Short-term outcomes of surgical treatment for primary ileocaecal Crohn's disease: Results of the Crohn's(urg) study, a multicentre, retrospective, comparative analysis between inflammatory and complicated phenotypes.

AIM: Recent evidence challenges the current standard of offering surgery to patients with ileocaecal Crohn's disease (CD) only when they present complications of the disease. The aim of this study was to compare short-term results of patients who underwent primary ileocaecal resection for either inflammatory (luminal disease, earlier in the disease course) or complicated phenotypes, hypothesizing that the latter would be associated with worse postoperative outcomes. METHOD: A retrospective, multicentre comparative analysis was performed including patients operated on for primary ileocaecal CD at 12 referral centres. Patients were divided into two groups according to indication of surgery for inflammatory (ICD) or complicated (CCD) phenotype. Short-term results were compared. RESULTS: A total of 2013 patients were included, with 291 (14.5%) in the ICD group. No differences were found between the groups in time from diagnosis to surgery. CCD patients had higher rates of low body mass index, anaemia (40.9% vs. 27%, p < 0.001) and low albumin (11.3% vs. 2.6%, p < 0.001). CCD patients had longer operations, lower rates of laparoscopic approach (84.3% vs. 93.1%, p = 0.001) and higher conversion rates (9.3% vs. 1.9%, p < 0.001). CCD patients had a longer hospital stay and higher postoperative complication rates (26.1% vs. 21.3%, p = 0.083). Anastomotic leakage and reoperations were also more frequent in this group. More patients in the CCD group required an extended bowel resection (14.1% vs. 8.3%, p: 0.017). In multivariate analysis, CCD was associated with prolonged surgery (OR 3.44, p = 0.001) and the requirement for multiple intraoperative procedures (OR 8.39, p = 0.030). CONCLUSION: Indication for surgery in patients who present with an inflammatory phenotype of CD was associated with better outcomes compared with patients operated on for complications of the disease. There was no difference between groups in time from diagnosis to surgery.

ECCO Guidelines on Therapeutics in Crohn's Disease: Surgical Treatment.

This article is the second in a series of two publications on the European Crohn's and Colitis Organisation [ECCO] evidence-based consensus on the management of Crohn's disease. The first article covers medical management; the present article addresses surgical management, including preoperative aspects and drug management before surgery. It also provides technical advice for a variety of common clinical situations. Both articles together represent the evidence-based recommendations of the ECCO for Crohn's disease and an update of prior ECCO guidelines.

Creation of an institutional preoperative checklist to support clinical risk assessment in patients with ulcerative colitis (UC) considering ileoanal pouch surgery.

Background: Total proctocolectomy with ileal pouch-anal anastomosis (IPAA) is the most established restorative operative approach for patients with ulcerative colitis. It has associated morbidity and the potential for major repercussions on quality of life. As such, patient selection is crucial to its success. The main aim of this paper is to present an institutional preoperative checklist to support clinical risk assessment and patient selection in those considering IPAA. Methods: A literature review was performed to identify the risk factors associated with surgical complications, decreased functional outcomes/quality of life, and pouch failure after IPAA. Based on this, a preliminary checklist was devised and modified through an iterative process. This was then evaluated by a consensus group comprising the pouch multidisciplinary team (MDT) core members. Results: The final preoperative checklist includes assessment for risk factors such as gender, advanced age, obesity, comorbidities, sphincteric impairment, Crohn's disease and pelvic radiation therapy. In addition, essential steps in the decision-making process, such as pouch nurse counselling and discussion regarding surgical alternatives, are also included. The last step of the checklist is discussion at a dedicated pouch-MDT. Discussion: A preoperative checklist may support clinicians with the selection of patients that are suitable for pouch surgery. It also serves as a useful tool to inform the discussion of cases at the MDT meeting.

Watchful Waiting After Radiological Guided Drainage of Intra-abdominal Abscess in Patients With Crohn's Disease Might Be Associated With Increased Rates of Stoma Construction.

Background: Management of spontaneous intra-abdominal abscess (IAA) in patients with Crohn's disease (CD) with radiologically guided percutaneous drainage (PD) was debated. Methods: This is a secondary analysis from a multicenter, retrospective cohort study of all the patients with CD who underwent PD followed by surgery at 19 international tertiary centers. Results: Seventeen patients (4.8%) who did not undergo surgery after PD were compared to those who had PD followed by surgical intervention 335/352 (95.2%). Patients who had PD without surgery were those with longer disease duration, more frequently had previous surgery for CD (laparotomies/laparoscopies), enteric fistula, on steroid treatment before and continue to have it after PD. Patients who had PD without subsequent surgical resection had a higher risk of stoma construction at later stages 8/17 (47.1%) versus 90/326 (27.6%) (P < .01). Patients with PD with no subsequent surgery had numerically higher rates of abscess recurrence 5/17 (29.4%) compared to those who had PD followed by surgery 45/335 (13.4%) the difference was not statistically significant (P = .07). Conclusions: Even with the low number of patients enrolled in this study who had PD of IAA without subsequent surgery, the findings indicate a markedly worse prognosis in terms of recurrence, length of stay, readmission, and stoma construction. Watchful waiting after PD to treat patients with spontaneous IAA might be indicated in selected patients with poor health status or poor prognostic factors.

DECIDE: Delphi Expert Consensus Statement on Inflammatory Bowel Disease Dysplasia Shared Management Decision-Making.

BACKGROUND AND AIMS: Inflammatory bowel disease colitis-associated dysplasia is managed with either enhanced surveillance and endoscopic resection or prophylactic surgery. The rate of progression to cancer after a dysplasia diagnosis remains uncertain in many cases and patients have high thresholds for accepting proctocolectomy. Individualised discussion of management options is encouraged to take place between patients and their multidisciplinary teams for best outcomes. We aimed to develop a toolkit to support a structured, multidisciplinary and shared decision-making approach to discussions about dysplasia management options between clinicians and their patients. METHODS: Evidence from systematic literature reviews, mixed-methods studies conducted with key stakeholders, and decision-making expert recommendations were consolidated to draft consensus statements by the DECIDE steering group. These were then subjected to an international, multidisciplinary modified electronic Delphi process until an a priori threshold of 80% agreement was achieved to establish consensus for each statement. RESULTS: In all, 31 members [15 gastroenterologists, 14 colorectal surgeons and two nurse specialists] from nine countries formed the Delphi panel. We present the 18 consensus statements generated after two iterative rounds of anonymous voting. CONCLUSIONS: By consolidating evidence for best practice using literature review and key stakeholder and decision-making expert consultation, we have developed international consensus recommendations to support health care professionals counselling patients on the management of high cancer risk colitis-associated dysplasia. The final toolkit includes clinician and patient decision aids to facilitate shared decision-making.

Prevalence of irritable bowel syndrome and its association with colorectal cancer: a systematic review and meta-analysis.

BACKGROUND: This study evaluates the risk of colorectal cancer (CRC) in patients with Irritable Bowel Syndrome (IBS). METHODS: A literature search was performed on MEDLINE, EMBASE, SCOPUS, and Google Scholar from inception to 31st January 2020 without any limitations on article type or language for studies reporting data on CRC on patients with IBS. A meta-analysis was performed to estimate the prevalence of CRC among patients with IBS. Data extraction was according to the PRISMA guidelines. The quality of the included studies was assessed according to the Newcastle Ottawa Scale. RESULTS: Twenty-one articles were eligible for data extraction and quantitative analysis. Of them, 11 were included in the meta-analysis (IBS n = 284 366, no-IBS n = 8 390 509). The pooled prevalence of CRC in patients with IBS was 0.96% (95% CI-0.184%-2.344%). The prevalence was lowest in the constipation-predominant IBS (pooled prevalence 1.126%. Patients with IBS-D and IBS-U had an equal pooled prevalence of CRC (2.49%). Eleven studies compared the prevalence of CRC in patients with IBS with a control population. The pooled OR was 2.8 (CI 2.305-3.294). CONCLUSIONS: There was an increased risk of CRC among patients diagnosed with IBS, primarily in the first year after IBS diagnosis. REGISTRATION: The review was registered on PROSPERO (CRD42021236707).

Factors associated with stoma formation in ileocolic resection for Crohn's disease and the development of a predictive scoring system.

PURPOSE: The likelihood of a stoma following ileocolic resection (ICR) for Crohn's disease (CD) is an important consideration. This study aims to identify the factors associated with an increased likelihood of a stoma and develop a predictive scoring system (SS). METHODS: Patient data were collected from St. Marks Hospital, London, UK and Humanitas Clinical and Research Center, Milan, Italy, on all patients who underwent an ICR for CD from 2005 to 2017. A logistic regression analysis was used for multivariate analysis. The SS was developed from the logistic regression model. The performance of the SS was evaluated using receiver operating characteristics area under the curve (AUROC). RESULTS: A total of 628 surgeries were included in the analysis. Sixty-nine surgeries were excluded due to missing data. The remaining 559 were divided into two cohorts for the scoring system's development (n = 434) and validation (n = 125). The regression model was statistically significant (p < 0.0001). The statistically significant independent variables included sex, preoperative albumin and haemoglobin levels, surgical access and simultaneous colonic resection. The AUROC for the development and validation cohorts were 0.803 and 0.905, respectively (p < 0.0001). Youden's index suggested the cut-off score of - 95.9, with a sensitivity of 87.6% and a specificity of 62.9%. CONCLUSIONS: Male sex, low preoperative albumin, anaemia, laparoscopic conversion and simultaneous colonic resection were associated with an increased likelihood of requiring a stoma and were used to develop an SS. The calculator is available online at https://rebrand.ly/CrohnsStoma .

Anal sphincter fatigability in assessing anal incontinence: A systematic review.

BACKGROUND: Diagnosing anal incontinence (AI) based on manometry results is challenging due to the variation of the normal values and overlap between patients with and without AI. This study aimed to perform a systematic review on the difference in sphincter fatigability between patients with and without AI. METHODS: MEDLINE, EMBASE, SCOPUS, and Google Scholar were searched. Studies were included if they included adult patients and assessed anal sphincter fatigability between using manometry. The effect size was estimated as the standardized mean difference (SMD) with 95% confidence intervals. A random-effects model was used. RESULTS: The database searches identified 125 unique articles, and five additional articles were identified from the reference list of articles. One hundred thirteen were excluded through title and abstract review. Nine articles were included in the final analysis. There was no statistically significant difference in the resting pressure between the two groups. Patients with AI had significantly lower squeeze pressure. There was no statistically significant difference between the groups in the fatigue rate. The FRI was significantly lower in patients with AI (SMD 1.636, p = 0.001). Approximately a third of the patients in one study were able to maintain a contraction for 20s without reducing pressure. There was significant heterogeneity in the studies. The data available were inadequate for more robust calculations. CONCLUSIONS: Sphincter fatigability, measured by the Fatigability Rate Index, has good discriminating power for anal incontinence. A standardized protocol needs to be followed by future researchers. Graphical Abstract The analysis used six studies with 413 patients to compare Fatigue Rate Index between patients with AI and controls. All studies reported a lower FRI in patients with incontinence and the FRI was significantly lower in patients with AI (standardized mean difference [SMD] 1.636, p= 0.001). Conflicting results were reported on the correlation between FRI and AI symptom scores.

Classifying perianal fistulising Crohn's disease: an expert consensus to guide decision-making in daily practice and clinical trials.

Perianal fistulising Crohn's disease is an aggressive disease phenotype that can have a substantial detrimental impact on patients' quality of life. Current biological understanding of perianal fistulising Crohn's disease remains inadequate and previous classification systems have not provided clear guidance on therapy in clinical practice nor on defining patient cohorts within clinical trials. We propose a new classification system for perianal fistulising Crohn's disease that was developed through a modified nominal group technique expert consensus process. The classification identifies four groups of patients. Key elements include stratification according to disease severity as well as disease outcome; synchronisation of patient and clinician goals in decision making, with a proactive, combined medical and surgical approach, on a treat to patient goal basis; and identification of indications for curative fistula treatment, diverting ostomy, and proctectomy. The new classification retains an element of flexibility, in which patients can cycle through different classes over time. Furthermore, with each specific class comes a paired treatment strategy suggestion and description of clinical trial suitability. The proposed classification system is the first of its kind and is an important step towards tailored standardisation of clinical practice and research in patients with perianal fistulising Crohn's disease.

Standardization of ileoanal J-pouch surgery technique: Quality assessment of minimally invasive ileoanal J-pouch surgery videos.

BACKGROUND: Ileal pouch anal anastomosis is a complex procedure associated with significant morbidity, with several complications after ileal pouch anal anastomosis surgery leading to pouch failure. The aim of the study is to evaluate the heterogeneity surrounding the technique of ileoanal J-pouch surgery by assessing the safety and quality of published online peer-reviewed surgical videos. METHODS: Ileal pouch anal anastomosis videos published on peer-reviewed surgical journals and video channels were edited and anonymized to demonstrate specific steps of the surgical procedure: mobilization and division of the rectum, formation of the ileoanal J-pouch reservoir, anastomosis, and lengthening techniques. The anonymized videos were presented to a group of reviewers with expertise in ileal pouch anal anastomosis blinded to the names and affiliations of the surgeons performing the procedure. Primary outcome was the rate of interobserver variability in the assessment of specific technical steps of the ileal pouch anal anastomosis surgery procedure. Secondary outcome was the appropriateness of the use of surgical videos review as an assessment tool for ileal pouch anal anastomosis surgery, measured as rate of reviewers being unable to answer for poor video quality. RESULTS: In total, 29 video fragments were distributed, and 13 assessors completed a 60-item survey, organized in 7 major domains. The survey completion rate was 93.4%. Out of a total 729 answers, in 23 (3.2%) the reviewers indicated they were unable to comment due to poor video image, and in 48 (6.5%) were unable to comment due to the particular step not being shown in the procedure. The proportion of assessors rating rectal mobilization technically appropriate ranged from 30.7% to 92.3% and from 7.7% to 69.2% for safety. The level of rectal division was considered appropriate in 0 to 53.8% of the videos, whereas the stapling technique used for rectal division was appropriate in 0 to 70% of the videos. CONCLUSION: Our study assessed published peer-reviewed videos on ileal pouch anal anastomosis surgery and reported heterogeneity in the safety of the demonstrated techniques. Blind assessment of published peer-reviewed ileal pouch anal anastomosis videos reported a high rate of unsafe or inappropriate technique for rectal mobilization and transection in the reviewed videos, with fair interobserver agreement among reviewers. There is a need for consensus on what is considered safe and appropriate in ileal pouch anal anastomosis surgery. Peer review of ileal pouch anal anastomosis surgery videos could facilitate training and accreditation in this complex procedure.

The Essential Role of a Multidisciplinary Approach in Inflammatory Bowel Diseases: Combined Medical-Surgical Treatment in Complex Perianal Fistulas in CD.

Perianal fistulizing Crohn's disease (PFCD) represents a challenging and complex disease phenotype. Patients typically suffer a more severe disease course than those without perianal complications and are often managing debilitating symptoms. Etiology is understood to be multifactorial, with genetic predisposition, microbiological insult, aberrant immunity, and mechanical factors all implicated. As a result, multimodal treatment strategies must be employed to achieve disease control and fistula closure. This requires the complimentary involvement of medical and surgical disciplines in order to ensure thorough assessment and treatment tailored to the individual scenario and patient goals. The aim of this article is to describe an overview of the various treatment strategies available for PFCD, focusing on how a synergistic approach is required to ensure maximal chances of success.

Multicentre derivation and validation of a colitis-associated colorectal cancer risk prediction web tool.

OBJECTIVE: Patients with ulcerative colitis (UC) diagnosed with low-grade dysplasia (LGD) have increased risk of developing advanced neoplasia (AN: high-grade dysplasia or colorectal cancer). We aimed to develop and validate a predictor of AN risk in patients with UC with LGD and create a visual web tool to effectively communicate the risk. DESIGN: In our retrospective multicentre validated cohort study, adult patients with UC with an index diagnosis of LGD, identified from four UK centres between 2001 and 2019, were followed until progression to AN. In the discovery cohort (n=246), a multivariate risk prediction model was derived from clinicopathological features using Cox regression. Validation used data from three external centres (n=198). The validated model was embedded in a web tool to calculate patient-specific risk. RESULTS: Four clinicopathological variables were significantly associated with AN progression in the discovery cohort: endoscopically visible LGD >1 cm (HR 2.7; 95% CI 1.2 to 5.9), unresectable or incomplete endoscopic resection (HR 3.4; 95% CI 1.6 to 7.4), moderate/severe histological inflammation within 5 years of LGD diagnosis (HR 3.1; 95% CI 1.5 to 6.7) and multifocality (HR 2.9; 95% CI 1.3 to 6.2). In the validation cohort, this four-variable model accurately predicted future AN cases with overall calibration Observed/Expected=1.01 (95% CI 0.64 to 1.52), and achieved 100% specificity for the lowest risk group over 13 years of available follow-up. CONCLUSION: Multicohort validation confirms that patients with large, unresected, multifocal LGD and recent moderate/severe inflammation are at highest risk of developing AN. Personalised risk prediction provided via the Ulcerative Colitis-Cancer Risk Estimator ( www.UC-CaRE.uk ) can support treatment decision-making.

Lack of anti-TNF drugs levels in fistula tissue - a reason for nonresponse in Crohn's perianal fistulating disease?

INTRODUCTION: Anti-TNF therapy is recommended as treatment for patients with Crohn´s perianal fistulas. However, a significant proportion of patients have a sub-optimal response to anti-TNF therapy. Higher serum levels of anti-TNF agents have been associated with improved outcomes in perianal Crohn's disease. Currently, it is unknown whether anti-TNF agent levels can be detected in tissue from fistula tracts themselves and whether this is associated with response. AIMS AND METHODS: We undertook a pilot study to measure fistula tissue levels of anti-TNF medication (infliximab and adalimumab). We used a previously validated targeted proteomic technique, employing ultraperformance liquid chromatography-mass spectrometry, to detect/quantify anti-TNF drugs. Biopsies were obtained from fistula tracts of patients with Crohn's disease on maintenance treatment; with idiopathic (cryptoglandular) fistula tissues used as negative controls as well as positive controls (by spiking the latter tissues with anti-TNF drugs). RESULTS: Tissue was sampled from the fistula tracts of seven patients with Crohn's perianal disease (five patients were on adalimumab and two patients were on infliximab). The anti-TNF drugs, infliximab and adalimumab, were not detected in fistula samples from any of the Crohn's patients despite detection in 'spiked' positive control samples. CONCLUSION: Absence of detection of the anti-TNF drugs in fistula tissue raises the question on the role of tissue penetrance of anti-TNF drugs in response to therapy. Further work is required in a larger number of patients to validate the findings observed and investigate if any correlation exists between tissue and serum levels of anti-TNF and clinical outcome. SUMMARY: Predicting response in Crohn's fistula patients on biologic therapy is difficult with no reliable biomarkers. This pilot study uses targeted proteomics to investigate the potential role of tissue drug levels in acting as a biomarker of treatment response.

A Multidisciplinary Approach to Rectal Cancer Treatment in Ulcerative Colitis Results in High Rate of Restorative Minimally Invasive Surgery.

BACKGROUND AND AIMS: Few recent studies focus on the treatment of rectal cancer in patients with ulcerative colitis. We report treatment options and results for this subset of patients with a multimodal approach at two European referral centres. METHODS: Ulcerative colitis patients diagnosed with rectal cancer arising at less than 15 cm from the anal verge between January 2010 and December 2020 were analysed. Demographics, clinical data, and details of medical and surgical treatment were retrieved from prospectively collected institutional databases. RESULTS: Of 132 patients with ulcerative colitis and concomitant colorectal cancer, rectal cancer was diagnosed in 46. The median time between disease onset and rectal cancer diagnosis was 17.5 years; 21/46 were preoperatively staged as early tumours [cT1-T2/N0]. Eleven patients received neoadjuvant chemoradiotherapy for locally advanced extraperitoneal adenocarcinoma, and the rest underwent surgery first. Over two-thirds of the procedures were restorative [68%]; a minimally invasive approach was used in 96% of patients, with no conversion to open. The median follow-up was 44 months. Local recurrence occurred in three patients [6%]. The cumulative 3-year cancer-specific survival rate was 94% [and the 3-year disease-free rate was 86%]. CONCLUSIONS: Rectal cancer in ulcerative colitis is a very complex condition. Our results show that surgery for rectal cancer can be delivered with excellent oncological and functional outcomes in patients with ulcerative colitis. A multidisciplinary discussion among surgeons, gastroenterologists, and medical oncologists is key to ensure the appropriate treatment pathway for individual patients.

Long-term Oncological Outcome of Segmental Versus Extended Colectomy for Colorectal Cancer in Crohn's Disease: Results from an International Multicentre Study.

BACKGROUND AND AIMS: Crohn's disease increases colorectal cancer risk, with high prevalence of synchronous and metachronous cancers. Current guidelines for colorectal cancer in Crohn's disease recommend pan-proctocolectomy. The aim of this study was to evaluate oncological outcomes of a less invasive surgical approach. METHODS: This was a retrospective database analysis of Crohn's disease patients with colorectal cancer undergoing surgery at selected European and US tertiary centres. Outcomes of segmental colectomy were compared with those of extended colectomy, total colectomy, and pan-proctocolectomy. Primary outcome was progression-free survival. Secondary outcomes included overall survival, synchronous and metachronous colorectal cancer, and major postoperative complications. RESULTS: Ninety-nine patients were included: 66 patients underwent segmental colectomy and 33 extended colectomy. Segmental colectomy patients were older [p = 0.0429], had less extensive colitis [p = 0.0002] and no preoperatively identified synchronous lesions [p = 0.0109].Median follow-up was 43 [31-62] months. There was no difference in unadjusted progression-free survival [p = 0.2570] or in overall survival [p = 0.4191] between segmental and extended colectomy. Multivariate analysis adjusting for age, sex, ASA score, and AJCC staging, confirmed no difference for progression-free survival (hazard ratio [HR] 1.00, p = 0.9993) or overall survival [HR 0.77, p = 0.6654]. Synchronous and metachronous cancers incidence was 9% and 1.5%, respectively. Perioperative mortality was nil and major complications were comparable [7.58% vs 6.06%, p = 0.9998]. CONCLUSIONS: Segmental colectomy seems to offer similar long-term outcomes to more extensive surgery. Incidence of synchronous and metachronous cancers appears much lower than previously described. Further prospective studies are warranted to confirm these results.

Emerging Data on Fistula Laser Closure (FiLaC) for the Treatment of Perianal Fistulas; Patient Selection and Outcomes.

Fistula laser closure (FiLaC) is a relatively new sphincter-sparing technique in fistula surgery that was initially reported in 2011. It involves the radial dissipation of laser energy in the fistula tract and, through a combination of coagulation and shrinkage of the tract, is proposed to result in progressive sealing of fistulas. Early studies have suggested minimal impact on continence and touted the advantage of minimal morbidity with potential of repeat procedures if the technique fails initially. Despite early promising results, ten years on, questions remain on the technique, patient selection and long-term outcomes. This narrative review assesses the evidence reported to-date of radially emitting laser fistula surgery in the treatment of perianal fistulas.

Current review of the management of fistulising perianal Crohn's disease.

Perianal manifestations of Crohn's disease constitute a distinct disease phenotype commonly affecting patients and conferring an increased risk of disability and disease burden. Much research has gone into management of fistulising manifestations, with biological therapy changing the landscape of treatment. In this article, we discuss the up-to-date surgical and medical management of perianal fistulas, highlighting current consensus management guidelines and the evidence behind them, as well as future directions in management.