Recurrence Of Crohn's Disease Research Articles

Tu1932 Differential Expression of MicroRNAs in Ileal Mucosa of Patients With Early, Recurrent and Late Crohn's Disease

Tu1932 Differential Expression of MicroRNAs in Ileal Mucosa of Patients With Early, Recurrent and Late Crohn's Disease

Su1384 Medical Prophylaxis After Ileocolic Resection for Crohn's Disease – No Need to Rush

Background: Crohn's disease (CD) most commonly affects the terminal ileum, with a majority of patients ultimately requiring ileocolic resection. Histologic and immunologic evidence suggests that mucosal inflammation occurs early after exposure of the neoterminal ileum to autologous luminal contents. Therefore, early medical prophylaxis has been advocated to prevent endoscopic recurrence of CD. The purpose of this study was to evaluate whether the timing of medical prophylaxis after ileocolic resection affects endoscopic recurrence of CD. Methods: A single institution, prospectively maintained database was queried for CD patients undergoing ileocolic resection over a 13-year period ending January 2013. Patients were included if they underwent postoperative endoscopy within 12-months of surgery and were started on medical therapy using 5-aminosalicylates (5ASA), immunomodulators, or biologic agents prior to their first postoperative endoscopy. Patients were divided into two groups; those started on medical prophylaxis within 4 weeks of surgery (Early) and those who receivedmedical prophylaxis 4 weeks or more after surgery (Late). The primary endpoint was endoscopic recurrence (defined as a Rutgeerts' endoscopic score of i2, i3, or i4 at first postoperative endoscopy). Secondary endpoints included time to endoscopic recurrence, and any radiological, clinical and surgical recurrence. Results: The 165 study patients had a mean age (SD) of 32.2 (14.6) years and 91 (55%) were male (Table). Mean time to starting medical therapy was 3.8 (2) weeks. 99 patients (60%) were in the Early prophylaxis group and 65 (40%) were in the Late prophylaxis group. Compared to the Early prophylaxis group, the Late prophylaxis group was treated more commonly with biologics (p<0.001) and less commonly with 5-ASA (p=0.007) or immunomodulators (p=0.004). At a mean endoscopy time of 6.8 (2.4) months, 65 patients (39%) had endoscopic recurrence; 39 (39%) in the Early group and 26 (39%) in the Late group. There was also no significant difference in clinical or surgical recurrence between the Early versus Late prophylaxis patient groups. Subgroups analysis of patients treated postoperatively with non-biologic medical prophylaxis, biologic alone, or biologic with other agents, showed no significant difference in endoscopic recurrence between Early and Late prophylaxis patient groups. Conclusion: Althoughmedical prophylaxis after ileocolic resection for CD has been shown to reduce endoscopic recurrence, it may be safe to wait until patients are out of the initial perioperative period prior to initiating medical prophylaxis without any adverse effects on endoscopic recurrence.

Risk and Management of Intra-Abdominal Abscess in Crohn's Disease Treated with Infliximab

Background and Aims: Infliximab (IFX) is a monoclonal antibody used to treat patients with Crohn's disease (CD). Intra-abdominal abscess formation is a major complication of CD with negative effects on patient prognosis. We have analyzed risk factors for abscess formation in CD patients treated with IFX. Methods: CD patients who received IFX between January 2000 and April 2011 at Keio University Hospital were analyzed retrospectively. Risk factors for abscess formation were assessed by univariate and multivariate logistic regression analyses. Results: Intra-abdominal abscess was seen in 15 of 258 patients. Univariate analyses showed serum C-reactive protein (CRP) concentration at 14 weeks after initiation of IFX (p = 0.021), serum albumin concentration at week 0 (p = 0.022) and week 14 (p = 0.004), the presence of anal lesions (p = 0.036), progression of intestine deformation (p = 0.015) and early loss of response to IFX (p < 0.0001) to be risk factors. Multivariate analysis showed that CRP concentration at 14 weeks [odds ratio (OR) 1.361] and loss of IFX response within 6 months (OR 5.361) were independent risk factors. Conclusions: Abscess formation should be suspected in patients with symptoms of CD recurrence during IFX therapy. Uncontrolled CRP concentration and early loss of response to IFX are risk factors.

Single port laparoscopic surgery for patients with complex and recurrent Crohn's disease

BackgroundSingle port laparoscopic surgery (SPLS) is a modified access technique allowing grouping of instruments at a single parietal site. It is intuitively appealing specifically for patients with Crohn's disease (CD) as its minimal invasiveness favors cosmesis and facilitates any future (re)operation. MethodsConsecutive patients presenting either electively or urgently for resectional surgery for CD over a 36month period were considered for SPLS using, by preference, a transumbilical ‘Surgical Glove Port’. Standard, straight laparoscopic instrumentation was used without additional resources. ResultsOf 33 consecutive, unselected patients, 28 (92%) had their procedure initiated by SPLS including those needing urgent intervention (n=15) and those with prior abdominal operation (n=8), obstruction (n=7), mass (n=6), fistula (n=6) and/or abscess (n=4). The median (range) age and BMI of the patients were 31 (17–69) years and 21.3 (18.6–28) kg/m2 respectively. 31 had ileocolonic resection (6 with recurrent disease) while two underwent segmental colectomy. No-one suffered intraoperative or anastomotic complication. Both conversion (15%) and postoperative complication (13 Clavian–Dindo complications — I: 8; II: 2; IIIa: 3) rates were predominantly reflective of patient and disease complexity. Median (range) postoperative day of discharge was 6 (3–33) overall and 5 (3–18) in those completed by SPLS. There was one early readmission (for infectiouscolitis) and median follow-up is now 21months. ConclusionsComplex and recurrent Crohn's resections can be performed by SPLS in the majority of patients presenting elective or urgently for surgery. The Surgical Glove Port performs capably and, by minimizing cost, can facilitate broad embrace of this approach.

A network meta-analysis on the efficacy of 5-aminosalicylates, immunomodulators and biologics for the prevention of postoperative recurrence in Crohn's disease

Background and aimsA number of agents have been evaluated in clinical trials to reduce the risk of postoperative recurrence in Crohn's disease (CD). The aim of this study was to compare the efficacy of 5-aminosalicylates, immunomodulators and biologics for postoperative prophylaxis of CD recurrence by using a network meta-analytical approach. MethodsPubMed, Embase, and Cochrane Library were searched (update to November 2013) to identify randomized placebo-controlled, or head-to-head trials among the three drug classes for prevention of postoperative CD relapse. The primary endpoint for efficacy was endoscopic recurrence, and the secondary outcomes were clinical recurrence and adverse events. We conducted a Bayesian network meta-analysis with a mixed treatment comparisons to combine both direct and indirect evidences. ResultsFifteen trials involving 1507 patients were included in this analysis. Biological agents were associated with a large and significant reduction of both endoscopic and clinical recurrence compared with placebo, 5-aminosalicylates, or immunomodulators. Immunomodulators showed greater efficacy in terms of endoscopic and clinical recurrence prophylaxis compared with 5-aminosalicylates or placebo, but with higher incidence of adverse events. 5-aminosalicylates were superior to placebo for prevention of clinical recurrence, without increasing the rate of side effect. Conclusions5-aminosalicylates, immunomodulators, and biologics are more efficacious than placebo for postoperative CD prevention. Biologics are found to be the most effective medications to prevent CD recurrence.

P338 Systematic versus endoscopy-driven treatment with azathioprine to prevent postoperative ileal Crohn's disease recurrence

P338 Systematic versus endoscopy-driven treatment with azathioprine to prevent postoperative ileal Crohn's disease recurrence

Postoperative Therapy With Infliximab Prevents Long-term Crohn’s Disease Recurrence

A previous randomized, placebo-controlled study showed that infliximab maintenance therapy prevented recurrence of Crohn's disease 1 year after an ileocolonic resection. We evaluated recurrence of Crohn's disease, on the basis of endoscopic examination and/or the need for additional surgical resection, beyond the first postoperative year. In a prospective, open-label, long-term follow-up study, 24 patients previously randomly assigned to receive infliximab for 1 year after an ileocolonic resection were given the option to continue, stop, or start infliximab therapy. The primary end point was the time to recurrence of Crohn's disease, on the basis of endoscopic evidence (endoscopic recurrence), from the initial assignment to postoperative infliximab or placebo. Secondary end points were rate of endoscopic recurrence, time to reoperation, and rate of surgical recurrence in relation to the total time on infliximab. All patients were followed for at least 5 years after surgery. Patients assigned to the infliximab group in the first year after surgery had a longer mean time to first endoscopic recurrence (1231 ± 747 days) than patients originally assigned to the placebo group (460 ± 121 days, P= .003). Colonoscopies identified Crohn's disease recurrence in 22.2% of patients who received long-term infliximab and in 93.9% of those not on infliximab (P < .0001). Compared with no infliximab, the adjusted rate ratio for being in endoscopic remission while on infliximab was 13.47 (95% confidence interval, 3.52-61.53; P= .0001). Patients originally assigned to the infliximab group had a mean longer time to surgery (1798 ± 359 days) than patients originally assigned to the placebo group (1058 ± 529 days, P= .04). The rate of surgical recurrence (required additional surgical resection) was significantly lower among patients who received infliximab for most of the follow-up period than patients who received it for shorter periods (20.0% vs 64.3%, P= .047). Postoperative infliximab maintenance beyond 1 year prevents recurrence of Crohn's disease.

Clinical and Endoscopic Recurrence after Surgical Resection in Patients with Crohn's Disease

Background/AimsThe natural history of Crohn's disease (CD) is characterized by a remitting and relapsing course and a considerable number of patients ultimately require bowel resection. Moreover, postoperative recurrence is very common. Relatively few studies have investigated the postoperative recurrence of CD in Korea. The aim of the current study was to assess postoperative recurrence rates - both clinical and endoscopic - in CD as well as factors influencing postoperative recurrence.MethodsElectronic medical records of patients who underwent surgery due to CD were reviewed and analyzed. Patients with incomplete surgical resection, a follow-up period of less than a year, and a history of strictureplasty or perianal surgery were excluded.ResultsOf 112 CD patients, 39 patients had history of bowel resection, and 34 patients met the inclusion criteria. Among them, 26 were male (76%) and the mean age of onset was 32.8 years. The mean follow-up period after operation was 65.4 months. Cumulative clinical recurrence rates were 8.8%, 12.5%, and 33.5% at 12, 24, and 48 months, respectively. Use of immunomodulators for prophylaxis was the only predictor of clinical recurrence in univariate analysis (P=0.042). Of 21 patients who had undergone follow-up colonoscopy after surgery, cumulative endoscopic recurrence rates were 33.3%, 42.9%, and 66.1% at 6, 12, and 24 months, respectively. No significant predicting factor for endoscopic recurrence was detected.ConclusionsPostoperative recurrence rates in Korean patients with CD are high, and endoscopic recurrence rates are comparable to those reported from Western studies. Appropriate medical prophylaxis seems to be important for preventing postoperative recurrence in CD.

Prevention of post-operative recurrence of Crohn’s disease

Endoscopic and clinical recurrence of Crohn's disease (CD) is a common occurrence after surgical resection. Smokers, those with perforating disease, and those with myenteric plexitis are all at higher risk of recurrence. A number of medical therapies have been shown to reduce this risk in clinical trials. Metronidazole, thiopurines and anti-tumour necrosis factors (TNFs) are all effective in reducing the risk of endoscopic or clinical recurrence of CD. Since these are preventative agents, the benefits of prophylaxis need to be weighed-against the risk of adverse events from, and costs of, therapy. Patients who are high risk for post-operative recurrence should be considered for early medical prophylaxis with an anti-TNF. Patients who have few to no risk factors are likely best served by a three-month course of antibiotics followed by tailored therapy based on endoscopy at one year. Clinical recurrence rates are variable, and methods to stratify patients into high and low risk populations combined with prophylaxis tailored to endoscopic recurrence would be an effective strategy in treating these patients.

What is the Important Issue to Prevent the Postoperative Crohn's Disease?

Crohn's disease (CD) is a chronic inflammatory disease that affects the entire gastrointestinal tract. Complications caused by CD, including strictures, perforations, and fistulas, often lead patients to undergo surgery, including intestinal resection. Several studies have reported that 50-80% of CD patients undergo the surgery during their lifetime.1 In Korea, Ye et al. reported that the cumulative probability of intestinal resection at 1, 5, and 10-15 years after a diagnosis of CD was 15.5%, 25.0%, and 32.8%, respectively.2 In a more extensive study by Park et al., the cumulative probability of intestinal resection at 10, 20, and 30 years after a diagnosis of CD was 43.5%, 70.0%, and 76.1%, respectively.3 These data suggest that the intestinal resection rate of Korean CD patients is not lower than that of Western patients and that Korean CD patients may, in fact, have a similar clinical course to Western CD patients. However, intestinal resection does not cure CD, and many patients suffer from postoperative recurrences of the disease. The recurrence of disease necessitates repeated intestinal resection, with up to 50% of patients undergoing additional surgery after 20 years.4 Ye et al. also reported that 30.8% of the patients who received an intestinal operation required a repeat operation after 10 years.2 Postoperative recurrence can be defined as clinical recurrence or endoscopic recurrence. Postoperative endoscopic recurrence (PER), which is usually quantified using a Rutgeerts scoring system,5 typically precedes clinical recurrence and PER was reported to occur in almost 58% of CD patients within 1 year of intestinal resection.6 In this issue, Lee et al. conducted a retrospective study to evaluate the factors influencing and recurrence rates of postoperative CD.7 Thirty-four patients who were regularly followed-up for at least 1 year after intestinal resection were analyzed. The mean follow-up period after intestinal resection was 65.4 months and their results showed a cumulative clinical recurrence rate of 8.8%, 12.5%, and 33.5% at 1, 2, and 4 years, respectively. Among 21 patients who had received colonoscopy after their intestinal resection, the cumulative PER was 42.9% and 66.1% at 1 and 2 years, respectively. Therefore, 27 out of 34 patients (79.1%) showed clinical or endoscopic recurrence after intestinal resection. Although the sample size in this study was small, and the duration of follow-up was relatively short, these results are comparable with data from Western countries. Given the increased incidence of CD in Korea and the resulting increase in intestinal resection, the prevention and management of postoperative recurrence is an important issue for Korean clinicians. As such, Lee et al.'s study-which is the first to report the recurrence rate and risk factors for CD after intestinal resection in Korea-is of particular relevance.7 A risk-stratified strategy involving tailored therapy according to high/low risk patient groups in order to prevent postoperative recurrence of CD was recently proposed. This postoperative management strategy included determining the risk factors of patients, identifying PER by performing colonoscopy 6-12 months after surgery, and promptly introducing preventive medications in order to reduce the recurrence rate. High-risk factors included smoking, perforating behavior, perianal disease, young age, repetitive surgery, and extensive bowel disease.8 In contrast, low-risk factors included the stricture behavior and old age at diagnosis. Until now, 5-aminosalicylates (5-ASA) and probiotics have not been proven to be effective in preventing postoperative recurrence of CD, whilst metronidazole has shown short-term benefits (3 months). Azathioprine/6-mercaptopurine (AZT/6-MP) has been proven to be effective and combined therapy with metronidazole and AZT/6-MP was more effective than metronidazole alone. In this issue, Lee et al. also demonstrated that patients who took immunomodulators to prevent postoperative recurrence had significantly lower recurrence rates than the 5-ASA group (P=0.042).7 These results are comparable with the large scale study by Park et al. in which early use of AZT was associated with a significantly delayed requirement for intestinal resection (hazard ratio: 0.63, 95% confidence interval: 0.46-0.85).3 Recent studies have also focused on the effectiveness of tumor necrosis factor (TNF)-α antagonists in treating and preventing PER, especially in high-risk patients. TNF-α antagonist therapy (including infliximab and adalimumab) seemed more effective than AZT in preventing and treating PER in many studies.9,10 Despite these studies being performed with few patients and without long-term follow-up, and although safety and cost issues should also be considered, the use of TNF-α antagonists is currently recommended as appropriate treatment in the high-risk patient group. In Korea, the efficacy of TNF-α antagonists in preventing the postoperative recurrence of CD has not yet been reported. Therefore, prospective large-scale studies are needed to clarify the burden of postoperative recurrence of CD and to determine the high-risk factors of recurrence in Korean CD patients. Furthermore, the efficacy of TNF-α antagonists in improving the long-term prognosis and quality of life of high-risk patients should be further investigated.

Role of bowel ultrasound in the management of postoperative Crohn's disease.

The use of biological and immunosuppressive therapy in Crohn's disease (CD) changed favorably the course of the disease and is currently suggested in the prevention of clinical recurrence. Symptomatic exacerbation is a feature of the natural course of the disease. Endoscopic recurrence may occur earlier than clinical manifestations and its rate is still high ever since the first year after surgery. The severity of mucosal lesions is highly predictive of a new flare of the disease so that the early detection of recurrence warrants strong therapeutic changes or a closer monitoring of the case. Endoscopy is at present the gold-standard technique for the diagnosis and grading of recurrence severity, but is poorly accepted by patients for its invasiveness. A simple and easy repeatable examination able to detect early signs of recurrence could be useful in the follow-up as an alternative or as a backing in the choice of the right timing for endoscopy in questionable cases. The use of bowel ultrasound (B-US) in the management of CD has grown in the past twenty years. Its accuracy in the real time detection of the disease and its complications, known since the 80's, together with the non-invasiveness, low cost and wide availability of the technique have influenced the extension of its clinical use in many referral centers in Europe. The latest generation of ultrasound scanners allows a precise and reproducible morphological assessment of the intestinal tract and the surrounding tissues and enables a complete evaluation of the disease. This review analyzes the literature history about B-US in the diagnosis of postoperative recurrence of CD and outlines the clinical implications of its use. Published works confirm a very good accuracy of B-US in the diagnosis of CD recurrence compared to endoscopy, also in the early phase. B-US shows a good correlation with Rutgeert's score grading, but does not prove significant association with C-reactive protein or CD Activity Index values. A wider use of B-US in the daily practice could allow to set a prompt diagnosis and an earlier and targeted treatment, probably sparing more invasive tests.

Successful treatment of postoperative fistula with infliximab in a patient with Crohn's disease.

Nearly 80% of patients with Crohn's disease (CD) require surgical treatment for complications or failure of medical management. We managed a 31-year-old man with CD who presented with a post-operative fistula. The patient had undergone surgery due to multiple strictures and a fistula. However, a new fistula developed that connected to the intraperitoneal abscess. Intravenous antibiotics were started and multiple percutaneous drainage tubes were inserted to treat the abdominal abscess. However, the amount of drainage was consistently high, even one month after the operation. To treat the postoperative fistula, 5 mg/kg of infliximab was started, and the amount of drainage decreased dramatically to less than 10 cc a day. Some studies have reported that infliximab decreases the recurrence of CD after surgery. The effect of infliximab on post-operative fistulas in patients with CD has not been sufficiently studied. Our results indicated that the use of infliximab to treat post-operative fistula should be explored further in future clinical studies.

Thiopurines Are Associated with a Reduction in Surgical Re-resections in Patients with Crohnʼs Disease

Combination therapy of thiopurines and anti-tumor necrosis factor alpha (TNF-α) antibodies is the most effective medical treatment of Crohn's disease (CD). Data on thiopurines and anti-TNF-α antibodies in preventing surgical recurrence (need for re-resection) of CD are scarce. Therefore, we analyzed which factors were involved in surgical recurrence of CD in a large cohort of patients with CD operated in a regional and a university hospital. This is a retrospective cohort study of 567 patients who underwent surgery for CD. Clinical data and risk factors for surgical recurrence were analyzed, focusing on medical therapy and hospital type. Overall, 237 (41.8%) patients developed a surgical recurrence, after a median of 70 (2-482) months. Before surgical recurrence, 235 patients (41.4%) and 116 patients (20.5%) used thiopurines and anti-TNF-α antibodies, respectively. Multivariate analysis identified 3 independent risk factors associated with surgical recurrence of CD. A higher risk was seen in patients with colonic disease compared with patients with ileal disease (hazard ratio, 1.56; 95% confidence interval, 1.10-2.21; P = 0.012) and in patients using multiple types of medication (hazard ratio, 1.38; 95% confidence interval, 1.25-1.54; P < 0.001). However, a lower risk was seen in patients using thiopurines (hazard ratio, 0.51; 95% confidence interval, 0.34-0.77; P = 0.001). Thiopurines are effective in preventing surgical recurrence of CD. The role of anti-TNF-α antibodies seems promising as well. Combination therapy of thiopurines and anti-TNF-α antibodies for prevention of surgical recurrence of CD should be studied in a randomized trial.

Récidive postopératoire de la maladie de Crohn: facteurs prédictifs et traitement médical d’entretien

The majority of patients with Crohn’s disease (CD) require the use of surgical treatment at some point in their evolution. However, disease recurrence is frequent. Some factors may influence the time to recurrence and the severity of symptoms. Knowledge of this risk of recurrence justifies the concept of limiting bowel resection and helps in the discussion of the prophylactic treatment of relapses after surgery. The purpose of this review is to review the risk factors for postoperative recurrence of CD and prophylactic treatment of recurrence. The factors contributing to recurrence after surgery for CD have been evaluated in numerous studies, but controlled studies are rare and the results are sometimes contradictory. The main question is how to prevent recurrence after surgery? Besides the proven role of tobacco (withdrawal should be mandatory), different drugs (sulfasalazine and aminosalicylates, metronidazole, immunosuppressants, probiotics and anti-TNF-alpha) have been tested through several controlled therapeutic trials. Drug candidates would be nitroimidazoles and immunosuppressants, and new therapeutic approaches evaluating better biological therapies should be performed to better elucidate their therapeutic role. The attitudes are clear after ileal or ileo-colic resection, but they are less clear after colonic or colorectal resection.

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.

Right Lower Quadrant Pain in a Patient With Inflammatory Bowel Disease of Undetermined Type

A 48-year-old man diagnosed with inflammatory bowel disease of undetermined type 6 years earlier presented with sharp nonradiating right lower quadrant pain. He denied fever, chills, nausea, vomiting, diarrhea, or anorexia. The patient had been in clinical remission on azathioprine and mesalamine. Physical examination was significant for right lower quadrant tenderness without rebound or guarding. His white blood cell count and hemoglobin were normal. A computed tomography scan demonstrated cecal inflammation with associated 5-cm phlegmon (Figure A, arrow). The appendix was not visualized. The terminal ileum appeared narrowed at the ileocecal valve. The patient was treated with antibiotics and bowel rest. Colonoscopy revealed a 4-cm nonobstructing mass in the cecum (Figure B). The remainder of the colon was normal without mucosal breaks or friability. Biopsies of the mass revealed normal colonic mucosa with mild inflammation and mild architectural change. Figure The patient underwent diagnostic laparoscopy revealing an abnormal enlarged appendix. Laparoscopic appendectomy was performed. The surgical specimen measured 5.6 × 4.5 × 3.0 cm and contained no masses. Histologic examination (Figure C; hematoxylin and eosin, bar = 200 μm; Courtesy of W. Sandy Twadell, MD) demonstrated transmural acute and chronic inflammatory infiltrates. Crypt destruction with microabscess formation (arrowhead) and architectural distortion in the form of crypt branching (small arrow) were present, as were poorly formed granulomas with focal giant cells (large arrows). The findings favored a diagnosis of Crohn's disease (CD), changing our patient's diagnosis to Crohn's colitis with appendiceal involvement. Data from our patient's initial diagnosis were reviewed. Colonoscopy revealed patchy colitis with moderate to severe ulceration. The terminal ileum was not intubated, although small bowel follow through revealed a normal fold pattern in the terminal ileum. Random biopsies demonstrated active colitis and areas of acutely inflamed granulation tissue without granulomas or chronic changes. Colonoscopy performed 1 year after diagnosis demonstrated pseudopolyps from the ascending to sigmoid colon and few erosions from the transverse to sigmoid colon. Biopsies revealed chronic active colitis without granulomas. Granulomatous involvement of the appendix is rare and is found in 0.1%–2% of all appendectomy specimens.1 Involvement of the appendix in patients with CD is as high as 40%2; however, symptomatic appendicitis caused by appendiceal CD is uncommon. Our patient developed appendicitis in the setting of mucosal healing of the colon while on immunosuppressive therapy. The reasons for this are unclear and speculative, but may be caused by persistent inflammation in the submucosa, mucosa, and/or serosa of the appendix resulting in luminal obstruction and appendicitis. It is also possible that lymphoid cells within the appendix served as a focal point for recurrent CD. Finally, we cannot exclude the possibility that our patient coincidentally developed “classic” appendicitis superimposed on histologic CD. Symptoms of granulomatous disease of the appendix are similar to acute appendicitis and include fever, right lower quadrant pain, nausea, and anorexia. Other causes of appendiceal granulomatous disease include infection (eg, Yersinia, Mycobacterium tuberculosis, Campylobacter), foreign body reaction, appendiceal or cecal diverticulitis, chronic beryllium poisoning, and sarcoidosis. Our patient did well postoperatively. Azathioprine and mesalamine were continued. He will begin surveillance colonoscopies next year.

Laparoscopic surgery for complex Crohn's disease

In primary Crohn's disease (CD), laparoscopic ileocolic resection has been shown to be both feasible and safe, and is associated with improved outcomes in terms of postoperative morbidity and length of hospital stay. At this time, it is unclear whether the laparoscopic approach can be routinely proposed as a safe procedure for patients with complex CD involving localized abscess, fistula or recurrent disease. The aim of this systematic literature review was to assess the feasibility and safety of laparoscopic surgery for complex or recurrent CD. In the current literature, there are nine non-randomized cohort studies, two of which were case-matched. The mean rate of conversion to open laparotomy reported in these series ranged from 7% to 42%. Morbidity rate and hospital stay following laparoscopic resection for complex CD were similar to those for initial resection or for non-complex CD. In summary, even though strong evidence is lacking and more contributions with larger size are needed, the limited experiences available from the literature confirm that the laparoscopic approach for complex CD is both feasible and safe in the hands of experienced IBD surgeons with extensive expertise in laparoscopic surgery. Further studies are required to confirm these results and determine precisely patient selection criteria.

Adalimumab Prevents Postoperative Crohn Disease Recurrence

Patients with Crohn disease have a high rate of postoperative recurrence, which few medical therapies can effectively prevent. Infliximab is one of

Adalimumab Is More Effective Than Azathioprine and Mesalamine at Preventing Postoperative Recurrence of Crohn's Disease: A Randomized Controlled Trial

Postsurgical recurrence of Crohn's disease (CD) is very frequent and, to date, only infliximab has been shown to be useful in preventing it. The efficacy of adalimumab (ADA) is poorly known. We evaluated whether the administration of ADA after resective intestinal surgery reduces postoperative CD recurrence. We randomly assigned 51 patients with CD who had undergone ileocolonic resection to receive after 2 weeks from surgery ADA at the dose of 160/80/40 mg every two weeks, azathioprine (AZA) at 2 mg/kg/day, or mesalamine at 3 g/day, and they were followed up for 2 years. The primary end point was the proportion of patients with endoscopic and clinical recurrence. Secondary end point was the assessment of quality of life by means of a previously validated questionnaire. The rate of endoscopic recurrence was significantly lower in ADA (6.3%) compared with the AZA (64.7%; odds ratio (OR)=0.036 (95% confidence interval (CI) 0.004-0.347)) and mesalamine groups (83.3%; OR=0.013 (95% CI 0.001-0.143)). There was a significantly lower proportion of patients in clinical recurrence in the ADA group (12.5%) compared with the AZA (64.7%; OR=0.078 (95% CI 0.013-0.464)) and mesalamine groups (50%; (OR=0.143 (95% CI 0.025-0.819)). The quality of life was higher in the ADA (202) than in the AZA (90; OR=0.028 (95% CI 0.004-0.196)) and mesalamine groups (98; OR=0.015 (95% CI 0.002-0.134)). The administration of ADA after intestinal resective surgery was greatly effective in preventing endoscopic and clinical recurrence of CD. Further larger studies are necessary to confirm the therapeutic advantage and to show the economic implications of biologic therapy in this field.

NASPGHAN Clinical Report on the Evaluation and Treatment of Pediatric Patients With Internal Penetrating Crohn Disease

Natural History of Pediatric Crohn Disease T he natural history of pediatric Crohn disease (CD) remains unpredictable, although some trends are observed that differentiate children from adults. Pediatric CD often presents with more severe disease and more frequent need for immunosuppressive therapy (1). Growth failure, present in 15% to 20% of patients, is a unique characteristic of pediatric CD not seen in adult-onset CD (2). Colonic disease distribution is common in patients younger than 10 years (1). The need for surgical intervention also varies, with 1 study reporting the actuarial risk of having undergone an extensive intestinal resection being 48.6% 5% in a childhood-onset group versus 14.6% 2% in the adult-onset group (P< 0.001) (1). More recently, long-term follow-up of patients enrolled in pediatric registries shows a cumulative surgical rate of 14% to 17% at 5 years and 28% at 10 years (3,4).