Early Endoscopic Recurrence Research Articles

Endoscopic postoperative recurrence rates in Crohn's disease in Korea: the beginning of a new approach?

Dear sir, It was with great interest that we read the article entitled Clinical and Endoscopic Recurrence after Surgical Resection in Patients with Crohn's Disease, recently published in this journal by Yang Woon Lee and colleagues.1 The article describes one of the first retrospective experiences with Korean patients regarding the rates of both clinical and endoscopic recurrence (ER) after surgical abdominal procedures for CD. In this study, the authors found an overall rate of ER of 71.4% (15 from 21) patients, in a mean follow-up period of 50.5 months. Although the study adds very important real world data and represents one of the first experiences on the topic of ER in Korean patients, some considerations are important in this data analysis and must be taken into consideration. First, the population of the study is somehow heterogeneous. A myriad of operations was performed as they fulfilled the inclusion criteria. Most of the western studies were performed only after ileocecal resections,2,3 and in this interesting Korean retrospective study, small bowel resections, segmental colectomies and other different procedures were also included. The Rutgeerts's score is not fully validated after different procedures, it is mostly widely used after ileocecal resections, and there is significant controversy if it can be applied after other operations, even with capsule endoscopy to detect recurrence.4 Moreover, most of the western studies consider the definition of ER as a Rutgeerts' score ≥i-2, considering the i-1 score as mucosal normality, differently of the criteria of the Korean study.1,2,3,4 However, only one patient in the sample presented as an i-1 after surgery, what would not influence significantly the final results of recurrence. There is quite a consensus in the literature that smoking, previous resections and penetrating CD are significant risk factors for ER in CD patients.3,5 The study did not find any risk factor, despite meticulous statistical analysis, maybe for 2 reasons: the small number of patients in the sample, or the possibility of a different genetic background in Korean CD patients, that can alter the phenotype of the disease in the country, as previously stated by the authors. We recently presented at the European Crohn's and Colitis Organisation (ECCO) congress the results from a database with patients from 7 referral centers from South America, Europe and Asia regarding the same topic as this interesting Korean study.6 In our experience, ER was observed in aproximately 32% of patients treated in Brazil, 38% of those treated in Japan and in 14% of patients treated in Italy (Fig. 1). These lower numbers, as compared to the Korean study, probably were observed due to the shorter follow-up period of 12 months in this database. However, they could also be a consequence of a similar strategy of postoperative prevention of recurrence that is actively practised in these referral centers.6 The differences between the Korean study as compared to ours, are also basically related to the different populations analyzed. Fig. 1 Early postoperative endoscopic recurrence (PER). Early PER rates from the observational MULTIPER database, with data compiled from 3 different countries. Despite these few considerations, we would like to congratulate the staff from the Catholic University of Korea for this new interesting information on ER after CD surgical procedures in Asian patients. We also hope that this data can impact in a near future in the prospective management of surgically-treated CD patients in Korea, increasing the number of colonoscopies or other endoscopic examinations performed 6 to 12 months after surgery, in order to detect early ER, optimize medical therapy if needed, and possibly to lead to a lower rate of recurrence in the long term and better control of the disease.

Strategies for the prevention of postoperative recurrence of Crohn's disease

To review the optimal strategy to prevent recurrence of Crohn's disease (CD) after surgery, with particular emphasis on the risk factors that predict postoperative recurrence, methods of monitoring for recurrence and medications used to prevent postoperative recurrence. MEDLINE and the Cochrane Library were searched for clinical trials and meta-analyses that studied postoperative recurrence and prophylactic medications in CD. The most significant factor that predicted postoperative recurrence was patient smoking status. Smokers had an increased risk of recurrence (odds ratio=2.15; 95% confidence interval (CI)=1.42-3.27). Similarly, perforating CD appeared to be associated with a higher recurrence rate compared with nonperforating CD (hazard ratio=1.50; 95% CI= 1.16-1.93). The optimal monitoring strategy for postoperative recurrence has yet to be established. Nonetheless, ileocolonoscopy is considered to be the gold standard. Noninvasive imaging techniques including contrast ultrasonography and capsule endoscopy appear to be useful for postoperative monitoring. A number of meta-analyses found that mesalazine, nitroimidazole antibiotics and purine analogues (azathioprine/6-mercaptopurine) significantly reduced the risk of postoperative recurrence when compared with placebo. Additionally, recent randomized controlled trials have suggested that an early intervention with infliximab is likely to prevent recurrence after ileocolonic resection. Likewise, in prospective studies, biological therapy (infliximab/adalimumab) reduced clinical and endoscopic CD activity in patients with early endoscopic recurrence after surgery. Although additional evidence is necessary, endoscopic monitoring and treatment step-up should be used to prevent postoperative recurrence of CD.

Intersphincteric proctectomy with end-colostomy for anorectal Crohn's disease results in early and severe proximal colonic recurrence

BackgroundPerianal Crohn's disease (CD) represents a more aggressive phenotype of inflammatory bowel disease and often coincides with proctocolitis. This study aims to assess the outcome of patients undergoing proctectomy with end-colostomy. MethodsA retrospective outcome analysis of 10 consecutive patients who underwent intersphincteric proctectomy with end-colostomy between February 2007 and May 2011 was performed. All patients suffered from refractory distal and perianal CD. The proximal colon was normal at endoscopy. All data were extracted from a prospectively maintained database. The main outcome parameter was disease recurrence and need for completion colectomy. ResultsSevere and early endoscopic recurrence in the proximal colon occurred in 9/10 patients at a median time interval of 9.5months (range: 1.9–23.6months). Despite protracted medical treatment, completion colectomy was necessary in 5 patients. One patient, who underwent a second segmental colectomy with a new end-colostomy, showed again endoscopic recurrence and is currently treated with anti-TNF agents. ConclusionsIntersphincteric proctectomy with colostomy seems to be an ineffective surgery for perianal CD with coexisting proctitis and results in a high risk of recurrence of the disease in the remaining colon. Therefore, despite a normal appearance of the proximal colon, a proctocolectomy with end-ileostomy seems to be the surgical approach of choice in these patients.

Infliximab for Early Endoscopic Recurrence in Patients with Crohn’s Disease

To the Editor, I read with great interest the recent article by Sorrentino et al. [1]. In their prospective study, patients with endoscopic recurrence (Rutgeerts score [2] C2) at 6 months after resection were treated with infliximab or mesalamine. At week 54, infliximab significantly improved endoscopic lesions including 54% with endoscopic remission. In contrast, none of the patients treated with mesalamine achieved endoscopic remission. We have previously reported similar results [3]. During 6-month treatment, endoscopic lesions (Rutgeerts score [2] C2 at 6 months after resection) were improved in 75% of patients (including 38% with complete mucosal healing) treated with infliximab versus none of the patients treated with mesalamine. In both studies [1, 3], infliximab significantly reduced clinical recurrence. From these results, infliximab appears to improve endoscopic lesions observed 6 months after surgery and reduce the incidence of clinical recurrence. There are a number of risk factors for recurrence after surgery for Crohn’s disease (CD), including smoking and perforating disease [4]. Although these factors can be recognized at the time of surgery, it is not easy to assess the precise risk of postoperative recurrence in an individual patient. Furthermore, these parameters are of limited use to identify patients at high risk of recurrence and to establish prophylactic strategy for postoperative recurrence. In contrast, the severity of endoscopic inflammation in the early postoperative period is a reliable risk factor for recurrence [2]. Patients with severe endoscopic lesions develop early clinical recurrence. In contrast, patients with no or very mild lesions have an uneventful postoperative clinical course. A randomized controlled trial (RCT) found that infliximab therapy initiated soon after surgery was useful for preventing recurrence [5]. However, this new agent cannot be recommended for all patients after surgery because of potential serious adverse events and high medical costs. It should be used for patients at high risk of recurrence. Patients with early endoscopic lesions are good candidates for infliximab therapy after surgery for CD. The results of the study by Sorrentino et al. [1] and our previous trial [3] support the use of infliximab for early postoperative CD recurrence. However, RCTs with a larger number of patients and a longer follow-up period are necessary to more accurately evaluate the efficacy of infliximab for early endoscopic lesions after surgery for CD.

Strategies for the Prevention of Postoperative Recurrence in Crohn's Disease: Results of a Decision Analysis

Nearly 70% of patients with Crohn's disease (CD) undergo surgical resection, with one-quarter subsequently developing clinical recurrence within 12 months. Several options exist for the prevention of postoperative recurrence in CD, but the comparative cost effectiveness of these competing strategies has not been previously analyzed. We developed a decision analytic model comprising five strategies--No Treatment, azathioprine (AZA), antibiotics (ABX), upfront infliximab (IFX), and tailored IFX that consisted of no upfront therapy with initiation of IFX in patients with severe endoscopic recurrence at 6 months. The base-case 1-year clinical recurrence rate was 24% with reduction in recurrence by 41%, 77%, and 99% for AZA, ABX, and IFX, respectively. A 1-year time horizon was used and sensitivity analyses were performed. At the base-case analysis, the ABX (0.82 quality-adjusted life years (QALYs)) and AZA (0.81 QALYs) arms were more effective and less expensive than the No Treatment strategy (0.80 QALYs). The most effective strategy was upfront IFX (0.83 QALYs); however, this was also the most expensive and resulted in a high incremental cost-effectiveness ratio (ICER) ($777,732/QALY) compared with no treatment. The tailored IFX arm was less effective than upfront use but had a more acceptable ICER. On increasing the recurrence rate to 78% (high-risk patients), upfront IFX resulted in 0.07 QALYs (ICER $130,580/QALY) gained compared with No Treatment, whereas ABX, AZA, and tailored IFX arms dominated No Treatment. Antibiotics are the most cost-effective option for preventing postoperative recurrence, but they have been associated with high rates of intolerance precluding widespread use. Upfront IFX is the most efficacious strategy but is not cost effective even in high-risk patients. Reserving IFX use for high-risk patients with early endoscopic recurrence is more cost effective than upfront use in all patients.

Plexitis as a predictive factor of early postoperative clinical recurrence in Crohn’s disease

Background and aims:A previous study suggested that the presence of myenteric plexitis in the proximal resection margins could be predictive of early endoscopic recurrence after ileocolonic or ileal resection for...

S1107 Plexitis As Predictive Factor of Early Postoperative Clinical Recurrence in Crohn's Disease

A previous study suggested that the presence of myenteric plexitis in the proximal resection margins could be predictive of early endoscopic recurrence after ileocolonic or ileal resection for Crohn's disease (CD). The aim of the present study was to assess the predictive value of plexitis for early clinical CD recurrence.All consecutive patients with ileocolonic or ileal resection for active CD in Lariboisière Hospital (Paris) between 1995 and 2006 were included. Clinical, surgical, histological and follow-up data were extracted from medical charts. Early clinical recurrence was defined as the reappearance of CD clinical manifestations requiring a specific treatment within 2 years postsurgery. The proximal resection margin was analysed using haematein eosin saffron (HES) staining and immunochemistry targeting mastocytes (anti-CD117 antibody) and lymphocytes (anti-CD3 antibody). Eosinophils were detected by HES staining. Ten cases of ileocolonic resections for caecal carcinoma served as controls.Data were available from 171 postoperative follow-up periods in 164 patients with CD. Early clinical recurrence of CD occurred in 28.1%. In multivariate analysis, factors associated with postoperative recurrence were active smoking (hazard ratio (HR) = 1.94; 95% CI 1.06 to 3.60; p = 0.033), submucosal plexitis with >or=3 mastocytes (HR = 1.87; 95% CI 1.00 to 3.46; p = 0.048) and a disease-free resection margin <5 cm (HR = 0.52; 95% CI 0.27 to 1.02; p = 0.059).Submucosal plexitis is associated with early clinical recurrence and could be taken into account in studies searching for new treatment strategies in the immediate postoperative period.

Impact of infliximab therapy after early endoscopic recurrence following ileocolonic resection of Crohnʼs disease: A prospective pilot study

The efficacy of infliximab for endoscopic recurrence after resection of Crohn's disease (CD) has not yet been reported. The aim of this prospective study was to investigate the impact of infliximab on early endoscopic lesions after resection for CD. Twenty-six patients maintaining clinical remission (CD activity index [CDAI] score <150) with mesalamine (3 g/day) after resection showed endoscopic recurrence in the neoterminal ileum at 6 months postoperatively (=baseline). Over the following 6 months, 10 patients were treated with continuous mesalamine (3 g/day), 8 patients were treated with azathioprine therapy (50 mg/day), and the other 8 patients were treated with infliximab therapy (5 mg/kg, every 8 weeks). During ileocolonoscopy at baseline and 6 months later, mucosal biopsies were taken for cytokine assays. During 6-month observation, no patients in the infliximab group, 3 (38%) in the azathioprine group, and 7 (70%) in the mesalamine group developed clinical recurrence (CDAI >or=150) (P = 0.01). At 6 months, endoscopic inflammation was improved in 75% of patients in the infliximab group, 38% in the azathioprine group, and 0% in the mesalamine group (P = 0.006). The mucosal interleukin (IL)-1beta, IL-6, and tumor necrosis factor-alpha levels significantly decreased in the infliximab group, while they significantly increased in the mesalamine group, and they did not change significantly in the azathioprine group. Infliximab therapy showed clear suppressive effects on clinical and endoscopic disease activity, and mucosal cytokine production in patients with early endoscopic lesions after resection. To confirm our conclusions, randomized controlled trials with a larger number of patients are necessary.

Non-invasive techniques for assessing postoperative recurrence in Crohn's disease

Postoperative recurrence after ileo-colonic resection is a feature of Crohn's Disease (CD), almost 73% of patients show endoscopic recurrence at 1 year and 90% at 3 years. After surgical resection for CD, symptoms may be related to the surgical resection itself. Moreover, the development of an early severe endoscopic recurrence within 1 year represents a risk factor for early clinical recurrence. On the basis of these observations, the early detection and assessment of asymptomatic endoscopic recurrence may allow a timely and appropriate treatment of CD patients after ileo-colonic resection. At this purpose, conventional colonoscopy with ileoscopy currently represents the gold standard for assessing CD recurrence, graded according to the Rutgeerts' score. Lesions compatible with CD recurrence can be also detected by conventional radiology, including small bowel follow through and enema, both associated with a high radiation exposure. Due to the ineluctable course of CD after resection, and to the need of a proper follow up for assessing CD recurrence, several alternative, non invasive techniques have been searched in order to assess the post-operative recurrence, including: faecal alpha 1-antitrypsin clearance, faecal calprotectin, 99Tc-HMPAO scintigraphy, virtual colonoscopy, ultrasonography and, more recently, wireless capsule endoscopy (WCE) and Small Intestine Contrast Ultrasonography (SICUS). Among these, current evidences suggest that in experienced hands, ultrasound examination by SICUS represents a non-invasive technique useful for assessing recurrence in CD patients under regular follow up after surgery. The same findings are suggested for WCE, although the impact risk related to the recurrence or to the surgical anastomosis itself limits the use of this non-invasive technique for assessing CD recurrence after surgery.

Multicenter randomized-controlled clinical trial of probiotics (Lactobacillus johnsonii, LA1) on early endoscopic recurrence of Crohnʼs disease after ileo-caecal resection

Seventy percent of Crohn's disease (CD) patients exhibit anastomotic recurrence within 1 year after ileo-caecal surgery. Recent clinical trials suggest the beneficial use of probiotics in the control of intestinal inflammation in pouchitis and ulcerative colitis. This study is a multicenter clinical trial evaluating the efficacy of an oral administration of the probiotic LAl on early post-operative endoscopic recurrence of CD. Seventy patients with CD were enrolled prior to elective ileo-caecal resection and randomly assigned after surgery to daily treatment with either Lactobacillus johnsonii, LA1, Nestle (1010 colony-forming units, CFU) (group A, n = 34) or placebo (group B, n = 36) for 12 weeks. The primary objective was to assess the effect of LAl on the endoscopic recurrence rate at 12 weeks. Stratification was performed according to smoking status at randomization. Seven and 14 patients were excluded in the LA1 and placebo groups, respectively. In intention-to-treat analysis, the mean endoscopic score was not significantly different between the two treatment groups at 3 months (LA1 versus placebo: 1.50 +/- 1.32 versus 1.22+/-1.37, treatment effect: P = 0.48, smoke effect: P = 0.72). The percentage of patients with severe recurrence (i3 + i4) was 21% and 15% in the LAl and placebo groups, respectively (P = 0.33). Using a per-protocol (PP) analysis, the mean endoscopic score was not significantly different between the two treatment groups (LAl versus placebo groups: 1.44 +/-1.31 versus 1.05 +/- 1.21, P = 0.32). The percentage of patients with severe recurrence (i3 + i4) was 19% and 9% in the LAl and placebo groups, respectively (P = 0.054). Clinical relapse rate (CDAI [CD activity index] > 150, with an increase of CDAI > 70 points or greater from baseline) in the LAl and placebo groups was 15% (4/27) and 13.5% (3/22), respectively (PP analysis: chi-square test, P = 0.91 and log-rank test: P = 0.79). Oral administration of the probiotic LA1 in patients with CD failed to prevent early endoscopic recurrence at 12 weeks after ileo-caecal resection.

The Value of Myenteric Plexitis to Predict Early Postoperative Crohn’s Disease Recurrence

Early ileocolonoscopy allows detection of recurrence after surgically induced remission of Crohn's disease (CD). Unequivocal histologic markers predicting recurrence have not been identified. We assessed the predictive value of neural lesions for early endoscopic CD recurrence and long-term reintervention risk. Ileocolonic resection specimens from 59 patients with CD and 21 control patients were histologically scored for typical inflammatory bowel disease lesions, neural hypertrophy, and presence and severity of inflamed ganglia and nerve bundles. Endoscopic recurrence was determined at 3 months in all patients and at 1 year in 32 patients as part of 2 prospective clinical trials. Myenteric plexitis of the proximal resection margin was present in 32 patients with CD (54%) in absence of surrounding inflammation. Patients with this feature had a higher endoscopic recurrence (Rutgeerts score >/=2) at 3 months (75% vs 41%; odds ratio, 4.36; 95% confidence interval, 1.44-13.23; P = .008) and at 1 year (93% vs 59%; odds ratio, 9.80; 95% confidence interval, 1.04-92.70; P = .041) and had a trend toward an earlier reintervention (mean, 7.00 vs 5.30 years; P = .174). The severity of myenteric plexitis in the proximal resection margin correlated with the severity of endoscopic recurrence at 3 months (r = 0.334, P = .010) and 1 year (r = 0.560, P = .001). Myenteric plexitis was the only consistent predictor of endoscopic recurrence. The presence of myenteric plexitis in proximal margins of ileocolonic resection specimens is predictive of early endoscopic CD recurrence.

This Month in Gastroenterology

This Month in Gastroenterology

Strategies in the prevention of post-operative recurrence in Crohn's disease

The majority of patients with Crohn's disease require resectional surgery in the course of their disease. Most of them will suffer symptomatic recurrence in the years after their operation, leading to new complications and sometimes repeated surgery. Clinical risk factors for early and evolutive recurrence have not been well identified. Smoking, perforating behaviour of the disease and ileal or ileocolonic location seem to predispose to early and aggressive recurrence. No clear prophylactic drug regime has been identified. Sulfasalazine and 5-ASA are only mildly protective and meta-analysis of all studies does not show superiority over placebo. Glucocorticosteroids are not efficacious. Nitroimidazole antibiotics, metronidazole and ornidazole prevent early endoscopic recurrence and postpone symptomatic relapse but are not well tolerated. Immunosuppression with azathioprine or 6-MP is attractive but hard data concerning their efficacy are still lacking. No data are available on the use of biologicals for the prevention of post-operative Crohn's disease. We need well designed and well powered multicentre trials to investigate the efficacy of different drugs for recurrence prophylaxis.

Correlation between early endoscopic recurrence and reoperative surgery in Chrohn's disease

Correlation between early endoscopic recurrence and reoperative surgery in Chrohn's disease