Efficacy of Anal Fistula Plug in Closure of Crohn’s Anorectal Fistulas

Purpose The efficacy of Surgisis^? anal fistula plug in closure of Crohn’s anorectal fistula was studied. Methods Patients with Crohn’s anorectal fistulas were prospectively studied. Diagnosis was made by histologic, radiographic, or endoscopic criteria. Variables recorded were: number of fistula tracts (primary openings), presence of setons, and current antitumor necrosis factor therapy. Under general anesthesia and in prone jackknife position, patients underwent irrigation of the fistula tract by using hydrogen peroxide. Each primary opening was occluded by using a Surgisis^? anal fistula plug. Superficial tracts amenable to fistulotomy were excluded. Results Twenty consecutive patients were prospectively enrolled, comprising a total of 36 fistula tracts. At final follow-up, all fistula tracts had been successfully closed in 16 of 20 patients, for an overall success rate of 80 percent. Thirty of 36 individual fistula tracts (83 percent) were closed at final follow-up. Patients with single fistulas (with 1 primary opening) were most likely to have successful closure using the anal fistula plug. Successful closure was not correlated with the presence of setons or antitumor necrosis factor therapy. Conclusions Closure of Crohn’s anorectal fistula tracts using Surgisis^? anal fistula plug is safe and successful in 80 percent of patients and 83 percent of fistula tracts. Closure rates were higher with single tracts than complex fistulas with multiple primary openings. Dr. David Armstrong has a patent‐licensing agreement with the manufacturer of Surgisis^? (Cook Surgical, Inc., Bloomington, IN).     

Saccharomyces boulardii in Maintenance Treatment of Crohn’s Disease

The possible role of Saccharomyces boulardii, a nonpathogenic yeast with beneficial effects on the human intestine, in the maintenance treatment of Crohns disease has been evaluated. Thirty-two patients with Crohns disease in clinical remission (CDAI < 150) were randomly treated for six months with either mesalamine 1 g three times a day or mesalamine 1 g two times a day plus a preparation of Saccharomyces boulardii 1 g daily. Clinical relapses as assessed by CDAI values were observed in 37.5% of patients receiving mesalamine alone and in 6.25% of patients in the group treated with mesalamine plus the probiotic agent. Our results suggest that Saccharomyces boulardii may represent a useful tool in the maintenance treatment of Crohns disease. However, in view of the products cost, further controlled studies are needed to confirm these preliminary data.     

Efficacy of Adalimumab in Korean Patients with Crohn’s Disease

Background/Aims

Adalimumab is effective for both remission induction and the maintenance of Crohn’s disease (CD) in Western countries. We evaluated the efficacy of adalim-umab in the conventional step-up treatment approach for CD in Korea.

Methods

We retrospectively reviewed 62 patients with CD who were treated with adalimumab. Their Crohn’s disease activity index (CDAI) was measured at weeks 4, 8, and 52. Clinical remission was defined as a CDAI score <150. Induction and maintenance outcomes were analyzed.

Results

Forty-one patients (66.1%) achieved a reduction of 70 CDAI points at week 8. Among them, 28 (45.2%) achieved clinical remission at week 8, 20 (32.3%) maintained remission at week 52. The absence of prior anti-tumor necrosis factor (TNF) therapy and Montreal classification L1 at baseline predicted clinical remission at week 8 in the multivariate logistic regression analysis. In the Cox proportional hazards model, the hazard ratio for the secondary loss of response during maintenance therapy after clinical remission induction was significantly higher in patients who showed initial mild CDAI severity or Montreal classification A3.

Conclusions

In our study, anti-TNF therapy-naive and Montreal classification L1 were associated with adalimumab efficacy as induction therapy in CD. Further studies are warranted to determine the prognostic factors for the long-term response after adalimumab therapy.     

Validation of the Treatment Satisfaction Questionnaire for Crohn’s Disease (TSQ-C)

Treatment satisfaction is used to capture the full impact of disease on patients lives. Currently, no instruments exist to evaluate satisfaction with pharmacologic therapy in patients with Crohns disease (CD). The purpose of this study was to evaluate the psychometric properties of a treatment satisfaction questionnaire for CD (TSQ-C). The 36-item questionnaire was completed by CD patients who reported taking 5-aminosalicylic acid derivatives to treat their CD. Measures used in the validation study were the Inflammatory Bowel Disease Questionnaire (IBDQ), Crohns Work Activity Impairment Index (CWAII), and patient reports of clinical indicators (e.g., number of active flares and medications taken). Exploratory factor analysis was used to evaluate the items and subscale structure. Internal consistency reliability and concurrent and discriminant validity were assessed using Cronbachs alpha, Pearson correlation coefficients, and analysis of variance. A total of 813 CD patients participated, with the majority being Caucasian (95.9%), female (67.0%), and 34 years old (86.1%). Patient-rated severity of CD was mild (49.3%), moderate (41.7%), and severe (7.5%). The final TSQ-C consisted of 32 items, with six subscales (Symptoms, Satisfaction, Expectations, Physician Relationships, Bother, and Cost), with each subscale score ranging from 1 to 6. Cronbachs values ranged from 0.63 (Cost) to 0.94 (Symptoms). Strong correlations were observed among the IBDQ, CWAII, and the Satisfaction and Symptoms subscales of the TSQ-C. TSQ-C subscales, particularly Symptoms and Satisfaction, significantly discriminated among levels of number of flares per year, patient-rated disease severity, and number of medication classes. The TSQ-C demonstrated excellent validity and reliability and appears to be a useful tool for evaluating satisfaction with pharmacologic therapy among patients with CD.     

Local Injection of Infliximab for the Treatment of Perianal Crohn’s Disease

PURPOSE Perianal disease is a serious complication of Crohns disease and its surgical management is still controversial. It has been suggested that the local injection of infliximab has resulted in some potential benefit. This pilot study analyzed the feasibility and safety of such therapy in selected patients with severe perianal Crohns disease.METHODS The study included 15 patients with complex perianal Crohns disease in which sepsis was not controllable using surgical and medical therapy. Among them, four had previously undergone intravenous infusion of infliximab with no significant response, nine had contraindications for intravenous infusion, and two had associated stenosing ileitis and severe coloproctitis. The injection of 15 to 21 mg of infliximab, associated with surgical treatment, was performed at the internal and external orifices and along the fistula tract. Efficacy was measured by a complete morphologic evaluation using a personal score.RESULTS No major adverse effects were reported. Ten of 15 patients healed after 3 to 12 infusions.CONCLUSIONS Local injection of infliximab adjacent to the fistula tract of perianal Crohns disease is safe and may help in fistula healing. A controlled, randomized trial is required to prove the value.     

Adalimumab Treatment in Children with Refractory Crohn’s Disease

Information on safety and efficacy of adalimumab in children with Crohn’s disease (CD) is limited. We present a case-series of 14 children with severe CD treated with adalimumab during a 3.5-year period. Fourteen children (nine boys, five girls), aged 13.9 years (range 1.9–19.1) were treated with adalimumab during 12.5 months (range 7–42). All had steroid or immunosuppression-drugs refractory disease. Ten patients (71%) had been previously treated with infliximab, 13/14 were treated with different immunosuppressive drugs and all were steroid-dependent or resistant. Seven children (50%) showed full clinical response and 5/14 (35%) improved partially. Two children (15%) had loss of response after a period of transient improvement. Adalimumab treatment enabled complete steroids withdrawal in 8/14 (57%) of steroid-dependent children. Currently, five children are in complete remission with adalimumab monotherapy for a median 14 months (range 9–24). Adalimumab may induce and maintain remission in children with severe, refractory CD. Prospective safety and efficacy confirmation of this data in children is necessary.     

Long-Term Durability of Crohn’s Disease Treatment with Infliximab

BACKGROUND: There is a paucity of data providing insight into the durability of Crohn's disease treatment with infliximab for periods longer than 12 months. Our aim was to assess the long-term durability of infliximab therapy. MATERIALS AND METHODS: A total of 198 Crohn's patients under a maintenance regimen with infliximab, with at least a 30-month follow-up, were evaluated retrospectively. Long-term response maintenance was estimated using Kaplan-Meier analysis. The effect of specific variables was calculated using logistic regression and proportional hazard regression analyses. RESULTS: Maintenance of response rates at 72 months was estimated to be 66.4% for initial responders and 58.2% for all patients treated. Concurrent immunomodulators enhanced response maintenance in all patients treated, particularly if started >3 months before the initiation of infliximab therapy. Smoking significantly decreased the maintenance of response in initial responders. CONCLUSIONS: Infliximab treatment of Crohn's disease is reasonably durable beyond 12 months. Concurrent immunosuppressive therapy may increase - and smoking may decrease - long-term response maintenance.     

Anorectal Carcinoma After Infliximab Therapy in Crohn’s Disease: Report of a Case

Infliximab, monoclonal antibody against tumor necrosis factor α, is an effective agent in the therapy of Crohn’s disease. Although therapy with infliximab is generally well tolerated, there is an obvious concern about the effect of this treatment on the incidence of cancer. We report a case of mucinous anorectal adenocarcinoma observed in a 39-year-old patient with long-standing Crohn’s disease after therapy with two courses of infliximab. The carcinoma was discovered fortuitously after abdominoperineal resection. Despite clear margins, the tumor recurred in a few months and progressed during combination chemotherapy. Although there is currently no definitive proof of a causal link between infliximab therapy and cancer, the present observation and other reports in the literature should lead to a careful evaluation of the possibility of increased cancer risk in patients treated with this new agent. Supported by a grant of Ministry of Education of the Czech Republic CEZ-MŠMT 115000021 and Research Project MZO 00179906.     

Treatment of Crohn’s Disease with Leflunomide as Second-Line Immunosuppression

The aim of this study was to assess the potential of leflunomide, an immunosuppressant in rheumatoid arthritis, as a second-line immunosuppression treatment of patients with Crohn's disease refractory or intolerant to azathioprine. The study cohort consisted of 24 patients. The primary end point was steroid-free remission, and secondary end points were changes in the Crohn's disease activity index (CDAI) and steroid intake, responsiveness of arthralgias and adverse events. Results were expressed in medians (quartiles). The remission rate increased from 21 to 42% by week 16 (P < 0.05). In the intention-to-treat analysis, the CDAI decreased from 219 to 87 (P = 0.018) and the steroid intake from 25 to 3 mg/day (P = 0.033). In the per-protocol analysis, the CDAI decreased from 182 to 87 (P = 0.0183) and the steroid intake from 45 to 4 mg/day (P = 0.0778). Patients with arthralgias improved significantly. However, adverse side effects were frequent. Leflunomide may improve disease activity, especially in terms of arthralgias, and reduce steroid intake. Adverse events were more frequent in our patients than has been reported in controlled studies for rheumatoid arthritis but corresponded to those found in post-marketing studies.     

Update on the Management of Crohn’s Disease

Crohn’s disease (CD) is a chronic inflammatory disorder characterized by focal, asymmetric, transmural inflammation of any part of the luminal gastrointestinal tract of uncertain etiology and an unpredictable course. The available treatment options include aminosalicylates, budesonide and systemic corticosteroids, antibiotics, immunomodulators,methotrexate and anti-TNF agents. This review discusses recent developments in the treatment of CD and provides a comprehensive update on management of patients with CD based on the data from randomized controlled trials. Pique     

Treatment of fistulizing Crohn’s disease in children

Opinion statement Patients with Crohn’s disease are at risk for developing both internal and external fistulae. These can be asymptomatic incidental radiologic findings or causes of incontinence, chronic pain, abscesses, and sepsis. They can have a devastating impact on quality of life. Careful prospective studies of therapy are few in adult medicine and entirely lacking in the pediatric age group. Assessment and management require a coordinated effort between gastroenterologist, radiologist, and surgeon. Principles of management include surgical drainage of infection combined with medical therapy. Only infliximab has been studied in prospective, double-blinded fashion and clearly shown to be of use in the short term. There is good evidence that metronidazole may be useful acutely and that 6-mercaptopurine azathioprine may help to maintain closure. Diverting ostomies are of very limited value and corticosteroids seem to make matters worse. There are many other therapies that have been reported to be helpful in small, uncontrolled studies.     

Treatment of peri-anal fistula in Crohn’s disease

Anal fistulas are a common manifestation of Crohn’s disease(CD). The first manifestation of the disease is often in the peri-anal region, which can occur years before a diagnosis, particularly in CD affecting the colon and rectum. The treatment of peri-anal fistulas is difficult and always multidisciplinary. The European guidelines recommend combined surgical and medical treatment with biologic drugs to achieve best results. Several different surgical techniques are currently em-ployed. However, at the moment, none of these tech-niques appear superior to the others in terms of healing rate. Surgery is always indicated to treat symptomatic, simple, low intersphincteric fistulas refractory to medi-cal therapy and those causing disabling symptoms. Ut-most attention should be paid to correcting the balance between eradication of the fistula and the preservationof fecal continence.     

Efficacy of T2 in Active Crohn’s Disease: A Prospective Study Report

To date few therapies have been shown to reliably prevent the evolution of Crohn’s disease (CD). The traditional Chinese medicine, Tripterygium wilfordii Hook F (TWHF), has both immunomodulatory and anti-inflammatory activities. Our aim was to investigate the potential efficacy of T2, the major constituent of extracts of TWHF, in inducing remission of active CD. Twenty adult patients with active CD were enrolled to be treated with T2 pills (60 mg daily) for 12 weeks. Plasma levels of C-reactive protein (CRP), tumor necrosis factor (TNF)-α, and interleukin (IL)-1β were measured at entry and every 2 weeks thereafter until week 12. At each visit the CD Activity Index (CDAI) was calculated. The CD Endoscopic Index of Severity was measured at entry and week 12. Sixteen patients completed the study. A significant decrease in serum levels of CRP, TNF-α, and IL-1β occurred rapidly after commencement of treatment. CDAI scores showed a rapid decline during the first 8 weeks and reached their lowest at week 10. Endoscopic improvements were observed at week 12. In conclusion, T2 appears to be effective for the treatment of mildly or moderately active CD. Further controlled studies are warranted for this promising drug.     

Efficacy of Mesenchymal Stromal Cells for Fistula Treatment of Crohn’s Disease: A Systematic Review and Meta-Analysis

Background and Aim

The introduction of mesenchymal stromal cells (MSCs) has changed the management of Crohn’s fistula, while it remains controversial. The aim of this study was to provide an overview of efficacy and optimum state of MSCs treatment on Crohn’s fistula.

Methods

Studies reporting MSCs treatment on Crohn’s fistula were searched and included. A fixed-effects model was used to assess the efficacy of MSCs, and outcomes of healing and recurrence were used to evaluate the best states of MSCs intervention.

Results

Fourteen articles were enrolled (n = 477). Pooled analysis showed MSCs had a significant efficacy compared to other treatments [risk difference: 0.21 (0.09, 0.32), P = 0.000]. Notably, after MSCs treatment, the group of Crohn’s disease activity index (CDAI) baseline >150 group had a higher healing rate (HR) and a clinical response (a change in CDAI of >50 points) (79.17 ± 8.78 vs. 47.54 ± 15.90, P = 0.011) compared to CDAI baseline of <150. The duration time of CD and fistulas had a negative correlation with HR accompanied by MSC therapy (r = ?0.900, ?0.925). Then, a moderate dose MSCs (2–4 × 10⁷ cells/ml) had a higher HR (80.07%) and lower recurrence rate (RR 13.98%) compared to other dosages. Moreover, adipose-derived MSCs therapy had an advantage over bone marrow-derived MSCs in terms of low RR (7.4 ± 4.28 vs. 13.39 ± 0.89).

Conclusions

The evidence supported the effect of MSCs at a more appropriate time of Crohn’s fistula. And CDAI baseline (the points >150) has been a candidate for evaluating effectiveness of MSCs application on Crohn’s fistula.

     

Patient Preferences Between Surgical and Medical Treatment in Crohn’s Disease

Purpose Crohn’s disease poses difficult choices in which the most appropriate treatment option is not always obvious. When this state of uncertainty exists, patients’ preferences should have an increasingly important part of clinical decision making. The purpose of this study was to compare patients’ preferences for surgical intervention in Crohn’s disease with the preferences of surgeons and gastroenterologists. Methods Outpatients with Crohn’s disease were interviewed to quantify their preferences for six scenarios by using the prospective preference measure. An identical questionnaire was mailed to all Australian and New Zealand colorectal surgeons and a random sample of 300 Australian gastroenterologists. Results Forty-one of 123 patients with Crohn’s disease (33 percent), 92 of 127 colorectal surgeons (72 percent), and 74 of 272 gastroenterologists (27 percent) participated. There were significant differences between patients and gastroenterologists for three of six scenarios and between surgeons and gastroenterologists in four of six scenarios. Seventy-six percent of gastroenterologists were willing to gamble to avoid an ileocolic resection compared with 37 percent of surgeons (chi-squared = 25.44; P < 0.0001) and 39 percent of patients (chi-squared = 15.44; P < 0.001). Conclusions Patients and clinicians were able to trade and gamble life expectancy as a measure of preference for varying hypothetical surgical treatments, even though these treatment options impacted on quality of life rather than survival. Patients’ preferences did not align with clinicians. For most scenarios, colorectal surgeons’ preferences were significantly different to those of gastroenterologists. Dr. Byrne was supported by the Notaras Fellowship from the University of Sydney, the Section of Colon and Rectal Surgery of the Royal Australasian College of Surgeons, and the Training Board of the Colorectal Surgical Society of Australasia. Presented at the Tripartite Colorectal Meeting, Dublin, Ireland, July 5 to 7 2005. Reprints are not available.     

Durability of Infliximab Dose Intensification in Crohn’s Disease

Background  

Dose intensification is a common approach to treat Crohn’s disease (CD) patients who lose response to infliximab maintenance therapy. Few studies have reported upon its long-term efficacy or predictors of response.     

The Fate of the Ileal Pouch in Patients Developing Crohn’s Disease

PURPOSE Recent studies have suggested that a subset of patients with Crohns colitis may have a favorable outcome after ileal pouch-anal anastomosis and have advocated elective ileal pouch-anal anastomosis in selected patients with Crohns disease. We have not offered ileal pouch-anal anastomosis to patients with known Crohns disease, but because of the overlap in clinical presentation of ulcerative colitis and indeterminate colitis, some patients receiving an ileal pouch-anal anastomosis are subsequently found to have Crohns disease. We review our experience with these patients to identify potential preoperative predictors of ultimate pouch failure.METHODS Patients with a final diagnosis of Crohns disease were identified from an ileal pouch-anal anastomosis registry. These patients are followed prospectively. Preoperative and postoperative clinical and pathologic characteristics were evaluated as predictors of outcome. Median (range) values are listed.RESULTS Thirty-two (18 females) patients (4.1 percent) with a final diagnosis of Crohns disease were identified from a registry of 790 ileal pouch-anal anastomosis patients (1980–2002). Patients underwent ileal pouch-anal anastomosis in two stages (11 patients) or three stages (21 patients). The preoperative diagnosis was ulcerative colitis in 24 patients and indeterminate colitis in 8 patients. Median follow-up was 153 (range, 13–231) months. The median time from ileal pouch-anal anastomosis to diagnosis of Crohns disease was 19 (range, 0–188) months. Complications occurred in 93 percent, including perineal abscess/fistula (63 percent), pouchitis (50 percent), and anal stricture (38 percent). Pouch failure (excision or current diversion) occurred in nine patients (29 percent) at a median of 66 (range, 6–187) months. Two of these 9 patients had preoperative anal disease (not significant). Comparing patients with failed pouches (n = 9) to patients with functioning pouches (n = 23), post-ileal pouch-anal anastomosis perineal abscess (67 vs. 26 percent, P = 0.05) and pouch fistula (89 vs. 30 percent, P = 0.01) were more commonly associated with pouch failure. Preoperative clinical, endoscopic, and pathologic features were not predictive of pouch failure or patient outcome. For those with a functional pouch, 50 percent have been or are currently on medication to treat active Crohns disease. This group had six bowel movements in 24 (range, 3–10) hours, with leakage in 60 percent and pad usage in 45 percent.CONCLUSIONS Patients who undergo ileal pouch-anal anastomosis and are subsequently found to have Crohns disease experience significant morbidity. Preoperative characteristics, including the presence of anal disease, were not predictive of subsequent pouch failure. We choose not to recommend the routine application of ileal pouch-anal anastomosis in any subset of patients with known Crohns disease.Reprints are not available.