Role of surgery in severe ulcerative colitis in the era of medical rescue therapy

Despite the growing use of medical salvage therapy,colectomy has remained a cornerstone in managing acute severe ulcerative colitis(ASC) both in children and in adults.Colectomy should be regarded as a life saving procedure in ASC,and must be seriously considered in any steroid-refractory patient.However,colectomy is not a cure for the disease but rather the substitution of a large problem with smaller problems,including fecal incontinence,pouchitis,irritable pouch syndrome,cuffitis,anastomotic ulcer and stenosis,missed or de-novo Crohn's disease and,in young females,reduced fecundity.This notion has led to the widespread practice of offering medical salvage therapy before colectomy in most patients without surgical abdomen or toxic megacolon.Medical salvage therapies which have proved effective in the clinical trial setting include cyclosporine,tacrolimus and infliximab,which seem equally effective in the short term.Validated predictive rules can identify a subset of patients who will eventually fail corticosteroid therapy after only 3-5 d of steroid therapy with an accuracy of 85%-95%.This accuracy is sufficiently high for initiat-ing medical therapy,but usually not colectomy,early in the admission without delaying colectomy if required.This approach has reduced the colectomy rate in ASC from 30%-70% in the past to 10%-20% nowadays,and the mortality rate from over 70% in the 1930s to about 1%.In general,restorative proctocolectomy(ileoanal pouch or ileal pouch-anal anastomosis),especially the J-pouch,is preferred over straight pullthrough(ileo-anal) or ileo-rectal anastomosis,which may still be considered in young females concerned about infertility.Colectomy in the acute severe colitis setting,is usually performed in three steps due to the severity of the inflammation,concurrent steroid treatment and the generally reduced clinical condition.The first surgical step involves colectomy and constructing an ileal stoma,the second-constructing the pouch and the third-closing the stoma.This review focuses on the role of surgical treatment in ulcerative colitis in the era of medical rescue therapy.

Older adults with acute severe ulcerative colitis have similar steroid non-response and colectomy rates as younger adults

BACKGROUND There is paucity of data on outcomes of acute severe ulcerative colitis(ASUC)in older adults(≥60 years of age).AIM To assess steroid non-response rates during the index admission for ASUC in older adults.Secondary outcomes were response to medical rescue therapy and colectomy rates;at index admission,3 and 12 mo.METHODS This retrospective multicentre cohort study included ASUC admissions who received intravenous steroids between January 2013 and July 2020 at two tertiary hospitals.Electronic medical records were reviewed to collect clinical,biochemical,and endoscopic data.A modified Poisson regression model was used for analysis.RESULTS Of 226 ASUC episodes,45(19.9%)occurred in patients≥60 years of age.Steroid non-response rates were comparable in older adults and patients<60 years of age[19(42.2%)vs 85(47%),P=0.618],crude risk ratio(RR)=0.89[95%confidence interval(CI):0.61-1.30],adjusted RR=0.99(0.44-2.21).Rates of response to medical rescue therapy in older adults was comparable to the younger cohort[76.5%vs 85.7%,P=0.46,crude RR=0.89(0.67-1.17)].Index admission colectomy[13.3%vs 10.5%,P=0.598,crude RR=1.27(0.53-2.99),adjusted RR=1.43(0.34-6.06)],colectomy at 3 mo[20%vs 16.6%,P=0.66,crude RR=1.18(0.61-2.3),adjusted RR=1.31(0.32-0.53)]and colectomy at 12 mo[20%vs 23.2%,P=0.682,crude RR=0.85(0.45-1.57),adjusted RR=1.21(0.29-4.97)],were similar between the two groups.CONCLUSION In older adults with ASUC,the steroid non-response rate,response to medical rescue therapy,and colectomy rate at index admission,3 and 12 mo is similar to patients less than 60 years of age.

Treatment of acute severe ulcerative colitis using accelerated infliximab regimen based on infliximab trough level:A case report

BACKGROUND Acute severe ulcerative colitis (ASUC) is a complication of ulcerative colitisassociated with high levels of circulating tumor necrosis factor alpha, due to theintense inflammation and faster stool clearance of anti-tumor necrosis factordrugs. Dose-intensified infliximab treatment can be beneficial and is associatedwith lower rates of colectomy. The aim of the study was to present a case of apatient with ASUC and megacolon, treated with hydrocortisone and acceleratedscheme of infliximab that was monitored by drug trough level.CASE SUMMARYA 22-year-old female patient diagnosed with ulcerative colitis, presented withdiarrhea, rectal bleeding, abdominal pain, vomiting, and distended abdomen.During investigation, a positive toxin for Clostridium difficile and colonic dilatationof 7 cm consistent with megacolon were observed. She was treated with oralvancomycin for pseudomembranous colitis and intravenous hydrocortisone forsevere colitis, which led to the resolution of megacolon. Due to the persistentsevere colitis symptoms, infliximab 5 mg/kg was prescribed, monitored by drugtrough level (8.8 μg/mL) and fecal calprotectin of 921 μg/g (< 30 μg/g). Based onthe low infliximab trough level after one week from the first infliximab dose, thepatient received a second infusion at week 1, consistent with the acceleratedregimen (infusions at weeks 0, 1, 2 and 6). We achieved a positive clinical andendoscopic response after 6 mo of therapy, without the need for a colectomy.CONCLUSIONInfliximab accelerated infusions can be beneficial in ASUC unresponsive to thetreatment with intravenous corticosteroids. Longitudinal studies are necessary todefine the best therapeutic drug monitoring and treatment regimen for thesepatients.

Endoscopic ultrasonography in the evaluation of condition and prognosis of ulcerative colitis

BACKGROUND Ulcerative colitis(UC)is usually diagnosed through histopathology,enteroscopy,clinical symptoms,and physical findings;however,it is difficult to accurately evaluate disease severity.AIM To investigate the value of endoscopic ultrasonography(EUS)in the evaluation of the severity and prognosis of UC.METHODS Patients with UC who were seen in our hospital from March 2019 to December 2020 were eligible,and disease severity was evaluated according to the modified Truelove and Witts and Mayo scores.We performed EUS,calculated the UC endoscopic index of severity(UCEIS)and EUS-UC scores,and administered appropriate treatment.The UCEIS and EUS-UC scores of patients were assessed in relation to disease severity,and the correlations between UCEIS and EUS-UC scores and disease severity was also analyzed.The UCEIS and EUS-UC scores before and after treatment were also compared.RESULTS A total of 79 patients were included in this study.According to the Mayo Index,23,32,and 24 patients had mild,moderate and severe UC,respectively.The UCEIS and EUS-UC scores were higher in moderate cases(4.98±1.04 and 5.01±0.99,respectively)than in mild cases(1.56±0.82 and 1.64±0.91,respectively,P<0.05).Furthermore,the UCEIS and EUS-UC scores(7.31±1.10 and 7.59±1.02,respectively)were higher in severe cases than in moderate cases(P<0.05).According to the modified Truelove and Witts scores,21,36,and 22 patients were classified as having mild,moderate and severe disease,respectively.The UCEIS and EUS-UC scores were significantly higher in moderate disease(4.79±1.11 and 4.96±1.23,respectively)than in mild disease(1.71±0.78 and 1.69±0.88,respectively,P<0.05).Additionally,the UCEIS and EUS-UC scores in severe disease(7.68±1.22 and 7.81±0.90,respectively)were significantly higher than in moderate disease(P<0.05).The UCEIS and EUSUC scores were significantly and positively correlated with disease severity according to the modified Truelove and Witts score and Mayo score(P<0.05).The UCEIS and EUS-UC scores after 2 mo of treatment(3.88±0.95 and 4.01±1.14,respectively)and after 6 mo of treatment(1.59±0.63 and 1.64±0.59,respectively)were lower than the respective scores before treatment(5.93±1.79 and 6.04±2.01)(P<0.05).CONCLUSION EUS can clarify the status of UC and accurately evaluate the treatment response,providing an objective basis for formulation and adjustment of the treatment plan.

Comparison of fecal calprotectin levels and endoscopic scores for predicting relapse in patients with ulcerative colitis in remission

BACKGROUND Although the usefulness of endoscopic scores,such as the Mayo Endoscopic Subscore(MES),Ulcerative Colitis Endoscopic Index of Severity(UCEIS),and Ulcerative Colitis Colonoscopic Index of Severity(UCCIS),and biomarkers such as fecal calprotectin(FC)for predicting relapse in ulcerative colitis(UC)has been reported,few studies have included endoscopic scores for evaluating the entire colon.AIM To compare the usefulness of FC value and MES,UCEIS,and UCCIS for predicting relapse in patients with UC in clinical remission.METHODS In total,75 patients with UC in clinical and endoscopic remission who visited our institution between February 2019 and March 2022 were enrolled.The diagnosis of UC was confirmed based on the clinical presentation,endoscopic findings,and histology,according to the current established criteria for UC.Fecal samples were collected the day before or after the colonoscopy for measurement of FC.Endoscopic evaluations were performed using MES,UCEIS,and UCCIS.The primary outcome measure of this study was the assessment of the association between relapse within 12 mo and MES,UCEIS,UCCIS,and FC.The secondary outcome was the comparison between endoscopic scores and biomarkers in en-rolled patients with UC with mucosal healing.RESULTSFC and UCCIS showed a significant correlation with UCEIS (r = 0.537, P < 0.001 and r = 0.957, P < 0.001, respectively).Receiver-operating characteristic analysis for predicting MES 0 showed that the area under the curve ofUCCIS was significantly higher than that of FC (P < 0.01). During the 1-year observation period, 18 (24%) patientsexperienced a relapse, and both the FC and UCCIS of the relapse group were significantly higher than that of theremission group. The cut-off values for predicting relapse were set at FC = 323 mg/kg and UCCIS = 10.2. The areaunder the curve of the receiver-operating characteristic analysis for predicting relapse did not show a significantdifference between FC and UCCIS. The accuracy of the endoscopic scores and biomarkers in predicting relapse was86.7% for UCCIS, 85.3% for UCEIS, 76.0% for FC, and 73.3% for MES.CONCLUSIONThe three endoscopic scores and FC may predict UC relapse during clinical remission. Among these scores, UCEISmay be the most useful in terms of ease of evaluation and accuracy.

Clinical value of the Toronto inflammatory bowel disease global endoscopic reporting score in ulcerative colitis

BACKGROUND Endoscopic evaluation in diagnosing and managing ulcerative colitis(UC)is becoming increasingly important.Several endoscopic scoring systems have been established,including the Ulcerative Colitis Endoscopic Index of Severity(UCEIS)score and Mayo Endoscopic Subscore(MES).Furthermore,the Toronto Inflammatory Bowel Disease Global Endoscopic Reporting(TIGER)score for UC has recently been proposed;however,its clinical value remains unclear.AIM To investigate the clinical value of the TIGER score in UC by comparing it with the UCEIS score and MES.METHODS This retrospective study included 166 patients with UC who underwent total colonoscopy between January 2017 and March 2023 at the Affiliated Hospital of Qingdao University(Qingdao,China).We retrospectively analysed endoscopic scores,laboratory and clinical data,treatment,and readmissions within 1 year.Spearman’s rank correlation coefficient,receiver operating characteristic curve,and univariate and multivariable logistic regression analyses were performed using IBM SPSS Statistics for Windows,version 26.0(IBM Corp.,Armonk,NY,United States)and GraphPad Prism version 9.0.0 for Windows(GraphPad Software,Boston,Massachusetts,United States).RESULTS The TIGER score significantly correlated with the UCEIS score and MES(r=0.721,0.626,both P<0.001),showed good differentiating values for clinical severity among mild,moderate,and severe UC[8(4-112.75)vs 210(109–219)vs 328(219–426),all P<0.001],and exhibited predictive value in diagnosing patients with severe UC[area under the curve(AUC)=0.897,P<0.001].Additionally,the TIGER(r=0.639,0,551,0.488,0.376,all P<0.001)and UCEIS scores(r=0.622,0,540,0.494,and 0.375,all P<0.001)showed stronger correlations with laboratory and clinical parameters,including C-reactive protein,erythrocyte sedimentation rate,length of hospitalisation,and hospitalisation costs,than MES(r=0.509,0,351,0.339,and 0.270,all P<0.001).The TIGER score showed the best predictability for patients'recent advanced treatment,including systemic corticosteroids,biologics,or immunomodulators(AUC=0.848,P<0.001)and 1-year readmission(AUC=0.700,P<0.001)compared with the UCEIS score(AUC=0.762,P<0.001;0.627,P<0.05)and MES(AUC=0.684,P<0.001;0.578,P=0.132).Furthermore,a TIGER score of≥317 was identified as an independent risk factor for advanced UC treatment(P=0.011).CONCLUSION The TIGER score may be superior to the UCIES score and MES in improving the accuracy of clinical disease severity assessment,guiding therapeutic decision-making,and predicting short-term prognosis.

Remission endpoints in ulcerative colitis: A systematic review

AIM To summarize the current consensus on the defnition of remission and the endpoints employed in clinical trials.METHODSA bibliogragraphic search was performed from 1946 to 2016 sing online databases （National Library of Medicine’s PubMed Central Medline, OVID SP MEDLINE, OVID EMBASE, the Cochrane Library and Conference Abstracts） with key words： （“ulcerative colitis”） AND （“ulcerative colitis endoscopic index of severity” OR “UCEIS”） AND （“remission”） as well as （“ulcerative colitis”） AND （“ulcerative colitis disease activity index”） OR “UCDAI” OR “UC disease activity index” OR “Sutherland index”） AND （“remission”）.RESULTSThe search returned 37 and 116 articles for the UCEIS and UCDAI respectively. For the UCEIS, 12 articles were cited in the final analysis of which 9 validation studies have been identified. Despite the UCEIS has been more extensively validated in all three aspects （validity, responsiveness and reliability）, it has been little employed to monitor disease in randomised clinical trials. For the UCDAI, 37 articles were consider-ed for the final analysis. Although the UCDAI is only partially validated, 29 randomised clinical trials were acknowledged to use the UCDAI to determine endpoints and disease remission, though no clear protocol was identifed.CONCLUSIONAlthough the UCEIS has been more widely validated than the UCDAI, it has not been refected in the moni-toring of disease activity in clinical trials. Conversely, the UCDAI has been used in numerous large clinical trials to defne their endpoints and disease remission, however, it is challenging to determine the best possible outcomes due to a lack of homogeneity of the clinical trial protocols. Before determining a gold standard index, international agreement on remission is urgently needed to advance patient care.

Development and validation of novel models for the prediction of intravenous corticosteroid resistance in acute severe ulcerative colitis using logistic regression and machine learning

Background The early prediction of intravenous corticosteroid(IVCS)resistance in acute severe ulcerative colitis(ASUC)patients remains an unresolved challenge.This study aims to construct and validate a model that accurately predicts IVCS resistance.Methods A retrospective cohort was established,with consecutive inclusion of patients who met the diagnosis criteria of ASUC and received IVCS during index hospitalization in Peking Union Medical College Hospital between March 2012 and January 2020.The primary outcome was IVCS resistance.Classification models,including logistic regression and machine learning-based models,were constructed.External validation was conducted in an independent cohort from Shengjing Hospital of China Medical University.Results A total of 129 patients were included in the derivation cohort.During index hospitalization,102(79.1%)patients responded to IVCS and 27(20.9%)failed;18(14.0%)patients underwent colectomy in 3 months;6 received cyclosporin as rescue therapy,and 2 eventually escalated to colectomy;5 succeeded with infliximab as rescue therapy.The Ulcerative Colitis Endoscopic Index of Severity(UCEIS)and C-reactive protein(CRP)level at Day 3 are independent predictors of IVCS resistance.The areas under the receiver-operating characteristic curves(AUROCs)of the logistic regression,decision tree,random forest,and extreme-gradient boosting models were 0.873(95%confidence interval[CI],0.704–1.000),0.648(95%CI,0.463–0.833),0.650(95%CI,0.441–0.859),and 0.604(95%CI,0.416–0.792),respectively.The logistic regression model achieved the highest AUROC value of 0.703(95%CI,0.473–0.934)in the external validation.Conclusions In patients with ASUC,UCEIS and CRP levels at Day 3 of IVCS treatment appeared to allow the prompt prediction of likely IVCS resistance.We found no evidence of better performance of machine learning-based models in IVCS resistance prediction in ASUC.A nomogrambased on the logistic regression model might aid in the management of ASUC patients.

Comparing the clinical application values of the Degree of Ulcerative Colitis Burden of Luminal Inflammation(DUBLIN)score and Ulcerative Colitis Endoscopic Index of Severity(UCEIS)in patients with ulcerative colitis

Background:The significance of endoscopic evaluation in the diagnosis and management of ulcerative colitis(UC)has been widely recognized.Over the years,scholars have established several endoscopic scores.Herein,we assessed the clinical application value of the Mayo Endoscopic Subscore(Mayo ES),the Degree of Ulcerative Colitis Burden of Luminal Inflammation(DUBLIN)score,and the Ulcerative Colitis Endoscopic Index of Severity(UCEIS)score in UC patients,by comparing their correlation with disease activity and their predictive potential for treatment response and clinical outcomes.Methods:UC patients hospitalized from September 2015 to September 2019 were retrospectively analysed.We employed Spearman’s rank correlation coefficient to assess the linear association of the assessed endoscopic scores with the clinical parameters.The receiver-operating characteristic curve was applied to evaluate the predictive capabilities of the endoscopic scores for treatment escalation and 1-year readmission.Results:A total of 178 patients were enrolled;most of them(82%)suffered moderate or severe colitis.Among them,48(27%)patients received treatment escalation and 59(33%)were readmitted within 1 year.The DUBLIN and UCEIS scores demonstrated higher correlations with clinical parameters than the Mayo ES.The DUBLIN scores significantly differed between patients with mild,moderate,and severe colitis(all P<0.001).The UCEIS scores demonstrated the best predictabilities for treatment escalation and 1-year readmission with an area under the curve of 0.88 and 0.75,respectively.Compared to the UCEIS and DUBLIN scores,the predictive capabilities of the Mayo ES for treatment escalation(both P<0.001)and 1-year readmission(P<0.001 and P紏0.002,respectively)were lower.The UCEIS scores exhibited a significant difference between the steroid-responsive group and the steroid-dependent or steroid-refractory group(both P<0.001),while no significant differences in the Mayo ES and DUBLIN scores were found among the three groups(both P>0.05).Conclusion:This study demonstrates that both the DUBLIN and UCEIS scores outperform the Mayo ES in assessing disease severity and predicting treatment response and clinical outcomes in UC patients.

Cut-off value of ulcerative colitis endoscopic index of severity(UCEIS)score for predicting the need for pouch construction in ulcerative colitis:results of a multicenter study with long-term follow-up

Background Total proctocolectomy with ileal pouch–anal anastomosis(IPAA)was the first choice for the surgical treatment of the ulcerative colitis(UC)patients.The data on the predictive value of the ulcerative colitis endoscopic index of severity(UCEIS)for the need for IPAA in UC patients is scarce.We aimed to establish the UCEIS cut-off value to further analyse whether the UCEIS cut-off was suitable for predicting the need for IPAA in UC patients.Methods The clinical data of UC patients from June 1986 to March 2020 at our institute were retrospectively assessed.The UCEIS scores recorded at the time of the first colonoscopy after hospitalization were used in the study.Receiver operating characteristic curve analysis was performed to determine the UCEIS cut-off value for predicting the need for IPAA.Results A total of 283 UC patients were included in the study,with a median UCEIS of 4.During a median follow-up of 13 years,80 patients(28.3%)received surgery invention,among whom 75(93.8%)underwent IPAA surgery and 5(6.2%)received subtotal colectomy with permanent ostomy.A UCEIS cut-off of 6 had the most significant area under the curve of 0.769 for predicting the need for IPAA(P<0.001),with a sensitivity of 72.0%and specificity of 81.8%.UCEIS≥6 was an independent predictive factor for the need for IPAA(P<0.001)and malignant transformation(P=0.010).Patients with UCEIS≥6 had a significantly shorter IPAA-free survival time than those with UCEIS<6(P<0.001).Conclusions UCEIS≥6 may be a threshold value for decision-making for IPAA and should be recommended for UC patients for reducing the incidence of malignant transformation.