Pharmacological treatment of postoperative recurrence of Crohn's disease: Protocol for systematic review and network meta-analysis.

BACKGROUND: Crohn's disease (CD) is a chronic inflammatory condition primarily affecting the digestive system. When dealing with complex cases like intestinal blockages or perforations, surgery becomes the primary treatment option. However, surgery doesn't offer a complete cure, and the possibility of recurrence remains. To manage CD recurrence after surgery, various treatment choices are available, including steroids, monoclonal antibodies, immunomodulators, and further surgery. Regrettably, the current body of evidence doesn't definitively establish which of these treatments is the most effective and safe. Thus, our research aims to provide insights into the Validity and security of different treatment approaches for managing CD recurrence after surgery. METHODS: Search of EMBASE, PubMed, Web of Science Core Collection and the Cochrane Central Register of Controlled Trials will be conducted to include researches that examine the validity of treatments for recurrent CD after surgery. Our analysis will distinguish between two types of studies: randomized controlled trials (RCTs) and non-randomized studies with at least two different treatments, each evaluated separately. We will employ Bayesian network meta-analyses to systematically compare the effectiveness and safety of these treatments. Additionally, subgroup analyses will be performed according to recurrence status and postoperative prophylactic medication. To clarify the variation of studies, sensitivity analyses will be performed. And we may use meta-regression as an additional approach if relevant data are available. We will also rigorously access the certainty of evidence using the Grading of Recommendations, Assessment, Development, and Evaluation framework. DISCUSSION: This analysis will provide a comprehensive assessment of the latest evidence on available treatments for patients with postoperative recurrence of CD, which will provide recommendations for clinical practice. TRIAL REGISTRATION: Systematic review registration INPLASY2023110021. (DOI: 10.37766/inplasy2023.11.0021).

Serum amyloid A for predicting prognosis in patients with newly diagnosed Crohn's disease.

OBJECTIVE: Serum amyloid A (SAA) was found to be positively correlated with the activity of Crohn's disease (CD); however, its prognostic value remains uncertain. Here, we examined its predictive ability in newly diagnosed CD and explored genetic association. METHODS: This retrospective cohort study included patients newly diagnosed as CD at the First Affiliated Hospital of Sun Yat-sen University between June 2010 and March 2022. We employed receiver operating characteristic curve, Cox proportional hazard regression models and restricted cubic splines to investigate the prognostic performance of SAA for surgery and disease progression. To assess possible causality, a two-sample Mendelian randomisation (MR) of published genome-wide association study data was conducted. RESULTS: During 2187.6 person-years (median age, 28 years, 72.4% male), 87 surgery and 153 disease progression events were documented. A 100-unit increment in SAA level generated 14% higher risk for surgery (adjusted HR (95% CI): 1.14 (1.05-1.23), p=0.001) and 12% for disease progression (1.12 (1.05-1.19), p<0.001). Baseline SAA level ≥89.2 mg/L led to significantly elevated risks for surgery (2.08 (1.31-3.28), p=0.002) and disease progression (1.72 (1.22-2.41), p=0.002). Such associations were assessed as linear. Adding SAA into a scheduled model significantly improved its predictive performances for surgery and disease progression (p for net reclassification indexes and integrated discrimination indexes <0.001). Unfortunately, no genetic causality between SAA and CD was observed in MR analysis. Sensitivity analyses showed robust results. CONCLUSION: Although causality was not found, baseline SAA level was an independent predictor of surgery and disease progression in newly diagnosed CD, and had additive benefit to existing prediction models.

Development of a nomogram for postoperative surgical site infections in patients undergoing bowel resection for Crohn's disease.

BACKGROUND: Surgical site infection (SSI) is a significant concern due to its potential to cause delayed wound healing and prolonged hospital stays. This study aims to develop a predictive model in patients with Crohn's disease. METHODS: We conducted single-factor and multi-factor logistic regression analyses to identify risk factors, resulting in the development of a logistic regression model and the creation of a nomogram. The model's effect was validated by employing enhanced bootstrap resampling techniques, calibration curves, and DCA curves. Finally, we investigated the risk factors for wall and intra-abdominal infections separately. RESULTS: 90 of 675 patients (13.3 %) developed SSI. Several independent risk factors for SSI were identified, including higher postoperative day one neutrophil count (p = 0.033), higher relative blood loss (p = 0.018), female gender (p = 0.021), preoperative corticosteroid use (p = 0.007), Montreal classification A1 and L2 (p < 0.05), previous intestinal resection (p = 0.017), and remaining lesions (p = 0.015). Additionally, undergoing strictureplasty (p = 0.041) is a protective factor against SSI. These nine variables were used to develop an SSI prediction model presented as a nomogram. The model demonstrated strong discrimination (adjusted C-statistic=0.709, 95 % CI: 0.659∼0.757) and precise calibration. The decision curve showed that the nomogram was clinically effective within a probability threshold range of 3 % to 54 %. Further subgroup analysis revealed distinct risk factors for wall infections and intra-abdominal infections. CONCLUSION: We established a new predictive model, which can guide the prevention and postoperative care of SSI after Crohn's disease bowel resection surgery to minimize its occurrence rate.

Evaluation of adverse clinical outcomes in patients with inflammatory bowel disease receiving different sequences of first- and second-line biologic treatments: findings from ROTARY.

BACKGROUND: Patients with inflammatory bowel disease (IBD) are at risk of developing dysplasia and, subsequently, colorectal cancer (CRC) owing to chronic inflammation. Patients may also experience other severe disease complications, such as hospitalization and surgery. Several biologics are available for the treatment of patients with IBD and some patients require multiple lines of treatment owing to loss of response or tolerability to their prescribed biologic. Previous studies suggest that the choice of initial biologic treatment may impact the outcomes of later treatment lines. In this study, we assessed adverse clinical outcomes in patients with Crohn's disease (CD) or ulcerative colitis (UC) who received different biologic treatment sequences. METHODS: ROTARY part B was a retrospective cohort study using the Optum® Clinical Database that evaluated the incidences of IBD-related hospitalization, IBD-related surgery, dysplasia, CRC, and infections in patients with CD or UC who received two biologics successively. First-line biologics included adalimumab, infliximab, ustekinumab (CD only), and vedolizumab; second-line biologics included infliximab and adalimumab. RESULTS: In patients with CD, the treatment sequence of ustekinumab to infliximab was associated with the highest overall incidences of hospitalization (51.9%), surgery (40.7%), CRC (3.7%), and infection (37.0%). Vedolizumab followed by an anti-tumor necrosis factor alpha (anti-TNFα) treatment was associated with a significantly lower risk of experiencing an adverse medical event (hospitalization, surgery, or infection) than two successive anti-TNFα treatments (odds ratio, 1.526; 95% confidence interval, 1.004-2.320; P < 0.05). In patients with UC, the treatment sequence of vedolizumab to adalimumab resulted in the lowest overall incidence of adverse outcomes (20.3%, 6.3%, 0.0%, 6.3%, and 4.7% for hospitalization, surgery, CRC, dysplasia, and infection, respectively). CONCLUSIONS: We describe differences in adverse clinical outcomes associated with sequencing of biologics in patients with CD or UC and demonstrate favorable results in patients who received vedolizumab as a first-line biologic. These results provide potential guidance to clinicians choosing sequences of biologic treatments in patients with IBD.

Epidemiological investigation of different types of Crohn's disease patients undergoing first abdominal surgery in the era of biological agents: a population-based cohort study.

BACKGROUND: Before the era of biological agents, most Crohn's disease patients required at least one intestinal resection surgery after diagnosis. However, clinical data regarding the abdominal surgery rates for Crohn's disease patients in the era of biological agents is not yet fully clear and needs to be updated. MATERIALS AND METHODS: We retrospectively collected clinical data from 1115 Crohn's disease patients diagnosed and treated medically at The Second Xiangya Hospital of Central South University from January 2016 to January 2024. Using abdominal intestinal resection surgery as a clinical outcome, propensity score matching was employed to eliminate confounding factors. We explored the timing and proportion of abdominal surgery in patients with different Montreal classifications of Crohn's disease during the natural course of the disease, as well as the impact of the duration of the natural course and the use of biological agents on surgical outcomes. RESULTS: Montreal classification type B had the greatest impact on Crohn's disease surgery, especially with a higher proportion of type B3 patients undergoing surgery. Type A1 Crohn's disease patients underwent surgery earlier than types A2 and A3. The occurrence of behavior changes (B Change) during the natural course of the disease is a poor prognostic signal, indicating a significantly increased likelihood of surgery. The duration of the natural course from the onset of gastrointestinal symptoms to diagnosis and clinical observation outcomes did not directly affect the likelihood of surgery in Crohn's disease patients. Compared with Crohn's disease patients who did not receive biological agents, the surgery rate was significantly lower in patients who used biological agents. Additionally, Crohn's disease patients who received biological agents within 1 month of diagnosis had a significantly lower likelihood of undergoing surgical intervention. Moreover, Crohn's disease patients who received biological agent treatment within 19 months of the onset of gastrointestinal symptoms also had a significantly lower likelihood of undergoing surgery than other Crohn's disease patients. CONCLUSIONS: In the era of biological agents, the risk of surgical intervention varies among Crohn's disease patients with different Montreal classifications, particularly when there is type B3 disease or a B Change. Clinicians should pay closer attention to surgical indications in such cases. For Crohn's disease patients, shortening the natural course before diagnosis and early use of biological agents after diagnosis can significantly reduce the risk of abdominal surgery.

Small bowel Crohn's disease neglected by gastroenterologists and anorectal surgeons with a 7-year delay in diagnosis: A case report.

RATIONAL: Small bowel Crohn's disease (SBCD) is a common site of Crohn's disease (CD). However, owing to the anatomical characteristics of the small bowel and the limitations of traditional examination methods, the detection and diagnosis of SBCD remain difficult. Gastroenterologists and anorectal surgeons should pay more attention to improving the early diagnosis rate, so as to improve the prognosis of patients and reduce the probability of surgery due to complications. PATIENT CONCERNS: Here, we presented a case of a young male with severe localized pain in the right kidney area and fever but no weight loss or diarrhea, who had a history of perianal abscess surgery 7 years ago and an elevated platelet count reviewing his previous medical examination report. DIAGNOSES: SBCD was not diagnosed until complications of intestinal fistula developed 7 years after perianal abscess surgery. INTERVENTIONS: Anti-infection treatment was administered due to elevated inflammatory markers and evidence of infection on computed tomography scan, and exclusive enteral nutrition (EEN) was then performed because of the diagnosis of SBCD. Although the infection was absorbed by the treatment with EEN, a laparoscopic modified partial enterectomy was finally performed due to the complication of intestinal fistula. OUTCOMES: The patient was discharged on the seventh postoperative day without postoperative complications and started biologic therapy 2 weeks after surgery because he had high-risk factors for postoperative recurrence. The pathological report revealed the involvement of the ileum in CD, and confirmed the existence of the intestinal fistula. LESSONS: Gastroenterologists and anorectal surgeons should be aware that perianal abscess could be the first manifestation of SBCD; even if typical CD manifestations are absent, proper further examinations are necessary based on the comprehensive analysis of clinical data of patients. In addition, the platelet count deserves attention in patients with potentially possible CD. More importantly, it is important to emphasize the importance of EEN in adult CD patients.

Comparative real-world outcomes between ustekinumab, infliximab, and adalimumab in bio-naïve and bio-experienced Crohn's disease patients: a retrospective multicenter study.

BACKGROUND: Numerous studies have compared the efficacy of ustekinumab (UST) and anti-TNF agents [infliximab (IFX) or adalimumab(ADA)] in moderate to severe Crohn's disease (CD) patients. This study aims to compare the efficacy of UST, IFX, and ADA while differentiating between bio-naïve and bio-experienced patients, which is an underexplored aspect, particularly in Asia. METHODS: We conducted a retrospective multi-center study from 2012 to 2023, categorizing patients into bio-naïve and bio-experienced groups. We evaluated clinical remission rates after induction therapy and clinical outcomes, including CD-related hospitalization, intestinal resection, and drug discontinuation during maintenance therapy. RESULTS: Among the 214 bio-naïve CD patients, 60 received UST, 108 received IFX, and 46 received ADA. After 1:1 propensity score matching between UST and anti-TNF agents groups, 59 patients were analyzed in each group (45 in the IFX group and 14 in the ADA group). We found no significant differences in clinical remission rates (P = 0.071), CD-related hospitalization (P = 0.800), intestinal resection (P = 0.390), or drug discontinuation (P = 0.052) between the UST, IFX, and ADA groups in bio-naïve CD patients. In bio-experienced CD patients, with 35 in the UST group and 13 in the anti-TNF agents group, the UST group showed a lower risk of drug discontinuation (P = 0.004) than the anti-TNF agents group. CONCLUSIONS: This study suggests that UST, IFX, and ADA are equally effective in bio-naïve CD patients, while in bio-experienced patients, mostly with previous exposure to anti-TNF agents, UST may offer superior drug durability.

Management of complications in patients with an ileostomy: an umbrella review of systematic reviews for the EndOTrial Consortium.

BACKGROUND: Standardized clinical care processes for patients with Crohn's disease (CD) and a permanent ileostomy (PI) are lacking. The EndOTrial consortium aims to address this gap by developing pathways for care. METHODS: In this umbrella review, we searched major databases for relevant systematic reviews (SRs) or scoping reviews (ScR) published until January 5, 2024. Screening, data extraction, and quality appraisal (AMSTAR 2) were performed by two independent reviewers. RESULTS: Of 1349 screened papers, 22 reviews met our inclusion criteria, including 20 SRs (eight with meta-analysis) and 2 ScRs. None exclusively focused on PI. Furthermore, nine reviews did not mention patients with inflammatory bowel disease (IBD), and only two reviews included patients with high-output ileostomy, highlighting a large evidence gap. The identified reviews covered six categories with nine types of interventions, including ostomy care pathways, peristomal skin care, patient education, clinical management of high-output stoma, management and prevention of postoperative ileus, dietary and nutritional support, nursing and supporting care, telemedicine, and self-management interventions. Most SRs including nursing interventions for stoma care highlighted nurses' role in a variety of standard and specialized treatments. Notably, none of the reviews exclusively examined disease recurrence, stoma pouching systems or adhesives, behavioral interventions, or mental health in patients living with ileostomy. CONCLUSIONS: Evidence for best practice interventions to treat complications and improve quality of life in patients living with an ileostomy for CD is limited and heterogeneous. These results outline the need for standardized clinical care processes and pathways tailored to the unique needs of this patient population.

Effect of Kono-S anastomosis on reducing postoperative recurrence rates in Crohn's disease: a systematic review and meta-analysis.

BACKGROUND: Kono-S anastomosis has gained increasing interest although evaluation of its impact on reducing Crohn's recurrence shows conflicting results. This study aimed to evaluate the short- and long-term outcomes for patients with Crohn's disease requiring surgery with Kono-S compared to conventional anastomosis. METHODS: A systematic review and meta-analysis included patients with Crohn's disease treated with bowel resection and Kono-S anastomosis reconstruction versus a comparator arm of conventional anastomosis technique. Recurrence outcomes examined were endoscopic recurrence rates, mean postoperative Rutgeerts score, surgical recurrence, clinical recurrence, and postoperative biologics use. Short-term postoperative outcomes include anastomotic leaks, surgical site infection, postoperative ileus, and mean operative time. RESULTS: A total of 873 studies were identified with 15 remaining after abstract review encompassing 1501 patients, 765 with Kono-S and 736 with conventional anastomosis. Recurrence was significantly lower in the Kono-S arm, with endoscopic recurrence rates of 41% vs 48% (RR 0.86, 95% CI 0.73-1.00, p = 0.05) and surgical recurrence rates of 2.7% vs 21.0% (RR 0.13, 95% CI 0.06-0.30, p < 0.001). There was a significantly lower anastomotic leak rate in the Kono-S arm when compared to conventional anastomosis, 1.7% vs 4.9% (RR 0.37, 95% CI 0.19-0.74, p = 0.005). Mean operative time was similar between both groups. CONCLUSIONS: Kono-S is a safe and feasible anastomotic technique with lower rates of endoscopic and surgical postoperative recurrence. While we await further trials to substantiate this benefit, Kono-S anastomosis should be considered as an important tool in the armamentarium of a surgeon in anastomotic construction to reduce recurrence.

Real-World Long-Term Persistence and Surgical Procedure-Free Period Among Bio-naïve Patients with Crohn's Disease and Fistula Initiated on Ustekinumab.

INTRODUCTION: Fistula is a common complication of Crohn's disease (CD). Treatment with biologics has been associated with fistula healing. Long-term persistence is an important factor for a chronic inflammatory process such as fistula. This study described 24-month persistence and time-to-surgery endpoints among bio-naïve patients with CD and intestinal fistula who were initiated on ustekinumab. METHODS: Adults with CD and any enteric or perianal fistula initiated on ustekinumab (index date) between September 23, 2016, and March 2, 2022, were selected from the IQVIA PharMetrics® Plus database and followed up to 24 months. Persistence on ustekinumab (no gaps in days of supply of > 120 days) and composite endpoints of being persistent while on monotherapy and persistent while corticosteroid free were also assessed. The date of surgery was defined as the date of first claim for any CD-related surgeries. Persistence and time-to-surgery endpoints were assessed from the index date until the earliest of discontinuation (event), immunomodulator or other biologic use (event), corticosteroid use (event), date of surgery (event), 24-month follow-up or data end (censoring) using Kaplan-Meier analyses. RESULTS: The sample included 445 patients (mean age: 42.8 years; 56.6% female). The most common type of fistula was anal fistula (36.0%). At 24 months after ustekinumab initiation, 64.2% of patients remained persistent (95% confidence interval [CI] 55.8-71.4). Furthermore, 53.3% of patients were persistent while on monotherapy (95% CI 45.1-60.7), and 45.6% of patients were persistent while being corticosteroid free (95% CI 36.9-53.8). At 24 months, 22.8% (95% CI 17.0-30.3) of patients underwent any CD-related surgery. CONCLUSION: This study quantified long-term persistence on ustekinumab among bio-naïve patients with CD and fistula. Over half of patients initiated on ustekinumab were persistent and persistent while on monotherapy 24 months after initiation. Time-to-surgery estimate was comparable to existing evidence. These findings support ustekinumab as a treatment option for long-term management of CD with fistula.

Temporary diverting loop ileostomy in Crohn's disease surgery; indications and outcome.

INTRODUCTION: Crohn's disease can present with complex surgical pathologies, posing a significant risk of morbidity and mortality for patients. The implementation of a loop ileostomy for selected patients may help minimize associated risks. METHODS: In this retrospective cohort study, we investigated the utilization of temporary fecal diversion through the creation of a loop ileostomy in Crohn's surgery. Closure of all ostomies involved a hand-sewn single-layer technique. We then conducted bivariate analysis on 30-day outcomes for closures, focusing on favorable recovery defined as the restoration of bowel continuity without the occurrence of two challenges in recovery: newly developed organ dysfunction or the necessity for reoperation. RESULTS: In total, 168 patients were included. The median age of the patients was 38 years (IQR 27-51). The most common indication for a loop ostomy was peritonitis (49%). After ileostomy closure, 163 patients (97%) achieved favorable recovery, while five encountered challenges; four (2.4%) underwent abdominal surgery, and one (0.6%) developed acute renal failure requiring dialysis. Two patients (1.2%) had a re-creation of ileostomy. Patients encountering challenges were older (56 [IQR 41-61] vs. 37 [IQR 27-50]; p 0.039) and more often required secondary intention wound healing (40% vs. 6.7%; p 0.049) and postoperative parenteral nutrition following their index surgery (83% vs. 26%; p 0.006). CONCLUSION: Selectively staging the Crohn's disease operations with a loop ileostomy is a reliable practice with low morbidity and high restoration rates of bowel continuity. Our hand-sewn single-layer technique proves effective in achieving successful surgical recovery.

Assessing robotic-assisted surgery versus open approach in penetrating Crohn's disease: advantages and outcomes in ileocolic resection.

INTRODUCTION: Penetrating Crohn's disease (CD) often necessitates surgical intervention, with the open approach traditionally favored. Robotic-assisted surgery offers potential benefits but remains understudied in this complex patient population. Additionally, the lack of standardized surgical complexity scoring in CD hinders research and comparisons. METHODS: We retrospectively analyzed adult patients with penetrating CD who underwent either robotic-assisted ileocolic resection (RICR) or open ileocolic resection (OICR) at our institution from January 2007 to December 2021. We assessed endpoints, including length of stay, complications, readmissions, reoperations, and other perioperative outcomes. RESULTS: RICR demonstrated safety outcomes comparable to OICR. Importantly, RICR patients experienced significantly reduced estimated blood loss (p < 0.0001), shorter hospital stays (median 4.5 days versus 6.9 days; p = 0.01), lower surgical site infection rates (0% versus 15.4%; p = 0.01), and decreased 30-day readmission rates (0% versus 15.4%; p = 0.01). Linear regression analysis revealed the need for additional strictureplasties (coefficient: 84.8; p = 0.008), colonic resections (coefficient: 41.7; p = 0.008), and estimated blood loss (coefficient: 0.07; p = 0.002) independently correlated with longer operative times). CONCLUSION: Robotic-assisted surgery appears to be a safe and potentially beneficial alternative for the surgical management of penetrating CD, offering advantages in perioperative outcomes reducing length of stay, blood loss, surgical site infection rates, and readmission rates. Further validation with larger cohorts is warranted.

Transanal circumferential pouch advancement for treatment of pouch vaginal fistulae.

BACKGROUND: Ileal pouch anal anastomosis (IPAA) circumferential pouch advancement (CPA) involves full-thickness transanal 180-360° dissection of the distal pouch, allowing the advancement of healthy bowel to cover the internal opening of a vaginal fistula. We aimed to describe the long-term outcomes of this rare procedure. METHODS: Patients with IPAA who underwent transanal pouch advancement for any indication between 2009 and 2021 were included. Demographics, operative details, and outcomes were reviewed. An early fistula was defined as occurring within 1 year of IPAA construction. Clinical success was defined as resolution of symptoms necessitating CPA, pouch retention, and no stoma at the time of follow-up. Figures represent the median (interquartile range) or frequency (%). RESULTS: Over a 12-year period, nine patients were identified; the median age at CPA was 41 (36-44) years. Four patients developed early fistula after index IPAA, and five developed late fistulae. The median number of fistula repair procedures prior to CPA was 2 (1-2). All patients were diagnosed with ulcerative colitis at the time of IPAA and all late patients were re-diagnosed with Crohn's disease. Four (44.4%) patients had ileostomies present at the time of surgery, three (33.3%) had one constructed during surgery, and two (22.2%) never had a stoma. The median follow-up time was 11 (6-24) months. Clinical success was achieved in four of the nine (44.4%) patients at the time of the last follow-up. CONCLUSIONS: Transanal circumferential pouch advancement was an effective treatment for refractory pouch vaginal fistulas and may be offered to patients who have had previous attempts at repair.

Management of Complications in Crohn's Disease.

Complications of Crohn's disease reach far beyond postsurgical leak, infection, and enterocutaneous fistula. Malnutrition, intestinal failure, and recurrent disease all will require ongoing attentions. The management of these patients may further be complicated by the need for chronic immunosuppression. The underlying principles continue to include optimization of nutritional status, and preservation of bowel length when possible. However, there have been several recent advances in both the medical and surgical management of the disease. Understanding the contribution of the mesentery to inflammation, new surgical techniques such as the Kono-S anastomosis and extended mesenteric resection is decreasing the need for repeated resections.

Outcomes after right-sided colon surgery in Crohn's disease versus cancer.

BACKGROUND: Surgery for Crohn's disease (CD) is considered to have more complications due to the underlying inflammation, immunosuppression, and malnutrition. We sought to study the outcomes of right-sided colonic resection in patients with CD and patients with cancer at a high-volume tertiary center utilizing a standardized perioperative protocol. METHODS: This is a retrospective study of outcomes for all patients with CD or patients undergoing ileocolic resection or right hemicolectomy with ileocolic anastomosis at a single institution from 2013 to 2022. Patients were excluded if they simultaneously underwent another procedure or ostomy creation. Data were analyzed using Wilcoxon rank-sum and chi-squared tests for univariate analyses, and logistic and linear regressions for multivariate analyses. RESULTS: In total 141 patients with CD and 589 patients with cancer were included. Patients with CD were significantly younger with lower body mass index and less likely to have comorbidities, including diabetes and hypertension. Patients with CD were less likely to have a smoking history or prior abdominal surgery, but more likely to be on steroids. Both groups had similar rates of laparoscopy, intraoperative complications, and blood loss. Despite the preoperative and intraoperative differences, both patients with CD and patients with cancer had similar lengths of stay (LOS), readmission, reoperation, and mortality rates. None of the surgical outcomes differed significantly between the two groups. On multivariate analysis, CD diagnosis was not associated with reoperation, readmission, mortality, or LOS while controlling for other characteristics. CONCLUSIONS: With the use of standardized perioperative protocols, surgery for CD at a high-volume center with expertise in CD can be performed with comparable results to other indications like cancer.

Effect of mesenteric sparing or extended resection in primary ileocolic resection for Crohn's disease on postoperative endoscopic recurrence (SPICY): an international, randomised controlled trial.

BACKGROUND: Retrospective research suggests that excision of the affected mesentery can improve outcomes after an ileocoecal resection in Crohn's disease. However, prospective data from randomised controlled trials are scarce. We aimed to compare rates of postoperative recurrence in patients with Crohn's disease who underwent extended mesenteric resection. METHODS: This international, randomised controlled trial was done in six hospitals and tertiary care centres in the Netherlands and Italy. Eligible patients were aged 16 years or older and had Crohn's disease that was previously confirmed by endoscopy in the terminal ileum or ileocolic region (L1 or L3 disease), with an imaging update in the past 3 months (ultrasound, MRI, or CT enterography). Eligible patients were scheduled to undergo primary ileocolic resection with ileocolic anastomosis. Enrolled patients were assigned by use of simple random allocation (1:1) to either extended mesenteric resection (intervention) or conventional mesenteric sparing resection (control). The primary endpoint was endoscopic recurrence 6 months after surgery. Analyses were done in all patients with primary endpoint data, excluding those who had no anastomosis, a postoperative diagnosis other than Crohn's disease, or withdrew consent. This trial was registered with ClinicalTrials.gov, NCT04538638. FINDINGS: Between Feb 19, 2020, and April 24, 2023, we assessed 217 patients for eligibility. 78 patients were excluded due to failure to meet the inclusion criteria or refusal to participate. 139 patients were enrolled and randomly assigned to either extended mesenteric resection (n=71) or mesenteric sparing resection (n=68). All 139 patients underwent surgery. Six patients were excluded after random assignment due to withdrawal of consent (n=2), postoperative diagnosis other than Crohn's disease (n=2) and no anastomosis performed (in case of a stoma; n=2). Two patients were lost to follow-up, and two more patients deviated from the protocol by undergoing investigations other than endoscopy 6 months after. 133 patients were included in the baseline analysis (67 in the extended resection group and 66 in the sparing resection group) of whom 57 (43%) were male. Baseline characteristics were similar between the groups, and median patient age was 36 years (IQR 25-54). 131 patients were analysed for the primary outcome. There was no difference between groups in the rate of endoscopic recurrence at 6 months after surgery (28 [42%] of 66 patients in the extended mesenteric resection group vs 28 [43%] of 65 patients in the mesenteric sparing resection group, relative risk 0·985, 95% CI 0·663-1·464; p=1·0). Five (8%) of 66 patients in the extended mesenteric resection group had anastomotic leakage within the 30 days after surgery, as did one (2%) of 65 in the mesenteric sparing group. Postoperative complications of Clavien-Dindo grade IIIa or higher were reported in seven (11%) patients in the mesenteric resection group and five (8%) in the mesenteric sparing group. INTERPRETATION: Extended mesenteric resection was not superior to conventional resection with regard to endoscopic Crohn's disease recurrence. These data support the guideline-recommended mesenteric sparing approach. FUNDING: Topconsortia voor Kennis en Innovatie-Topsector Life Sciences & Health.