Long-term outcome after intestinal resection for Crohn's disease

Objective. To assess the need for intestinal repeat resection for recurrence of Crohn's disease in patients observed for more than 20 years after the first resection. Material and methods. Data were gathered retrospectively from the medical records of 53 (28 F) consecutive patients with Crohn's disease from May 1954 to December 2002. Median age at first intestinal resection was 24.5 (range 13–65) years, and median observation time thereafter was 26.5 (20.1–48.6) years. Disease location and behaviour were defined according to the Vienna classification. Results. The 53 patients had an average 2.7 and a median 2 intestinal resections. Out of 144 intestinal resections (77.1%) 111 were performed during the first three operations; no alterations in distribution of ileal, ileocolic and colic resections were found. From the first to the third operation there was an increase in penetrating disease from 15% to 39% (p=0.046) concomitant with a decrease in stricturing disease from 72% to 44% (p=0.048) of the patients. There was also a corresponding decrease in ileocolic disease from 45% to 5% (p=0.003) and a tendency towards an increase in ileal disease from 38% to 67%. One patient died (1.8%) from rectosigmoid perforation after the third resectional operation. Six patients needed reoperation (11.3%) for ileus, anastomotic bleeding, rectosigmoidal perforation and abdominal pain. Thirty-four patients (64.2%) needed intestinal repeat resection (median 8.3 years) during 25.3 years after the first repeat resection. Conclusions. This study indicates a diminution of Crohn's disease activity with time, as demonstrated by no need for intestinal repeat resection more than 25 years after the first resection.     

Risk factors for surgery and postoperative recurrence: analysis of a south China cohort with Crohn's disease

Abstract

Background and aims. To investigate the risk factors for primary surgery and postoperative recurrence in a cohort of Chinese Crohn's disease (CD) patients. Methods. Medical notes of consecutive diagnosed patients from 2003 until 2010 were reviewed. Fifty-seven postoperative patients – finished regular follow-up – were recruited for postoperative recurrence analysis. Results. One hundred eleven of 323 (34.4%) patients of this cohort underwent primary surgery. The cumulative frequency of resection was 16.6%, 35.4%, 53%, and 94.5% for 1, 5, 10, and 30 years, respectively, after onset of disease. Male (OR: 1.994; 95% CI: 1.291–3.078, p = 0.002), stricture (OR: 4.832; 95% CI: 3.064–7.621, p = 0.000), or penetrating (OR: 4.923; 95% CI: 3.060–7.919, p = 0.000) were associated with an increased risk for primary surgery, while early use of immunomodulators was (OR: 0.438; 95% CI: 0.218–0.880, p = 0.020) associated with a decreased risk. Fifty-seven (21.1%) patients were diagnosed as postoperative clinical recurrence and the cumulative recurrence rates were 6.1%, 17.1%, and 36.8% for 1, 2, and 3 years, respectively. Perianal disease was associated with an increased risk for clinical recurrence (OR: 5.606; 95% CI: 1.59–19.766, p = 0.007). Conclusions. The operation frequency is high in CD. Male, penetrating, and stricture diseases are associated with an increased risk for primary surgery while early use of immunomodulators is associated with a decreased risk. The postoperative recurrence rate is also high. Patients with perianal disease are at higher risk for clinical recurrence.     

Low serum trough levels are associated with post-surgical recurrence in Crohn's disease patients undergoing prophylaxis with adalimumab

BackgroundWhether therapeutic drug monitoring of biologic therapy can predict the efficacy of adalimumab to prevent postoperative Crohn's disease recurrence is unknown.AimTo investigate whether adalimumab trough levels and anti-adalimumab antibodies correlate with endoscopic and clinical outcomes in a series of patients treated with prophylactic adalimumab monotherapy after resective surgery.MethodsPost hoc analysis of a randomized, mesalamine-controlled trial. Adalimumab trough levels and antibodies were analysed every 8 weeks for 2 years using an homogeneous mobility shift assay.ResultsAt two years, 1/6 patient had clinical recurrence and 1/6 patient had endoscopic and clinical recurrence. At baseline (9.5 vs. 14.4 mcg/mL) and during follow-up [7.5 (4.4–9.8) vs. 13.9 (8.9–23.6) mcg/mL, p < 0.01], median adalimumab trough levels in patients with clinical or endoscopic recurrence were lower than in those who maintained remission. Persistent antibodies-against-adalimumab were detected in the patient with both endoscopic and clinical recurrence.ConclusionMeasurement of adalimumab trough levels and anti-adalimumab antibodies after surgery could be useful to further reduce postoperative recurrence.     

Risk factors that predict the requirement of aggressive therapy among Chinese patients with Crohn's disease

OBJECTIVES: Crohn's disease is now increasingly considered as a disabling disease. Conventionally, the disease is managed by step‐up therapy. In recent years, the top‐down strategy has been proposed and is thought to benefit the patients in whom the condition is likely to rapidly deteriorate toward disabling. However, this strategy has severe adverse effects which have to be weighed against its benefits. The aim of this study is to identify the risk factors that can predict the requirement of top‐down therapy among Chinese patients. METHODS: We included 207 Chinese patients who had histories of Crohn's disease for ≥5 years, or those who had Crohn's disease for <5 years and at least one criterion of disabling disease. The risk factors related to the 5‐year disabling course and the 2‐year disabling course of Crohn's disease were separately analyzed in the same cohort by logistic regression. RESULTS: Among the 207 patients, the rate of disabling disease was 80.19% for 5‐year, and 71.01% for 2‐year. The risk factors of age <40 years at diagnosis, steroids requirement for treating acute exacerbation, and presence of perianal disease at diagnosis were significantly associated with a 5‐year disabling course. In the same cohort, the risk factors related to 2‐year disabling course were likewise steroids requirement for treating acute exacerbation and presence of perianal disease at diagnosis. CONCLUSION: The risk factors associated with disabling Crohn's disease, which entails the requirement of top‐down therapy in Chinese patients, are requirement of steroids for treating acute exacerbation and the presence of perianal disease at diagnosis.     

Tailored treatment according to early post-surgery colonoscopy reduces clinical recurrence in Crohn's disease: A retrospective study

Background

After intestinal resection for Crohn's disease, the severity of endoscopic recurrence in the first year following surgery is predictive of clinical outcome. Aim of the study was to assess the impact on clinical recurrence of tailored therapy based on endoscopic findings in the first year following surgery for Crohn's disease.

Methods

All patients who underwent an intestinal resection for Crohn's disease between 1995 and 2005 at Saint-Louis Hospital were retrospectively included. Time-to-clinical recurrence was compared in two groups: patients who had systematic ileocolonoscopy 6–12 months after intestinal surgery with tailored treatment according to the severity of endoscopic lesions (group C) and patients without systematic endoscopic evaluation (group NC).

Results

132 patients (group C = 90, group NC = 42) were included. Probabilities of clinical recurrence were significantly lower in group C (21% and 26% at 3 and 5 years, respectively) compared with group NC (31% and 52% at 3 and 5 years respectively, p = 0.01).

Conclusion

Tailored treatment according to endoscopic assessment after ileocolonic resection is significantly associated with reduced clinical recurrence rate.     

Influence of Saccharomyces boulardii on the intestinal permeability of patients with Crohn's disease in remission

Objective. Crohn's disease (CD) is characterized by a reduction in mucosal integrity that permits antigen penetration into the intestinal tissue. The administration of probiotics has been suggested to improve the barrier function of the mucosa. The objective of this study was to evaluate the influence of Saccharomyces boulardii on the intestinal permeability in CD. Material and methods. Thirty-four patients were randomized according to the Vienna classification for treatment with either placebo or Saccharomyces boulardii. Baseline medications (mesalamine, azathioprine, prednisone, metronidazole and/or thalidomide) were maintained. Intestinal permeability (lactulose/mannitol ratio) was evaluated immediately before the beginning of treatment and at the end of the first and third treatment month. Fifteen healthy volunteers were also submitted for the intestinal permeability test. Results. In volunteers, the lactulose/mannitol ratio was 0.005±0.0037, whereas this value was 0.021±0.01 in patients with CD (p=0.001). In the placebo group, there was an increase in lactulose/mannitol ratio by 0.004±0.010 (p=0.12) at the end of the third month. In the S. boulardii group, there was an improvement in intestinal permeability, with a decrease in the lactulose/mannitol ratio by 0.008±0.006 (p=0.0005) in the same period. Conclusions. Patients with CD in remission present alterations in the integrity of the intestinal mucosal barrier according to lactulose/mannitol ratio. S. boulardii added to baseline therapy improved intestinal permeability in these patients, even though complete normalization was not achieved.     

Preoperative risk factors for early recurrence in patients with resectable pancreatic ductal adenocarcinoma after curative intent surgical resection

Background: Postoperative early recurrence(ER) in patients with pancreatic ductal adenocarcinoma(PDAC) is frequently encountered after curative intent surgery. Nonetheless, clinical significance and risk factors of ER after surgery for PDAC have not been extensively investigated. The aim of this study was to determine preoperative risk predictors for ER in patients with PDAC after upfront surgery. Methods: Eighty-one consecutive patients with PDAC who underwent curative intent surgical resection at Kangbuk Samsung Hospital between January 2004 and May 2015 were enrolled. ER was defined as tumor relapse within 6 months after surgery. Results: ER occurred in 26 patients(32.1%), whereas 49 patients(60.5%) had late recurrence( ≥ 6 months after surgery), and 6 patients had no recurrence(7.4%). Univariate analysis showed that C-reactive protein(CRP) 3.0 mg/dL, modified Glasgow prognostic score(mGPS) = 2, decrease of total lymphocyte count by 50% of baseline value in the preoperative period, prognostic nutritional index(PNI) 45, neutrophilto-lymphocyte ratio(NLR) ≥ 3, and preoperative maximum standardized uptake value(SUVmax) were significantly associated with ER. Multivariate logistic regression analysis revealed that CRP 3.0 mg/dL, decrease of total lymphocyte count by 50% of baseline value, and preoperative SUVmax were significant and independent contributors of ER in patients with resectable PDAC who underwent curative intent surgery. Conclusions: Postoperative ER for resectable PDAC was frequent with poor prognosis after curative intent upfront surgery. It is reasonable to suggest that there is a subgroup of resectable PDAC patients at highrisk of ER and neoadjuvant therapy should be considered in these patients in a clinical trial setting.     

Usefulness of the capsule endoscopy Crohn's disease activity index in assessing the necessity of early additional treatment in patients with Crohn's disease in clinical remission

The Capsule Endoscopy Crohn''s Disease Activity Index (CECDAI) was recently reported as a new scoring system to evaluate the mucosal lesions of patients with Crohn''s disease (CD). We investigated whether CECDAI is useful for assessing the necessity of early additional treatment in patients with CD in clinical remission.Twenty-one patients with small intestinal CD in clinical remission underwent capsule endoscopy (CE). The CECDAI and Lewis score (LS) were used to evaluate the intestinal lesions. We analyzed the correlations between several biomarkers and CECDAI or LS and examined the changes in therapeutic regimens based on the CECDAI.CE identified intestinal abnormalities in most CD patients in clinical remission: 81.0% and 85.7%, as assessed using CECDAI and LS, respectively. A significant positive correlation was observed between the CDAI and LS (P = .025), as well as between CDAI and CECDAI (P = .014) in these cases. Compared to LS, CECDAI scores were more evenly distributed. No significant correlations were observed between endoscopic scores and serum markers, including CRP, hemoglobin, and albumin levels. Additional treatment was performed significantly more often in patients with moderate-severe disease activity (CECDAI ≥5.8) (P = .012) than in those with normal (CECDAI <3.5) and mild (3.5≤CECDAI<5.8) disease activity. Resection of the small intestine did not affect the small bowel transit time or CE score.CECDAI is useful in evaluating mucosal lesions in small bowel CD patients in clinical remission and helps in assessing the requirement for additional treatment for these patients, including those who undergo intestinal resection.     

Population‐based cases control study of inflammatory bowel disease risk factors

Background and Aim: The rapid increase in inflammatory bowel disease (IBD) incidence confirms the importance of environment in its etiology. We aimed to assess the role of childhood and other environmental risk factors in IBD. Methods: A population‐based case‐control study was carried out in Canterbury, New Zealand. Participants comprised 638 prevalent Crohn's disease (CD) cases, 653 prevalent ulcerative colitis (UC) cases and 600 randomly‐selected sex and age matched controls. Exposure rates to environmental risk factors were compared. Unadjusted and adjusted odds ratios (OR) with 95% confidence intervals (CI) are presented. Results: A family history of IBD (CD OR 3.06 [2.18–4.30], UC OR 2.52 [1.90–3.54]), cigarette smoking at diagnosis (CD OR 1.99 [1.48–2.68], UC OR 0.67 [0.48–0.94]), high social class at birth (CD and UC trend, P < 0.001) and Caucasian ethnicity (CD OR 2.04 [1.05–4.38], UC OR 1.47 [1.01–2.14]) were significantly associated with IBD. City living was associated with CD (P < 0.01). Being a migrant was associated with UC (UC OR 1.40 [1.14–2.01]). Having a childhood vegetable garden was protective against IBD (CD OR 0.52 [0.36–0.76], UC OR 0.65 [0.45–0.94]) as was having been breast‐fed (CD OR 0.55 [0.41–0.74], UC OR 0.71 [0.52–0.96]) with a duration‐response effect. Appendicectomy, tonsillectomy, infectious monomucleosis and asthma were more common in CD patients than controls (P < 0.01). Conclusions: The importance of childhood factors in the development of IBD is confirmed. The duration‐response protective association between breast‐feeding and subsequent development of IBD requires further evaluation, as does the protective effect associated with a childhood vegetable garden.     

Treatment response and colonic gene expression in patients with Crohn's disease

Objective. Responses and adverse events to medication vary greatly among patients with Crohn's disease (CD). The aim of this study was to investigate whether global gene expression profiles could predict such responses and possible side effects. Material and methods. Tissue specimens from the descending colon were obtained from 32 CD patients (in 18 patients from areas without inflammation and in 14 patients from inflamed areas). Gene profiling was done using the Affymetrix Human Genome U133 Plus 2.0 GeneChip array. Hybridization data were analyzed with dChip software. Results. There were no differentially expressed genes between six patients who responded well to azathioprine and four who did not. No differences were found between 12 patients with adverse events to azathioprine and 9 patients who tolerated this drug. Sixteen patients who were not glucocorticoid-dependent had no differentially expressed genes as compared with 15 glucocorticoid-dependent patients. Six patients who responded well to infliximab had only one differentially expressed gene as compared to four patients who did not. Conclusions. DNA microarray analyses did not show differentially expressed genetic profiles from colonic mucosal cells obtained from groups of patients classified according to therapeutic criteria.