Crohn's Disease-related Surgery Research Articles

Postoperative Ustekinumab Drug Levels and Disease Activity in Patients with Crohn's Disease.

This study investigated how post-operative ustekinumab levels relate to surgery type, endoscopic, biochemical, and clinical outcomes in patients with Crohn's Disease. A retrospective study of patients with Crohn's Disease with a disease-related operation between 2016 and 2022 assessed outcomes based on ustekinumab levels. Patients were included if they had an ustekinumab trough level within two years post-operatively. Patients were separated into groups based on whether their ustekinumab trough levels were adequate, defined as ≥ 4μg/mL, or suboptimal < 4μg/mL. A subset of patients with ustekinumab levels taken within two years both before and after surgery was compared to non-surgical treatment-escalated controls outside the initial patient set. Harvey-Bradshaw index was used to evaluate clinical disease activity. Rutgeert's and Simple Endoscopic Score for Crohn's Disease was used to evaluate endoscopic disease activity. C-reactive protein and fecal calprotectin values were collected to evaluate the molecular inflammatory disease state. CBC data were used to evaluate anemia. Forty-four patients were identified, which had ustekinumab levels after Crohn's Disease-related surgery. Twelve of these patients had pre-operative levels and were compared to 26 non-surgical treatment-escalated controls. No relationship between ustekinumab levels and endoscopic or clinical disease activity post-operatively was found. This also held true when looking at different surgery types. Adequate levels of ustekinumab post-operatively yielded lower risk of anemia. Surgery itself did not have an impact on ustekinumab levels. This study provided new insights into how post-operative ustekinumab levels impact several factors in patients having undergone Crohn's disease-related surgery.

Physical Activity Levels and Social Cognitive Theory Correlates among Adults with Crohn's Disease: Preliminary Results from a Cross-Sectional Analysis.

There is increasing research and clinical interest in physical activity (PA) as an adjuvant therapy for improving health outcomes among persons with Crohn's disease. To date, little is known regarding PA behavior and its cognitive and behavioral correlates in Crohn's disease. Thus, we assessed self-reported PA and its social cognitive theory (SCT) correlates in a sample of persons with Crohn's disease. Data on demographic and clinical characteristics, disease activity, leisure-time PA, and SCT variables were collected from 30 participants with Crohn's disease (90% White, 60% female) through an online survey. SCT variables assessed included exercise self-efficacy, social support, outcome expectations, goal setting, and planning. Analyses involved comparing PA levels and SCT survey scores using independent sample t-tests and non-parametric bivariate correlations. The majority of participants were in clinical remission (60%) and over half (57%) were classified as physically active, yet the mean PA level was lower than normative values for adults. Females (n = 18) and participants who reported previous surgery for Crohn's disease (n = 18) were almost twice as physically active as male participants and those without a history of Crohn's disease-related surgery, respectively (p's < 0.05). Overall, participants who reported greater exercise goal setting behaviors had higher levels of PA (rs = 0.34; p < 0.05). These findings highlight lower overall levels of PA in persons with Crohn's disease, and exercise goal setting represents a potential target of behavior change interventions for increasing PA in this population.

Finger clubbing in inflammatory bowel disease: association with upper small bowel lesions and need of surgery in Crohn's disease.

Finger clubbing has been associated with inflammatory bowel disease (IBD). In a prospective single-center study, we aimed to assess the frequency of finger clubbing in a cohort of IBD patients. Whether finger clubbing is associated with clinical characteristics of IBD was also investigated. IBD patients with a detailed clinical history were enrolled. Finger clubbing was assessed by visual inspection. Data were expressed as median (range), chi-square, t-test. Multivariate logistic regression analysis was used to assess risk factors for finger clubbing, when considering demographic and clinical characteristics, smoking habits and chronic pulmonary diseases (CPD). Finger clubbing was searched in 470 IBD patients: 267 Crohn's disease and 203 ulcerative colitis. Finger clubbing was more frequent in Crohn's disease than in ulcerative colitis: 45/267 (16.8%) vs. 15/203 (7.3%) [odds ratio (OR), 2.54 (1.37-4.70); P = 0.003]. Crohn's disease involved the ileum (59.9%), colon (4.5%), ileum-colon (25.8%) and upper gastrointestinal (GI) (9.8%). Ulcerative colitis extent included proctitis (E1) (13.4%), left-sided (E2) (43.3%) and pancolitis (E3) (43.3%). Upper GI lesions, but not other Crohn's disease localizations, were more frequent in patients with finger clubbing [9/45 (20%) vs. 17/222 (7.7%); P = 0.032]. Crohn's disease-related surgery was more frequent in patients with finger clubbing [36/45 (80%) vs. 107/222 (48.1%); P < 0.001]. In Crohn's disease, the only risk factors for finger clubbing were upper GI lesions and Crohn's disease-related surgery [OR, 2.58 (1.03-6.46), P = 0.04; OR, 4.07 (1.86-8.91), P = 0.006]. Ulcerative colitis extent was not associated with finger clubbing [E1: OR, 0.27 (0.02-3.44), P = 0.33; E2: OR, 0.93 (0.24-3.60), P = 0.92; E3:OR, 0.64 (0.22-1.86), P = 0.59]. In ulcerative colitis, but not in Crohn's disease, finger clubbing was more frequent in smokers [13/15 (86.6%) vs. 99/188 (52.6%); P = 0.01] and in patients with CPD [5/15 (33.3%) vs. 16/188 (8.5%); P = 0.002]. Smoking and CPD were the only risk factors for finger clubbing in ulcerative colitis [OR, 7.18 (1.44-35.78), P = 0.01; OR, 10.93 (2.51-47.45), P = 0.001]. In the tested IBD population, finger clubbing was more frequent in Crohn's disease than in ulcerative colitis. In Crohn's disease, upper GI lesions and history of Crohn's disease-related surgery were risk factors for finger clubbing, suggesting the possible role of finger clubbing as a subclinical marker of Crohn's disease severity.

JINLING (Judicious INdex of Luminal INflammation Grade) score, an effective indicator to assess inflammation severity in Crohn's disease.

With the increasing demand for individualized treatment in Crohn's disease, a score for accurate evaluation of inflammation grade will be of great significance. We have developed the JINLING score to assess inflammation severity for Crohn's disease, which incorporates an endoscopic score (SES-CD) and a 2-item patient-reported outcome (PRO2). The aim of this study was to examine the performance of JINLING score in evaluating inflammation grade and the correlation with the clinical outcomes. The correlation between JINLING score and Global Histologic Disease Activity Score (GHAS), fecal calprotectin (FCP), and C-reactive protein (CRP) level was performed in an exploration phase with a retrospective data set. The data on clinical outcomes including medication effects, Crohn's disease-related surgery and biochemical results were collected from a single-center prospective validation cohort. JINLING score correlated significantly with FCP, CRP, and hemoglobin in the exploration cohort (all P < 0.05). The receiver operating characteristic (ROC) curves based on a threshold Crohn's disease activity index value of 150, GHAS of 4, and FCP of 60 μg/g to identify disease activity, all showed a higher area under the curve with JINLING score than SES-CD or PRO2 alone. In the validation cohort, patients with high inflammation grade (JINLING ≥4) had higher GHAS, CRP, and FCP than low inflammation grade patients. High JINLING score was associated with an increased risk of treatment failure (hazard ratio 2.93; 95% confidence interval 1.13-7.61, P = 0.021). This newly developed index served well for quantifying inflammation grade and predicting clinical outcomes. JINLING score has the potential to facilitate clinical decision-making and personalized therapy for Crohn's disease patients.

692 Low Levels of Ustekinumab Despite Dose Escalation Is a Risk Factor for Surgery

INTRODUCTION: Ustekinumab is an IL-12/23 inhibitor used for the treatment of Crohn's disease (CD). Previous studies have suggested that dose escalation to every 4-week intervals can be beneficial in patients who do not achieve a clinical response on every 8-week maintenance dosing. However, safety and efficacy is unknown in CD patients escalated to more frequently than every 4-week intervals in patients who continue to have low trough drug levels. METHODS: We performed a retrospective chart review of patients on ustekinumab for CD who had dosing escalation to every two weeks (Q2) due to persistent low drug levels (&lt;5 µg/mL) despite being on q4 weeks (Q4) maintenance dosing and clinically losing response. RESULTS: Out of 200 CD patients on ustekinumab 90 mg subcutaneous (SQ) maintenance in our IBD program, 112 underwent reactive therapeutic drug monitoring for loss of response or incomplete response to therapy. Of the 112 with drug levels, none had anti-drug antibodies, but 80 patients had levels &lt;5 mcg/mL. All 80 patients were frequency escalated to q4 week dosing. Of these, 12 patients continued to have low ustekinumab trough levels at week 4 (&lt;5 mcg/mL) and thus were escalated to Q2 week dosing. Eight of the 12 patients had IV reinduction dosing prior to dose escalation to Q2 frequency. Of the 12 patients, 6 (50%) required surgery for their active Crohn's disease. These patients were on Q2 week dosing for median of 16 weeks (range 1-68) prior to surgery. All 6 (100%) were able to be de-escalate to less frequent dosing after surgery. Two patients that were unable to de-escalate their dosing frequency are planning for surgery in the near future. The remaining four patients were able to de-escalate to Q4 dosing after clinical response. See full details in Table 1. No adverse events unrelated to their Crohn's disease, including infections or other safety markers were noted. CONCLUSION: Low levels of ustekinumab despite escalation of dosing to every 2 weeks may suggest a need for Crohn's disease related surgery. In our study, all patients who underwent surgery were able to de-escalate to lower dosing frequency suggesting that high inflammatory disease burden contributed to the low levels of ustekinumab. Further studies are needed to assess the safety and efficacy of high frequency dosing of ustekinumab.

1690 Management of Non-Malignant Enterocutaneous Fistula Using Fully Covered Stent

INTRODUCTION: Postoperative enterocutaneous fistula (ECF) has a reported prevalence of 3.6% in general surgery, and up to 35% in Crohn disease-related surgery. ECFs can be of low-output, drain &lt; 200 mL/day, or of high-output, drain &gt; 500 mL/day, which unlikely to heal spontaneously. ECFs can cause metabolic disturbances, fluid loss, and malnutrition. CASE DESCRIPTION/METHODS: Case 1: A 54-year-old man with a history of colonic transmural necrosis status post multiple surgeries and end transverse colostomy placement, presented with a two-week history of passing stool from the lateral aspect of his peristomal incision, consistent with enterocutaneous fistula. The 2 fistulae ends were seen on the skin, laterally to the stoma (Figure 2c), and both other ends were identified in the stoma lumen. CT fistulogram confirmed the fistulae. After advancing the endoscope into the stoma, a 2 cm friable stenosis was seen (Figure 1a). The fistulae tracts were treated with silver nitrate and were injected with fibrin glue. A 20 mm × 6 cm fully-covered stent was placed (Figure 1b) and sutured in place. A month later the fistulae had healed (Figure 2d), with no recurrence reported. Case 2: A 64-year-old man with a history of metastatic mucinous appendiceal cancer status post multiple abdominal surgeries, referred for his recurrent ECF. CT scan showed air tracking outside the colon at the level of the cutaneous fistula site. Water-soluble contrast pushed through the rectum showed an occlusion with contrast extravasation is seen in the fistula (Figure 3e). Sigmoidoscopy confirmed the site of obstruction and the area of leakage. A fully covered stent was placed to relieve the obstruction and cover the fistula (Figure 3f). Initially, the fistula output resolved, but when the stent was removed a month later, the fistula output returned. So, a stent was placed again and was sutured to the colon. The patient is now asymptomatic and having normal bowel movements. DISCUSSION: ECF can cause significant morbidity and affect the quality of life. Surgical repair of ECF has a recurrence rate as high as 36% and is associated with high mortality especially in malnourished patients. Thus, endoscopic intervention using fully-covered stents can be helpful in healing the fistulae. In these 2 cases, the placement of a fully-covered stent relieved the coexisting obstruction, diverted the flow away from the fistula, and simultaneously covered the fistula end. The patients experienced relief of fistula symptoms and avoided them major surgical intervention. Watch the video: http://bit.ly/30BIvtw.

Early combined immunosuppression may be effective and safe in older patients with Crohn's disease: post hoc analysis of REACT.

Physicians may be reluctant to prescribe combined immunosuppression in older patients with Crohn's disease due to perceived risk of treatment-related complications. To evaluate the impact of age on risk of Crohn's disease-related complications in patients treated with early combined immunosuppression vs conventional management in a post hoc analysis of the randomised evaluation of an algorithm for Crohn's treatment (REACT), a cluster-randomised trial. We compared efficacy (time to major adverse outcome of Crohn's disease-related surgery, hospitalisation or serious complications; corticosteroid-free clinical remission) and safety outcomes at 24months, between patients aged <60 vs ≥60years randomised to early combined immunosuppression or conventional management, using Cox proportional hazard analysis or modified Poisson model. In the early combined immunosuppression arm, patients with failure to achieve clinical remission within 4-12weeks of corticosteroids were treated with a combination of tumour necrosis factor-α antagonist plus anti-metabolite and sequentially escalated in a stepwise algorithm. Of 1981 patients, 311 were ≥60years (15.7%; 173 randomised to early combined immunosuppression and 138 to conventional management). Over 24months, 10% of older patients developed Crohn's disease-related complications (early combined immunosuppression vs conventional management: 6.4% vs 14.5%) and 14 patients died (3.5% vs 5.8%). There was no difference between younger and older patients in risk of achieving corticosteroid-free clinical remission (<60years, early combined immunosuppression (72.6%) vs conventional management (64.4%): relative risk [RR], 1.06 [95% CI, 0.98-1.15] vs ≥60years, early combined immunosuppression (74.8%) vs conventional management (63.0%): RR, 1.09 [0.90-1.33], P-interaction=0.78) or time to major adverse outcome (<60years: hazard ratio [HR], 0.71 [0.53-0.96] vs ≥60years: HR, 0.69 [0.31-1.51], P-interaction=0.92) with early combined immunosuppression vs conventional management. We observed no difference in efficacy and safety of early combined immunosuppression compared to conventional management in older and younger patients. Early combined immunosuppression may be considered as a treatment option in selected older patients with Crohn's disease with suboptimal disease control. Clinical Trial Identifier: NCT01030809.

Development of Clinical Prediction Models for Surgery and Complications in Crohn's Disease.

Crohn's disease-related complications account for a substantial proportion of inflammatory bowel disease-associated health care expenditure. Identifying patients at risk for complications may allow for targeted use of early therapeutic interventions to offset this natural course. We aimed to develop risk prediction models for Crohn's disease-related surgery and complications. Using data from the Randomised Evaluation of an Algorithm for Crohn's Disease cluster-randomised clinical Trial [REACT], which involved 1898 patients from 40 community practices, separate prediction models were derived and internally validated for predicting Crohn's disease-related surgery and disease-related complications [defined as the first disease-related surgery, hospitalisation, or complication within 24 months]. Model performance was assessed in terms of discrimination and calibration, decision curves, and net benefit analyses. There were 130 [6.8%] disease-related surgeries and 504 [26.6%] complications during the 24-month follow-up period. Selected baseline predictors of surgery included age, gender, disease location, Harvey-Bradshaw Index [HBI] score, stool frequency, antimetabolite or 5-aminosalicylate use, and the presence of a fistula, abscess, or abdominal mass. Selected predictors of complications included those same factors for surgery, plus corticosteroid or anti-tumour necrosis factor use, but excluded 5-aminosalicylate use. Discrimination ability, as measured by validated c-statistics, was 0.70 and 0.62 for the surgery and complication models, respectively. Score charts and nomograms were developed to facilitate future risk score calculation. Separate risk prediction models for Crohn's disease-related surgery and complications were developed using clinical trial data involving community gastroenterology practices. These models could be used to guide Crohn's disease management. External validation is warranted.

DOP039 Postoperative infectious complications in Crohn's disease: results from PRACTICROHN study

Background: Crohn's disease (CD) surgery is related to postoperative complications in 11 to 14% of all cases. Infectious complications (IC) are the most common. The aim of this study is to describe the prevalence and factors associated with the postoperative IC in a cohort of patients with CD Methods: PRACTICROHN was a study that included patients aged ≥18 years-old from 26 spanish centers who underwent CD-related ileocolonic or ileorectal resection with ileocolonic or ileorectal anastomosis between January 2007 and December 2010. Clinical data and treatments, including surgery was retrospectively collected from medical records. IC analyzed were: intra-abdominal abscess, wound infection, catheter-related sepsis and extra-abdominal infections. Categorical variables were compared with the χ2 test or Fisher'sexact test Kaplan-Meier method was used to assess time to clinical recurrence and a log-ranktest to obtain statistical significance. Results: Three hundred and sixty four patients were analyzed (mean age 32 years [SD13], 50% men). Median time from CD diagnosis to surgery was 6 years (IQR 1–12). Indication for surgery was: structuring disease (n=169, 48%), penetrating (n=114, 45%), penetrating +stricturing (n=51, 14%) and/or resistance to treatment (n=21, 6%). Sixty nine patients presented some IC (19%), with a hospitalization of median 19 days (IQR 10–30) vs 9 days (IQR 7–12) in patients without IC (p<0.001). The most frequent IC were wound infection (33/69, 48%) and abscess (28/69, 40%); extra-abdominal infections (12/69, 17%) and infections of the catheter (4/69,5%). No IC was associated with mortality. IC were more frequent in patients in which perforation was the reason for surgery (11/69 vs 27/69 p=0.048). No differences in IC were observed related to age, gender, smoking habit location or length of intestinal resections. No treatment was correlated with a higher rate of IC. Conclusions: 19% of patients who underwent a CD related surgery presented a postoperative IC, with perforation as the most common cause of surgery-associated IC. Type of CD treatments was not associated with the ocurrence of IC.

Assessment of Factors That Predict Postoperative Prophylaxis Use in Patients Who Undergo Crohnʼs-related Surgeries

Introduction: Despite medical therapies, up to 70% of Crohn's disease (CD) patients will require surgery in their lifetime. Over 75% of these patients will develop evidence of endoscopic recurrence after one year of surgery which can be prevented with the use of post-operative prophylaxis with immunosuppressives. We studied a group of patients who underwent CD related surgeries to identify factors including race that may predict being placed on post-operative prophylaxis with immunomodulator and/or biologic therapy. Methods: With Institutional Review Board approval, the medical records of our institution were queried to identify consecutive African American (AA) and Caucasian (C) patients who underwent surgery for CD from December 1, 2009 to December 1, 2011. A retrospective chart review was performed using electronic medical records. Patients were considered for postoperative prophylaxis if they had one or more of the following moderate to high risk predictive factors for recurrence: jejunal or extensive ileal-colonic disease, history of prior resection, fistulizing disease, progression to surgery despite immunomodulators, early age of surgery ( < 30), and smoking. Statistical analysis included descriptive statistics, Chi-square analysis for categorical variables, and a logistic regression model. Results: A total of 77 patients were included in the study. 42% were AA and 43% were female. The mean age was 40 years old. Indications for surgery included obstruction, which was the most common, followed by complicated fistulizing disease, medically refractory disease, and perforation. 47% had a previous CD related surgery. Of these 69 patients (89.6%) were felt to be appropriate for postoperative prophylaxis. Table 1 highlights the proportion of eligible patients started on immunosuppressives and who followed up with a gastroenterologist within 3 months postoperatively based on ethnicity. In a logistic regression model (table 2), adjusting for age, ethnicity, and prior CD surgery, the only significant predictor of starting post-operative therapy was seeing a gastroenterologist within 3 months (OR 6.5, 95% CI 1.6-26, p=0.008).Table 1: Comparison of postoperative prophylactic immunosuppressive use and gastroenterologist follow up in a cohort of African American (AA) and Caucasian (C) CD patientsConclusion: When comparing multiple factors including ethnicity, prior CD surgery, age, and GI physician follow up, the only significant predictor of starting post-operative immunosuppressive therapy was follow up with a gastroenterologist. Institution of measures to assure follow up may help to prevent further complications of CD in those who undergo surgery.Table 2: Predictors of post-operative prophylactic immunosuppressive use utilizing multivariate logistic regression model

NOD2/CARD15 mutations in Polish and Bosnian populations with and without Crohn's disease: prevalence and genotype-phenotype analysis

Data on prevalence and phenotypic consequences of nucleotide-binding oligomerisation domain 2/caspase recruitment domains 15 (NOD2/CARD15) variants in Crohn's disease (CD) population in Poland and Bosnia and Herzegovina (B&amp;H) are nonexistent. We aimed to determine the prevalence of NOD2/CARD15 mutations and their association with disease phenotype in Polish and Bosnian patients with CD and in healthy controls. We prospectively recruited 86 CD patients and 83 controls in Poland and 30 CD patients and 30 controls in B&amp;H, 229 in total. We determined the prevalence of NOD2/CARD15 mutations and their association with the disease phenotype according to Montreal classification. Participants were genotyped for Leu1007fsinsC and Gly908Arg mutations. At least one CD-associated allele was found in 29/86 (33.7%) of Polish CD patients and in 9/83 (10.8%) of healthy controls (p&lt;0.001). In both CD patients and controls in Bosnian sample, at least one NOD2 mutation was found in equal number of patients (3/30; 10%) with all of the NOD2 mutation positive CD patients being homozygous, while controls being heterozygous. In Polish sample, perianal disease was less frequent in CD patients with any NOD2 mutation (1/21; 4.8%) compared to those without (11/41; 26.8%; p=0.046). Higher percentage of patients with NOD2 mutations had history of CD related surgery when compared with those without mutations (66.7% vs. 43.3%; p=0.05). The risk for CD is increased in patients with NOD2 mutations (Poland) and especially in the presence of homozygous NOD2 mutations (Poland and Bosnia). The presence of variant NOD2 alleles is associated with increased need for surgery and reduced occurrence of perianal disease.

P158. Short-term MRE predictors of need in Crohn's disease related surgery

P158. Short-term MRE predictors of need in Crohn's disease related surgery

Hemoglobin and hematocrit levels in the prediction of complicated Crohn's disease behavior--a cohort study.

BackgroundMarkers that predict the occurrence of a complicated disease behavior in patients with Crohn's disease (CD) can permit a more aggressive therapeutic regimen for patients at risk. The aim of this cohort study was to test the blood levels of hemoglobin (Hgb) and hematocrit (Hct) for the prediction of complicated CD behavior and CD related surgery in an adult patient population.MethodsBlood samples of 62 CD patients of the German Inflammatory Bowel Disease-network “Kompetenznetz CED” were tested for the levels of Hgb and Hct prior to the occurrence of complicated disease behavior or CD related surgery. The relation of these markers and clinical events was studied using Kaplan-Meier survival analysis and adjusted COX-proportional hazard regression models.ResultsThe median follow-up time was 55.8 months. Of the 62 CD patients without any previous complication or surgery 34% developed a complication and/or underwent CD related surgery. Low Hgb or Hct levels were independent predictors of a shorter time to occurrence of the first complication or CD related surgery. This was true for early as well as late occurring complications. Stable low Hgb or Hct during serial follow-up measurements had a higher frequency of complications compared to patients with a stable normal Hgb or Hct, respectively.ConclusionsDetermination of Hgb or Hct in complication and surgery naïve CD patients might serve as an additional tool for the prediction of complicated disease behavior.

Obesity is Associated With Poor Surgical Outcome in Crohn's Disease.

BackgroundPublished data suggest a link between obesity and adverse outcomes in Crohn’s disease (CD). We aimed to test the hypothesis that obese CD patients would be more likely than non-obese CD patients to have poor surgical outcome when undergoing surgery for a complication of CD.MethodsWe designed a retrospective cohort study to test our hypothesis. The population comprised of adult CD patients who underwent CD related surgery at a tertiary referral center. The exposed and unexposed cohorts were represented by patients who were obese vs. non-obese at the pre-op visit respectively. Outcome was represented by successful vs. unsuccessful surgical outcome as deemed by the treating clinician.ResultsNinety CD patients were eligible for inclusion into this cohort study of which 36 were obese (exposed cohort) and 54 were non-obese (unexposed cohort). Among obese CD patients, 64% had an unsuccessful surgical outcome vs. 41% with unsuccessful surgical outcome among the non-obese. Based on unadjusted bivariate analysis, potential confounders identified included age and type of surgery. Gender distribution, disease duration, ethnicity, tobacco use, steroid use, traditional and biological immune modulator use and clinical disease activity were similar between the two groups. Logistic regression adjusted for age and type of surgery revealed that obese CD patients were approximately 2.5 times more likely to have a poor surgical outcome than patients with CD who were not obese (P = 0.05 OR 2.53 95% CI 0.99 - 6.52). BMI as a continuous variable (adjusted for age and type of surgery) appeared to be associated with poor surgical outcome (P = 0.06 OR 1.07 95% CI 0.99 - 1.15).ConclusionsObesity may be associated with poor surgical outcome in CD patients.

Association of Susceptibility Variants With Non-Perianal Crohn's Disease-Related Surgery

Association of Susceptibility Variants With Non-Perianal Crohn's Disease-Related Surgery

Relationship between clinical features of Crohn??s disease and the risk of developing extraintestinal manifestations

Crohn's disease is frequently associated with extraintestinal manifestations. The aim of this study was to evaluate the degree of association between the development of extraintestinal manifestations, the clinical forms of Crohn's disease according to the Vienna Classification and to the presence of several potential risk factors of the disease. One hundred and seventy-three consecutive Crohn's disease patients were studied. Sex, smoking habits, previous Crohn's disease-related surgery, family history of Crohn's disease, steroid dependency, steroid resistance and the presence of at least one mutant allele in any of the three considered variants of CARD15 gene were considered as potential risk factors. The Vienna Classification was applied, and the presence of extraintestinal manifestations was evaluated. A total of 61 (35.3%) patients developed extraintestinal manifestations. They were more frequently seen in women than in men (41.1 vs. 26.7%), (odds ratio 1.92, 95% confidence interval: 0.99-3.70; P=0.05) and in steroid-dependent patients than in steroid responders (61.1 vs. 28.5%), (odds ratio 3.94, 95% confidence interval: 1.83-8.49; P<0.01). No relationship was found in general between the extraintestinal manifestations of Crohn's disease and smoking habits, previous Crohn's disease-related surgery, a family history of Crohn's disease, steroid resistance and CARD15 mutations. Such relationships were, however, detected for some individual extraintestinal manifestations as between both smoking habits (odds ratio 9.09, 95% confidence interval: 1.15-71.66; P<0.05) and the G908R CARD15 mutation (odds ratio 4.76, 95% confidence interval: 1.11-20.43; P<0.05), respectively, and erythema nodosum. Patients with any colonic involvement of Crohn's disease (L2+L3) suffered from extraintestinal manifestations of the disease more frequently than patients without colonic involvement (42.7 vs. 25.9%, respectively; odds ratio 2.12, 95% confidence interval: 1.10-4.07; P<0.05). Female gender, steroid-dependency and colonic involvement are associated with the risk of developing extraintestinal manifestations of Crohn's disease.

Utility of Serological Markers in Predicting the Early Occurrence of Complications and Surgery in Pediatric Crohn's Disease Patients

Many Crohn's disease (CD) patients develop complications (fistulae and abscesses), and require surgery, often repeatedly and at variable instances. Identifying serological markers that determine their early or repeated manifestation can enable implementing more aggressive preventive strategies. Our objective was to study the ability of serological markers for predicting development of early (first) and recurrent complications or requirement for surgery. Serum anti-Saccharomyces cervisiae (ASCA) (IgA & IgG) and perinuclear antineutrophil cytoplasmic antibodies (pANCA) were assayed close to diagnosis in a pediatric cohort of CD patients identified between 1996 and 1998. At diagnosis and follow-up, information was acquired on demographic and clinical features of disease. Relation between ASCA and clinical events was studied using adjusted Cox-proportional hazards modeling. The relative rates of recurrent clinical events according to the marker measures were compared. The mean age (SD) at diagnosis was 11.2 (3.4) yr. Among 139 patients, 35 (25.9%) and 31 (22.3%) acquired one or more CD related surgery or complication, respectively. Time to occurrence of the first complication was lower among patients ASCA+ (IgA or IgG) (hazards ratio (HR) = 2.33; 95% confidence interval (CI) = 0.99-5.50) and among those with higher ASCA-IgA titers (HR = 1.20; 95% CI = 1.08-1.34). The rates of recurrent complications were higher among those positive or with higher ASCA titers. ASCA did not predict time to undergoing surgery independent of complications, and was unrelated to the occurrence of recurrent surgeries. Our study shows that serum ASCA measured close to diagnosis can determine the occurrence of early complications in pediatric CD. Preventive treatment targeted toward these susceptible patients could potentially modify the disease course.

Association of NOD2/CARD15 mutations with previous surgical procedures in Crohn's disease

The aim of this study is to assess the importance of NOD2/CARD15 gene mutations as prognostic factors for surgical indications in Crohn's disease. PATIENTS AND EXPERIMENTAL DESIGN: A total of 165 Crohn s disease patients were studied, considering previous surgery related to Crohn's disease. We analyzed for previous surgery in global procedures as well as separately for the two main surgical indications: ileal resection and fistula treatment. The need for appendectomy was also studied. All patients were genotyped for the three CARD15 mutations, and association studies were developed using Chi-square statistics and Fisher's exact test whenever appropriate. Carriers of the G908R or 1007fs mutation needed surgery more frequently, both for ileal resection and fistula repair. In contrast, appendectomy was not associated with CARD15 mutations. As previously reported in this population, the R702W mutation does influence parameters of disease or need of surgery. The need for Crohn's disease-related surgery is higher in carriers of the G908R or 1007fs CARD15 mutation in the Galician population. Nevertheless, the frequency of these mutations does not allow their use to predict the course of disease.