The colitis may be microscopic, but the diarrhea is not: update on the treatment of microscopic colitis and immune checkpoint inhibitor colitis.

PURPOSE OF REVIEW: Microscopic colitis is an inflammatory disease of the colon that presents as watery diarrhea with minimal to normal endoscopic changes on colonoscopy. It encompasses two common subtypes, lymphocytic colitis and collagenous colitis, which are both treated similarly.Immune checkpoint inhibitor colitis is among the most common immune-related adverse events. Endoscopic and histological findings range from normal colonic mucosa to inflammatory bowel like changes. This review article provides update in treatment and management of microscopic colitis and immune checkpoint inhibitor colitis (ICPi colitis). RECENT FINDINGS: Recent studies on microscopic colitis have focused on the successful use of immunomodulators such as biologics for treatment of budesonide refractory microscopic colitis cases. Microscopic colitis does not confer an added risk for colorectal cancer.With the increasing usage of immunotherapy agents, immune checkpoint inhibitor colitis is becoming more common. ICPi colitis can be successfully managed with steroids, with treatment stepped up to biologics for moderate to severe cases or for mild cases that do not respond to steroids. Immunotherapy agents can be carefully re-introduced in mild cases, after treatment of ICPi colitis. SUMMARY: Biologics can be used to treat budesonide refractory microscopic colitis. ICPi colitis can be managed with steroids and biologics in moderate to severe cases.

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.

Bile Acid Sequestrant Therapy in Microscopic Colitis.

GOALS: There is an unmet need in investigating corticosteroid-sparing treatments for induction and maintenance of remission in microscopic colitis (MC). The authors' aim was to evaluate the outcomes of patients with MC treated with bile acid sequestrants (BAS). BACKGROUND: MC is a common chronic diarrheal illness. Budesonide is effective induction therapy, but relapses are high after cessation of treatment. STUDY: Our cohort consisted of patients enrolled in our institutional MC registry, a biorepository of histology-confirmed diagnoses of MC. Patients receiving BAS for the treatment of MC were reviewed at each clinical visit for efficacy or ability to decrease budesonide maintenance dosing. RESULTS: The authors included 79 patients (29 collagenous colitis and 50 lymphocytic colitis) with a median follow-up period of 35 months (range, 1 to 120). Most patients were female individuals (78%) and the median age was 69 years (range, 29 to 87). BAS therapy was used in 21 patients who were budesonide-naive, with a response rate of 76% (16/21). In patients treated previously with budesonide, 46 patients were budesonide-dependent and given BAS as maintenance therapy. Of these patients, 23 (50%) were able to decrease their budesonide dosing and 9 (20%) were able to stop budesonide completely. Seven of 46 patients (15%) stopped BAS because of intolerance, perceived lack of benefit, or treatment of concomitant diarrhea illness. CONCLUSIONS: BAS may be an effective corticosteroid-sparing option in the treatment of MC and should be considered after budesonide induction. Larger controlled studies are needed to confirm the efficacy for long-term maintenance and tolerability of BAS in patients with MC.

Nonsteroidal anti-inflammatory drug exposure and the risk of microscopic colitis.

BACKGROUND: Medication consumption has been suggested as a risk factor for microscopic colitis (MC), but studies of varying design have yielded inconsistent results. Our aim was to evaluate the association between medications and MC. METHODS: A hybrid cohort of prospectively identified patients undergoing colonoscopy with biopsies for suspicion of MC (N = 144) and patients with MC enrolled within three months of diagnosis into an MC registry (N = 59) were surveyed on medication use. Medication use was compared between patients with and without diagnosis of MC by chi-squared test and binomial logistic regression adjusted for known risk factors of MC: age and gender. RESULTS: In total, 80 patients with MC (21 new, 59 registry) were enrolled. Patients with MC were more likely to be older (p = 0.03) and female (p = 0.01) compared to those without MC. Aspirin and other non-steroidal anti-inflammatory drugs were more commonly used among patients who developed MC (p < 0.01). After controlling for age and gender, these medications remained independent predictors of MC with odds ratio for any non-steroidal anti-inflammatory drug use of 3.04 (95% CI: 1.65-5.69). No association between MC and other previously implicated medications including proton pump inhibitors and selective serotonin reuptake inhibitors was found. CONCLUSIONS: In this cohort of patients with chronic diarrhea, we found use of aspirin and non-steroidal anti-inflammatory drugs, but not other implicated medications to be associated with the development of MC. Whether these drugs trigger colonic inflammation in predisposed hosts or worsen diarrhea in undiagnosed patients is unclear. However, we feel that these findings are sufficient to discuss potential non-steroidal anti-inflammatory drug cessation in patients newly diagnosed with MC.

Polygenic risk score is a predictor of adenomatous polyps at screening colonoscopy.

BACKGROUND: Single nucleotide polymorphism (SNP)-based polygenic risk scoring is predictive of colorectal cancer (CRC) risk. However, few studies have investigated the association of genetic risk score (GRS) with detection of adenomatous polyps at screening colonoscopy. METHODS: We randomly selected 1769 Caucasian subjects who underwent screening colonoscopy from the Genomic Health Initiative (GHI), a biobank of NorthShore University HealthSystem. Outcomes from initial screening colonoscopy were recorded. Twenty-two CRC risk-associated SNPs were obtained from the Affymetrix™ SNP array and used to calculate an odds ratio (OR)-weighted and population-standardized GRS. Subjects with GRS of < 0.5, 0.5-1.5, and > 1.5 were categorized as low, average and elevated risk. RESULTS: Among 1,769 subjects, 520 (29%) had 1 or more adenomatous polyps. GRS was significantly higher in subjects with adenomatous polyps than those without; mean (95% confidence interval) was 1.02 (1.00-1.05) and 0.97 (0.95-0.99), respectively, p < 0.001. The association remained significant after adjusting for age, gender, body mass index, and family history, p < 0.001. The detection rate of adenomatous polyps was 10.8%, 29.0% and 39.7% in subjects with low, average and elevated GRS, respectively, p-trend < 0.001. Higher GRS was also associated with early age diagnosis of adenomatous polyps, p < 0.001. In contrast, positive family history was not associated with risk and age of adenomatous polyps. CONCLUSIONS: GRS was significantly associated with adenomatous polyps in subjects undergoing screening colonoscopy. This result may help in stratifying average risk patients and facilitating personalized colonoscopy screening strategies.

Screening Colonoscopy Withdrawal Time Threshold for Adequate Proximal Serrated Polyp Detection Rate.

INTRODUCTION: For adequate adenoma detection rate (ADR), guidelines recommend a mean withdrawal time (MWT) of ≥ 6 min. ADR has been shown to correlate strongly with proximal serrated polyp detection rate (PSP-DR), which is another suggested quality measure for screening colonoscopy. However, the impact of directly measured withdrawal time on PSP-DR has not been rigorously studied. We examined the relationship between MWT to ADR and PSP-DR, with the aim of identifying a functional threshold withdrawal time associated with both increased ADR and PSP-DR. METHODS: This was a retrospective study of endoscopy and pathology data from average-risk screening colonoscopy examinations performed at a large system with six endoscopy laboratories. A natural language processing tool was used to determine polyp location and histology. ADR and PSP-DR were calculated for each endoscopist. MWT was calculated from colonoscopy examinations in which no polyps were resected. RESULTS: In total, 31,558 colonoscopy examinations were performed, of which 10,196 were average-risk screening colonoscopy examinations with cecal intubation and adequate prep by 24 gastroenterologists. When assessing the statistical significance of increasing MWT by minute, the first significant time mark for PSP-DR was at 11 min at a rate of 14.2% (p = 0.01). There was a significant difference comparing aggregated MWT < 11 min compared to ≥ 11 min looking at the rates of adenomas [OR 1.65 (1.09-2.51)] and proximal serrated polyps [OR 1.81 (1.06-3.08)]. While ADR linearly correlated well with MWT (R = 0.76, p < 0.001), the linear relationship with PSP-DR was less robust (R = 0.42, p = 0.043). CONCLUSION: In this large cohort of average-risk screening colonoscopy, a MWT of 11 min resulted in a statistically significant increase in both ADR and PSP-DR. Our data suggest that a longer withdrawal time may be required to meet both quality metrics.

Decreased colorectal cancer and adenoma risk in patients with microscopic colitis.

INTRODUCTION: Microscopic colitis is currently considered to harbor no increased risk for colorectal cancer, based on a few small studies with limited long-term follow-up. Our aim was to identify patients with microscopic colitis, and to compare long-term rates of colorectal cancer or adenoma to a control group of patients without microscopic colitis. METHODS: We reviewed the records of patients diagnosed with microscopic colitis, as identified by a hospital-based pathology database from January 2000 to August 2008. Clinical factors, including history of adenoma or adenocarcinoma, and all colonoscopy findings, were recorded. Age and gender-matched patients without microscopic colitis served as the control in a 1:1 fashion. RESULTS: A total of 647 patients (153 male: 494 female) were identified with microscopic colitis (MC). Any history of colorectal cancer was detected in 1.92, 1.81, and 4.17% of patients with collagenous colitis (CC), lymphocytic colitis (LC), and controls, respectively (P = 0.095, P = 0.040, P = 0.015 for CC, LC, and all MC, respectively, comparing to controls). Overall, covariate-adjusted risk (odds ratio) of any history of colorectal cancer and colorectal adenoma in MC patients was 0.34 (95% confidence interval [CI] 0.16-0.73, P = 0.006) and 0.52 (95% CI 0.50-0.76, P < 0.0001), respectively. The mean duration of follow-up was 4.63 years, with 147/647 (22.7%) of patients with clinical follow-up >7 years. CONCLUSIONS: In this case-control study involving a large retrospective cohort, microscopic colitis is negatively associated with the risk for colorectal cancer and adenoma. Further studies are required to determine a temporal relationship between microscopic colitis and the future development of colorectal neoplasia.

Review of the microscopic colitides.

Microscopic colitis is a common cause of chronic diarrhea in predominantly older adults. Incidence rates of microscopic colitis (including lymphocytic and collagenous colitis) have increased over time to levels comparable to other forms of inflammatory bowel disease. The possibility of drug-induced microscopic colitis is an important consideration when evaluating these patients, although this concept requires further investigation. There are few controlled treatment trials in microscopic colitis, with much of the data on treatment coming from retrospective studies. In patients with microscopic colitis, a systematic approach to therapy often leads to satisfactory control of symptoms. In this review, we will provide an updated assessment of the epidemiology, diagnosis, and treatment of microscopic colitis.

Microbiota-based Therapies Clostridioides difficile infection that is refractory to antibiotic therapy.

Clostridioides difficile infection (CDI) has had a devastating impact worldwide with significant rates of mortality, especially among the elderly. Despite effective antibiotics, the incidence of recurrent CDI (rCDI) is increasing and more difficult to treat with antibiotics alone. Fecal Microbiota Transplantation (FMT) has emerged as a consistently effective treatment for rCDI. Mechanisms for FMT are not entirely understood, but remain an area of active investigation. There have been recent safety reports with the use of FMT regarding transmission of pathogens in a few patients that have led to serious illness. With appropriate screening, FMT can be safely administered and continue to have a significant impact on eradication of rCDI and improve the lives of patients suffering from this disease. In this review, we summarize current treatments for CDI with a focus on microbiota-based therapies used for antibiotic refractory disease.

An audit of inpatient stool ova and parasite (O&P) testing in a multi-hospital health system.

BACKGROUND & OBJECTIVES: Stool ova and parasite (O&P) examinations are routinely ordered initial tests in patients admitted to the hospital with acute diarrhea, despite low test positivity rates. We examined the diagnostic yield of inpatient stool O&P exams and identified risk factors associated with positive tests. METHODS: A retrospective, case-control analysis of inpatients admitted with diarrhea, who underwent O&P examination, was conducted. Clinical and demographic variables of cases were compared with age-and gender-matched controls via uni- and multivariate conditional logistic regression analyses. RESULTS: The yield of inpatient O&P exams was 2.15% (37/1723). Blastocystisspp. represented the most common parasites. All patients with positive tests, excluding Blastocystisspp., had at least one of the following risk factors: smoking, prior parasitic disease, HIV-positive status, travel to an endemic area, and institutionalization. CONCLUSIONS: Superfluous inpatient stool O&P exams confer a financial and labor burden to hospital systems. Stool O&P exams should be restricted to individuals admitted to the hospital for <3 days, having diarrhea >7 days and possessing at least one of the following risk factors: smoking, prior parasitic disease, HIV-positive status, travel to an endemic area, and institutionalization. Such selective testing can confer a 51% reduction in testing, costs, and labor.

Cost-effectiveness of 5-aminosalicylic acid therapy for maintenance of remission in ulcerative colitis.

OBJECTIVES: Oral 5-aminosalicylic acid (5-ASA, mesalamine) is effective in inducing and maintaining remission in ulcerative colitis (UC). The relative benefits and costs of maintenance 5-ASA therapy are uncertain. Our aims were to evaluate this strategy's potential cost-effectiveness. METHODS: We constructed a Markov model to compare two strategies over 2 yr: (a) no maintenance 5-ASA, with 5-ASA 4.8 g/day given for flares, (b) maintenance 5-ASA 2.4 g/day, escalated and maintained at 4.8 g/day after the first flare. In both arms, the failure to induce remission led to other treatments, as needed: prednisone, parenteral corticosteroids, cyclosporine, 6-mercaptopurine, infliximab, and colectomy. RESULTS: Without maintenance 5-ASA, the mean flares per person were 1.92, and the mean cost per person was $3,402. With maintenance 5-ASA providing a relative risk of flare of 0.7 at 5-ASA cost of $198/month, flares per person decreased to 1.38 at a cost of $8,810/flare prevented. Maintenance 5-ASA increased discounted quality-adjusted life-years per person (QALYs per person) from 1.75 to 1.77 at a discounted cost of $224,000/QALY gained. The results were most sensitive to the flare risk reduction and cost of 5-ASA, the utilities of being in remission without or with 5-ASA, and the colectomy rates. At $15/month (the cost of sulfasalazine), maintenance 5-ASA cost $640/flare prevented and $16,300/QALY gained. CONCLUSION: Maintenance 5-ASA therapy decreases UC flares, but its cost may be substantial, depending on society's willingness to pay. If sulfasalazine can be tolerated and yields comparable benefits, sulfasalazine maintenance therapy is likely to be cost-effective. The cost per QALY gained by 5-ASA maintenance is highly dependent on the quality of life while taking versus not taking maintenance 5-ASA, highlighting the importance of patients' preferences.

Prevalence, Pathogenesis, Diagnosis, and Management of Microscopic Colitis.

Microscopic colitis (MC), which is comprised of lymphocytic colitis and collagenous colitis, is a clinicopathological diagnosis that is commonly encountered in clinical practice during the evaluation and management of chronic diarrhea. With an incidence approaching the incidence of inflammatory bowel disease, physician awareness is necessary, as diagnostic delays result in a poor quality of life and increased health care costs. The physician faces multiple challenges in the diagnosis and management of MC, as these patients frequently relapse after successful treatment. This review article outlines the risk factors associated with MC, the clinical presentation, diagnosis and histologic findings, as well as a proposed treatment algorithm. Prospective studies are required to better understand the natural history and to develop validated histologic endpoints that may be used as end points in future clinical trials and serve to guide patient management.

Rectal Optical Markers for In Vivo Risk Stratification of Premalignant Colorectal Lesions.

PURPOSE: Colorectal cancer remains the second leading cause of cancer deaths in the United States despite being eminently preventable by colonoscopy via removal of premalignant adenomas. In order to more effectively reduce colorectal cancer mortality, improved screening paradigms are needed. Our group pioneered the use of low-coherence enhanced backscattering (LEBS) spectroscopy to detect the presence of adenomas throughout the colon via optical interrogation of the rectal mucosa. In a previous ex vivo biopsy study of 219 patients, LEBS demonstrated excellent diagnostic potential with 89.5% accuracy for advanced adenomas. The objective of the current cross-sectional study is to assess the viability of rectal LEBS in vivo. EXPERIMENTAL DESIGN: Measurements from 619 patients were taken using a minimally invasive 3.4-mm diameter LEBS probe introduced into the rectum via anoscope or direct insertion, requiring approximately 1 minute from probe insertion to withdrawal. The diagnostic LEBS marker was formed as a logistic regression of the optical reduced scattering coefficient [Formula: see text] and mass density distribution factor D. RESULTS: The rectal LEBS marker was significantly altered in patients harboring advanced adenomas and multiple non-advanced adenomas throughout the colon. Blinded and cross-validated test performance characteristics showed 88% sensitivity to advanced adenomas, 71% sensitivity to multiple non-advanced adenomas, and 72% specificity in the validation set. CONCLUSIONS: We demonstrate the viability of in vivo LEBS measurement of histologically normal rectal mucosa to predict the presence of clinically relevant adenomas throughout the colon. The current work represents the next step in the development of rectal LEBS as a tool for colorectal cancer risk stratification.

Non-IBD colitides (eosinophilic, microscopic).

Microscopic colitis includes the terms lymphocytic colitis and collagenous colitis, and is a common cause of chronic diarrhoea in older adults. The incidence of microscopic colitis has increased over time and has reached levels comparable to other forms of inflammatory bowel disease. In this chapter, an updated review on the epidemiology, diagnosis and treatment of microscopic colitis has been provided. There is limited data available about eosinophilic colitis, which is the least common of the eosinophilic GI disorders. It is important to rule out the secondary causes of colonic eosinophilia in patients with suspected eosinophilic colitis.

Current and past cigarette smoking significantly increase risk for microscopic colitis.

BACKGROUND: Cigarette smoking is an important environmental factor affecting inflammatory bowel disease. The role of smoking has not been rigorously studied in microscopic colitis (MC). The aim of this study was to compare the association of cigarette smoking in individuals with MC compared to a control population without MC. METHODS: We reviewed the records of patients with a clinical and histologic diagnosis of collagenous colitis (CC) or lymphocytic colitis (LC). Clinical history, including alcohol and smoking status at the time of diagnosis of MC, were reviewed. In this case-control study, age- and gender-matched patients without diarrhea presenting for outpatient colonoscopy served as the control population. RESULTS: We analyzed a total of 340 patients with MC: 124 with CC and 216 with LC. Overall, any smoking status (former or current) was associated with MC (odds ratio [OR] 2.12, 95% confidence interval [CI]: 1.56-2.88). This risk was more prominent in current smokers (adjusted OR 5.36, 3.81, and 4.37 for CC, LC, and all MC, respectively, 95% CI all greater than 1). The association of smoking was not significantly affected by gender or average alcohol consumption. CONCLUSIONS: In our study population, cigarette smoking is a risk factor for the development of both forms of microscopic colitis. There were no significant differences between LC and CC, and current smoking and the development of microscopic colitis affected men and women similarly. We feel that these data are sufficient to discuss the potential risks of tobacco use in patients with microscopic colitis.

Colonoscopic treatment of acute diverticular hemorrhage using endoclips.

Although colonoscopy is used in the diagnostic evaluation of patients with diverticular hemorrhage, data on colonoscopic treatment outcomes are limited. We reviewed records of inpatients undergoing colonoscopy to identify patients that were colonoscopically diagnosed and treated for acute diverticular hemorrhage. Eleven patients with acute diverticular hemorrhage had active bleeding (n = 7) or non-bleeding visible vessel (n = 4) at colonoscopy. Endoclip treatment (preceded by epinephrine injection in 64%) achieved hemostasis in all patients without procedural complications. Patients were discharged within three days without evidence of early rebleeding. During a median follow-up of 15 months, late recurrent bleeding occurred in two patients (18.2%). Colonoscopic treatment of patients with acute diverticular hemorrhage using endoclips appears to be effective and safe, with high rates of immediate and long-term success. Colonoscopy should be considered in patients with suspected acute diverticular hemorrhage, as it may enable definitive therapy without the need for more invasive treatment.

Cost-effectiveness of extending Medicare coverage of immunosuppressive medications to the life of a kidney transplant.

Unless they maintain Medicare status through disability or age, kidney transplant recipients lose their Medicare coverage of immunosuppression 3 years after transplantation. A significant transplant survival advantage has previously been demonstrated by the extension of Medicare immunosuppressive medication coverage from 1 year to 3 years, which occurred between 1993 and 1995. The United States Renal Data System (USRDS) was analyzed for recipients of kidney transplants from 1995 to 1999. Using a Markov model, we estimated survival and costs of the current system of 3-year coverage compared with lifetime immunosuppression coverage. Results were calculated from the perspectives of society and Medicare. Extension of immunosuppression coverage produced an expected improvement from 38.6% to 47.6% in graft survival and from 55.4% to 61.8% in patient survival. The annualized expected savings to society from lifetime coverage was $136 million assuming current rates of transplantation. Medicare would break-even compared with current coverage if the fraction of patients using extended coverage was <32%. The extension would be cost-effective to Medicare if this fraction was <91%. Extended Medicare immunosuppression coverage to the life of a kidney transplant should result in better transplant and economic outcomes, and should be considered by policy makers.