christopher J Puntasecca Danielle Polevoi Samuel JS Rubin Stephan Rogalla Division of Gastroenterology and Hepatology Stanford University School of MedicineRedwood CityCA 94063United States Department of Radiology Molecular Imaging Program at StanfordStanford UniversityStanfordCA 94305United States Stanford University School of Medicine Stanford UniversityStanfordCA 94063United States

Antimicrobial peptides(AMP)are highly diverse and dynamic molecules that are expressed by specific intestinal epithelial cells,Paneth cells,as well as immune cells in the gastrointestinal(GI)*** play critical roles in maintaining tolerance to gut microbiota and protecting against enteric *** that disruptions in tolerance to commensal microbiota and loss of barrier function play major roles in the pathogenesis of inflammatory bowel disease(IBD)and converge on the function of AMP,the significance of AMP as potential biomarkers and novel therapeutic targets in IBD have been increasingly recognized in recent *** this frontier article,we discuss the function and mechanisms of AMP in the GI tract,examine the interaction of AMP with the gut microbiome,explore the role of AMP in the pathogenesis of IBD,and review translational applications of AMP in patients with IBD.

关键词： Antimicrobial peptides Inflammatory bowel disease Ulcerative colitis Crohn’s disease Gut microbiome Biomarkers

p38γand p38δas biomarkers in the interplay of colon cancer and inflammatory bowel diseases

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Cancer Communications 2022年第9期42卷 897-901页

作者： Pilar Fajardo Maria Taskova Miguel A.Martín-Serrano Jonas Hansen Sofie Slott Anna K.Jakobsen Marie-Louise Wibom Beñat Salegi Alberto Muñoz Antonio Barbachano Arpita Sharma john Mark gubatan Aida Habtezion Juan J.Sanz-Ezquerro Kira Astakhova Ana Cuenda Department of Immunology and Oncology National Centre of Biotechnology/Consejo Superior de Investigaciones CientíficasDarwin 3Madrid 28049Spain PhD Programme in Molecular Bioscience Doctoral SchoolUniversidad Autónoma de MadridMadrid 28049Spain Department of Chemistry Technical University of Denmark2800 Kongens LyngbyDenmark Adolphe Merkle Institute University of FribourgChemin des Verdiers 41700 FribourgSwitzerland Stanford School of Medicine StanfordCA 94305USA Instituto de Investigaciones Biomédicas“Alberto Sols” Consejo Superior de Investigaciones CientíficasUniversidad Autónoma de MadridMadrid 28029Spain Centro de Investigación Biomédica en Red-Cáncer Instituto de Salud Carlos IIIMadrid 28029Spain Instituto de Investigación Sanitaria del Hospital Universitario La Paz Madrid 28029Spain Department of Medicine Division of Gastroenterology and HepatologyStanford University School of MedicineStanfordCA 94305USA Department of Molecular and Cellular Biology Centro Nacional de Biotecnología/Consejo Superior de Investigaciones CientíficasDarwin 3Madrid 28049Spain

Dear Editor,Colorectal cancer(CRC)is the second leading cause of cancer death according to the World Health *** with inflammatory bowel disease(IBD),ulcerative colitis(UC)or Crohn’s disease(CD)are at increased risk of developing colitis-associated CRC(CAC)[1];however,our understanding of the inflammationcancer interplay at the molecular level is still limited.

关键词： inflammatory death p38 CRC