Immune checkpoint inhibitor-induced colitis:A comprehensive review

Immune checkpoint inhibitors(ICIs) are monoclonal antibodies that target downregulators 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.

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.

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.

Ipilimumab associated colitis: An Ipi Colitis case series at Med Star 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.

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 χ~2 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.

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.

Tofacitinib for the treatment of ulcerative colitis: A review of the literature

Ulcerative colitis (UC) is a chronic immune-mediated inflammatory condition affecting the colon. Recently, tofacitinib, an oral small molecule that is an inhibitor of the Janus kinase signal transduction pathway, was proven efficacious for inducing and maintaining remission in adult patients with moderate to severe UC in three global Phase III studies. The purpose of this review is to summarize existing data on the efficacy, safety, and quality of life issues related to use tofacitinib as well as highlight recent real-world experience with this drug among patients with UC.