Immune Checkpoint Inhibitor Enterocolitis vs Idiopathic Inflammatory Bowel Disease.

Immune checkpoint inhibitors have revolutionized management of advanced malignancies. However, their use is frequently complicated by immune related adverse events (irAEs), immune checkpoint inhibitor enterocolitis (IMEC) being the most common toxicity. IMEC is a distinct form of bowel inflammation that is highly reminiscent of idiopathic inflammatory bowel disorders (Crohn's disease, ulcerative colitis, and microscopic colitis). In this review, we highlight the similarities and differences in the pathophysiology, clinical presentation, evaluation, and management of these overlapping immune inflammatory bowel disorders. IMEC is an inflammatory bowel disease-like irAE that occurs as an outcome of disruption of intestinal immune surveillance and gut dysbiosis. Clinical and endoscopic presentation of both entities is strikingly similar, which often guides management. Though well established in inflammatory bowel disease, little is known about the long term outcomes of IMEC.

IL12/23 Blockade for Refractory Immune-Mediated Colitis: 2-Center Experience.

INTRODUCTION: Immune checkpoint inhibitor-mediated colitis (IMC) is commonly managed with steroids and biologics. We evaluated the efficacy of ustekinumab (UST) in treating IMC refractory to steroids plus infliximab and/or vedolizumab. RESULTS: Nineteen patients were treated with UST for IMC refractory to steroids plus infliximab (57.9%) and/or vedolizumab (94.7%). Most of them had grade ≥3 diarrhea (84.2%), and colitis with ulceration was present in 42.1%. Thirteen patients (68.4%) attained clinical remission with UST, and mean fecal calprotectin levels dropped significantly after treatment (629 ± 101.5 mcg/mg to 92.0 ± 21.7 mcg/mg, P = 0.0004). DISCUSSION: UST is a promising therapy for the treatment of refractory IMC.

Immune Checkpoint Inhibitor-Induced (Type 3) Autoimmune Pancreatitis.

PURPOSE OF REVIEW: Immune checkpoint inhibitors (ICI) have revolutionized cancer care and work primarily by blocking CTLA-4 (cytotoxic T-lymphocyte-associated protein 4), and/or PD-1 (programmed cell death protein 1), and/or PD-L1 (programmed death-ligand 1), thereby providing highly efficacious anti-tumor activity. However, this unmitigated immune response can also trigger immune related adverse events (irAEs) in multiple organs, with pancreatic irAEs (now referred to as type 3 Autoimmune pancreatitis (AIP) being infrequent. RECENT FINDINGS: Type 3 AIP is a drug-induced, immune mediated progressive inflammatory disease of the pancreas that may have variable clinical presentations viz., an asymptomatic pancreatic enzyme elevation, incidental imaging evidence of pancreatitis, painful pancreatitis, or any combination of these subtypes. Management is largely supportive with intravenous fluid hydration, pain control and holding the inciting medication. Steroids have not been shown to demonstrate a clear benefit in acute management. A rapid development pancreatic atrophy is observed on imaging as early as 1 year post initial injury. Type 3 AIP is a chronic inflammatory disease of the pancreas that though predominantly asymptomatic and mild in severity can lead to rapid organ volume loss regardless of type of clinical presentation and despite steroid therapy.

Ileo-colonic lymphoma: presentation, diagnosis, and management.

PURPOSE OF REVIEW: The gut-associated lymphoid tissue (GALT), the bulk of which is located in the ileo-colonic region comprises the lymphoid cells of the gastrointestinal tract and confers specific immunological responses. Repetitive antigenic stimulation of these cells predispose to a monoclonal proliferation of this tissue and the eventual development of lymphoma. The gastrointestinal tract is the most commonly involved site of extranodal lymphomas. This review will focus primarily on lymphomas of the ileo-colonic region (defined as the terminal ileum, the colon, and the rectum). We will discuss the epidemiology, pathogenesis, and presentation as well as current practices in diagnosis and management. RECENT FINDINGS: Despite the majority of the GALT to be located in the ileo-colonic region of the gut, the lymphomas in this location are relatively rare. However, the overall annual incidence of ileo-colonic lymphomas is steadily increasing. This entity has a varied spectrum of clinical presentations. Ileo-colonoscopy with adequate targeted biopsies can serve as a gold standard for definitive diagnosis. Ileo-colonic lymphomas may be managed with chemotherapy alone while surgery is reserved for highly aggressive tumors or clinical emergencies. Radiation is not a preferred adjuvant treatment for lymphomas in this location of the gut. Adequate endoscopic surveillance measures and tools to potentially prevent recurrence and improve the overall prognosis of this disease are lacking. SUMMARY: Ileo-colonic lymphomas are rare and can present with varied symptoms and signs. Endoscopy with adequate sampling can aid in making a definitive diagnosis. Chemotherapy can be highly effective in management while surgery is indicated for emergency presentations. Adequate endoscopic surveillance tools are lacking, yet imperative to prevent recurrence and improve prognosis.

Outcomes of Budesonide as a Treatment Option for Immune Checkpoint Inhibitor-Related Colitis in Patients with Cancer.

BACKGROUND: Current treatment guidelines for moderate to severe colitis (IMC) secondary to immune checkpoint inhibitors (ICI) recommend systemic corticosteroids as the primary therapy in conjunction with biologics, namely infliximab and/or vedolizumab. We aimed to explore the efficacy and safety of oral budesonide in the treatment of IMC. METHODS: We performed a retrospective analysis at MD Anderson Cancer Center of adult cancer patients with a confirmed (based on clinical, radiographic and laboratory assessment) diagnosis of IMC between 1 January 2015 and 31 November 2022, treated with budesonide. Data collection included demographics, oncologic history, IMC-related information and outcomes up to 6 months after the last dose of ICI. RESULTS: Our sample (n = 69) comprised primarily of Caucasian (76.8%) females (55.1%). The majority of patients received combination therapy with anti-PD-1/L1 and anti-CTLA-4 (49.3%), and the most common malignancy treated was melanoma (37.6%). The median grade of diarrhea was 3 and of colitis was 2. Of the 50 patients who underwent endoscopic evaluation, a majority had non-ulcerative inflammation (64%) and active colitis on histology (78%). Budesonide was used as primary treatment at onset of IMC in 56.5% patients, as well as a bridging therapy from systemic corticosteroids in 33.3%. Less than half of the patients (44.9%) required additional therapies such as biologics or fecal microbiota transplant. Additionally, 75.3% of patients achieved full remission of IMC and 24.6% had a recurrence of IMC. ICI was resumed in 31.9% of patients and 17.4% received other forms of cancer therapies. CONCLUSIONS: Budesonide may be an effective strategy to treat and prevent the recurrence of IMC. The remission rates observed in our analysis with budesonide alone are comparable to systemic corticosteroids. Patients that require an extended duration of steroid exposure and those with moderate to severe colitis may benefit from budesonide given its lower risk of infection and complications. Furthermore, we observe that budesonide may serve as a successful bridge from systemic corticosteroids with subsequent biologic treatment. Larger prospective studies are necessary to determine the role of budesonide as well as its safety profile.

Vitamin D Receptor Gene Single Nucleotide Polymorphisms and Association With Vitamin D Levels and Endoscopic Disease Activity in Inflammatory Bowel Disease Patients: A Pilot Study.

BACKGROUND: Inflammatory bowel diseases (IBDs) comprise a heterogenous group of chronic gastrointestinal disorders that are multifactorial in etiology. Experimental in vitro and in vivo studies suggest that intestinal vitamin D receptor (VDR) signaling plays a role in modulating the immune response in IBD as a cause and/or a consequence of chronic inflammation. AIM: The aim of this study is to study the associations between vitamin D receptor gene single nucleotide polymorphisms(SNPs), vitamin D levels, and endoscopic disease activity in IBD. METHODS: This is a cross-sectional analysis of IBD patients who underwent endoscopic evaluation at a tertiary care hospital. Demographic variables, IBD disease type and location, medical therapies, vitamin D levels, and endoscopic disease activity were collected. Colonic biopsies obtained were investigated for the presence of VDR SNPs: ApaI, TaqI, BsmI, FokI, and Tru9I. RESULTS: Patients in endoscopic remission had higher vitamin D levels compared with those with inflammation found on endoscopy (P = <0.001). Patients with lower vitamin D levels were homozygous for Fok ancestral alleles (P = 0.0045). With regard to endoscopic disease activity, we found no differences in mutations of any of the VDR SNPs in our sample. CONCLUSIONS: The association between the presence of the ancestral FokI and lower vitamin D levels suggests a multifactorial etiology for vitamin D deficiency in IBD. Higher vitamin D levels in those in endoscopic remission compared with lower levels in those with active inflammation suggests that the impact of VDR gene SNP on disease activity may be overcome with replacement therapy.

Correlation of menstrual distress to severity of gastrointestinal symptoms in inflammatory bowel disease patients.

Inflammatory bowel diseases (IBD), namely, Crohn's disease (CD) and ulcerative colitis (UC) are idiopathic chronic, relapsing, inflammatory diseases of the gastrointestinal (GI) tract. Triggers for disease flares include medications, infection, acute stress, and the menstrual cycle. Varying ovarian hormone levels i.e. prostaglandins and progesterone may exaggerate GI symptoms in IBD. We aimed to determine the relationship between quality of life, endoscopic and clinical disease activity and the menstrual cycle among females with IBD through a questionnaire based cross-sectional study. The first 75 women of child-bearing age seen at IBD clinic completed a questionnaire incorporating the short IBD questionnaire (SIBDQ). Menstrual symptoms were evaluated using the validated Moos Menstrual Distress Questionnaire (MDQ) to measure cyclical peri-menstrual symptoms. Endoscopic disease severity was assessed using the Rutgeert's score (post ileo-cecal resection patients) or Simple Endoscopic Score for CD and the Mayo score for UC. There was a statistically negative correlation between MDQ and SIBDQ scores (p<0.001); i.e. patients with lower menstrual distress scores had better quality of life. We found no correlation between the SIBDQ, MDQ and endoscopic scores (p = 0.094, 0.626 respectively). Previous studies suggest that the severity of menstrual symptoms correlate with a poorer quality of life among women with IBD. However, this may not be reflective of the endoscopic disease severity. Larger studies are necessary to evaluate adjusting medication closer to menstrual period and adding supportive therapy peri-menstrually in anticipation of symptoms.

Gastrointestinal lymphoma: the new mimic.

BACKGROUND: Gastrointestinal (GI) lymphomas comprise a group of distinct clinicopathological entities of B- or T- cell type, with primary gastrointestinal Hodgkin lymphoma being extremely uncommon. The GI tract is the predominant site of extranodal non-Hodgkin lymphoma accounting for 30-40% of all extranodal lymphomas. In the Western world, the stomach is the most commonly involved site followed by the small bowel. Several chronic inflammatory and immune-mediated disorders which predispose to accelerated cell turnover may lead to the malignant transformation of gut lymphocytes and ultimately manifest as GI lymphoma. The challenge for the clinical gastroenterologist is that these tumors may have varied presentations, ranging from nonspecific symptoms such as dyspepsia or bloating to abdominal pain, nausea, vomiting, GI bleeding, diarrhea, weight loss or bowel obstruction. OBJECTIVE: We illustrate the range of presentations of GI lymphoma with examples based on consecutive cases evaluated at our institution over a 6-month period. These cases demonstrate how appropriately directed endoscopic evaluation with biopsies has the potential to provide a definitive diagnosis and allow the patient to proceed to definitive therapy. CONCLUSIONS: The GI tract is the most commonly involved site for extranodal lymphoma with the stomach being most frequently involved organ. Chronic Helicobacter pylori infection, celiac disease, inflammatory bowel disease and autoimmune disorders may predispose to GI lymphoma. This heterogenous group of diseases has varied presentations that may mimic several other GI clinico-pathologic entities. GI lymphomas may be diagnosed with appropriately directed endoscopic evaluation coupled with generous tissue sampling and expert pathologic assessment. Management may range from antibiotic therapy, in the case of Helicobacter pylori-associated gastric MALT lymphoma, to chemotherapy with or without radiation and, in rare instances, surgery. There are presently no guidelines to direct endoscopic surveillance of GI lymphomas following treatment.