Risk factors for endoscopic postoperative recurrence in patients with Crohn's Disease: a protocol for systematic review and meta-analysis.

BACKGROUND: Crohn's disease (CD) is a chronic condition characterized by a high recurrence rate after surgery, which seriously affects the quality of life of patients. Many studies have explored the risk factors for the recurrence of CD after surgery, there is a lack of meta-analysis focusing on endoscopic postoperative recurrence (ePOR) as a clinical outcome. Therefore, this paper aims to identify the risk factors for ePOR in CD patients through systematic review and meta-analysis. METHODS: PubMed, Embase, Cochrane Library, and Web of Science databases were searched for related literature from inception to 17th October 2023. Two researchers independently screened the literature and extracted information. Data analysis was performed using Stata18.0. RESULTS: Twenty-three papers were included, with 5 case-control studies and 18 cohort studies. The National Institutes of Health quality assessment tool rated 17 studies as good and 6 studies as fair. The sample size of the 23 studies ranged from 40 to 346, and the number of patients with ePOR ranged from 23 to 169. The results of multivariate meta-analysis showed that smoking [OR = 2.06, 95% CI (1.65, 2.57), P = 0.0001], previous ileocolonic resection [OR = 1.71, 95% CI (1.23, 2.38), P = 0.002], disease localization at ileocolic resection [OR = 2.68, 95% CI (1.38, 5.22), P = 0.004], perianal disease [OR = 1.47, 95% CI (1.07, 2.03), P = 0.017], and anastomotic scattered ulcer [OR = 3.39, 95% CI (1.83, 6.28), P = 0.001] were risk factors for ePOR in CD patients. Postoperative prophylactic medication [OR = 0.53, 95% CI (0.38,0.75), P = 0.0001] was a protective factor for ePOR in CD patients. CONCLUSIONS: This systematic review identified multiple factors for ePOR in CD patients, as well as a protective factor. However, the number of articles included was limited. More high-quality clinical studies are required to further validate the conclusions. TRIAL REGISTRATION: This study was registered in the International Prospective Register of Systematic Reviews (PROSPERO) (CRD42023483671).

Reversal Surgery for Split Stoma with Peristomal Incision is Associated with Improved Postoperative Outcome in Patients with Crohn's Disease.

BACKGROUND: Temporary stoma formation is common in Crohn's disease (CD), while stoma reversal is associated with postoperative morbidity. This study aimed to evaluate the postoperative outcomes of split stoma reversal, SSR (i.e., exteriorization of proximal and distal ends of the stoma through a small common opening) and end stoma closure, ESC (i.e., the proximal stump externalized, and distal end localized abdominally. METHODS: Patients with CD who underwent stoma reversal surgeries between January 2017 and December 2021 were included. Demographic, clinical, and postoperative data were collected and analyzed to evaluate outcomes of reversal surgery. RESULTS: A total of 255 patients who underwent stoma reversal surgeries met the inclusion criteria. SSR was superior to ESC in terms of operative time (80.0 vs. 120.0, p = 0.0004), intraoperative blood loss volume (20.0 vs. 100.0, p = 0.0002), incision length (3.0 vs. 15.0, p < 0.0001), surgical wound classification (0 vs. 8.3%, p = 0.04), postoperative hospital stay (7.0 vs. 9.0, p = 0.0007), hospital expense (45.6 vs. 54.2, p = 0.0003), and postoperative complications (23.8% vs. 44.3%, p = 0.0040). Although patients in the ESC group experienced more surgical recurrence than those in the SSR group (8.3% vs. 3.2%) during the follow-up, the Kaplan-Meier curve analysis revealed no statistical difference (p = 0.29). CONCLUSIONS: The split stoma can be recommended when stoma construction is indicated in patients with Crohn's disease.

Multimodal Prehabilitation for Patients with Crohn's Disease Scheduled for Major Surgery: A Narrative Review.

Approximately 15-50% of patients with Crohn's disease (CD) will require surgery within ten years following the diagnosis. The management of modifiable risk factors before surgery is essential to reduce postoperative complications and to promote a better postoperative recovery. Preoperative malnutrition reduced functional capacity, sarcopenia, immunosuppressive medications, anemia, and psychological distress are frequently present in CD patients. Multimodal prehabilitation consists of nutritional, functional, medical, and psychological interventions implemented before surgery, aiming at optimizing preoperative status and improve postoperative recovery. Currently, studies evaluating the effect of multimodal prehabilitation on postoperative outcomes specifically in CD are lacking. Some studies have investigated the effect of a single prehabilitation intervention, of which nutritional optimization is the most investigated. The aim of this narrative review is to present the physiologic rationale supporting multimodal surgical prehabilitation in CD patients waiting for surgery, and to describe its main components to facilitate their adoption in the preoperative standard of care.

Clinical Significance of Prognostic Nutrition Index in Patients with Crohn's Disease after Primary Bowel Resection.

PURPOSE: Although advancements in medical treatments have been made, approximately half of patients with intestinal Crohn's disease (CD) require intestinal resections during their lifetime. It is well-known that the nutritional status of CD patients can impact postoperative morbidity. The objective of this study was to evaluate the clinical significance of prognostic nutritional index (PNI) in patients with intestinal CD who underwent primary bowel resection. MATERIALS AND METHODS: We retrospectively investigated patients who were diagnosed with CD and underwent intestinal surgery at Severance Hospital between January 2005 and October 2018. The patients were divided into two groups: PNI ≤40 (n=150) and PNI >40 (n=77). We assessed the clinical significance of PNI in terms of the incidence of postoperative infectious complications (PICs) and the postoperative recurrence of CD. RESULTS: The low PNI group had significantly higher rates of infectious complications (32.0% vs. 10.4%, p=0.001) compared to the high PNI group. Multivariable analysis identified low PNI (≤40) and longer operation time (>180 min) as independent risk factors associated with PICs [odds ratio (OR)=2.754, 95% confidence interval (CI)=1.140-6.649, p=0.024; OR=2.986, 95% CI=1.451-6.143, p=0.003]. PICs were significantly associated with surgical recurrence (hazard ratio=2.217, 95% CI=1.064-4.617, p=0.034). CONCLUSION: Preoperative PNI could serve as a predictive factor for PICs in CD patients who undergo intestinal resection. Additionally, PICs are significantly associated with a higher risk of surgical recurrence in CD.

Totally Laparoscopic Ileocolic Resection with Intracorporeal Anastomosis for Crohn's Disease: A Comparative Study.

BACKGROUND: Although minimally invasive surgery for Crohn's disease has been validated in previous studies, most of those reports have referred to laparoscopic-assisted procedures with an extra-corporeal anastomosis. OBJECTIVES: To evaluate the short- and long-term outcomes of total laparoscopic ileocolic resection with an intracorporeal anastomosis for Crohn's disease patients. METHODS: We conducted a single-center retrospective review of all patients who underwent primary ileocolic resection for Crohn's disease between 2010 and 2021. Group A included 34 patients who underwent total laparoscopic ileocolic resection with intracorporeal anastomosis. Group B comprised 144 patients who underwent an open or laparoscopic-assisted procedure. RESULTS: No differences were noted in operative time (mean 167 minutes vs. 152 minutes, P = 0.122), length of stay (median 6.4 days vs. 7.5 days, P = 0.135), readmission rates (11.8% vs. 13.2%, P = 1), and microscopic involvement of surgical margins (7.7% vs. 18.5%, P = 0.249). Group A had significantly fewer postoperative surgical site infections (2.9% vs. 22.2% respectively, P = 0.013), with no differences in other complications prevalence. After a median follow-up of 46 months, there were similar rates of endoscopic recurrence (47.1% vs. 51.4%, P = 0.72), clinical recurrence (35.3% vs. 47.9%, P = 0.253), and surgical recurrence (2.9% vs. 4.9%, P = 0.722). CONCLUSIONS: Total laparoscopic ileocolic resection with intracorporeal anastomosis for Crohn's disease is safe and resulted in favorable outcomes in terms of postoperative wound healing. The long-term disease recurrence rates were like those of laparoscopic-assisted and open ileocolic resection.

What is the rate of definitive stoma after subtotal colectomy for inflammatory bowel disease? A nationwide study of 1860 patients.

AIM: Some patients with inflammatory bowel disease (IBD) require subtotal colectomy (STC) with ileostomy. The recent literature reports a significant number of patients who do not undergo subsequent surgery and are resigned to living with a definitive stoma. The aim of this work was to analyse the rate of definitive stoma and the cumulative incidence of secondary reconstructive surgery after STC for IBD in a large national cohort study. METHOD: A national retrospective study (2013-2021) was conducted on prospectively collected data from the French Medical Information System Database (PMSI). All patients undergoing STC in France were included. The association between definitive stoma and potential risk factors was studied using univariate and multivariate analyses. RESULTS: A total of 1860 patients were included (age 45 ± 9 years; median follow-up 30 months). Of these, 77% (n = 1442) presented with ulcerative colitis. Mortality and morbidity at 90 days after STC were 5% (n = 100) and 47% (n = 868), respectively. Reconstructive surgery was identified in 1255 patients (67%) at a mean interval of 7 months from STC. Seveny-four per cent (n = 932) underwent a completion proctectomy with ileal pouch anal anastomosis and 26% (n = 323) an ileorectal anastomosis. Six hundred and five (33%) patients with a definitive stoma had an abdominoperineal resection (n = 114; 19%) or did not have any further surgical procedure (n = 491; 81%). Independent risk factors for definitive stoma identified in multivariate analysis were older age, Crohn's disease, colorectal neoplasia, postoperative complication after STC, laparotomy and a low-volume hospital. CONCLUSION: We found that 33% of patients undergoing STC with ileostomy for IBD had definitive stoma. Modifiable risk factors for definitive stoma were laparotomy and a low-volume hospital.

The use of opioids nine months after surgery for Crohn's disease - a nationwide cohort study.

BACKGROUND: The risk of chronic opioid use after surgery for Crohn's disease (CD) is not known. AIM: The aim of this study is to examine the chronic opioid use after surgery according to age at time of surgery and to opioid use prior to surgery. METHODS: This nationwide cohort study included patients with a first surgery for CD (January 1, 1996 through 2021). We examined prescribed opioids 9 months after surgery and estimated adjusted odds ratios (OR) for chronic opioid use in elderly (≥60 years), adults (≥40 and <60 years), and young adults (≥18 and <40 years) according to opioid use prior to surgery. Chronic opioid use was defined as prescriptions in at least two of three consecutive quarters. RESULTS: A total of 797 patients had surgery as elderly, 1603 as adults, and 2786 as young adults. Across all age groups, 18%-38% received opioid prescriptions throughout 9 months after surgery, if opioids were prescribed prior to surgery. If opioids were not prescribed prior to surgery, the corresponding proportions were 2%-5%. If patients were prescribed opioids (≥1) prior to surgery, the adjusted ORs (95% CIs) for their chronic use after surgery in elderly, adults, and young adults were 10.37 (6.77-15.88), 10.48 (7.74-14.19), and 6.55 (4.93-8.72), respectively. CONCLUSION: Clinicians should be aware that in patients with a need for opioids before surgery, the surgery may not change the need for opioids. Future research should examine effective analgesic strategies that help minimise opioid use in this population.

Positive resection margins in Crohn's disease are a relevant risk factor for postoperative disease recurrence.

Postoperative disease recurrence in Crohn's disease represents a relevant issue despite recent advancements in surgical and medical therapies. Additional criteria are necessary to improve the identification of patients at risk and to enable selective therapeutic approaches. The role of resection margins on disease recurrence remains unclear and general recommendations are lacking. A single-center retrospective analysis was performed including all patients who received ileocecal resection due to Crohn's disease. Resection margins were analyzed by two independent pathologists and defined by histopathological criteria based on previous consensus reports. 158 patients were included for analysis with a median follow up of 35 months. While postoperative morbidity was not affected, positive resection margins resulted in significantly increased rates of severe endoscopic recurrence at 6 months (2.0% versus 15.6%, p = 0.02) and overall (4.2% versus 19.6%, p = 0.001), which resulted in significantly increased numbers of surgical recurrence (0% versus 4.5%, p = 0.04). Additionally, positive margins were identified as independent risk factor for severe endoscopic disease recurrence in a multivariate analysis. Based on that, positive margins represent an independent risk factor for postoperative endoscopic and surgical disease recurrence. Prospective studies are required to determine whether extended resection or postoperative medical prophylaxis is beneficial for patients with positive resection margins.

Impact of antitumour necrosis factor therapy on surgery in inflammatory bowel disease: a population-based study.

OBJECTIVE: It is unclear whether widespread use of biologics is reducing inflammatory bowel disease (IBD) surgical resection rates. We designed a population-based study evaluating the impact of early antitumour necrosis factor (TNF) on surgical resection rates up to 5 years from diagnosis. DESIGN: We evaluated all patients with IBD diagnosed in Cardiff, Wales 2005-2016. The primary measure was the impact of early (within 1 year of diagnosis) sustained (at least 3 months) anti-TNF compared with no therapy on surgical resection rates. Baseline factors were used to balance groups by propensity scores, with inverse probability of treatment weighting (IPTW) methodology and removing immortal time bias. Crohn's disease (CD) and ulcerative colitis (UC) with IBD unclassified (IBD-U) (excluding those with proctitis) were analysed. RESULTS: 1250 patients were studied. For CD, early sustained anti-TNF therapy was associated with a reduced likelihood of resection compared with no treatment (IPTW HR 0.29 (95% CI 0.13 to 0.65), p=0.003). In UC including IBD-U (excluding proctitis), there was an increase in the risk of colectomy for the early sustained anti-TNF group compared with no treatment (IPTW HR 4.6 (95% CI 1.9 to 10), p=0.001). CONCLUSIONS: Early sustained use of anti-TNF therapy is associated with reduced surgical resection rates in CD, but not in UC where there was a paradoxical increased surgery rate. This was because baseline clinical factors were less predictive of colectomy than anti-TNF usage. These data support the use of early introduction of anti-TNF therapy in CD whereas benefit in UC cannot be assessed by this methodology.

Stapled versus hand-sewn anastomoses after bowel resection in patients with crohn disease.

BACKGROUND: Anastomosis configuration is an essential step in treatment to restore continuity of the gastrointestinal tract following bowel resection in patients with Crohn's disease (CD). However, the association between anastomotic type and surgical outcome remains controversial. This retrospective study aimed to compare early postoperative complications and surgical outcome between stapler and handsewn anastomosis after bowel resection in Crohn's disease. METHODS: Between 2001 and 2018, a total of 339 CD patients underwent bowel resection with anastomosis. Patient characteristics, intraoperative data, early postoperative complications, and outcomes were analyzed and compared between two groups of patients. Group 1 consisted of patients with stapler anastomosis and group 2 with handsewn anastomosis. RESULTS: No significant difference was found in the incidence of postoperative surgical complications between the stapler and handsewn anastomosis groups (25% versus 24.4%, p = 1.000). Reoperation for complications and postoperative hospital stay were similar between the two groups. CONCLUSION: Our analysis showed that there were no differences in anastomotic leak, nor postoperative complications, mortality, reoperation for operative complications, or postoperative hospital stay between the stapler anastomosis and handsewn anastomosis groups.

Mesenteric-based surgery for Crohn's disease: evidence and perspectives.

Postoperative anastomotic recurrence of Crohn's disease is challenging and can lead to symptom recurrence and further surgery. The mesenteric pole of the intestine is the initial site of macroscopic anastomotic recurrence, and the mesentery may play an important role in recurrence after surgical resection. Therefore, "mesenteric-based surgery" has gained increasing attention by clinicians. However, the role of mesentery in the postoperative recurrence remains controversial. This review will examine mesenteric changes in Crohn's disease, proposed roles for mesentery in disease progression, and the potential for mesenteric-based surgery in the surgical management of Crohn disease.

Risk factors for surgery in stricturing small bowel Crohn's disease: A retrospective cohort study from the GETAID pédiatrique.

OBJECTIVES: Previous studies have shown rates of surgical resection of up to 41% in stricturing pediatric Crohn's disease (CD). In this retrospective multicenter study, our aims were to identify clinical risk factors and magnetic resonance enterography (MRE) features of small bowel strictures associated with surgery. METHODS: Pediatric patients with symptomatic stricturing small bowel CD (defined as obstructive symptoms or proximal dilatation on MRE) confirmed by MRE between 2010 and 2020 were recruited from 12 French tertiary hospitals. Patient characteristics were compared by surgical outcome multivariable Cox regression. RESULTS: Fifty-six patients (61% boys) aged 12.2 ± 2.7 years at diagnosis of CD were included. Median duration of CD before diagnosis of stricture was 11.7 months (interquartile range [IQR]: 25-75: 1.2-29.9). Nineteen (34%) patients had stricturing phenotype (B2) at baseline. Treatments received  before stricture diagnosis included MODULEN-IBD (n = 31), corticosteroids (n = 35), antibiotics (n = 10), anti-TNF (n = 27), immunosuppressants (n = 28). Thirty-six patients (64%) required surgery, within 4.8 months (IQR: 25-75: 1.8-17.3) after stricture diagnosis. Parameters associated with surgical resection were antibiotic exposure before stricture diagnosis (adjusted odds ratio [aOR]: 15.62 [3.35-72.73], p = 0.0005), Crohn's disease obstructive symptoms score (CDOS) > 4 (aOR: 3.04 [1.15-8.03], p = 0.02) and dilation proximal to stricture >28 mm (aOR: 3.62 [1.17-11.20], p = 0.03). CONCLUSION: In this study, antibiotic treatment before stricture diagnosis, intensity of obstructive symptoms, and diameter of dilation proximal to small bowel stricture on MRE were associated with risk for surgical resection.

Surgical management of duodenal crohn's disease.

BACKGROUND: Operative options for duodenal Crohn's disease include bypass, stricturoplasty, or resection. What factors are associated with operation selection and whether differences exist in outcomes is unknown. METHODS: Patients with duodenal Crohn's disease requiring operative intervention across a multi-state health system were identified. Patient and operative characteristics, short-term surgical outcomes, and the need for future endoscopic or surgical management of duodenal Crohn's disease were analyzed. RESULTS: 40 patients underwent bypass (n = 26), stricturoplasty (n = 8), or resection (n = 6). Median age of diagnosis of Crohn's disease was 23.5 years, and over half of the patients had undergone prior surgery for CD. Operation type varied by the most proximal extent of duodenal involvement. Patients with proximal duodenal CD underwent bypass operations more commonly than those with mid- or distal duodenal disease (p = 0.03). Patients who underwent duodenal stricturoplasty more often required concomitant operations for other sites of small bowel or colonic CD (63%) compared to those who underwent bypass (39%) or resection (33%). No patients required subsequent surgery for duodenal CD at a median follow-up of 2.8 years, but two patients required endoscopic dilation (n = 1 after stricturoplasty, n = 1 after resection). CONCLUSION: Patients who require surgery for duodenal Crohn's disease appear to have an aggressive Crohn's disease phenotype, represented by a younger age of diagnosis and a high rate of prior resection for Crohn's disease. Choice of operation varied by proximal extent of duodenal Crohn's disease.

Parenteral n-3 polyunsaturated fatty acids supplementation improves postoperative recovery for patients with Crohn's disease after bowel resection: a randomized, unblinded controlled clinical trial.

BACKGROUND: The postoperative inflammatory response is associated with postoperative recovery in surgery. n-3 (ω-3) polyunsaturated fatty acids have been reported to lower inflammation. The postoperative role of parenteral n-3 polyunsaturated fatty acids supplementation on outcomes in Crohn's disease after bowel resection is unclear. OBJECTIVES: We aimed to investigate the effects of postoperative parenteral n-3 polyunsaturated fatty acids supplementation in Crohn's disease. METHODS: A prospective randomized, unblinded controlled clinical trial was conducted for patients with Crohn's disease who underwent bowel resection between May 2019 and February 2022. Postoperative complications, complete blood count, serum biochemical values, and cytokine concentrations were compared in patients with and without parenteral n-3 polyunsaturated fatty acids supplementation for 5 d postoperatively. RESULTS: There were 268 patients randomly assigned in the analysis, with 134 in the control group (a mix of long-chain and medium-chain fats at 1.0 g/kg/d) and 134 in the treatment group (long-chain, medium-chain, and n-3 polyunsaturated fats at 1.2 g/kg/d). Twenty-six did not complete the allocated treatment, and 8 patients were lost to follow-up. The intention-to-treat analysis and the per-protocol analysis showed that there were a significant reduction in overall complication rates (22.4% compared with 49.3%; P < 0.001 and 21.8% compared with 38.2%; P = 0.006) and postoperative stay (8.8 ± 4.5 d compared with 11.2 ± 6.8 d; P = 0.001 and 8.7 ± 4.0 d compared with 11.5 ± 7.3 d; P < 0.001) in patients with parenteral n-3 polyunsaturated fatty acids supplementation compared with patients in the control group. In the secondary outcomes, the mean ± standard deviation of interleukin (IL)-6 (17.11 ± 2.14 pg/mL compared with 30.50 ± 5.14 pg/mL; P = 0.014), IL-1ß (2.01 ± 0.05 pg/mL compared with 2.24 ± 0.09 pg/mL; P = 0.019), tumor necrosis factor-α (2.09 ± 0.06 pg/mL compared with 2.29 ± 0.06 pg/mL; P = 0.029), and C-reactive protein concentrations (51.3 ± 4.2 mg/L compared with 64.4 ± 5.3 mg/L; P = 0.050) on postoperative day 5 in the treatment group were much lower than those in the control group. CONCLUSIONS: Parenteral n-3 polyunsaturated fatty acids supplementation promotes postoperative recovery in patients with Crohn's disease following bowel resection, with fewer complications and reduced inflammatory cytokines. This trial was registered at clinicaltrials.gov as NCT03901937 at https://classic. CLINICALTRIALS: gov/ct2/show/NCT03901937?term=NCT03901937&cond=Crohn+Disease&draw=2&rank=1.

The need for surgery in pediatric patients with inflammatory bowel disease treated with biologicals.

PURPOSE: Inflammatory bowel disease (IBD) in childhood often presents with a more extensive and more aggressive disease course than adult-onset disease. We aimed to evaluate if biological treatment started in childhood decreases the need for intestinal surgery over time. METHODS: This was a retrospective, single-center, cohort study. All pediatric patients with IBD initiated to biological therapy at the Children's Hospital, were included in the study and followed up to the first surgical procedure or re-operation in their adulthood or until 31.12.2021 when ≥ 18 of age. Data were collected from the pediatric registry of IBD patients with biologicals and medical charts. RESULTS: A total of 207 pediatric IBD patients were identified [150 with Crohn´s disease (CD), 31 with ulcerative colitis (UC), 26 with IBD unclassified (IBDU)] of which 32.9% (n = 68; CD 49, UC 13, IBDU 6) underwent intestinal surgery. At the end of a median follow-up of 9.0 years (range 2.0-25.9), patients reached a median age of 21.4 years (range 18-36). Patients who had intestinal surgery in childhood were more likely to have IBD-related surgery also in early adulthood. The duration of the disease at induction of the first biological treatment emerged as the only risk factor, with a longer duration in the surgical group than in patients with no surgery. CONCLUSION: Despite initiation of biological treatment, the risk of intestinal surgery remains high in pediatric IBD patients and often the need for surgery emerges after the transition to adult IBD clinics.

Beyond diagnosis: investigating hospital referral impact on biological treatment initiation, hospital admission, and surgery patterns in inflammatory bowel disease - a Danish population based study.

OBJECTIVES: Early biological treatment in patients with inflammatory bowel disease (IBD) is important in disease control. Previous studies have suggested that patients with IBD from Non-Academic Hospitals were less likely to receive biologics. The aims of this study were (1) to use the granular data in the clinical database, GASTROBIO, to study detailed differences in time from IBD diagnosis to first administration of biologics, hospital admission, and surgery in patients referred to Academic Hospitals versus to Non-Academic Hospitals, and (2) to explore differences in disease extent, behavior, and indication for biological treatment. MATERIAL AND METHODS: This was a retrospective cross-sectional descriptive population-based quality study of patients with IBD initiating biologics in the North Denmark Region between 2016 and 2018. Data from GASTROBIO were extracted, namely demographic data, time of diagnosis, biological treatments with indications, hospital admission, and surgery. RESULTS: Of the 146 patients included, 84 were from the Academic and 62 from the Non-Academic Hospitals. No significant differences in median time from diagnosis to (1) treatment, (2) hospital admission or (3) IBD surgery between the groups were observed. A higher percentage of patients with luminal Crohn's disease were treated with biologics at the Academic Hospital (78% and 66%). CONCLUSIONS: Based on the findings of this population-based study, we found no evidence that the referral area had a significant impact on the duration from diagnosis to the initiation of biological treatment, hospital admissions, or surgery. However, the data suggested that fewer patients with luminal Crohn's disease were referred to biologics from Non-Academic Hospitals.