Endoscopic Relapse Research Articles

Value of histological activity in predicting endoscopic relapse among patients of ulcerative colitis in endoscopic remission

Objective: To investigate the value of histological evaluation in predicting endoscopic relapse among patients with ulcerative colitis (UC) who were in endoscopic remission, and to compare the usefulness of various histological scoring systems. Methods: Histological sections from 61 patients with UC who were in endoscopic remission were retrospectively analyzed, at Peking University Third Hospital, Beijing, China from January 2015 to June 2021. They were subdivided into endoscopic persistent remission group (remission group, n=31, Mayo endoscopic score 0) and endoscopic relapse group (relapse group, n=30, Mayo endoscopic score≥1) according to the results of the first endoscopic reexamination after the biopsy. Histological evaluation was performed using the Geboes score (GS) and its simplified version (SGS), the Nancy index (NI) and the Robarts histopathological index (RHI). The median and maximum histological scores for each case in all biopsies were recorded. Univariate comparisons were performed using chi-squares and multivariate analysis using binary logistic regression. The values of four histological evaluation systems for predicting endoscopic relapse among UC patients in endoscopic remission were analyzed using receiver operating characteristic (ROC) curves. Results: Significant differences were observed between the remission and relapse groups. The differences were more pronounced in the maximum histological scores; the mean and highest results of area under the ROC curve scores (AUC) for GS, SGS, NI, and RHI were 0.657, 0.668, 0.682, 0.691, and 0.866, 0.863, 0.864, 0.869, respectively. The differences were statistically significant (P<0.05). The corresponding best cut-offs were GS≥2B.1, SGS≥2B.1, NI≥2, and RHI≥2.5, respectively, which meant mild active inflammation histologically, while there was no statistical difference of AUC among the four histological scoring indices (P>0.05). Univariate and multivariate analyses revealed statistically significant differences in the number of neutrophils in the epithelium and lamina propria (P<0.05). Conclusions: Biopsies from UC patients in endoscopic remission may still have histological active inflammation which appears to correlate with endoscopic relapse. Four commonly used histological scoring systems can be used to assess the risk of endoscopic relapse among UC patients in endoscopic remission. The patients who more likely have endoscopic relapse seem to have a histological score greater than the cut-off value (i.e., mild histological activity). The maximum histological scores can accurately predict the risk of endoscopic relapse, while the presence of epithelial and laminar propria neutrophil infiltrates can independently predict the endoscopic relapse in these patients. Considering the utility and convenience in routine practice, NI is recommended for evaluating histological inflammatory activity.

Pan-enteric Capsule Endoscopy to Characterize Crohn's Disease Phenotypes and Predict Clinical Outcomes in Children and Adults: The Bomiro Study.

Pan-enteric capsule endoscopy (PCE) provides useful information for the management of Crohn's disease (CD), especially in children. No study has evaluated the ability of PCE to characterize CD phenotypes and outcomes in children and adults. In a prospective multicenter observational study, we recruited patients with CD >6 years from 4 centers in Italy. Patients underwent clinical, biomarker assessment and PCE. Lesions were graded using the PCE system. For each segment, the most common lesion (MCL), the most severe lesion (MSL), and the extent of involvement were defined. Disease severity, extent, and clinical outcomes were compared between children and adults. A logistic regression analysis was used to identify predictive factors for negative outcomes in both age groups. One hundred ninety-four consecutive patients (adults/children: 144/50) were evaluated for a total of 249 procedures. Children were more likely to have extensive disease, particularly in the colon. Higher MCL scores were independently associated with treatment escalation (odds ratio [OR], 4.09; 95% CI, 1.80-9.25; P = .001), while >30% disease extent was more indicative of clinical and endoscopic relapse (OR, 2.98; 1.26-7.08; P = .013). Disease extent was the only factor associated with endoscopic recurrence in children (OR, 4.50; 95% CI, 1.47-13.77; P = .008), while severe lesions in adults provided a better predictor of treatment escalation (OR, 4.31; 95% CI, 1.52-12.1; P = .006). Postexamination, PCE contributed to a change of therapy in 196/249 (79%) of the procedures. PCE allowed the characterization of CD phenotypes in children and adults by assessing disease severity and extent, which are of different importance in predicting clinical outcomes in these age groups.

P756 Efficacy and safety of medical therapies for maintenance of surgically induced remission in Crohn’s disease: A systematic review and network meta-analysis

Abstract Background Approximately half of patients with Crohn’s disease (CD) undergo surgical resection in first decade after diagnosis. Majority experience disease recurrence following surgery requiring further intervention. There is limited evidence on efficacy of medical therapies in this setting. We performed a network meta-analysis to evaluate comparative efficacies of medical therapies for the prevention of clinical and endoscopic relapse after surgical resection. Methods We searched MEDLINE, Embase, and Cochrane Central Register of Controlled Trials between inception and October 2023 for randomised controlled trials (RCTs). Outcomes assessed were clinical relapse, endoscopic relapse, and safety outcomes including adverse events (AE), withdrawal due to AE, and serious AE. We performed random-effects network meta- analysis using a frequentist approach, and estimated relative risk (RRs), 95% CI values and used GRADE to ascertain certainty of evidence. Results A total of 37 RCTs comprising 4411 patients were included. On network meta-analysis of clinical relapse outcome, there was moderate certainty of evidence favouring adalimumab (RR 0.14, 95% CI [0.03-0.7]) over placebo with number needed to treat (NNT) of 3. There was low certainty of evidence supporting 5-amainosalycilates (RR 0.81, 95% CI [0.71-0.92]; NNT of 13) and purine analogues (RR 0.82, 95% CI [0.72-0.93]; NNT of 14) but the effect size was trivial (Figure 1). Whereas for endoscopic relapse outcome, vedolizumab (RR 0.23, 95% CI [0.07-0.8]) and adalimumab (RR 0.32, 95% CI [0.17-0.62], low certainty) and infliximab (RR 0.63, 95% CI [0.48-0.82], low certainty) were the only agents superior to placebo but not purine analogues (RR 0.87, 95% CI [0.7-1.08], very low certainty), 5-ASA (RR 1.04, 95% CI [0.85-1.26], very low certainty), antibiotics (RR 1.13, 95% CI [0.83-1.53], very low certainty), probiotics (RR 1.15, 95% CI [0.94-1.39], very low certainty), vitamin-D (RR 0.9, 95% CI [0.62-1.31], very low certainty) and curcumin (RR 1.17, 95% CI [0.73-1.87], low certainty). On analysis of total adverse events outcomes, all therapies were safe. Conclusion On network meta-analysis, adalimumab had a large magnitude of effect size for preventing clinical and endoscopic relapse (low certainty), vedolizumab a large magnitude for preventing endoscopic relapse (low certainty) and 5-ASA a small magnitude result for preventing clinical relapse (low certainty). Overall certainty of evidence is very low to low suggesting need for further research in this field.

P577 Histological Remission Leads to Less Endoscopic Flare-up in Moderate-to-Severe, Biologics Experienced Ulcerative Colitis Patients: A Comprehensive Retrospective Cohort Study

Abstract Background In the management of inflammatory bowel disease (IBD), adopting a treat-to-target strategy has proven beneficial. Current therapeutic targets primarily focus on achieving endoscopic remission. However, the significance of histological remission as a potential target. However, it remains underexplored in Asian populations. We aimed to investigate the role of histological remission in clinical outcomes among ulcerative colitis (UC) patients already in endoscopic remission. Methods In this retrospective cohort study, we enrolled moderate to severe, biologics experienced UC patients with endoscopic remission, defined as endoscopic Mayo subscore 0 point during June 2017 and September 2023 in Chang Gung Memorial Hospital, Linkou. Then the patients were divided into histological remission (HR) and non-histological remission (non-HR) groups according to histological Nancy index (NI). HR was defined as NI 0 point, and others belonged to non-HR group. Comparative analyses were performed between two groups regarding baseline characteristics, one year follow up and end of follow-up clinical outcomes. The location of biopsy was active inflammatory lesion, if no active lesion, we performed routine biopsy over rectum, 15cm level from anal verge. We took at least 4 pieces biopsy over each location. Results We enrolled 42 moderate-to-severe, biologics experienced UC patients (HR group, 23 patients and non-HR group, 19 patients) with endoscopic remission. The average follow-up duration was 17.6 months. In non-HR group, NI scores were categorized as follows: 1 point (42.1%), 2 points (31.6%), 3 points (21.1%), and 4 points (5.3%). Baseline characteristics showed no significant differences between the two groups. In terms of outcomes, the HR group demonstrated a significantly lower endoscopic relapse rate (26.1% vs. 68.4%, P=0.006) and better results in Kaplan-Meier survival analysis (log-rank P=0.015) at the end of the follow-up period. The HR group also exhibited a reduction in clinical relapses, emergency department visits, and hospital admissions. Although these differences did not attain statistical significance, this phenomenon is likely attributable to the study's constrained sample size. Conclusion In moderate-to-severe UC patients who are biologics-experienced and in endoscopic remission, achieving histological remission is associated with a reduced rate of endoscopic relapse.

The use of calgranulin-C (S100A12) and fecal zonulin as possible non-invasive markers in children with inflammatory bowel disease: a clinical study.

Our data suggest that f-S100A12 and FC are both useful non-invasive biomarkers in the management of pediatric IBD in follow up and in monitoring endoscopic and clinical relapse. • Fecal calprotectin (FC), fecal S100A12 (f- S100A12), and fecal zonulin represent potential noninvasive markers of gut inflammation. • Since S100A12 is predominantly expressed by granulocytes, high levels of f-S100A12 should be more specific for inflammation than FC. • FC and f-S100A12 were correlated to each other and despite the lack of correlation with disease location, they were associated with endoscopic inflammation and clinical relapse in children with IBD. • No significant correlations were found between f-zonulin and the inflammatory parameters.

Clinical significance and long-term prognosis of ulcerative colitis patients with appendiceal orifice inflammation

BackgroundAppendiceal orifice inflammation (AOI) or peri-appendiceal red patch is a skip lesion with segments of continuous colitis from the rectum. Frequently observed in ulcerative colitis (UC) patients, this lesion might be associated with proximal extension in some studies. However, the clinical significance of this lesion and long-term outcomes including therapy remain unclear. Thus, the aim of this study was to evaluate the clinical implication of AOI during long-term periods in patients with UC.MethodsWe retrospectively reviewed 376 patients with UC who performed complete colonoscopic examinations between April 2000 and December 2020. We compared clinical characteristics and outcomes of patients manifesting AOI with those who did not show AOI during a mean follow-up period of 66.1 months. Long-term outcomes included maximal extent of colitis, proximal extension, therapeutic medical histories, UC-related hospitalization, and relapse.ResultsNinety-eight (26.1%) patients showed AOI without evidence of inflammation in the right colon. Mild disease activity at the diagnosis of UC was more included in patients with AOI than in those without AOI. Other baseline characteristics including disease extent, smoking history, external intestinal manifestation, and terminal ileal ulceration were not significantly different between the two groups. During follow-up periods, patients with and without AOI showed no significant difference in proximal extension, Mayo endoscopic score at the last endoscopic examination, UC-related hospitalization, or relapse. Of medication history, patients with AOI were less included in the group treated with high-dose aminosalicylates than those without AOI. However, therapeutic histories of steroids, immunosuppressive agents, and biologics were not significantly different. Of 62 patients with AOI who underwent follow-up colonoscopy, 36 (58.1%) showed resolution of AOI. Clinical outcomes of the resolution group were not different than those of the non-resolution group. Biopsy results of 77 patients with AOI showed chronic active or erosive colitis.ConclusionsLong-term outcomes of UC patients with AOI were not different from those without AOI. Outcomes of resolution and non-resolution groups of AOI patients were not different either. Thus, AOI might have no prognostic implication in distal UC patients.

Serum calprotectin is useful to confirm inflammatory bowel disease activity but not to predict relapse

Serum calprotectin (SC), a novel biomarker of inflammatory bowel diseases (IBD), has been recently investigated with conflicting results. The purpose of this study was to assess the ability of SC to predict relapse in IBD patients treated by biologic therapies, and to evaluate the correlation between SC, clinical and endoscopic relapse and other biomarkers as fecal calprotectin (FC) and C-reactive protein (CRP).

Infliximab trough level combined with inflammatory biomarkers predict long-term endoscopic outcomes in Crohn's disease under infliximab therapy.

BACKGROUNDInfliximab trough level (ITL) severely affects therapeutic outcomes of Crohn’s disease (CD) patients under infliximab (IFX). Recently, frontier research has focused on identifying ITL based on different therapeutic targets. Although previous studies have elaborated clinical value of ITL monitoring on short-term outcomes in CD patients during therapy, studies contraposing the predictive value of ITL on long-term endoscopic outcomes in CD patients are still scarce domestically and overseas. AIMTo explore the predictive value of ITL in combination with inflammatory biomarkers on long-term endoscopic outcomes in CD with clinical remission during IFX maintenance therapy.METHODSCD patients with endoscopic remission under long-term IFX maintenance therapy in the First Affiliated Hospital of Zhejiang Chinese Medicine University from January 2012 to December 2020 were collected. ITL and inflammatory biomarkers were continuously monitored during the therapy. The Step I study was conducted from weeks 14 to 54 of IFX treatment. The Step II study was conducted from weeks 54 to 108 of IFX treatment. Endoscopic outcomes were defined as endoscopic activity (Crohn’s disease endoscopic index of severity score > 2 points or Rutgeerts score > i1) and endoscopic remission (Crohn’s disease endoscopic index of severity score ≤ 2 points or Rutgeerts ≤ i1). Endoscopic relapse free survival was defined as endoscopic remission at the beginning of the study stage and maintaining endoscopic remission during the study stage.RESULTSAt week 14, low ITL [odds ratio (OR) = 0.666, 95% confidence interval (CI): 0.514-0.862, P < 0.01] and high fecal calprotectin (FCP) level (OR = 1.002, 95%CI: 1.001-1.004, P < 0.01) increased the risk of endoscopic activity at week 54. At week 54, low ITL (OR = 0.466, 95%CI: 0.247-0.877, P < 0.01) and high C-reactive protein (CRP) level (OR = 1.590, 95%CI: 1.007-2.510, P < 0.01) increased the risk of endoscopic activity at week 108. At week 14, ITL ≤ 5.60 μg/mL [area under the curve (AUC) = 0.83, 95%CI: 0.73-0.90, P < 0.001] and FCP > 238 μg/g (AUC = 0.82, 95%CI: 0.72-0.89, P < 0.001) moderately predicted endoscopic activity at week 54. ITL ≤ 5.60 μg/mL in combination with FCP > 238 μg/g indicated 82.0% possibility of endoscopic activity. At week 54, ITL ≤ 2.10 μg/mL (AUC = 0.85, 95%CI: 0.72-0.93, P < 0.001) and CRP > 3.00 mg/L (AUC = 0.73, 95%CI: 0.60-0.84, P = 0.012) moderately predicted moderate endoscopic activity at week 108. ITL ≤ 2.10 μg/mL in combination with CRP > 3.00 mg/L indicated 100.0% possibility of endoscopic activity. From weeks 14 to 54 of IFX treatment, patients with ITL > 5.60 μg/mL had higher rate of endoscopic relapse free survival than those with ITL ≤ 5.60 μg/mL (95.83% vs 46.67%). From weeks 54 to 108 of IFX treatment, patients with ITL > 2.10 μg/mL had higher rate of endoscopic survival free relapsed rate than those with ITL ≤ 2.10 μg/mL (92.68% vs 30.77%).CONCLUSIONCombination of ITL, CRP, and FCP contribute to long-term endoscopic prognosis monitoring. During IFX maintenance treatment, low ITL, high CRP level, and high FCP level were independent risk factors of CD patients with clinical remission in adverse endoscopy outcomes within 1-year follow-up.

P249 Serum calprotectin is useful to confirm Inflammatory Bowel Disease activity but is not effective to predict relapse

Abstract Background Serum calprotectin (SC), a novel biomarker of inflammatory bowel diseases (IBD), has been recently investigated with conflicting results. The purpose of this study was to assess the ability of SC for predicting disease relapse in patients with IBD treated by biologic therapies, and to evaluate the correlation between SC and clinical and endoscopic relapse and with other biomarkers including fecal calprotectin (FC) and C-reactive protein (CRP). Methods All consecutive IBD patients in deep remission (clinical and endoscopic or imaging remission) were recruited in this prospective study and followed 12 months. Blood and stool samples were collected for SC, serum CRP and FC measurement. SC was measured the day of inclusion (baseline, D0), 3 months (M3) and 6 months (M6) later and in case of relapse during the study period. Relapse was defined as clinical, biomarkers, or endoscopic/imaging activity. So, firstly, we looked at evolution of SC before relapse to analyze a predicting value of loss of response (LOR). We also compared SC for patients with active IBD and those with symptoms without inflammation. Results Among the 119 patients included, 54 (46.4%) patients experienced a disease relapse during follow-up. When we looked at the kinetic of SC during follow-up, median SC levels did not increase in patients who relapsed: 3.15 µg/l at baseline, 3.38 µg/l at M3, 3.33 µg/l at M6 and 3.99 µg/l in case of relapse (p=0.63). We compared SC during relapse with patients in endoscopic remission but clinical symptoms which defined secondary Irritable Bowel Syndrome, we found that SC levels were higher in active IBD and similar between the groups of patients with IBS or deep remission (3.05µg/l IBS vs 2.99µg/l remission vs 5.1µg/l for relapsers, p=0.04). In patients with clinical symptoms, SC presents a good predictive value for relapse. (AUROC 0.764, IC95: 0.68–0.88), giving a sensitivity of 72% with a specificity of 77%, using a cut-off value of 4.45mg/ml. A weak, but significant correlation was found between SC and FC levels (r=0.35, P= 0.001). A combined score with CRP, FC and SC didn’t improve its diagnostic accuracy. Conclusion SC was significantly higher in patients with relapse compared to those in endoscopic remission with or without clinical symptoms. It seemed that it permit to oppose patients with active IBD and those with symptoms of IBS. However, it failed to predict relapse.

P159 Faecal S100A12 as a non-invasive marker of inflammatory activity in Inflammatory Bowel Disease

Abstract Background Calgranulin-C (f-S100A12) and zonulin are considered faecal marker of intestinal inflammation. The aim of our study was to evaluate f-S100A12 and fecal zonulin as alternative markers in the follow-up of IBD children to monitore the disease activity and to predict the clinical and endoscopic relapse, compared with FC and serum inflammatory markers. Methods Between September 2019 and March 2020, we prospectively enrolled all IBD pediatric patients, both Crohn’s Disease (CD) and Ulcerative Colitis (UC). S100A12, zonulin and faecal calprotectin (FC) were determined by enzyme-linked immunosorbent assay (ELISA). Results One hundred seventeen consecutive children, 39.3% with CD and 71 60.7% with UC were enrolled. No differences were found for FC, f-S100A12 and zonulin values in UC and CD. In both CD and UC there was a direct correlation between FC and f- S100A12 levels (r=0.54; p&amp;lt;0.001 and r = 0.63; p&amp;lt;0.001, respectively). F-S100 correlated directly with fibrinogen (r=0.32; p=0.038), platelets count (r=0.35; p=0.021), WBC (r=0.39; p=0.009) and SES CD (r=0.459, p=0.004) and inversely with hemoglobin (r= -0.40; p=0.0077), hematocrit (r=-0.43; p=0.015). In patient with UC we found a direct correlation between f-S100 and CRP (r=0.252; p=0.040) and platelet count (r=0.254; p=0.038). There was no correlation between f-S100A12 and PUCAI or PCDAI score. No association was found between Paris and fecal biomarkers evaluated both in CD and UC. No significant correlation were found between zonulin and the different parameters studied. Conclusion Our data suggest that f-S100A12 and FC but not F-zonulin are useful non-invasive biomarkers in the management of pediatric IBD in follow up and to monitor endoscopic relapse in CD patients.

Assessment of a new score for capsule endoscopy in pediatric Crohn's disease (CE-CD).

Background and study aims Two scores have been implemented to standardize capsule endoscopic (CE) findings in patients with Crohn’s disease (CD): Lewis score (LS) and Capsule Endoscopy Crohnʼs Disease Activity Index (CECDAI). Both have limitations and are not well validated in the pediatric population. The aim of our study was to assess a new score (capsule endoscopy – Crohn’s disease index, CE-CD) in pediatric patients with CD and to compare it to preexisting scores. Patients and methods This was a double-center, retrospective study involving pediatric subjects with CD who underwent CE. Correlation analyses between CE-CD, endoscopy scores and noninvasive markers of disease activities were performed. The ability of different CE scores to predict clinical and endoscopic outcomes was evaluated with regression and survival analyses. Results A total of 312 subjects were analyzed. The CE-CD score showed a moderate (Pearson’s r = 0.581, P < 0.001) and strong (r = 0.909, P < 0.001) association with LS and CECDAI, respectively. CE-CD was a statistically significant predictor of hospitalization (hazard ratio [HR]1.061), treatment escalation (HR 1.062), steroid therapy (HR 1.082), clinical (HR 1.064) and endoscopic (HR 1.060) relapse over the twenty-four months ( P < 0.001). Subjects with mucosal inflammation according to CE-CD (CE-CD ≥ 9) had worse outcomes compared to patients without inflammation (CE-CD < 9) (Log rang test < 0.001). Conclusions The CE-CD score is a simple, reliable, reproducible, and predictive score for evaluation of small bowel inflammation in pediatric patients with CD. Prospective validation is needed to confirm the applicability of this new index in clinical practice.

Histological inflammatory activity can predict endoscopic relapse in patients with ulcerative colitis who have achieved mucosal healing.

Current therapeutic goals in ulcerative colitis (UC) include clinical and endoscopic remission, named mucosal healing (MH). Despite MH, a proportion of patients suffer a clinical relapse, which has been related to histological inflammation. We aimed to identify which histopathological features or histopathological index cut-off was associated with endoscopic relapse (ER) in UC patients with MH. Retrospective analysis of UC patients who underwent surveillance colonoscopy showing complete MH (endoscopic Mayo subscore=0) with random biopsies, and at least one more endoscopy along the follow-up. After a consensus meeting, expert pathologist performed histological assessment according to Simplified Geboes Score (SGS), Nancy Index (NI) and Robarts Histopathological Index (RHI). Other histopathological features were also evaluated. Patients were followed until ER or last endoscopy performed showing persistence of MH. A total of 95 patients (150 colonoscopies) were included. After mean follow-up of 31.2 months (SD 21.7), 33 patients (34.7%) suffered ER. Neutrophils in lamina propria (OR 2.6; P = 0.037), within the epithelium (OR 2.6; P = 0.03), SGS ≥3.1 (OR 2.6; P = 0.037), NI ≥2 (OR 2.6; P = 0.03) and RHI ≥5 (OR 2.6; P = 0.037) were associated with ER in univariate analysis. In multivariate analysis, eosinophils in the lamina propria (HR 2.5; P = 0.01) and clinical remission<12 months (HR 3.2; P = 0.002) were associated with ER. Histopathological findings in UC patients who have achieved endoscopic MH may predict ER. Standardized histopathology reports according to the presence of neutrophils, eosinophils or to defined cut-off of validated histopathologic indexes may represent a useful tool to predict ER and should be considered at therapeutic and surveillance decision process.

Discrete terminal ileal ulcers in patients diagnosed with ulcerative colitis: clinical significance and natural course

BackgroundTerminal ileal (TI) ulcers are occasionally detected in asymptomatic individuals and mostly resolve without any treatment. In patients with ulcerative colitis (UC), TI ulcers are infrequently observed without evidence of backwash ileitis. However, the clinical significance and natural course of the lesions are unclear. The aim of our study was to evaluate the frequency and clinical implications of TI ulcers in patients with UC.MethodsWe retrospectively reviewed 397 patients with UC via successful TI intubation during colonoscopy. We compared the clinical characteristics of patients manifesting TI ulcers with those who did not. The natural course of TI lesions was also investigated during the follow-up periods.ResultsForty-one patients (10.3%) showed TI ulcers without evidence of inflammation in the right colon. The patients with and without TI ulcers were not different in terms of baseline characteristics, disease activity and extent at the time of the UC diagnosis, proximal extension, Mayo endoscopic score at the last endoscopic examination, medication history, UC-related hospitalization, and relapse during follow-up periods. Of the 30 patients who underwent follow-up colonoscopy in patients with TI ulcers, 23 (76.7%) showed resolution of TI ulcer. In addition, patients with remaining TI ulcers did not differ in disease activity and biopsy results compared with those with resolving TI ulcers.ConclusionsDiscrete TI ulcers are more common in patients with UC, compared with the healthy cohort. No significant clinical impact on disease extension and severity is found.

P321 Cessation of Anti-Tumour Necrosis Factor Therapy in Patients with Perianal Fistulizing Crohn’s Disease: Individual Patient Data Meta-Analysis of 323 patients from 12 studies

Abstract Background The risk of relapse after anti-tumour necrosis factor [TNF] therapy cessation in Crohn’s disease [CD] patients with perianal fistulas is unclear. We aimed to assess the risk of relapse after anti-TNF cessation in a large cohort and to identify risk factors. Methods A systemic literature search was conducted to identify cohort studies reporting on the incidence of relapse after cessation of anti-TNF therapy in CD patients. Individual patient data [IPD] were requested from the original study cohorts. Inclusion criteria for IPD-meta-analysis (IPD-MA) included age ³ 18 years, perianal fistulizing CD as indication for start of anti-TNF therapy, minimal treatment duration ³3 doses, and remission of luminal and perianal CD at cessation of anti-TNF therapy. Primary outcome was CD relapse [either perianal or luminal]. Perianal fistula relapse was defined as recurrence of draining perianal fistula related to previous or new fistula tracks, or abscess. Luminal relapse was defined as a clinical, biochemical, endoscopic, or radiological relapse requiring treatment or dose optimization of IBD medication or surgery. In a secondary analysis, risk factors associated with relapse were assessed using multivariate logistic regression analysis. Results A total of 307 patients from 12 studies in 9 countries were included in this IPD-MA. The median duration of anti-TNF treatment prior to therapy cessation was 14 months [IQR 6.1 – 29.9]. In 272/307 patients [89%] anti-TNF therapy was started for active perianal fistula and in 34 [11%] for both active perianal fistula and luminal CD. 169 patients [55%] developed a relapse [either perianal or luminal] after a median follow-up after cessation of 25 months [IQR 12 – 54]. Overall cumulative incidence of relapse was 31% and 43% at 1 and 2 years after anti-TNF cessation. Risk factor for CD relapse include upper GI involvement (L4) [HR 1.9], whereas older age [A3 vs A1, HR 0.48] and continuation of concomitant immunomodulators [HR 0.62] were protective factors. For a subgroup of patients with active perianal fistula and in luminal remission at start of anti-TNF, the cumulative incidence relapse rates were 25% and 43% at 1 and 2 years. No considerable differences in risk factors were found within this subgroup regarding risk of recurrence. Of the 179 patients who relapsed, 104 were retreated with anti-TNF with a response rate of 85%. Conclusion According to this IPD-MA, approximately two-thirds of CD patients with perianal fistula remain in remission with regard to fistulizing and luminal disease during 2 years after cessation of anti-TNF therapy. Further risk stratification based on perianal fistula characteristics is required.

Defer No Time, Delays Have Dangerous Ends (William Shakespeare)

Question: A 22-year-old man was diagnosed with eosinophilic esophagitis (EoE) at the age of 9 years in 2007. Already on initial endoscopic presentation, severe stricture formation was described requiring bougie dilation (3 sessions within the first 6 months). Subsequently, treatment with swallowed topical steroids was initiated. After having achieved clinical remission, the patient stopped therapy after 6 months. However, 2 months after withdrawal of steroids, the patient developed a clinical, endoscopic, and histological relapse.

Effect of N-acetylcysteine on remission maintenance in patients with ulcerative colitis: A randomized, double-blind controlled clinical trial

BackgroundThe use of antioxidant agents is suggested as a complementary therapy in UC patients for the prevention of flares. Considering the potent antioxidant activity of N-acetylcysteine (NAC), in the present study we aimed to assess the effect of this supplement on remission maintenance in patients with ulcerative colitis (UC). MethodsIn the present double-blind randomized controlled clinical trial, 168 volunteer UC patients who were on high dose corticosteroid and Mesalamine for flare-up management, were recruited. The patients received 800 mg NAC or placebo for 16 weeks. Simultaneously, the prednisolone dose was tapered. The patients were followed up six more weeks post-intervention. The primary efficacy of the treatment was remaining in remission. The secondary outcomes were the endoscopic relapse, serum level of hs-CRP, hemoglobin, and fecal calprotectin level. ResultsDuring 22 weeks follow up, 25 patients experienced relapses, six of them were in the NAC group and 19 of them were in the placebo group. There was a significant difference between the NAC and placebo groups regarding the relapse-free period (P = 0.007). Compared with the NAC group, significantly more patients in the placebo group had an endoscopic relapse (p < 0.001). At the end of the intervention period (16 weeks) and 6 weeks post-intervention, the mean fecal calprotectin, serum erythrocyte sedimentation rate, and hs-CRP levels were significantly lower in the NAC group compared with the placebo group (p < 0.05). ConclusionThe findings indicated that NAC had a significantly more positive effect on the maintenance of remission compared with placebo in UC patients that were in the steroid-tapering phase of therapy.

Modern drainage interventions in the surgical treatment pancreatic cyst

Purpose. To evaluate the capabilities of modern minimally invasive interventions under the beam guidance in the surgical treatment of pancreatic cysts.&#x0D; Materials and Methods. The results of the examination and treatment of 88 patients with pancreatic cysts. Percutaneous puncture drainage under ultrasonographic guidance holds 56 patients, endoscopic transmural drainage of cysts by ultrasonography- in 32.&#x0D; Results. After performing percutaneous drainage of cysts positive results were observed in 42 (75,0%) patients. Relapses cystic formations were observed in 14 (25.0%) patients. Endoscopic transmural drainage under ultrasonography noted one intraoperative complication perforation of the stomach wall. 6 patients had a good result. Term follow up of patients ranged from 10 months to 3 years.&#x0D; During endoscopic transmural drainage stent dislocation and relapse of cysts were not detected in all operated patients after 6 months, Long-term results were observed only in 11 patients.&#x0D; Conclusions. Percutaneous external drainage of pancreatic cysts is an effective intervention in 75% of patients. A fairly high percentage (25%) of relapses is due to the fact that long-term external drainage do not allow to achieve complete obliteration of the cyst cavity in its connection with the main pancreatic duct and preservation of ductal hypertension of the pancreas. Endoscopic installation of a stent between the hand cavity and the lumen of the stomach allows you to create conditions for a constant outflow of cyst contents into the stomach and eliminate pancreatic hypertension. The effectiveness of internal drainage is determined by the duration of stent functioning, as well as the possibility of forming an internal cystogastric fistula (3 figs, bibliography: 8 refs).

Patients' Educational Program Could Improve Azathioprine Adherence in Crohn's Disease Maintenance Therapy.

Aim To determine the risk factors of nonadherence to azathioprine (AZA) maintenance therapy for Crohn's disease (CD) and to evaluate the influence of patients' educational program on adherence to AZA maintenance therapy. Methods Patients receiving AZA as maintenance therapy for CD were enrolled. Demographic data, clinical data, and usage information were collected. Univariate and multivariate analyses were performed to identify the risk factors of nonadherence. Then, patients' educational program was conducted. One year after the program, the improvements in adherence and relapse rates were compared between educational and noneducational groups. Results A total of 378 CD patients receiving AZA as maintenance therapy were enrolled from September 2008 to September 2018. Nonadherence occurred in 43.9% (166/378) of patients. Univariate analysis revealed that young age, education, alcoholism, anxiety, depression, concern belief, and lack of necessity belief and AZA knowledge were risk factors of nonadherence (P < 0.05). Multivariate logistic regression showed that anxiety (OR 6.244, 95% CI 2.563–15.213), depression (OR 3.801, 95% CI 1.281–11.278), and concern belief (OR 19.531, 95% CI 3.393–120.732) were independent risk factors of nonadherence. Necessity belief (OR 0.961, 95% CI 0.925–0.999) and AZA knowledge (OR 0.823, 95% CI 0.758–0.903) were protective factors of adherence. One year after the AZA educational program, the necessity belief, AZA knowledge, and adherence of the educational group significantly improved (P < 0.05). Concern belief was significantly lower in the educational group than that in the noneducational group (P < 0.05). Moreover, the noneducational group suffered significantly higher endoscopic relapse rates than that the educational group (15.9% vs. 30.1%, P = 0.035). Conclusions Nonadherence occurred frequently in CD patients receiving AZA maintenance therapy. Educational programs could improve patients' adherence mainly by promoting their beliefs and knowledge of AZA and could reduce relapse rates during treatment.

Probiotics for maintenance of remission in ulcerative colitis.

Probiotics for maintenance of remission in ulcerative colitis.

Normalization of C-Reactive Protein Predicts Better Outcome in Patients With Crohn's Disease With Mucosal Healing and Deep Remission.

OBJECTIVES:Therapeutic targets for Crohn's disease (CD) have evolved from clinical and biological remission to mucosal healing (MH) and deep remission (DR). MH is defined as disappearance of ulceration, whereas DR is defined as a combination of clinical remission and MH. Limited data are available regarding differences in long-term outcomes of these patients reaching these targets. We thus aimed to evaluate patients' long-term clinical outcomes using different composite remission parameters.METHODS:We performed a retrospective cohort study comparing long-term outcomes of patients with different remission parameters, including MH and DR with or without normalization of C-reactive protein (CRPnorm). The primary outcome was CD-associated intestinal surgery, and secondary outcomes included CD-related hospitalizations, clinical relapse (CR), or endoscopic recurrence (ER).RESULTS:One hundred ninety-five patients with MH at follow-up endoscopy were divided into 3 groups: DR-only (n = 53), DR + CRPnorm (n = 106), and MH-only (n = 36). At the follow-up (median 46.0 months), 25 patients had undergone CD-related bowel surgery, 44 had CD-related hospitalizations, and 66 experienced CR. Of 151 patients who underwent follow-up colonoscopy after the index colonoscopy for MH, 96 experienced ER. Among the 3 groups, patients in the DR + CRPnorm group had the lowest risk of clinical or endoscopic relapse. The DR group had a lower rate of CR than the MH-only group (P = 0.03); there was no difference in the rate of CD-related surgery, hospitalizations, or ER.DISCUSSION:Patients with DR combined with a normalized CRP showed better outcomes than those with DR only. The outcomes of patients with MH were similar to those of patients with DR, except for shorter flare-free survival.