Objectives Invasive endoscopy and fecal calprotectin remain the standard for monitoring of ulcerative colitis (UC) However, these procedures are resource- and time-consuming, and patients are reluctant to participate. As neutrophil granulocytes are mediators of inflammation in UC, we evaluated the biomarker capacity of two novel markers of neutrophil activation. We investigated the association between these markers and clinical disease scores and their ability to distinguish between patients with UC and healthy individuals. Materials and methods In a prospective study setting, blood samples were collected from 68 consecutive patients with a suspected flare of UC and from 71 healthy controls. Neutrophil Reactivity Intensity (Neut-RI) and Neutrophil Granularity Intensity (Neut-GI) were analyzed using the automated hematology analyzer Sysmex XN-9000. ROC curve analysis assessed the ability to discriminate between controls and UC patients. In patients, the Mayo score, Simple Clinical Colitis Activity Index (SCCAI) score, fecal calprotectin and C-reactive protein (CRP) were recorded. Spearman's correlation coefficients between clinical data and the novel markers were calculated. Results Neut-RI and Neut-GI levels were significantly higher among patients than controls (p < 0.001). Neut-RI discriminated between patients and controls (AUC 0.756, 95% CI 0.676; 0.837) and correlated significantly with Mayo score and SCCAI (Spearman's Rho 0.40/0.27). No such correlations were found for fecal calprotectin or CRP. Furthermore, Neut-RI discriminated patients with proctitis from patients with more widespread disease (p < 0.05). Conclusions Neut-RI significantly correlated with disease activity in UC patients and proved superiority to fecal calprotectin. Neut-RI could be a promising low-cost, non-invasive biomarker for disease activity in UC.

BACKGROUND:In individuals with inflammatory bowel disease (IBD), low-grade dysplasia (LGD) is a risk factor for advanced neoplasia, that is, high-grade dysplasia and colorectal cancer. Over recent decades, advances in IBD management and endoscopic surveillance have been implemented; however, it remains unclear whether these developments have influenced the incidence of LGD and advanced neoplasia. OBJECTIVE:To describe contemporary trends in the population-level incidence of LGD and advanced neoplasia in IBD. DESIGN:We conducted a nationwide Danish cohort study (1990-2022) using national healthcare registers. IBD was defined at the second recorded healthcare contact with an IBD diagnosis. Annual age-standardised incidence rates (IRs) per 1,000 IBD patient-years were calculated for LGD and advanced neoplasia. Incidence rate ratios (IRRs) relative to 1990 were estimated using Poisson regression. RESULTS:Among 78,126 individuals with IBD, we identified 6,814 incident cases of LGD and 1,987 of advanced neoplasia. The IR of LGD increased from 0.68 per 1,000 IBD patient-years in 1990 to 4.41 in 2022 (IRR 6.47, 95% confidence interval (CI) 3.99-10.49), with a sustained increase after the introduction of the national general colorectal cancer screening programme in 2014. In contrast, the IR of advanced neoplasia remained stable (IRR 1.10, 95% CI 0.59-2.07). CONCLUSION:The incidence of IBD-related LGD increased markedly over the study period, particularly after the introduction of the national general colorectal cancer screening programme in 2014, whereas the incidence of advanced neoplasia remained stable. These findings highlight the need for robust risk stratification to identify individuals who may benefit from surveillance.

OBJECTIVE:Pro-inflammatory T-cell responses dominate in Crohn's disease (CD). This may result from a dysbalanced expression of co-stimulatory and inhibitory T-cell receptors. The present study investigated if a dysbalanced co-stimulatory and inhibitory T-cell receptor expression are present in CD and can be rebalanced by anti-TNFα treatment. METHODS:Mucosal biopsies from 27 patients with active CD receiving anti-TNF treatment were examined for the mRNA levels of the co-stimulatory 4-1BB and inhibitory PD-1 T-cell receptor. Levels of mRNA were compared between inflamed and noninflamed tissue, and before and after treatment. Peripheral T cells from 12 healthy controls (HC) and 11 active CD patients were evaluated for their expression of 4-1BB and PD-1 by flow cytometry. RESULTS:The 4-1BB mRNA levels in inflamed mucosa were upregulated (> 2-fold) compared with uninflamed mucosa (p < 0.05). Anti-TNFα treatment reduced the 4-1BB and PD-1 mRNA levels in the inflamed gut tissue (p < 0.05). In in vitro activated T cells, the percentage of both 4-1BB and PD-1 positive CD4+ and CD8+ T cells increased more than 1.5 fold compared with HC (p < 0.05). The 4-1BB/PD-1 ratio on activated peripheral T cells was significantly reduced in CD after anti-TNF therapy (p < 0.05). CONCLUSIONS:A dysbalanced mucosal proinflammatory co-stimulatory T cell receptor expression was present in active CD and modified by anti-TNFα treatment. However, anti-TNFα treatment did not normalize the expression of 4-1BB or PD-1 on peripheral T cells although a modest increased immunoregulatory capacity could be demonstrated.

BACKGROUND AND AIMS:Existing findings on outcomes of anti-tumor-necrosis-factor (TNF) therapy in patients with inflammatory bowel diseases (IBD) are largely based on retrospective studies. We aimed to investigate real-world outcomes of anti-TNF therapy and predictors thereof in a prospective IBD cohort. METHODS:In a Danish multicenter cohort of adult bio-naïve patients with IBD treated with anti-TNF, we assessed clinical response and remission to induction therapy using clinical disease activity scoring indices at Week 14. In patients who continued treatment beyond the induction period, we also assessed loss of response (LOR), drug withdrawal, and major IBD surgery during maintenance therapy. RESULTS:This study included 774 patients (706 infliximab, 68 adalimumab) followed for a median duration of 125 weeks Clinical response was achieved in 209/331 (67.4%) of ulcerative colitis (UC) and 125/197 (74.0%) of Crohn's disease (CD) patients, while 143/331 (46.1%) UC and 81/197 (47.9%) CD patients achieved clinical remission. In 294 UC and 309 CD patients received maintenance therapy, while 86/294 (29.3%) UC and 78/309 (25.2%) CD patients experienced LOR. Active smoking and less severe disease activity predicted favorable outcomes in UC, while short disease duration, colonic disease, nonstricturing behavior, and concomitant immunomodulator therapy predicted favorable outcomes in CD. CONCLUSIONS:Clinical response was achieved in 2 in 3 UC and 3 in 4 CD patients, meanwhile, one-third of UC and one-fourth of CD patients experienced LOR despite the short disease duration in this study. Several clinical features were associated with outcomes and may be useful predictors of anti-TNF treatment response.

PURPOSE:Patients with intestinal inflammatory diseases such as ulcerative colitis (UC), Crohn's disease (CD), and microscopic colitis (MC) are excluded from clinical trials with immune checkpoint inhibitors (ICI) because of concerns of exacerbating their underlying immune-mediated disease. This study evaluated the risk of developing disease activity or checkpoint inhibitor checkpoint inhibitor-mediated enterocolitis (IMC). MATERIALS AND METHODS:We performed a nationwide, retrospective cohort study in Denmark, analyzing patients with UC, CD, and MC diagnosed with cancer and treated with ICIs between 2010 and 2024. RESULTS:Eighty-five patients were included, and IMC was observed in 39 (46%) patients. Of these, 15 cases were mild, allowing 61 (72%) patients to continue ICI treatment. Multivariate logistic analysis showed that patients with CD had a lower odds ratio (OR) for developing IMC compared with patients with UC and MC (OR, 0.07, P = .02). When compared with a control cohort without intestinal disease (n = 81), patients with UC, CD, and MC had a significantly higher risk of developing IMC when treated with anti-PD-1/anti-PD-L1 inhibitors, with a hazard ratio of 4.93, P < .001. CONCLUSION:Patients with CD appear to have a lower risk of IMC than those with UC and MC. Despite an increased risk of IMC and severe IMC in patients with UC, CD, and MC, 72% of the patients were able to continue first-line treatment with ICI. Treatment with ICI in patients with UC, CD, and MC is overall well tolerated and should be considered on the basis of the same criteria as in patients without intestinal diseases.

Chronic anal fissures in patients with Crohn’s disease (CD) remain a significant therapeutic challenge, particularly when linked to active perianal disease. Conventional treatments often fail, highlighting the need for alternative approaches. This study explores the efficacy and safety of freshly collected autologous adipose tissue injection (AATI) for treating chronic fissures in patients with CD. Nine patients with CD with anal fissures were included. The primary outcome was complete healing (CH) at 3 months after last AATI, defined as full fissure re-epithelialization and complete pain relief. Secondary outcomes included changes in defecation pain (visual analog scale [VAS]), anal discomfort (VAS), Perianal Disease Activity Index (PDAI), and St. Mark’s Incontinence Score (SMIS). Five patients (56

Single nucleotide polymorphisms (SNPs) in the endoplasmic reticulum aminopeptidase 1 (ERAP1) and ERAP2 genes have been associated with susceptibility to various immune-mediated inflammatory diseases (IMIDs). We utilized a unique cohort from the National Centre for Autoimmune Diseases (NCAS) to investigate whether specific SNPs in ERAP1 and ERAP2 act as a shared genetic susceptibility factor across various IMIDs. The study population comprised 171 patients from the NCAS cohort with two or more IMIDs and 57 healthy controls. Using real-time PCR allelic discrimination methods, we genotyped specific SNPs in ERAP1 (rs30187, rs27524), ERAP2 (rs2248374) and HLA-C (rs4406273). The distribution of ERAP1 and ERAP2 risk/minor alleles, genotypes and haplotypes was similar in the NCAS cohort and in healthy controls. When stratifying for HLA-C*06:02 positive psoriasis patients, a disease-associated haplotype A-A-T (rs2248374, rs27524, rs30187) was identified, significantly increasing the odds for having psoriasis and one or more IMIDs (OR = 3.41, 95 % CI: 1.32 - 8.78, p = 0.008). While SNPs in ERAP1 and ERAP2 may not constitute a shared susceptibility factor across all IMIDs, this study suggests a complex interaction between HLA types, ERAP1, and ERAP2, potentially influencing the development of certain MHC-I-associated disorders.

BACKGROUND & AIMS:Perianal fistulation is a challenging phenotype of Crohn's disease, with significant impact on quality of life. Historically, fistulae have been classified anatomically in relation to the sphincter complex, and management guidelines have been generalized, with lack of attention to the clinical heterogenicity seen. The recent 'TOpClass classification system' for perianal fistulizing Crohn's disease (PFCD) addresses this issue, and classifies patients into defined groups, which provide a focus for fistula management that aligns with disease characteristics and patient goals. In this article, we discuss the clinical applicability of the TOpClass model and provide direction on its use in clinical practice. METHODS:An international group of perianal clinicians participated in an expert consensus to define how the TOpClass system can be incorporated into real-life practice. This included gastroenterologists, inflammatory bowel disease surgeons, and radiologists specialized in PFCD. The process was informed by the multi-disciplinary team management of 8 high-volume fistula centres in North America, Europe, and Australia. RESULTS:The process produced position statements to accompany the classification system and guide PFCD management. The statements range from the management of patients with quiescent perianal disease to those with severe PFCD requiring diverting-ostomy and/or proctectomy. The optimization of medical therapies, as well as the use of surgery, in fistula closure and symptom management is explored across each classification group. CONCLUSION:This article provides an overview of the system's use in clinical practice. It aims to enable clinicians to have a pragmatic and patient goal-centered approach to medical and surgical management options for individual patients with PFCD.

IL-22 facilitates mucosal healing by directly inducing epithelial regeneration and barrier integrity, which is essential for achieving remission and thereby treating inflammatory bowel disease. Here, we evaluated efficacy of a novel lipidated IL-22 alone and in combination with immunomodulatory agents in addressing chronic dextran sodium sulfate (DSS)-induced colitis in mice and demonstrated action of IL-22 on mucosal healing. Mice were treated with DSS, followed by various doses of lipidated IL-22, anti-TNF antibody, fingolimod, or anti-mouse α4β7 integrin antibody. Additionally, gene expression was determined in colonic biopsies from ulcerative colitis patients to assess effects of IL-22 stimulation. Lipidated IL-22 significantly improved all aspects of chronic DSS-induced colitis in mice, with dose-dependent efficacy. Combinations of a range of immunomodulatory agents with lipidated IL-22 showed further additive reductions in disease activity, significantly greater than those of monotherapies. Immunohistochemistry revealed that lipidated IL-22 increased epithelial cell proliferation and reduced CD3+ T-cell infiltration, indicating enhanced mucosal healing. This was further supported gene expression data from colonic biopsies from ulcerative colitis patients after IL-22 stimulation. Given the challenges in achieving long-term remission in IBD due to inflammation and mucosal damage, lipidated IL-22 presents a promising treatment option that directly promotes mucosal healing, unlike traditional immunomodulatory therapies.

BACKGROUND AND AIMS:Individuals with inflammatory bowel disease (IBD) and related low-grade dysplasia (LGD) have an elevated risk of developing high-grade dysplasia (HGD) or colorectal cancer (CRC). The magnitude of this risk and the influence of risk factors, such as the calendar year of diagnosis and exposure to medical therapy, remain uncertain. We therefore investigated the 15-year cumulative incidence of HGD or CRC and the impact of potential risk factors using Danish healthcare registers. METHODS:We conducted a nationwide cohort study of all Danish individuals diagnosed with IBD-related LGD between 1997 and 2023. Individuals with prior colectomy, HGD, CRC, or familial adenomatous polyposis were excluded. The cumulative incidence of subsequent HGD or CRC was estimated, treating death and colectomy as competing risks. Multivariable Cox regression assessed hazard ratios (HRs) for potential risk factors. RESULTS:Among 7455 individuals, the 15-year cumulative incidence of HGD and/or CRC following IBD-related LGD was 6.3% (95% confidence interval CI: 5.5-7.2). The risk declined over time, with lower hazards in 2017-2020 (HR: 0.45 [95% CI: 0.30-0.67]) and 2020-2023 (HR: 0.24 [95% CI: 0.14-0.43]) compared with 1997-2010. Anti-TNF-α therapy (≥5 doses) showed a non-significant trend toward reduced risk (HR: 0.32 [95% CI: 0.09-1.11]). Identified risk factors included: age (per 5 years: HR: 1.11 [95% CI: 1.06-1.17]), IBD duration (per 5 years: HR: 1.13 [95% CI: 1.07-1.19]), having a first-degree relative with CRC (HR: 1.73 [95% CI: 1.12-2.68]), episodes of elevated fecal calprotectin (per episode in the 5 years prior to inclusion: HR: 1.14 [95% CI: 1.02-1.27]), and high-dose prednisone use in the year prior to inclusion (HR: 1.53 [95% CI: 1.01-2.31]). CONCLUSION:Among Danish individuals with IBD-related LGD, the overall 15-year cumulative incidence of subsequent HGD or CRC was 6.3% and has declined markedly over time. In addition to established risk factors, including age, IBD duration, family history of CRC, and elevated fecal calprotectin, we found that high-dose prednisone use was associated with an increased risk.

BACKGROUND:Ileal pouch-anal anastomosis (IPAA) is a standard surgical procedure for ulcerative colitis (UC) and familial adenomatous polyposis. However, pouch-related fistulae (PRF) are a significant complication. There is no consensus on the optimal treatment for PRF. OBJECTIVE:This study evaluated the effectiveness of autologous adipose tissue injection (AATI) as a treatment for PRF. METHODS:Twenty-one patients with IPAA and a total of 29 PRF were treated with AATI. Patients who did not achieve healing after the first treatment were offered repeated injections. Patients were followed for a median of 16 months after AATI. Outcomes including clinical healing, treatment complications, and recurrence of PRF were registered. RESULTS:After a single treatment with AATI, 48% of the fistulae were clinically healed. Repeated treatments increased the healing rate to 69%. An additional 14% responded to AATI by reduced secretion from PRF. The procedure was well tolerated with minimal complications. CONCLUSION:AATI appears to be a safe, minimally invasive, and sphincter-saving treatment for PRF with promising healing rates. Further studies with larger cohorts are necessary to validate these findings.

INTRODUCTION:A no-biopsy approach has been suggested for diagnosing coeliac disease (CD) in adult patients. This approach is already well established in diagnosing children with CD. This study aimed to evaluate the accuracy of IgA anti-tissue transglutaminase (IgA anti-tTG) in predicting duodenal mucosal lesions diagnostic of CD in adult patients. METHODS:We included all patients aged ≥ 18 years referred for CD diagnostics at our department in the period from 1 January 2019 to 31 December 2023 with raised IgA anti-tTG levels and in whom duodenal biopsies had been evaluated for CD-specific lesions. Data regarding IgA anti-tTG levels and duodenal histology evaluated by the modified Marsh classification were retrieved from the patient records. RESULTS:A total of 235 adult patients had positive IgA anti-tTG levels and an available duodenal histology. High IgA anti-tTG levels (> 10 × upper limit of normal (ULN)) were associated with more severe enteropathy. The PPV of IgA anti-tTG for identifying Marsh ≥ 2 or 3 lesions increased when the serological cut-off was raised. The positive predictive value of IgA anti-tTG > 10 × ULN was 99.2% (95% CI: 95.8-100%) and 97.7% (95% CI: 93.4-99.5%) for predicting Marsh ≥ 2 and 3 lesions, respectively. CONCLUSIONS:This study confirms that high titers of IgA anti-tTG may accurately identify adults with diagnostic duodenal mucosal lesions associated with CD. Our data support the use of a no-biopsy approach for diagnosing CD in adults with high IgA anti-tTG titers. FUNDING:None. TRIAL REGISTRATION:Not relevant.

Abstract Background Fistula cancer is a rare and often devastating diagnosis in patients with perianal fistulising Crohn’s disease (CD). Fistula cancer management is a complex process requiring multi-disciplinary effort. However, given the low incidence and subsequent lack of data and clinical trials in the field, there is little to no guidance on screening and management of fistula cancer. To inform clinical practice, we developed consensus guidelines on fistula cancer in perianal fistulising Crohn’s disease by multidisciplinary experts from the international TOpCLASS consortium. Methods We performed a systematic review of the literature by standard methodology, using the Newcastle-Ottawa quality assessment tool. Data were retrieved from articles according to these domains: epidemiology and risk factors, clinical presentation, diagnostics, staging, and treatment. We developed consensus statements using a Delphi consensus approach. Participants included gastroenterologists, surgeons, radiologists, and pathologists. We performed two rounds of voting: (1) online survey followed by statement edits and (2) hybrid meeting with discussion until over 80% consensus was achieved for each statement. Results Of 550 articles identified, 99 were eligible, and 80 articles were included. The overall quality of evidence was low. Seven statements were accepted in the final consensus (Table 1). Patients with longstanding (>10 years) perianal fistulising CD should be considered at small but increased risk of developing fistula cancer, including anal squamous cell cancer (SCC) and anorectal carcinoma. Risk factors for anal SCC, including human papilloma virus (HPV), should be considered. Clinical signs and symptoms of fistula cancers are non-specific, and several case reports included asymptomatic patients. New or refractory/progressive perianal symptoms should prompt evaluation for fistula cancer. There was no consensus on timing or frequency of screening in patients with asymptomatic perianal fistula. Regarding diagnostics, multiple modalities may be required, including repeated exam under anesthesia with biopsy. Multidisciplinary team efforts were deemed central for the management of fistula cancers. Conclusion Clinicians managing patients with perianal fistulising CD should be aware of the risk of fistula cancers, including anal SCC and anorectal carcinoma. Our expert consensus recommends consideration of patient factors including duration of fistulas, HPV status, and perianal symptoms, and gives guidance on diagnostic modalities and treatment considerations. Multidisciplinary coordination of care is paramount, and more studies in the field are needed.

Intestinal macrophages and fibroblasts act as microenvironmental sentinels mediating inflammation and disease progression in Crohn’s disease (CD). We aimed to establish the effects of fecal supernatants (FSs) from patients with CD on macrophage and fibroblast phenotype and function. FS were obtained by ultracentrifugation, and the metabolites were analyzed. Monocyte-derived M2 macrophages and fibroblasts were conditioned with FS, and secreted proteins, surface proteins and gene expression were analyzed. M2 macrophage efferocytosis was evaluated. Patients with CD (n = 15) had a skewed fecal metabolite profile compared to healthy subjects (HS, n = 10). FS from CD patients (CD-FS) induced an anti-inflammatory response in M2 macrophages with higher expression of IL-10, IL1RA and CD206 as compared to healthy FS (HS-FS) while the efferocytotic capacity was unaltered. CD-FS did not affect extracellular matrix production from fibroblasts, but increased expression of the pro-inflammatory proteins IL-6 and MCP-1. Conditioned media from M2 macrophages treated with CD-FS modulated gene expression in fibroblasts for TGFβ superfamily members and reduced IL-4 expression compared to HS-FS. We show that M2 macrophages and fibroblasts react abnormally to the fecal microenvironment of CD patients, resulting in altered protein expression related to inflammation but not fibrosis. This implies that the gut microbiota and its metabolites have an important role in the generation and/or perpetuation of inflammation in CD.

Background and Aims: Reliable and easily accessible objective markers of disease activity to predict long-term treatment outcomes in severe ulcerative colitis [UC] are missing. We aimed to investigate if intestinal ultrasound [IUS] might predict long-term outcomes in hospitalised patients with severe UC, treated with intravenous [IV] corticosteroids. Methods: Hospitalised patients with severe UC and IUS inflammation (bowel wall thickness [BWT] > 3.0 mm) starting IV corticosteroids were recruited at three university hospitals in Denmark. IUS was performed before treatment and 48 +/- 24 h, 6 +/- 1 days, and 3 months after treatment initiation. Time until colectomy or need for new interventions was registered together with Mayo score at 3 months and partial Mayo score [pMayo] at 12 months. Follow-up time was 12 months. Results: In the final analysis, 56 patients were included; 45 [80%] patients needed intervention, including nine colectomies, during the 12-month follow-up. After 48 +/- 24 h, no patient with a BWT < 3 mm needed a colectomy, p = 0.04. BWT >= 4 mm showed an increased risk of colectomy {odds ratio 9.5 (95% confidence interval [CI] 1.5-186), p = 0.03}, whereas a BWT >= 3 mm showed an increased risk of intervention (3.6 [1.1-12.5], p = 0.03). A BWT >= 4 mm resulted in a significantly shorter time until both colectomy, p = 0.03, and treatment intensification (mean days 75 [95% CI 24-127] vs 176 [119-233], p = 0.005). However, neither IUS parameters nor pMayo score, C-reactive protein [CRP], haemoglobin, or p-albumin could predict remission at 3 and 12 months. Conclusion: BWT, assessed at 48 h post intravenous corticosteroid initiation in patients hospitalised with severe UC, may identify patients with an increased risk of short- and long-term colectomy and predict a more aggressive short-term disease course.

Background Biological treatment failure is common in patients with ulcerative colitis (UC), but the predictive value of baseline histological activity is unknown.Aims We aimed to investigate the associations between baseline histological activity and outcomes after biological treatment in patients with UC.Methods Adult biological-na & iuml;ve patients with UC (n = 150) were followed prospectively during biological treatment. Histological activity was assessed using the Nancy Index and Geboes score. Endoscopic activity was assessed using the Mayo Endoscopic Subscore (MES). Associations with outcomes were assessed in multivariable models. Associations between histological, endoscopic, and biochemical activity were assessed using Spearman's correlation.Results In biological-treated patients with UC, severe histological activity at baseline was independently associated with colectomy risk during the induction period (Nancy 2 vs 4: odds ratio [OR] 0.18, 95% CI 0.01-0.61, P = 0.024; Nancy 3 vs 4: OR 0.12, 95% CI 0.02-0.63, P = .019; Geboes 3 vs 5: OR 0.06, 95% CI 0.00-0.57, P = .033; Geboes 4 vs 5: OR 0.13, 95% CI 0.01-0.69, P = 0.032) and total follow-up (Nancy 2 vs 4: HR 0.23, 95% CI 0.06-0.98, P = 0.046; Nancy 3 vs 4: HR 0.13, 95% CI 0.04-0.47, P = 0.002; Geboes 4 vs 5: HR 0.28, 95% CI 0.08-0.93, P = 0.038). Meanwhile, baseline MES was not independently associated with colectomy risk. Histological activity was correlated with MES and the levels of C-reactive protein, hemoglobin, and albumin, but not calprotectin.Conclusions Severe histological activity at baseline as characterized by a higher Nancy Index or Geboes score independently predicted colectomy risk in biological-treated UC patients, whereas MES did not. Thus, histological assessment should be encouraged before initiating biological treatment. This study evaluated the impact of baseline histological disease activity on biological treatment failure in patients with ulcerative colitis and showed that severe histological disease activity is independently associated with the risk of colectomy, whereas endoscopic disease activity is not.

BACKGROUND:Surgical management for patients with inflammatory ileocecal Crohn's disease (CD) could be a reasonable alternative to second-line medical treatment. AIM:To assess short and long-term outcomes of patients operated on for inflammatory, ileocecal Crohn's disease. METHODS:A retrospective analysis of patients intervened at four referral hospitals during 2012-2021 was performed. RESULTS:211 patients were included. 43% of patients underwent surgery more than 5 years after diagnosis, and 49% had been exposed to at least one biologic agent preoperatively. 89% were operated by laparoscopy, with 1.6% conversion rate. The median length of the resected bowel was 25 cm (7-92) and three patients (1.43%) received a stoma. Median follow-up was 36 (17-70) months. The endoscopic recurrence-free survival proportion at 24, 48, 72, 96, and 120 months was 56%, 52%, 45%, 38%, and 33%, respectively. The clinical recurrence-free survival proportion at 24, 48, 72, 96, and 120 months was 83%, 79%, 76%, 74%, and 74%, respectively. In multivariate analysis, previous biological treatment (HR=2.01; p = 0.001) was associated with a higher risk of overall recurrence. CONCLUSION:Surgery in patients with primary inflammatory ileocecal CD is associated with good postoperative outcomes, low postoperative morbidity with reasonable recurrence rates.