Influencing factors and preventive measures of infectious complications after intestinal resection for Crohn's disease.

The optimal timing of thiopurine (azathioprine or 6-mercaptopurine) administration is controversial issue in treatment of Crohn's disease (CD) with poor prognostic factors. We performed a nationwide population-based study to investigate the impact of timing of thiopurine treatment on first intestinal resection in CD with poor prognostic factors. Using the National Health Insurance claims data, we collected data on newly diagnosed patients with CD between 2004 and 2015. Among them, patient who have at least two risk factors for progression (diagnosis at age <40 years, systemic corticosteroid treatment <3 months after diagnosis, and perianal fistula at diagnosis) and those received thiopurine treatment within 2 years of diagnosis were enrolled to the analysis. Patients with thiopurine prescription days <70% (255 days) per year were excluded. We quantified the impact of timing of thiopurines on the risk of first bowel resective surgery using a Cox regression model. Following variables including age, gender, single poor prognostic factors, and hospital volume were controlled. Timing of thiopurine was classified into three categories (<6 months, 6–12 months, 12–24 months). We identified 1,134 eligible patients with CD. During 5473 person-years follow-up, intestinal resection was performed in 177 (15.6%) patients. Compared with patients received thiopurine within 6 months, patients treated at 6–12 months showed statistically non-significant increase in the risk of surgery (hazard ratio 1.30, 95% confidence interval 0.85–2.00, p = 0.225), meanwhile, the risk of surgery was significantly increased in patients started thiopurine at 12–24 months after diagnosis (hazard ratio 1.62, 95% confidence interval 1.10–2.40, p = 0.015). Compared with patients received thiopurine within 6 months, 62% of increase for surgery risk was observed in patients started thiopurine at 12–24 months. Our results suggest that initiation of thiopurine within 1 year after diagnosis may be considered in CD patients with poor prognostic factors.

ABSTRACTBackgroundLimited data are available on the management and outcomes of postoperative Crohn's disease (CD) in older patients. We aimed to describe the management of CD in the postoperative setting and assess surgical postoperative recurrence (POR) in this population.MethodsThis was a case‐control study including all adult patients with CD from the ENEIDA registry who had undergone a first intestinal resection with ileo‐colonic anastomosis. Patients were grouped according to their age at the time of the first surgery in older (over 60 years) subjects and controls (between 18 and 60 years of age).ResultsA total of 3982 (535 older subjects and 3454 controls) underwent a first intestinal resection for CD with an ileo‐colonic anastomosis. Time from CD diagnosis to surgery was significantly longer in older patients (114 ± 128 vs. 93 ± 97 months; p < 0.001). Older patients also had a lower proportion of penetrating CD (25% vs. 39%; p < 0.0001) and perianal disease (14% vs. 25%; p < 0.0001). A significantly lower proportion of older patients started preventive therapies for POR (32% vs. 51%; p < 0.0001). The cumulative risk of surgical POR was 3.2%, 5.3% and 10.1% in the older group and 3.6%, 6.6% and 14.2% in the control group at three, five and 10 years, respectively (p = 0.093). In the multivariate logistic regression analysis, only prevention with thiopurines was associated with a lower risk of surgical POR.ConclusionsAlthough postoperative preventive therapy with immunomodulators or biologicals is prescribed less often in older patients after a first intestinal resection, they develop surgical POR as often as younger adult patients.

Although the nature and frequency of postoperative complications after intestinal resection in patients with inflammatory bowel disease have been previously described, short-term readmission has not been characterized in population-based studies. We therefore assessed the risk of postoperative complications and emergent readmissions after discharge from an intestinal resection. We used a Canadian provincial-wide inpatient hospitalization database to identify 2638 Crohn's disease (CD) and 559 ulcerative colitis (UC) admissions with intestinal resection from 2002 to 2011. We identified the cumulative risk of in-hospital complication and emergent readmission within 90 days after discharge along with predictors for both outcomes using a Poisson regression for binary outcomes. The cumulative risks of in-hospital postoperative complications and 90-day emergent readmission were 23.8% and 12.6%, respectively in CD and 33.3% and 11.1%, respectively in UC. The predictors for in-hospital postoperative complications for CD and UC included older age, comorbidities, and open laparatomy for CD, additional predictors included emergent admission, stoma surgery, and concurrent resection of both small and large bowel. The predictors for 90-day readmission for CD included a postoperative complication (risk ratio, 1.61; 95% confidence interval, 1.30-2.01), emergent admission (risk ratio, 1.39; 95% confidence interval, 1.12-1.73), and stoma formation (risk ratio, 1.49; 95% confidence interval, 1.15-1.93) at the hospitalization requiring surgery. Readmission and postoperative complications are common after intestinal resection in CD and UC. Clinicians should closely monitor surgical patients who required emergent admission, undergo surgery with stoma formation, or develop in-hospital postoperative complications to anticipate need for readmission or interventions to prevent readmission.

Due to the complexity and numerous comorbidities associated with Crohn's disease (CD), the incidence of postoperative complications is high, significantly impacting the recovery and prognosis of patients. Consequently, additional studies are required to precisely predict short-term major complications following intestinal resection (IR), aiding surgical decision-making and optimizing patient care. To construct novel models based on machine learning (ML) to predict short-term major postoperative complications in patients with CD following IR. A retrospective analysis was performed on clinical data derived from a patient cohort that underwent IR for CD from January 2017 to December 2022. The study participants were randomly allocated to either a training cohort or a validation cohort. The logistic regression and random forest (RF) were applied to construct models in the training cohort, with model discrimination evaluated using the area under the curves (AUC). The validation cohort assessed the performance of the constructed models. Out of the 259 patients encompassed in the study, 5.0% encountered major postoperative complications (Clavien-Dindo ≥ III) within 30 d following IR for CD. The AUC for the logistic model was 0.916, significantly lower than the AUC of 0.965 for the RF model. The logistic model incorporated a preoperative CD activity index (CDAI) of ≥ 220, a diminished preoperative serum albumin level, conversion to laparotomy surgery, and an extended operation time. A nomogram for the logistic model was plotted. Except for the surgical approach, the other three variables ranked among the top four important variables in the novel ML model. Both the nomogram and RF exhibited good performance in predicting short-term major postoperative complications in patients with CD, with the RF model showing more superiority. A preoperative CDAI of ≥ 220, a diminished preoperative serum albumin level, and an extended operation time might be the most crucial variables. The findings of this study can assist clinicians in identifying patients at a higher risk for complications and offering personalized perioperative management to enhance patient outcomes.

Rates of Intestinal Resection and Colectomy in Inflammatory Bowel Disease Patients After Initiation of Biologics: A Cohort Study

Growth before and after intestinal resection for Crohn's disease (CD) was examined in a group of children, adolescents, and young adults. Retrospective chart review of patients who had intestinal resections as clinical management of complications of CD between 1985 and 1996. Pre- and postoperative measurements of weight and height were reviewed. Z-scores were computed for weight-forage (WAZ), height-for-age (HAZ), and weight-for-height (WHZ). Two tailed t tests were used to compare postoperative growth patterns. Significance was defined as p < 0.05. Twenty-five subjects (8 females, mean age 16.2+/-2.8 years with one operation, and 3 males, mean age 15.7 years with multiple operations) were identified. There were significant improvements in the postoperative growth patterns of subjects who had one operation: HAZ (-1.28+/-1.45 versus -0.98+/-1.37, p = 0.041), WAZ (-1.35+/-1.02 versus -0.74+/-0.93, p = 0.0006) and WHZ (-0.64+/-0.95 versus -0.23+/-0.81, p = 0.036). Furthermore, the magnitude of postoperative weight gain directly correlated with the age at CD diagnosis, R2 = 0.16, p = 0.046. Trends towards improved postoperative WAZ (-0.83 versus -0.49) and HAZ (-0.47 versus -0.27) were also observed in the three subjects who had multiple operations. The pattern of weight and height growth was improved after intestinal resection for CD. Nonetheless, close monitoring of postoperative growth is necessary especially in children diagnosed with CD at a young age.

Growth before and after intestinal resection for Crohn's disease (CD) was examined in a group of children, adolescents, and young adults. Retrospective chart review of patients who had intestinal resections as clinical management of complications of CD between 1985 and 1996. Pre- and postoperative measurements of weight and height were reviewed. Z-scores were computed for weight-for-age (WAZ), height-for-age (HAZ), and weight-for-height (WHZ). Two tailed t tests were used to compare postoperative growth patterns. Significance was defined as p < 0.05. Twenty-five subjects (8 females, mean age 16.2 ± 2.8 years with one operation, and 3 males, mean age 15.7 years with multiple operations) were identified. There were significant improvements in the postoperative growth patterns of subjects who had one operation: HAZ (−1.28 ± 1.45 versus −0.98 ± 1.37, p = 0.041), WAZ (−1.35 ± 1.02 versus −0.74 ± 0.93, p = 0.0006) and WHZ (−0.64 ± 0.95 versus −0.23 ± 0.81, p = 0.036). Furthermore, the magnitude of postoperative weight gain directly correlated with the age at CD diagnosis, R2 = 0.16, p = 0.046. Trends towards improved postoperative WAZ (−0.83 versus −0.49) and HAZ (−0.47 versus −0.27) were also observed in the three subjects who had multiple operations. The pattern of weight and height growth was improved after intestinal resection for CD. Nonetheless, close monitoring of postoperative growth is necessary especially in children diagnosed with CD at a young age.

Quality of life during one year of postoperative prophylactic drug therapy after intestinal resection in Crohn’s patients: Results of the APPRECIA trial

Crohn's disease clinical trials utilize the Crohn's Disease Activity Index (CDAI) to measure primary endpoint assessments of clinical recurrence and remission. We evaluated the extent of agreement between clinical recurrence/remission as defined by the CDAI and endoscopic recurrence 1 year after intestinal resection for Crohn's disease (CD). Twenty-four CD patients who had been randomly assigned to a postoperative clinical trial had 1 year clinical, endoscopic, and histological assessment for disease recurrence. The primary endpoint was the extent of agreement between endoscopic recurrence and clinical recurrence 1 year after intestinal resection for CD. Secondary endpoints were extent of agreement between endoscopic recurrence and the surrogate markers of CD activity, i.e., histological activity, sedimentation rate, and C-reactive protein (CRP). Twelve of the 24 patients (50%) were in endoscopic remission (i0, i1) and 12 (50%) had endoscopic recurrence (i2, i3, or i4). There was good agreement between endoscopy and histological activity scores (intraclass correlation coefficient = 0.53, kappa coefficient = 0.58). In contrast, there was little to no relationship between endoscopy and CDAI scores; median CDAI scores for endoscopy scores of i0/i1, i2, i3, and i4 were 118, 76, 156, and 78, respectively (P for trend = 0.88). The kappa coefficient (of agreement) between endoscopy score ± 2 and CDAI score ± 150 was 0.12 (exact P = 0.68), indicating poor agreement. Similarly, there was no consistent association observed between endoscopy scores and mean CRP and ESR values at week 54. The CDAI shows poor agreement with endoscopic recurrence 1 year after intestinal resection. Endoscopic recurrence should be the primary endpoint of future postoperative studies and ileocolonoscopy the gold standard test to detect postoperative recurrence.

To identify predictors of early symptomatic recurrence of Crohn's disease (CD) after surgical resection. We studied a cohort of 128 patients who had undergone at least one intestinal resection for CD. Factors that might predict early recurrence were documented for analysis using a standardized pro forma. These comprised age, gender, family history, extra-intestinal manifestations, smoking, complicated disease at first presentation, site of disease, preoperative inflammatory markers, involvement of resection margins, orientation and method of anastomosis and postoperative medical therapy. All symptomatic recurrences were confirmed by endoscopic, radiological, or operative means. We defined early recurrence as that which occurred within 36 months of first surgery. Univariate analysis was conducted to compare the distribution of each factor in those who developed early recurrence (n = 48) and those who remained disease free for the first 36 months (n = 50). Of the 128 patients studied, 98 fulfilled the inclusion criteria of at least 36 months of follow up. Of these patients, 48 (49%) patients developed recurrence. Trends towards fewer early recurrences were seen in patients with colonic disease (33%vs 56%, P = 0.068). Of the current smokers, 60% developed early recurrence compared with 43% of nonsmokers (P = 0.269). All other factors examined were similarly distributed between the two groups. Metronidazole as adjuvant treatment does not appear to protect against early symptomatic recurrence. This study shows that early symptomatic postoperative recurrence of CD remains unpredictable. Against expectation, abstinence from smoking and postoperative adjuvant metronidazole did not appear to protect against early symptomatic recurrence.

Smoking and a lack of immunosuppressive (IS) therapy are considered risk factors for intestinal surgery in Crohn's disease (CD). Good evidence for the latter is lacking. The objective of this study was to evaluate the impact of thiopurine treatment on surgical recurrence in patients after first intestinal resection for CD and its possible interaction with smoking. Data on 326 patients after first intestinal resection were retrieved retrospectively, and subjects were grouped according to their postoperative exposure to thiopurines. Treatment with either azathioprine (AZA) or 6-mercaptopurine (6-MP) was recorded on 161 patients (49%). Smoking status was assessed by directly contacting the patients. Surgical recurrence occurred in 151/326 (46.3%) patients after a median time of 71 (range 3-265) months. Cox regression revealed a significant reduction of re-operation rate in patients treated with AZA/6-MP for > or = 36 months as compared with patients treated for 3-35 months, for less than 3 months, and to those without postoperative treatment with AZA/6-MP (P=0.004). Cox regression analysis revealed treatment with thiopurines for > or = 36 months (hazard ratio (HR) 0.41; 95% confidence interval (CI) 0.23-0.76, P=0.004) and smoking (HR 1.6; 95% CI 1.14-2.4, P=0.008) as independent predictors for surgical recurrence. Furthermore, longer duration of disease tended to be protective (HR 0.99; 95% CI 0.99-1.0, P=0.067). Long-term maintenance treatment with AZA/6-MP reduces the risk of surgical recurrence in patients with CD. We also identified smoking as a risk factor for surgical recurrence.

A previous study reported a three-fold rise in the incidence of juvenile-onset Crohn's disease in Scottish children and a marginal fall in ulcerative colitis between 1968 and 1983. The present study aimed to document the incidence of juvenile-onset inflammatory bowel disease between 1981 and 1995 and examine temporal trends between 1968 and 1995 in Scotland. Scotland (latitude 55-60 degrees N) has a total area of 77 837 km2 (30 405 square miles) and includes four urban centres each with a population of over 100,000. The Scottish hospital discharges linked database was used to identify 1002 patients less than 19 years old who were coded as having inflammatory bowel disease between 1981 and 1997. All case notes were reviewed and diagnoses verified. Incident cases were defined as those with symptom onset before or at 16 years of age between 1 January 1981 and 31 December 1995. During the 15 year period 1981-1995, 438 incident cases of Crohn's disease and 227 of ulcerative colitis were identified, giving standardized incidences of 2.5 cases and 1.3 cases per 100,000 population per year for Crohn's disease and ulcerative colitis respectively. On 31 December 1995 there were 150 children < or = 16 years of age with Crohn's disease and 101 with ulcerative colitis, giving crude prevalences of 13.7 cases per 100,000 population for Crohn's disease and 9.2 for ulcerative colitis. The continuing rise in Crohn's disease incidence between 1981 and 1995 fits that predicted by linear trend analysis of the 1968-1983 data. The incidence of Crohn's disease in the 12-16 age range almost doubled between 1981 and 1995 and was greater for males than females. Ulcerative colitis incidence was thought to show a slight fall in the 1968-1983 data, but this is reversed in the 1981-1995 data. The incidence of juvenile-onset Crohn's disease continues to rise in Scotland and the prevalence has increased by 30% since 1983. Unlike the previous report from Scotland, the incidence of juvenile-onset ulcerative colitis also is apparently rising. Whether this represents a real rise in incidence, or merely the inclusion of milder cases which were not previously hospitalized remains uncertain.

Neutralizing autoantibodies (Abs) against granulocyte-macrophage colony-stimulating factor (GM-CSF Ab) have been associated with stricturing ileal Crohn's disease (CD) in a largely pediatric patient cohort (total 394, adult CD 57). The aim of this study was to examine this association in 2 independent predominantly adult inflammatory bowel disease patient cohorts. Serum samples from 742 subjects from the NIDDK IBD Genetics Consortium and 736 subjects from Australia were analyzed for GM-CSF Ab and genetic markers. We conducted multiple regression analysis with backward elimination to assess the contribution of GM-CSF Ab levels and established CD risk alleles and smoking on ileal disease location in the 477 combined CD subjects from both cohorts. We also determined associations of GM-CSF Ab levels with complications requiring surgical intervention in combined CD subjects in both cohorts. Serum samples from patients with CD expressed significantly higher concentrations of GM-CSF Ab when compared with ulcerative colitis or controls in each cohort. Nonsmokers with ileal CD expressed significantly higher GM-CSF Ab concentrations in the Australian cohort (P = 0.002). Elevated GM-CSF Ab, ileal disease location, and disease duration more than 3 years were independently associated with stricturing/penetrating behavior and intestinal resection for CD. The expression of high GM-CSF Ab is a risk marker for aggressive CD behavior and complications including surgery. Modifying factors include environmental exposure to smoking and genetic risk markers.

In this population-based 7-year follow-up of incident patients with ulcerative colitis (UC) or Crohn's disease (CD), we aimed to describe disease progression and surgery rates in an era influenced by the increased use of immunosuppressants and the introduction of biological therapy. From 1 January 2003 to 31 December 2004, all incident cases (562) of patients diagnosed with UC, CD, or inflammatory bowel disease unclassified in a well-defined Copenhagen area were registered. Medical records were reviewed from 1 November 2011 to 30 November 2012, and clinical data were registered. Clinical data on surgery, cancer, and death were cross-checked with register data from national health administrative databases in order to include missed data. In total, 513 patients (213 CD and 300 UC) entered the follow-up study. Twenty-six patients changed diagnosis during the follow-up. Changes in disease localization and behavior in CD according to the Vienna classification were observed in 23.9% and 15.0% of the patients, respectively, during follow-up. In total, 28.3% of the 300 UC patients had disease progression during the follow-up. The overall use of systemic steroids, immunomodulators, and anti-tumor necrosis factor agents in CD was 86.4%, 64.3%, and 23.5%, respectively. The rate of first-time intestinal resection in CD was 29.1% (n=62), and the 7-year cumulative risk was 28.5%. The cumulative risk of colectomy in UC was 12.5% at 7 years. UC and CD are dynamic diseases that progress in extent and behavior over time. The resection rate in CD and the colectomy rate in UC are still relatively high, although the rates seem to have decreased compared with historic data, which could be due to an increase in the use of immunomodulating therapy.

Twelve patients with Crohn disease aged from 11.3 to 17.1 years, underwent intestinal resection. Eight were prepubertal or in early puberty and 4 in mid or late puberty. Pre-operative assessment included acceleration and compression barium studies and total colonoscopy. In six patients the surgical indication was failure of medical management and in six intestinal obstruction. All but one were in remission 12 months after surgery. Height velocities in the eight pre and early pubertal patients increased dramatically during 6- and 12-month post operative measurement periods compared with preoperative growth. Height velocities in the mid and late pubertal patients showed much less increase. In selected patients, surgical treatment can induce remission resulting in catch-up growth and sustained growth acceleration. In prepubertal and early pubertal patients surgery is likely to improve final adult height.