Check this out: treatment paradigms in immune-checkpoint inhibitor colitis.

PURPOSE OF REVIEW: Immune checkpoint inhibitors (ICI) have become a pillar of cancer therapy for many people around the world. However, up to two-thirds of all patients undergoing ICI therapy will have immune-related adverse events (irAEs), including immune-checkpoint inhibitor colitis (ICIC). This review summarizes the most valuable and currently available information about the mechanism, diagnosis, and management of ICIC. RECENT FINDINGS: Recent findings include several developments on the leading theories for the mechanisms of ICIC such as the role of the gut microbiome. New emerging therapy strategies include tocilizumab, ustekinumab, mycophenolate mofetil, and calcineurin inhibitors. SUMMARY: The occurrence of irAEs remains a limiting factor for the use of immunotherapy in cancer treatment. Prompt diagnosis of ICIC with endoscopy and histologic confirmation can lead to early utilization of known effective treatments such as corticosteroids, infliximab, vedolizumab, and other emerging therapy strategies. We summarize the key points of this review article in our abstract video, Supplemental Digital Content 1, http://links.lww.com/COG/A44.

Fecal Microbiota Transplantation Is Highly Effective in Real-World Practice: Initial Results From the FMT National Registry.

BACKGROUND & AIMS: Fecal microbiota transplantation (FMT) is used commonly for treatment of Clostridioides difficile infections (CDIs), although prospective safety data are limited and real-world FMT practice and outcomes are not well described. The FMT National Registry was designed to assess FMT methods and both safety and effectiveness outcomes from North American FMT providers. METHODS: Patients undergoing FMT in clinical practices across North America were eligible. Participating investigators enter de-identified data into an online platform, including FMT protocol, baseline patient characteristics, CDI cure and recurrence, and short and long-term safety outcomes. RESULTS: Of the first 259 participants enrolled at 20 sites, 222 had completed short-term follow-up at 1 month and 123 had follow-up to 6 months; 171 (66%) were female. All FMTs were done for CDI and 249 (96%) used an unknown donor (eg, stool bank). One-month cure occurred in 200 patients (90%); of these, 197 (98%) received only 1 FMT. Among 112 patients with initial cure who were followed to 6 months, 4 (4%) had CDI recurrence. Severe symptoms reported within 1-month of FMT included diarrhea (n = 5 [2%]) and abdominal pain (n = 4 [2%]); 3 patients (1%) had hospitalizations possibly related to FMT. At 6 months, new diagnoses of irritable bowel syndrome were made in 2 patients (1%) and inflammatory bowel disease in 2 patients (1%). CONCLUSIONS: This prospective real-world study demonstrated high effectiveness of FMT for CDI with a good safety profile. Assessment of new conditions at long-term follow-up is planned as this registry grows and will be important for determining the full safety profile of FMT.

Quality of Care Program Reduces Unplanned Health Care Utilization in Patients With Inflammatory Bowel Disease.

INTRODUCTION: There is significant variation in processes and outcomes of care for patients with inflammatory bowel disease (IBD), suggesting opportunities to improve quality of care. We aimed to determine whether a structured quality of care program can improve IBD outcomes, including the need for unplanned health care utilization. METHODS: We used a structured approach to improve adult IBD care in 27 community-based gastroenterology practices and academic medical centers. Patient-reported outcomes (PRO) and health care utilization were collected at clinical visits. Outcomes were monitored monthly using statistical process control charts; improvement was defined by special cause (nonrandom) variation over time. Multivariable logistic regression was applied to patient-level data. Nineteen process changes were offered to improve unplanned health care utilization. Ten outcomes were assessed, including disease activity, remission status, urgent care need, recent emergency department use, hospitalizations, computed tomography scans, health confidence, corticosteroid or opioid use, and clinic phone calls. RESULTS: We collected data prospectively from 20,382 discrete IBD visits. During the 15-month project period, improvement was noted across multiple measures, including need for urgent care, hospitalization, steroid use, and opioid utilization. Adjusted multivariable modeling showed significant improvements over time across multiple outcomes including urgent care need, health confidence, emergency department utilization, hospitalization, corticosteroid use, and opioid use. Attendance at monthly coached webinars was associated with improvement. DISCUSSION: Outcomes of IBD care were improved using a structured quality improvement program that facilitates small process changes, sharing of best practices, and ongoing feedback. Spread of these interventions may facilitate broad improvement in IBD care when applied to a large population.

Health Economic Impact of a Multicenter Quality-of-Care Initiative for Reducing Unplanned Healthcare Utilization Among Patients With Inflammatory Bowel Disease.

INTRODUCTION: A multicenter adult inflammatory bowel disease learning health system (IBD Qorus) implemented clinical care process changes for reducing unplanned emergency department visits and hospitalizations using a Breakthrough Series Collaborative approach. METHODS: Using Markov decision models, we determined the health economic impact of participating in the Collaborative from the third-party payer perspective. RESULTS: Across all 23 sites, participation in the Collaborative was associated with lower annual costs by an average of $2,528 ± $233 per patient when compared with the baseline period. DISCUSSION: Implementing clinical care process changes using a Collaborative approach was associated with overall cost savings. Future work should examine which specific interventions are most effective and whether such cost savings are sustainable.

Depression and the Aberrant Intestinal Microbiome.

Depression is one of the most common mental health disorders affecting adults in the United States. The current treatment is the combination of pharmacotherapy and psychotherapy. Recently, the evidence linking gut microbiome dysregulation to the development of depression has grown. The pathophysiology is currently poorly understood, although leading hypotheses include involvement of the hypothalamic-pituitary-adrenal axis, a bidirectional relationship between the gut microbiome and the central nervous system, and production of signaling molecules by the gut microbiome. Available and emerging treatments of the aberrant microbiome include antidepressants, antibiotics, diet modification, probiotics, and fecal microbiota transplant. This article explores the interconnectivity of gut microbiota and depression and treatments targeted toward the gut, reviews the gastroenterologist's potential role in managing gut dysbiosis in patients with depression, and highlights research topics to be addressed to create evidence-based guidelines.

Improving sessile serrated adenoma detection rates with high definition colonoscopy: A retrospective study.

BACKGROUND: Sessile serrated adenomas (SSAs) are important premalignant lesions that are difficult to detect during colonoscopy due to poor definition, concealment by mucous caps, and flat appearance. High definition (HD) colonoscopy may uniquely aid in the detection of these inconspicuous lesions compared to standard definition (SD) colonoscopes. In the absence of existing clinical guidelines to obligate the use of HD colonoscopy for colorectal cancer screening in average-risk patients, demonstrating the benefit of HD colonoscopy on SSA detection rate (SSADR) may help strengthen the evidence to recommend its use in all settings. AIM: To evaluate the benefit of HD colonoscopy compared to SD colonoscopy on SSADR in average-risk patients undergoing screening colonoscopy. METHODS: Data from screening colonoscopies for patients aged 50-76 years two years before and two years after the transition from SD colonoscopy to HD colonoscopy at our large, academic teaching center were collected. Patients with symptoms of colorectal disease, positive occult blood test, history of colon polyps, cancer, polyposis syndrome, inflammatory bowel disease or family history of colon cancer or polyps were excluded. Patients whose endoscopists did not perform colonoscopies both before and after scope definition change were also excluded. Differences in individual endoscopist SSADR, average SSADR, and overall SSADR with SD colonoscopy vs HD colonoscopy were also evaluated for significance. RESULTS: A total of 3657 colonoscopies met eligibility criteria with 2012 colonoscopies from the SD colonoscopy period and 1645 colonoscopies from the HD colonoscopy period from a pool of 11 endoscopists. Statistically significant improvements of 2.30% in mean SSADR and 2.53% in overall SSADR were noted with HD colonoscopy (P = 0.00028 and P = 0.00849, respectively). On the individual level, three endoscopists experienced statistically significant benefit with HD colonoscopy (+5.74%, P = 0.0056; +4.50%, P = 0.0278; +4.84%, P = 0.03486). CONCLUSION: Our study suggests that HD colonoscopy statistically significantly improves sessile serrated adenoma detection rate in the screening of average risk patients during screening colonoscopy. By improving the detection and removal of these lesions, adoption of HD colonoscopy may reduce the significant premalignant burden of sessile serrated adenomas.

Artificial intelligence in inflammatory bowel disease endoscopy: current landscape and the road ahead.

Inflammatory bowel disease is a complex chronic inflammatory disorder with challenges in diagnosis, choosing appropriate therapy, determining individual responsiveness, and prediction of future disease course to guide appropriate management. Artificial intelligence has been examined in the field of inflammatory bowel disease endoscopy with promising data in different domains of inflammatory bowel disease, including diagnosis, assessment of mucosal activity, and prediction of recurrence and complications. Artificial intelligence use during endoscopy could be a step toward precision medicine in inflammatory bowel disease care pathways. We reviewed available data on use of artificial intelligence for diagnosis of inflammatory bowel disease, grading of severity, prediction of recurrence, and dysplasia detection. We examined the potential role of artificial intelligence enhanced endoscopy in various aspects of inflammatory bowel disease care and future perspectives in this review.

Gastrointestinal hemorrhage in the setting of gastrointestinal cancer: Anatomical prevalence, predictors, and interventions.

BACKGROUND: Gastrointestinal hemorrhage (GIH) is a common complication with gastrointestinal cancers (GIC). There is no comprehensive research that examines GIH in different types of GIC. AIM: To study the prevalence, predictors, and interventions of GIH based on the anatomical location of GIC. METHODS: This is a retrospective analysis of the 2016-2018 National Inpatient Sample database, the largest inpatient care database in the United States. All adult inpatients (≥ 18-year-old) were included. ICD-10-CM codes were used to identify patients with GIH and GIC. Prevalence of GIH was obtained based on the anatomical location of GIC. Predictors of GIH in the GIC population were studied using multivariate analysis. Interventions including endoscopy were compared to the non-intervention group to determine the differences in inpatient mortality. RESULTS: Out of a total of 18173885 inpatients, 321622 (1.77%) cases had a diagnosis of GIC. Within GIC patients, 30507 (9.5%) inpatients had GIH, which was significantly (P < 0.001) more than the prevalence of GIH in patients without GIC (3.4%). The highest to lowest GIH rates are listed in the following order: Stomach cancer (15.7%), liver cancer (13.0%), small bowel cancer (12.7%), esophageal cancer (9.1%), colorectal cancer (9.1%), pancreatic cancer (7.2%), bile duct cancer (6.0%), and gallbladder cancer (5.1%). Within gastric cancer, the GIH rate ranged from 14.8% in cardia cancer to 25.5% in fundus cancer. Within small bowel cancers, duodenal cancers had a higher GIH rate (15.6%) than jejunal (11.1%) and ileal cancers (5.7%). Within esophageal cancers, lower third cancers had higher GIH (10.7%) than the middle third (8.0%) or upper third cancers (6.2%). When studying the predictors of GIH in GIC, socioeconomic factors such as minority race and less favorable insurances (Medicaid and self-pay) were associated with significantly higher GIH on multivariate analysis (P < 0.01). Chemotherapy and immunotherapy were also identified to have a lower risk for GIH [odds ratios (OR) = 0.74 (0.72-0.77), P < 0.001]. Out of 30507 GIC inpatients who also had GIH, 16267 (53.3%) underwent an endoscopic procedure, i.e., upper endoscopy or colonoscopy. Inpatient mortality was significantly lower in patients who underwent endoscopy compared to no endoscopy [5.5% vs 14.9%, OR = 0.42 (0.38-0.46), P < 0.001]. CONCLUSION: The prevalence of GIH in patients with GIC varies significantly based on the tumor's anatomical location. Endoscopy, which appears to be associated with a substantial reduction in inpatient mortality, should be offered to GIC patients with GIH. Nevertheless, the decision on intervention in the GIC population should be tailored to individual patient's goals of care, the benefit on overall care, and long-term survival.

Improving immunization strategies in patients with inflammatory bowel disease.

Patients with inflammatory bowel disease (IBD) are susceptible to varieties of opportunistic infections due to immunological changes in the setting of their disease and drug-induced immunosuppression. Even though numerous infections can be prevented by vaccine, vaccination in IBD patients is inadequate. Data showed only 9% were vaccinated against pneumococcal infection and 28% described commonly receiving influenza vaccine. This review article discusses the recent immunizations against influenza virus; pneumococcal infection; human papilloma virus; tetanus, diphtheria and pertussis; measles, mumps and rubella; varicella zoster; and herpes zoster for individuals diagnosed with IBD and those patients with drug-related immunosuppression. In addition, this review discusses concerns about IBD patients planning to travel abroad. Immunization status and screening for opportunistic infection need to be addressed in IBD patients at the time of diagnosis and they should be vaccinated accordingly. Generally, standard vaccination strategies should be pursued in IBD patients, although live vaccines should be avoided while they are not immunocompetent.

Safety and efficacy of fecal microbiota transplant in 9 critically ill patients with severe and complicated Clostridium difficile infection with impending colectomy.

OBJECTIVE: Significant data support the efficacy and safety of fecal microbiota transplant (FMT) in recurrent Clostridium difficile infection (CDI). The objective of our study was to determine the success rate of FMT in patients diagnosed with severe and complicated CDI with impending colectomy in the intensive care setting. METHODS: This was a 2-center study of 9 patients who met the criteria for severe and complicated CDI and had an impending colectomy. All 9 patients had failed conventional antibiotic therapy and were deemed too unstable to undergo a colectomy. Hence, FMT was considered to be the next step in managing their condition. RESULTS: Following FMT there was marked improvement in the patients' clinical status, with the resolution of diarrhea, reduced requirement for vasopressor, and the reduction in abdominal distention and pain. The primary cure rate of our study after a single round of FMT was 78% (7/9). Of the 9 patients 8 (88.88%) avoided a colectomy during the same hospital admission. the CDI-related death rate was 12.5% (1/9) and that of non-CDI was 12.5% (1/9). CONCLUSION: Our success with FMT in fulminant CDI shows that this therapeutic modality is a promising alternative to a colectomy and could be a potential bowel-saving intervention.

Immune checkpoint inhibitor-induced colitis: A comprehensive review.

Immune checkpoint inhibitors (ICIs) are monoclonal antibodies that target down-regulators of the anti-cancer immune response: Cytotoxic T-lymphocyte antigen-4, programmed cell death protein-1, and its ligand programmed death-ligand 1. ICIs have revolutionized the treatment of a variety of malignancies. However, many immune-related adverse events have also been described which mainly occurs as the immune system becomes less suppressed, affecting various organs including the gastrointestinal tract and causing diarrhea and colitis. The incidence of immune-mediated colitis (IMC) ranges from 1%-25% depending on the type of ICI and if used in combination. Endoscopically and histologically there is a significant overlap between IMC and inflammatory bowel disease, however more neutrophilic inflammation without chronic inflammation is usually present in IMC. Corticosteroids are recommended for grade 2 or more severe colitis while holding the immunotherapy. About one third to two thirds of patients are steroid refractory and benefit from infliximab. Recently vedolizumab has been found to be efficacious in steroid and infliximab refractory cases. While in grade 4 colitis, the immunotherapy is permanently discontinued, the decision is controversial in grade 3 colitis.

Role of colonoscopy in diagnosis of capecitabine associated ileitis: Two case reports.

BACKGROUND: Capecitabine is considered a first line agent in adjuvant therapy for breast and colorectal cancer. However, cases of severe diarrhea have been reported with increasing frequency in recent years. When diarrhea is severe and prolonged, capecitabine associated ileitis should be considered as a possible etiology. CASE SUMMARY: Herein, we present two cases of capecitabine ileitis, specifically involving the terminal ileum and ascending colon. We will demonstrate the disease course and treatment modalities applied to alleviate this condition, as well as discuss the merits of using colonoscopy to aid in diagnosis. CONCLUSION: Ultimately our cases demonstrate that symptomatic management with traditional anti-diarrheal medications is largely ineffective. Prompt recognition and discontinuation of capecitabine is an imperative step in proper management of this condition and colonoscopy with biopsy can be helpful when the diagnosis is unclear.

Long-Term Safety and Efficacy of Fecal Microbiota Transplantation in the Treatment of Clostridium difficile Infection in Patients With and Without Inflammatory Bowel Disease: A Tertiary Care Center's Experience.

BACKGROUND: Clostridium difficile infection (CDI) carries a large burden on the national public health with its high morbidity and mortality rates. Patients with inflammatory bowel disease (IBD) are generally at higher risk of infection, recurrence and complications. Therefore, the need for more reliable and safe therapy is necessary. Our study aims to evaluate long-term fecal microbiota transplant (FMT) outcomes in the general population compared to patients with IBD. METHODS: A single center long-term follow-up study was conducted to evaluate the outcomes of FMT in patients with and without IBD. Prior to FMT data including demographics, prior treatment of CDI and severity of symptoms were gathered via chart review. Post FMT, all patients were surveyed after 2 days, 30 days and > 1 year to assess clinical and laboratory response. Our study outcomes included primary cure rate (negative CDI testing > 1 year after single FMT), and secondary cure rate (negative CDI testing > 1 year after repeat FMT or after an additional course of antibiotic with or without repeat FMT). RESULTS: Seventy-eight patients with recurrent or refractory CDI and subsequent FMT treatment were included. Mean age was 57 years, and 69% were females and twenty-one (27%) had IBD. Primary cure rate was achieved in 77% of the cases while secondary cure rate reached 100% at the end of the study. IBD patients were younger with an average age of 47 years, and had more complains of abdominal pain (71%), and required escalation of therapy in 50% of patients. CONCLUSIONS: FMT was effective in the eradication of CDI in patients with and without IBD, but with no significant symptoms improvement in patients with IBD. Future randomized control studies are needed to examine the long-term progression of IBD and quality of life in patients treated with FMT compared to standard therapy of antibiotics for recurrent CDI.

Monitoring inflammatory bowel disease during pregnancy: Current literature and future challenges.

Inflammatory bowel disease has a high prevalence in women of childbearing age and can have a significant impact on pregnancy, from conceiving to carrying the pregnancy. Active disease during pregnancy is known to have negative effects on pregnancy outcomes; therefore, careful monitoring during this period is an important but challenging aspect of care and is crucial as it affects important management decisions. Recent data seems to suggest that endoscopy is a relatively safe procedure during all trimesters of pregnancy. Serum biomarkers such as C-reactive protein and fecal calprotectin are helpful non-invasive markers, but have shown conflicting results for correlation with disease activity in some initial studies. Further work is necessary to establish standard of care monitoring during pregnancy.

Post-endoscopic procedure satisfaction scores: Can we improve?

AIM: To organize post-procedure satisfaction data into a useful reference and analyze patient-centered parameters to find trends that influence patient satisfaction. METHODS: A robust database of two cohorts of outpatients that underwent an endoscopic procedure at Georgetown University Hospital at two separate three-month intervals ranging from November 2012 to January 2013 and November 2015 to January 2016 was compiled. Time of year was identical to control for weather/seasonal issues that may have contributed to the patient experience. The variables recorded included age, sex, body mass index (BMI), type of procedure, indication for procedure, time of the procedure, length of the procedure, type of prep used, endoscopist, satisfactory score, and comments/reasons for score. For continuous variables, differences in averages were tested by two sample t-test, Wilcoxon rank sum test, and ANOVA as appropriate. For categorical variables, differences in proportions between two groups were tested by χ2 test. Correlation test and linear regression analyses were conducted to examine relationships between length of procedure and continuous predictors. A P value < 0.05 used to indicate statistically significant relationship. RESULTS: The primary outcome of this study was to assess if telephone outreach after an endoscopic intervention was a satisfactory method of obtaining post-procedure satisfaction scores from patients at a tertiary care center. With the addition of post-procedure calls, instilled in January 2014, the response rate was 40.5% (508/1256 patients) from a prior completion rate of 3.4% (31/918) with the mail out survey initially. There was a statistically significant improved response rate pre and post intervention with P < 0001. The secondary outcome of this study was to assess if we could use predictive analytics to identify independent predictors of procedure length, such as gender, age, type of procedure, time of procedure, or BMI. The combined pre and post intervention data was used in order to optimize the power to identify independent predictors of procedure length. The total number of patient's data analyzed was 2174. There was no statistically significant difference in procedure length between males and females with P value 0.5282. However, there was a small (1 min), but statistically significant difference (P = 0.0185) in procedure length based on the time of day the procedure took place, with afternoon procedures having a longer duration than morning procedures. The type of procedure was an independent predictor of procedure length as demonstrated with P value < 0.0001. There is a statistically significant correlation between age and procedure length, although it is only a weak relationship with a correlation coefficient < 0.3. Contrary to patient age, BMI did not have a statistically significant correlation with procedure length (P = 0.9993), which was also confirmed by linear regression analysis. CONCLUSION: Our study proves calling patients after endoscopy improves post-procedure satisfaction response rates and changing procedural time allotment based on patient characteristics would not change endoscopic workflow.

Clinicopathologic significance of synchronous and metachronous adenomas in colorectal cancer.

PURPOSE: Colorectal cancers (CRCs) evolve from a multiple-step tumorigenesis and, morphologically, are characterized by adenoma. Colorectal cancers with adenomas have distinct clinical features, including reports of improved survival. It is hypothesized that this survival advantage is related to biologic differences in CRC with adenomas rather than earlier diagnosis or earlier stage of disease presentation. PATIENTS AND METHODS: A retrospective chart review of 569 patients treated from 1983 through 2002 was conducted. Data on age, sex, and survival; CRC stage, location, and recurrence; adenoma number, size, histology, and location; and colonoscopy history were analyzed. RESULTS: The mean patient age was 62 years (range, 17-90 years), and 54% of patients were men. The majority of CRCs were left-sided (67%). The American Joint Committee on Cancer stage distribution was 0/I (12%), II (21%), III (34%), and IV (33%). Colorectal cancer with synchronous adenoma was seen in 33% of cases; overall, CRC with adenoma comprised 42% of cases. The event-free survival and overall survival favored CRC with adenoma. After adjusting for age, disease stage, sex, and total number of colonoscopic examinations, the relative risk for an event was 1.51 (P < 0.003) for patients without adenomas versus those with adenomas. CONCLUSION: Colorectal cancer with adenoma represents a distinct population of patients with CRC. The apparent association seems to confer a survival advantage that is not based on age, sex, or disease stage. The survival benefit, although slightly less dramatic, remained significant even when controlled for the number of colonoscopies.

Ipilimumab associated colitis: an IpiColitis case series at MedStar Georgetown University Hospital.

Although ipilimumab has been shown to improve survival in patients with metastatic melanoma and cause regression of metastatic renal cell carcinoma, the associated immune-related toxicities are of concern. The resultant T cell activation by this monoclonal antibody causes an increased immune response, which has been associated with many immune-regulated adverse effects. One of the most concerning effects is the development of colitis. Upwards to 8% of patients have been reported to develop colitis, with 5% being severe (Grades 3-4). While initial treatment of such adverse effects is generally comprised of supportive and symptomatic treatment, more severe cases warrant the use of high dose steroids. Furthermore, use of anti-TNF agents is usually reserved for those cases that prove to be refractory to steroids. We describe a systematic case review of seven patients who developed gastrointestinal symptoms following initiation of ipilimumab immunotherapy, and present the steps in their evaluation, treatment and outcomes at our institution.

Diagnosis and management of common gastrointestinal tract infectious diseases in ulcerative colitis and Crohn's disease patients.

Management of inflammatory bowel disease (IBD), including ulcerative colitis and Crohn's disease, stretches beyond control of flares. Some infections of the gastrointestinal tract are more commonly seen in patients with IBD. Work from the Human Microbiome Project has been instrumental in our understanding of the interplay between the vast gut microbiota and host immune responses. Patients with IBD may be more prone to infectious complications based on their underlying inflammatory disease and variations in their microbiome. Immunosuppressant medications commonly used to treat patients with Crohn's and colitis also play a role in predisposing these patients to acquire these infections. Here, we present a detailed review of the data focusing on the most common infections of the gastrointestinal tract in patients with IBD: Clostridium difficile infections (CDI) and cytomegalovirus (CMV). We will discuss appropriate diagnostic tools and treatment options for these infections. Other less common infections will also be reviewed briefly. Studying the various infections of the gastrointestinal tract in these patients could enhance our understanding of the pathophysiology of IBD.