Optimising surgical anastomosis in ileocolic resection for Crohn's disease with respect to recurrence and functionality: two international parallel randomized controlled trials comparing handsewn (END-to-end or Kono-S) to stapled anastomosis (HAND2END and the End2End STUDIES).

BACKGROUND: The most common intestinal operation in Crohn's disease (CD) is an ileocolic resection. Despite optimal surgical and medical management, recurrent disease after surgery is common. Different types of anastomoses with respect to configuration and construction can be made after resection for example, handsewn (end-to-end and Kono-S) and stapled (side-to-side). The various types of anastomoses might affect endoscopic recurrence and its assessment, the functional outcome, and costs. The objective of the present study is to compare the three types of anastomoses with respect to endoscopic recurrence at 6 months, gastrointestinal function, and health care consumption. METHODS: This is a randomized controlled multicentre superiority trial, allocating patients either to side-to-side stapled anastomosis as advised in current guidelines or a handsewn anastomoses (an end-to-end or Kono-S). It is hypothesized that handsewn anastomoses do better than stapled, and end-to-end perform better than the saccular Kono-S. Two international studies with a similar setup will be conducted mainly in the Netherlands (End2End) and Italy (HAND2END). Patients diagnosed with CD, aged over 16 years in the Netherlands and 18 years in Italy requiring (re)resection of the (neo)terminal ileum are eligible. The first part of the study compares the two handsewn anastomoses with the stapled anastomosis. To detect a clinically relevant difference of 25% in endoscopic recurrence, a total of 165 patients will be needed in the Netherlands and 189 patients in Italy. Primary outcome is postoperative endoscopic recurrence (defined as Rutgeerts score ≥ i2b) at 6 months. Secondary outcomes are postoperative morbidity, gastrointestinal function, quality of life (QoL) and costs. DISCUSSION: The research question addresses a knowledge gap within the general practice elucidating which type of anastomosis is superior in terms of endoscopic and clinical recurrence, functionality, QoL and health care consumption. The results of the proposed study might change current practice in contrast to what is advised by the guidelines. TRIAL REGISTRATION: NCT05246917 for HAND2END and NCT05578235 for End2End ( http://www. CLINICALTRIALS: gov/ ).

Ustekinumab is a promising option for the treatment of postoperative recurrence of Crohn's disease.

BACKGROUND AND AIM: Postoperative recurrence (POR) following ileocolonic resection is a major concern in patients with Crohn's disease (CD). The role of ustekinumab (UST) in this setting is poorly known. METHODS: All consecutive CD patients with a baseline colonoscopy at 6-12 months from ileocolonic resection showing POR (Rutgeerts score ≥ i2) who were treated with UST after the baseline colonoscopy and with an available post-treatment endoscopy, were extracted from the cohort of the Sicilian Network for Inflammatory Bowel Diseases (SN-IBD). The primary outcome was endoscopic success, defined as reduction of at least one point of Rutgeerts score. The secondary outcome was clinical success, assessed at the end of follow-up. Reasons for clinical failure included mild clinical relapse (Harvey-Bradshaw index 5-7), clinically relevant relapse (Harvey-Bradshaw index > 7), and need for new resection. RESULTS: Forty-four patients were included (mean follow-up: 17.8 ± 8.4 months). The baseline postoperative colonoscopy showed severe POR (Rutgeerts score i3 or i4) in 75.0% of patients. The post-treatment colonoscopy was performed after a mean of 14.5 ± 5.5 months following initiation of UST. Endoscopic success was reported in 22 out of 44 (50.0%) patients, of whom 12 (27.3%) achieved a Rutgeerts score i0 or i1. Clinical success at the end of follow-up was reported in 32 out of 44 patients (72.7%); none of the 12 patients with clinical failure had achieved endoscopic success at post-treatment colonoscopy. CONCLUSIONS: Ustekinumab could be a promising option for the treatment of POR of CD.

Results of the Eighth Scientific Workshop of ECCO: Diagnosing Postoperative Recurrence of Crohn's Disease After an Ileocolonic Resection With Ileocolonic Anastomosis.

Despite the introduction of potent biologic therapies, many patients with Crohn's disease [CD] still require an ileocolonic resection [ICR] during the course of their disease. Furthermore, the need of redo ICR has not decreased over the past few decades, highlighting the need for better strategies to prevent and treat postoperative recurrence [POR]. The first step to develop such a strategy would be to define and standardise the description of POR with adequate diagnostic instruments. In this article, we will describe the different methodologies used to report POR [endoscopic, histological, radiological, biochemical, clinical, and surgical], and review their potential benefits and limitations, as well as the optimal timing of evaluation.

The Prevalence of Concomitant Skip Small Bowel Lesions in Crohn's Disease and Their Effects on Reoperation in Patients Undergoing Ileocolic Resection.

AIMS: Concomitant lesions in the small intestine are common in Crohn's disease (CD). This study aimed to detect the incidence of small bowel (SB) lesions in patients undergoing surgical resection for symptomatic ileocolic disease and whether concomitant SB lesions are associated with reoperation due to recurrent CD. METHODS: In this observational, historical cohort study, consecutive patients with CD undergoing primary ileocolic resection (ICR) from 2007 to 2019 were included. Clinical variables and intraoperative findings were extracted from a prospectively maintained database and analyzed by Cox proportional hazards regression models for identifying risk factors of reoperation. RESULTS: Of the 404 patients included, there were 202 (50%) patients having concomitant SB lesions, and 108 of them underwent concurrent surgical intervention for SB lesions whereas 94 did not. The presence of concomitant SB lesions was a risk factor for reoperation (p = 0.041). Subgroup analysis indicated that patients with concomitant uncomplicated SB lesions left in situ had a comparable rate of reoperation (p = 0.605) whereas patients having concomitant complicated SB lesions undergoing simultaneous surgical intervention showed a higher reoperation rate (P = 0.006) when compared with those without concomitant SB lesions. Interestingly, the adverse effects of concomitant SB lesions can be reversed in the setting of postoperative anti-TNF agents [HR 0.2; 95% CI (0.04-0.9); P=0.040]. CONCLUSIONS: Concomitant SB lesion(s), especially those complicated lesions, could be a risk factor for postoperative surgical recurrence in patients undergoing ICR. Active postoperative management strategies such as anti-TNF agents should be provided for these patients.

Has the Removing of the Mesentery during Ileo-Colic Resection an Impact on Post-Operative Complications and Recurrence in Crohn's Disease? Results from the Resection of the Mesentery Study (Remedy).

Some evidence suggests a reduction in clinical and surgical recurrence after mesenteric resection in Crohn's Disease (CD). The aim of the REsection of the MEsentery StuDY (Remedy) was to assess whether mesenteric removal during surgery for ileocolic CD has an impact in terms of postoperative complications, endoscopic and ultrasonographic recurrences, and long-term surgical recurrence. Among the 326 patients undergoing primary resection between 2009 and 2019 in two referral centers, in 204 (62%) the mesentery was resected (Group A) and in 122 (38%) it was retained (Group B). Median follow-up was 4.7 ± 3 years. Groups were similar in the peri-operative course. Endoscopic and ultrasonographic recurrences were 44.6% and 40.4% in Group A, and 46.7% and 41.2% in Group B, respectively, without statistically significant differences. The five-year time-to-event estimates, compared with the Log-rank test, were 3% and 4% for normal or thickened mesentery (p = 0.6), 2.8% and 4% for resection or sparing of the mesentery (p = 0.6), and 1.7% and 5.4% in patients treated with biological or immunosuppressants versus other adjuvant therapy (p = 0.02). In Cox's model, perforating behavior was a risk factor, and biological or immunosuppressant adjuvant therapy protective for surgical recurrence. The resection of the mesentery does not seem to reduce endoscopic and ultrasonographic recurrences, and the five-year recurrence rate.

Vedolizumab may be an effective option for the treatment of postoperative recurrence of Crohn's disease.

BACKGROUND: The role of Vedolizumab (VDZ) as therapeutic option for the postoperative recurrence of Crohn's disease (CD) following ileocolonic resection is unknown. AIMS: To assess the effectiveness of VDZ in this setting. METHODS: All consecutive CD patients with a baseline colonoscopy at 6-12 months from the ileocolonic resection showing postoperative recurrence (Rutgeerts score ≥i2) and treated with VDZ after the baseline colonoscopy were extracted from the cohort of the Sicilian Network for Inflammatory Bowel Diseases (SN-IBD). The primary outcome was endoscopic success, assessed at the first colonoscopy following initiation of VDZ and defined as reduction of at least one point of Rutgeerts score. The secondary outcome was clinical failure, assessed at one year and at the end of follow-up. RESULTS: Fifty-eight patients were included (mean follow-up: 24.8 ± 13.1 months). Endoscopic success was reported in 47.6% of patients. Clinical failure was reported in 19.0% of patients at one year, and in 32.8% of patients at the end of follow-up. A new resection was required in 7 patients (12.1%). CONCLUSIONS: VDZ may be an effective option for the treatment of postoperative recurrence of CD.

Correlation between endoscopy and intestinal ultrasound for the evaluation of postoperative recurrence of Crohn's disease. / Correlación entre la endoscopia y la ecografía intestinal para la evaluación de la recurrencia posquirúrgica de la enfermedad de Crohn.

OBJECTIVE: Intestinal ultrasound is considered to be a valid alternative for the evaluation of post-operative recurrence (POR) of Crohn's disease. The aim of this study is to assess the correlation between ultrasound and endoscopic findings. METHODS: Patients with Crohn's disease were retrospectively recruited who had undergone ileocecal resection, and for whom a colonoscopy and intestinal ultrasound had been performed for the detection of POR. Recurrence was assessed using the Rutgeerts score (RS). The ultrasound findings analysed were bowel wall thickness (BWT), parietal hyperaemia using power Doppler, loss of layer pattern and mesenteric fat hypertrophy. RESULTS: A total of 31 patients were included, of which 15 (48.4%) had no POR (RS<2b) and 16 (51.6%) had POR (RS≥2b). A statistically significant association was identified between BWT and the presence of endoscopic recurrence (a mean of 2.75mm vs. 5.68mm, P>0.001). There was also a statistically significant difference in hyperaemia between the 2groups (P=0.03). For wall thickness, an area under the ROC curve (AUC) of 92.9% was obtained, and with a cut-off point of 3.4mm, a sensitivity of 100% and specificity of 86.6%. When comparing with the most frequent biomarkers (fecal calprotectin and serum CRP), a higher AUC was obtained for wall thickness (72.3% and 72.3% vs. 92.9%). CONCLUSIONS: In our experience, ultrasound has high diagnostic efficacy in the detection of POR and can be considered a valid non-invasive alternative to endoscopy.

Single-cell protein activity analysis identifies recurrence-associated renal tumor macrophages.

Clear cell renal carcinoma (ccRCC) is a heterogeneous disease with a variable post-surgical course. To assemble a comprehensive ccRCC tumor microenvironment (TME) atlas, we performed single-cell RNA sequencing (scRNA-seq) of hematopoietic and non-hematopoietic subpopulations from tumor and tumor-adjacent tissue of treatment-naive ccRCC resections. We leveraged the VIPER algorithm to quantitate single-cell protein activity and validated this approach by comparison to flow cytometry. The analysis identified key TME subpopulations, as well as their master regulators and candidate cell-cell interactions, revealing clinically relevant populations, undetectable by gene-expression analysis. Specifically, we uncovered a tumor-specific macrophage subpopulation characterized by upregulation of TREM2/APOE/C1Q, validated by spatially resolved, quantitative multispectral immunofluorescence. In a large clinical validation cohort, these markers were significantly enriched in tumors from patients who recurred following surgery. The study thus identifies TREM2/APOE/C1Q-positive macrophage infiltration as a potential prognostic biomarker for ccRCC recurrence, as well as a candidate therapeutic target.

Quantifying the rate of recurrence of postoperative Crohn's disease with biological therapy. A meta-analysis.

OBJECTIVE: Preventing the postoperative recurrence (POR) of Crohn's disease (CD) poses a significant challenge to clinicians. With the advent of biologics, various studies have observed a reduction of recurrence after surgery. Hence, we performed a systematic review and meta-analysis to identify the rate of POR at different time points in the era of biologic use. METHODS: We performed a literature search using Medline and Embase databases for studies investigating biologics in preventing the POR of CD. Data were extracted, and a single-arm meta-analysis with generalized linear mixed model and Clopper-Pearson method for confidence interval (CI) was performed to identify endoscopic, clinical and surgical recurrence rates at 6 months and 1, 2 and 5 years postoperatively. RESULTS: Altogether 24 studies were included in the meta-analysis. The endoscopic, clinical and surgical POR rate with the use of anti-tumor necrosis factor (TNF)-α agents at 1 year was 21.72% (95% CI 16.28%-28.37%), 13.06% (95% CI 8.18%-18.92%) and 3.76% (95% CI 1.37%-9.91%), respectively. The 5-year recurrence rate was 84.21% (95% CI 72.35%-91.57%) and 17.49% (95% CI 9.17%-30.80%) for endoscopic and surgical recurrence, respectively. Subgroup analyses at 1 year for the type of anti-TNF-α agent or the timing of initiation after surgery showed no significant difference in endoscopic, clinical and surgical recurrence rates. CONCLUSIONS: Anti-TNF-α agents are effective at preventing clinical, endoscopic and surgical POR of CD. The timing of initiating biological therapy after surgery has no significant effect on the rate of POR. The efficacy of infliximab and adalimumab for postoperative recurrence prevention is similar.

Clinical Outcomes and Prognostic Factors of Salvage Stereotactic Body Radiotherapy for Post-Surgical Thoracic Oligo-Recurrence/Metastasis of Non-Small-Cell Lung Cancer.

PURPOSE: The study aimed to assess the efficacy and safety of stereotactic body radiotherapy (SBRT) using CyberKnife (CK) in patients with postoperative thoracic oligo-recurrence/metastasis of non-small-cell lung cancer (NLCLC), and to analyze the prognostic factors affecting overall survival after SBRT. PATIENTS AND METHODS: A total of 44 patients with postoperative thoracic oligo-recurrence/metastatic of NLCLC treated with SBRT were reviewed. Thoracic oligo-recurrence/was defined as 1-3 loco-regional confined to lung lobe, hilar/mediastinal lymph nodes, bronchial stump, or chest wall. Primary endpoints included local control (LC), overall survival (OS), progression-free survival (PFS) and toxicity. Prognostic factors that affected these patients were analyzed by the univariate and multivariate analysis by Kaplan-Meier methods and Cox regression models, respectively. RESULTS: The median follow-up time after salvage SBRT was 48.5 months. Measuring from the date of salvage SBRT, the median OS of the 44 patients was 52.60 (95% CI: 29.59-75.60) months. 1-,3-and 5-year OS rates were 97.7%, 65.3% and 47.7%, respectively. The 1-,3-year and 5-year LC rates were 97.7%, 85.1% and 80.1%, respectively. At 1, 3 and 5 years, the PFS rates were 77.1%, 28.8% and 5.3%, respectively. Multivariate analysis demonstrated that pre-SBRT neutrophil-to-lymphocyte ratio (NLR) and Charlson comorbidity index (CCI) were independent prognostic factors (p < 0.05). The treatment-related side-effects were well tolerated. No patients developed grade 3 or greater pulmonary toxicity. CONCLUSION: SBRT is a promising salvage therapeutic option for postoperative thoracic oligo-recurrence/metastasis of non-small-cell lung cancer with acceptable toxicity. Low pre-SBRT neutrophil-to-lymphocyte ratio (NLR) and low Charlson comorbidity index (CCI) were associated with a better prognosis and longer survival and might be considered as reliable and independent prognostic factors in these patients treated with SBRT.

Novel Genetic Variant Predicts Surgical Recurrence Risk in Crohn's Disease Patients.

BACKGROUND: We aimed to identify a model of clinical and genetic risk factors through hypothesis-free search across genome that can predict the surgical recurrence risk after the first abdominal surgery in CD patients. MATERIALS AND METHODS: Two independent inflammatory bowel disease (IBD) cohort studies were used to derive and validate the genetic risk profile. The study subjects were genotyped using Illumina Immunochip custom genotyping array. Surgical recurrence was defined as having the second or more abdominal bowel resections after the first abdominal surgery at the time of study enrollment; nonsurgical recurrence was defined as having no further abdominal resection after the first abdominal surgery. RESULTS: Among 372 CD patients who had at least 1 abdominal surgery at the study enrollment, 132 (35.5%) had subsequent surgical recurrence after their first abdominal surgery, and 240 (64.5%) required no subsequent abdominal surgery at the end of follow up. Among clinical factors, multivariable analysis showed that history of immunomodulatory use (odds ratio [OR], 3.96; P = 0.002) and early era of CD first surgery (OR, 1.12; P = 1.01E-04) remained significant. Genotypic association tests identified a genome-wide significant locus rs2060886 in TCF4 at chr18q21.2 associated with surgical recurrence risk (OR, dom, 4.10 [2.37-7.11]; P = 4.58E-08). CONCLUSIONS: Novel genetic locus rs2060886 in TCF4 was associated with surgical recurrence risk at genome-wide significance level among CD patients after their first abdominal surgery. Early era of CD first intestinal surgery predicts higher surgical recurrence risk. These results suggest that genetic variants may help guide the CD management strategy in patients at the highest risk of repeated abdominal surgeries.

Localization of recurrent lesions following ileocolic resection for Crohn's disease.

BACKGROUND: Crohn's disease (CD) recurrence can occur not only at the site of anastomosis but also elsewhere in the bowel following an ileocolic resection (ICR) procedure. The aims of the present study were to assess long-term outcomes of a primary ICR procedure for CD in consecutive patients and examine the location of the reoperation causative lesion. METHODS: We examined cases of surgery with ICR initially performed at our institution. Those with simultaneous multiple bowel resection or bowel resection with strictureplasty were excluded. RESULTS: A total of 169 patients who underwent ICR due to CD were enrolled. The median follow-up period was 12.6 years (range 4-27 years). A reoperation was needed in 45 (26.6%), of whom 14 had lesions causative of the reoperation at other than the anastomotic site. The most common causative lesion location was in the colon rather than the oral side of the small intestine. Furthermore, we investigated the relationship between presence of residual lesions following the initial surgery and lesions causative of reoperation. In the group without residual disease (n = 31), 29.0% (n = 9) had non-anastomotic lesions involved in indications for reoperation, while that was 35.7% (n = 5) in the group with residual disease (n = 14). CONCLUSIONS: Anastomotic site lesion is not the only causative factor for reoperation following ICR. Regular examinations and applicable treatment with awareness that the cause of reoperation is not limited to the site of anastomosis are important in these cases.

Recommendations of the Spanish Working Group on Crohn's Disease and Ulcerative Colitis (GETECCU) on the use of abdominal ultrasound in inflammatory bowel disease. / Recomendaciones del Grupo Español de Trabajo en Enfermedad de Crohn y Colitis Ulcerosa (GETECCU) sobre el empleo de la ecografía abdominal en la enfermedad inflamatoria intestinal.

Ultrasound has an excellent diagnostic performance when Crohn's disease is suspected, when performing an activity assessment, or determining the extension and location of Crohn's disease, very similar to other examinations such as MRI or CT. It has a good correlation with endoscopic lesions and allows the detection of complications such as strictures, fistulas or abscesses. It complements colonoscopy in the diagnosis and, given its tolerance, cost and immediacy, it can be considered as a good tool for disease monitoring. In ulcerative colitis, its role is less relevant, being limited to assessing the extent and activity when it is not possible with other diagnostic techniques or if there are doubts with these. Despite its advantages, its use in inflammatory bowel disease (IBD) is not widespread in Spain. For this reason, this document reviews the advantages and disadvantages of the technique to promote knowledge about it and implementation of it in IBD Units.

Elemental diet therapy plays a significant role in preventing surgical recurrence of Crohn's disease in the era of biologics.

PURPOSE: Most patients with Crohn's disease (CD) experience surgical recurrence. In this era of novel therapies, we conducted this study to clarify which treatments effectively decrease the risk of surgical recurrence in patients with CD. METHODS: The subjects of this retrospective study were 37 patients with CD. We created cumulative surgery rate curves and performed univariate and multivariate analyses. RESULTS: Univariate analysis revealed that patients who consumed an elemental diet (ED; ≥ 900 kcal/day), anti-tumor necrosis factor-alpha, and thiopurines had a significantly better prognosis than those who did not (p = 0.011, p = 0.025, and p = 0.0080, respectively). Multivariate analysis revealed that ED therapy and thiopurines were independent significant factors for controlling surgical recurrence (p = 0.046 and p = 0.032, respectively). Additional analyses showed that the most promising ED therapeutic dose was ≥ 1200 kcal/day, while an ED therapeutic dose of ≥ 900 kcal/day was acceptable. CONCLUSIONS: Although univariate analyses revealed that all three treatment strategies had significant effects on surgical recurrence in patients with CD, multivariate analysis revealed that only ED therapy was significantly associated with surgical recurrence rates. Thus, ED therapy plays an important role in the management of CD, even in the era of biological therapies.

Surgical Treatment for Crohn's Disease: A Role of Kono-S Anastomosis in the West.

More than 80% of patients with Crohn's disease (CD) will require surgical intervention during their lifetime, with high rates of anastomotic recurrence and stenosis necessitating repeat surgery. Current data show that pharmacotherapy has not significantly improved the natural history of postoperative clinical and surgical recurrence of CD. In 2003, antimesenteric hand-sewn functional end-to-end (Kono-S) anastomosis was first performed in Japan. This technique has yielded very desirable outcomes in terms of reducing the incidence of anastomotic surgical recurrence. The most recent follow-up of these patients showed that very few had developed surgical recurrence. This new approach is superior to stapled functional end-to-end anastomosis because the stumps are sutured together to create a stabilizing structure (a "supporting column"), serving as a supportive backbone of the anastomosis to help prevent distortion of the anastomotic lumen due to disease recurrence and subsequent clinical symptoms. This technique requires careful mesenteric excision for optimal preservation of the blood supply and innervation. It also results in a very wide anastomotic lumen on the antimesenteric side. The Kono-S technique has shown efficacy in preventing surgical recurrence and the potential to become the new standard of care for intestinal CD.

Genomics and precision surgery for head and neck squamous cell carcinoma.

The identification of the biological determinants that shape the response of tumors to medical therapies offers perspectives for better patient stratification and therapeutic targeting. Here, we discuss how genomics could help to improve the surgical treatment of head and neck squamous cell carcinoma (HNSCC). We examine the potential use of genomic analyses for: i) refining and standardizing the indications for surgery, ii) the choice of surgical procedure, and iii) the follow-up of patients with resected tumors. We highlight the studies that used genomics to explore the contribution of tumor biology to the outcome of surgery. We discuss the important developments that are challenging current surgical practice in HNSCC, such as neoadjuvant immunotherapy and the analysis of circulating DNA. Genomic analyses provide practical tools that could help improve the pathological diagnosis and staging of HNSCC, and increase the appreciation of the importance of tumor biology in the outcome of surgery. Identification of biomarkers will likely contribute to a move toward precision surgery of HNSCC, i.e. the personalization of surgical practice based on tumor biology.

Kono-S anastomosis after intestinal resection for Crohn's disease.

BACKGROUND: Kono-S anastomosis was described for the first time in 2011 and it showed a lower surgical recurrence rate in patients with Crohn's disease when compared to the standard technique. The aim of this review is to assess the safety and effectiveness of this surgical procedure by analyzing the data existing in the literature. MATERIALS AND METHODS: Pubmed, EMBASE and Scopus databases were used as data sources for a systematic comprehensive search of all studies where Kono-S anastomosis was performed in patients with Crohn's disease. Perioperative data and clinical outcomes were measured. RESULTS: Five studies described the use of Kono technique to restore intestinal continuity. Postoperative complications rates seem to be acceptable, with the exception of one case regarding the surgical site infection and bowel obstruction rates of one of the studies compared to the others. Surgical recurrence rate ranges from 0 to 3.4% with significant differences between Kono-S anastomosis and other techniques in the only two existing comparative studies. CONCLUSION: Kono's anastomosis seems to be a safe procedure with encouraging results on the reduction of the need for reoperation due to relapse, but the few existing studies do not allow to draw final conclusions. Further comparative, randomized studies, with appropriate sample size, follow up and endoscopic evaluation are necessary to establish the real benefits in the use of this hand-sewn antimesenteric anastomosis compared to a stapled wide lumen side-to-side anastomosis.

Surgical Recurrence at Anastomotic Site After Bowel Resection in Crohn's Disease: Comparison of Kono-S and End-to-end Anastomosis.

BACKGROUND: Anastomotic surgical recurrence after bowel resection in Crohn's disease patients is problematic. This study was performed to evaluate the increased risk of anastomotic surgical recurrence. METHODS: From 2006 to 2016, we performed anastomoses in 215 consecutive Crohn's disease patients. The cohort was divided into two groups: Kono-S anastomosis (n = 117) and end-to-end anastomosis (n = 98). Multivariate analysis of predictors of anastomotic surgical recurrence and Kaplan-Meier analysis for the 5-year anastomotic surgical recurrence rate were evaluated. RESULTS: The two groups showed no statistically significant differences in patient backgrounds. During a median follow-up of 54 months, 28 patients required anastomotic surgical recurrence [4 (3.4%) in the Kono-S group and 24 (24.4%) in the end-to-end group]. Six leaks (5.1%) were detected in the Kono-S group and 17 leaks (17.3%) in the end-to-end group; all were successfully treated conservatively. End-to-end anastomosis, leakage, age < 45 years, and body mass index of ≥ 18 kg/m2 at the first surgery had a higher risk of anastomotic surgical recurrence. Kono-S anastomosis significantly reduced the risk of anastomotic surgical recurrence after 1 year (odds ratio, 0.14). Anastomotic leakage influenced anastomotic surgical recurrence within 1 year (odds ratio, 4.84). The 5-year surgery-free survival rate at the anastomosis site with Kono-S anastomosis (95.0%) was significantly higher than that with end-to-end anastomosis (81.3%; P < 0.001). CONCLUSIONS: Anastomotic leakage after bowel resection in Crohn's disease patients increased anastomotic surgical recurrence within 1 year, and Kono-S anastomosis is associated with a low risk of anastomotic surgical recurrence after > 1 year.

Immediate prophylactic vs endoscopic or symptomatic-driven azathioprine treatment to prevent surgical recurrence after intestinal resection for Crohn's disease.

AIM: Azathioprine can prevent postoperative recurrences in Crohn's disease. We compared the efficacy of azathioprine in preventing surgical recurrence to explore whether immediate prophylaxis after surgery is better than azathioprine started after endoscopic or clinical recurrence. METHOD: Data of patients with intestinal resection and ileocolic anastomosis for Crohn's disease between 2006 and 2015 were retrieved from a prospectively maintained database. Patients were grouped according to the strategies of postoperative therapy with azathioprine. Univariate and multivariate proportional hazard Cox regression analyses were conducted to identify independent predictive factors for surgical recurrence. RESULTS: Only age equal to or less than 16 years at diagnosis was an independent risk factor for surgical recurrence in all 166 patients (P = 0.005). In patients with high risk of recurrence (27 in the symptom-driven group, 39 in the endoscopy-driven group and 69 in the immediate prophylaxis group), both immediate and endoscopy-driven azathioprine delayed and reduced surgical recurrence compared with symptom-driven azathioprine (P = 0.035, 0.019). Their efficacy in reducing surgical recurrence was confirmed by Cox regression analyses (hazard ratio 0.465, P = 0.045; hazard ratio 0.352, P = 0.028). Surgical recurrence was similar between the immediate and endoscopy-driven groups. In addition, age ≤ 16 at diagnosis was still an independent risk factor for surgical recurrence in this subgroup. CONCLUSIONS: In patients with high risk of recurrence, both immediate prophylactic azathioprine after surgery and azathioprine started after endoscopic recurrence can delay and reduce surgical recurrence compared with azathioprine started after clinical recurrence. In addition, azathioprine started immediately after surgery was not superior to azathioprine started after discovery of endoscopic recurrence.