Validation of a live animal model for training in endoscopic hemostasis of upper gastrointestinal bleeding ulcers.

BACKGROUND AND STUDY AIMS: The management of upper gastrointestinal bleeding requires training of the endoscopist. We aimed to validate a live animal model of bleeding ulcers for training in endoscopic hemostasis. MATERIALS AND METHODS: Bleeding ulcers were created by repeated grasp-and-snare gastric mucosectomies in pigs rendered "bleeders" by preadministration of clopidogrel, aspirin, and unfractionated heparin. The feasibility and reproducibility of the model (proportion of bleeding ulcers, number of ulcers per animal, and time needed to produce a bleeding ulcer) were prospectively evaluated in six animals. Ten endoscopic experts assessed the similarity of this pig model to human bleeding ulcers (four-point Likert scale). The training capabilities of the model for hemostatic techniques (needle injection, bipolar electrocoagulation, and hemoclipping) were evaluated in 46 fellows (four-point Likert scale). RESULTS: A total of 53 gastric ulcers were created in 6 animals (8.8 ± 1.5 ulcers/animal). Successful active ulcer bleeding (Forrest Ib) was achieved in 96.2 % of cases. Bleeding was moderate to abundant in 79 % of cases. Ulcerations consistently reached the submucosal layer. The mean (± SD) time taken to create a bleeding ulcer was 3.8 ± 0.6 minutes. Endoscopic experts assessed the realism of the ulcers and bleeding at 3.2 ± 0.7 and 3.6 ± 0.7 respectively on a four-point Likert scale. The training significantly improved the endoscopic skills of the 46 fellows (P < 0.0001) in all hemostatic techniques. CONCLUSIONS: The live porcine model of bleeding ulcers was demonstrated to be realistic, reproducible, feasible, time efficient, and easy to perform. It was favorably assessed as an excellent model for training in endoscopic treatment of bleeding ulcers.

Accuracy of imaging for predicting operative approach in Crohn's disease.

BACKGROUND: The aim of this study was to assess the accuracy of preoperative imaging in detecting the extent of disease and predicting the operative approach in patients with Crohn's disease. METHODS: Patients with Crohn's disease who were scheduled to undergo operation were evaluated before operation using computed tomography enteroclysis (CTE) and magnetic resonance enterography (MRE). Preoperative imaging findings were correlated with intraoperative and pathological findings to estimate the capabilities of preoperative imaging in detecting lesions due to Crohn's disease. The operative approach determined before surgery was compared with the procedure actually performed, which was based on intraoperative findings. RESULTS: Fifty-two patients with Crohn's disease were studied; 26 were evaluated before surgery with CTE and 26 with MRE. Eighty-nine lesions due to Crohn's disease were confirmed surgically (60 small bowel stenoses, 21 fistulas and 8 abscesses). CTE confirmed the presence of 38 of 41 lesions (sensitivity 93 per cent) and MRE 48 of 48 lesions (sensitivity 100 per cent); a correct estimation of the disease with an exact prediction of the operative approach was obtained in 49 (94 per cent) of 52 patients. Discrepant findings between preoperative imaging and operative findings were observed in three patients (6 per cent), who had CTE. CONCLUSION: Preoperative imaging using CTE or MRE is highly accurate for assessing Crohn's disease lesions before operation, allowing correct prediction of the operative approach.

Clinical trial: Preliminary efficacy and safety study of a new Budesonide-MMX® 9 mg extended-release tablets in patients with active left-sided ulcerative colitis.

BACKGROUND: Ulcerative colitis (UC) is a chronic inflammatory disease with relapses. Many patients need systemic corticosteroids to induce clinical remission. AIM: Efficacy and safety of Budesonide-MMX® 9 mg tablets, a new oral, extended-release formulation, were evaluated in patients suffering from active, left-sided UC with colitis activity index (CAI) <14. METHODS: 36 patients were treated once daily for 4 weeks with Budesonide-MMX® 9 mg tablets or placebo. In an additional 4-week period, all patients received Budesonide-MMX®. CAI, endoscopic index and histology were assessed after 4 and 8 weeks. Primary end-point was remission, and/or CAI reduction by 50% after 4 weeks. Morning cortisol was assayed after 4 and 8 weeks, and a short ACTH-test was performed at week 8. RESULTS: 32 patients were analysed. After 4 weeks, 47.1% of the patients in the Budesonide-MMX® 9 mg tablets group achieved the primary end-point vs. 33.3% of patients on placebo. In addition, 47.1% of budesonide patients and another 33.3% of placebo recipients improved without remission by 4 weeks. The CAI reduction was significant with Budesonide (p<0.0001) tablets and not with placebo (p=0.1). Neither morning cortisol nor pituitary-adrenal axis was more frequently suppressed with Budesonide tablets than with placebo. CONCLUSIONS: Budesonide-MMX® 9 mg tablets induced a fast and significant clinical improvement of active left-sided UC without suppression of adrenocortical functions and without important toxicity EudraCT number 2004-000896-33.

Continual monitoring of intraepithelial lymphocyte immunophenotype and clonality is more important than snapshot analysis in the surveillance of refractory coeliac disease.

OBJECTIVE: An aberrant immunophenotype and monoclonality of intraepithelial lymphocytes (IELs) are frequently found in refractory coeliac disease (RCD). However, the utility of continual monitoring of IEL immunophenotype and clonality in the surveillance of RCD remains to be studied. DESIGN: The diagnostic and follow-up biopsies from 33 patients with CD, 7 with suspected RCD, 41 with RCD and 20 with enteropathy-associated T cell lymphoma (EATL) (including 11 evolved from RCD) were investigated by CD3epsilon/CD8 double immunohistochemistry and PCR-based clonality analysis of the rearranged T cell receptor (TCR) genes. RESULTS: An aberrant immunophenotype (CD3epsilon(+)CD8(-) IELs > or =40%) and monoclonality were detected occasionally in CD biopsies, either transiently in patients with CD not compliant with a gluten-free diet or in those who subsequently developed suspected RCD, RCD or EATL. In contrast, the aberrant immunophenotype and monoclonality were found in 30 of 41 (73%) and 24 of 37 (65%) biopsies, respectively, at the time of RCD diagnosis. Among the patients with RCD who did not show these abnormalities in their diagnostic biopsies, 8 of 10 (80%) and 5 of 11 (45%) cases gained an aberrant immunophenotype and monoclonality, respectively, during follow-up. Irrespective of whether detected in diagnostic or follow-up biopsies, persistence of both abnormalities was characteristic of RCD. Importantly, the presence of concurrent persistent monoclonality and aberrant immunophenotype, especially > or =80% CD3epsilon(+)CD8(-) IELs, was a strong predictor of EATL development in patients with RCD (p=0.001). CONCLUSIONS: Continual monitoring of both immunophenotype and clonality of IELs is more important than snapshot analysis for RCD diagnosis and follow-up, and could provide a useful tool for surveillance of patients at risk of EATL.

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 Crohn's disease (CD). The aim of the present study was to assess the predictive value of plexitis for early clinical CD recurrence. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

[Chronic intestinal pseudo-obstruction and anti-Hu syndrome: 13 years of follow-up without neoplasia]. / Pseudo-obstruction intestinale chronique et syndrome des anti-Hu: 13 ans de suivi sans apparition de néoplasie.

Chronic intestinal pseudo-obstruction (CIPO) is a heterogeneous group of rare disorders characterised by symptoms of intestinal obstruction with no mechanical evidence of obstruction. It is caused by ineffective intestinal contractions due to visceral neuropathy and/or neuropathy. In adults, CIPO is mostly secondary. The most common causes are metabolic disorders, connective tissue disorders, neuropathic drug related injuries, paraneoplasic and post-infectious syndromes and amyloidosis. Secondary forms of CIPO have been reported with anti-Hu antibodies. This corresponds to an antineuronal antibody that recognizes a protein expressed in the nuclei of neuron (ANNA-1) and neoplasic cells. The anti-Hu antibody must be searched for in patients over 40 years old with CIPO (associated with small cell lung cancer in 75% of cases). Recently, the association of CIPO and the anti-Hu antibody has been described without associated neoplasia. We report a case of an association of CIPO and anti-Hu antibody without cancer after 13 years of follow-up.

Factors that predict conversion in 69 consecutive patients undergoing laparoscopic ileocecal resection for Crohn's disease: a prospective study.

PURPOSE: This prospective study was designed to identify factors that could predict conversion in patients undergoing first laparoscopic ileocecal resection for Crohn's disease. METHODS: Between 1998 and 2004, 69 consecutive patients (32 males; mean age, 32 +/- 9 years) who had undergone a first laparoscopic ileocecal resection for Crohn's disease were included in a prospective study. Twenty-one patients (30 percent) were converted into laparotomy. Possible factors for conversion were analyzed by both univariate and multivariate analyses. RESULTS: No patient died. Four patients (9 percent; 2 in each group) required five reoperations because of intraperitoneal hemorrhage (n = 1), anastomotic fistula (n = 3), and small-bowel obstruction (n = 1). Mean hospital stay was significantly increased in converted compared with laparoscopic patients (9 +/- 4 vs. 7 +/- 3 days; P < 0.05). On univariate analysis, more than three episodes of acute flare of Crohn's disease (P = 0.02), male gender (P = 0.03), preoperative immunosuppressive drugs (P = 0.04), intra-abdominal abscess or fistula at the time of laparoscopy (P = 0.02), and resection of other intestinal segment (P = 0.02) were factors that predicted conversion. On multivariate analysis, recurrent medical episodes of Crohn's disease (odds ratio, 2; 95 percent confidence interval, 1-4), and intra-abdominal abscess or fistula at the time of laparoscopy (odds ratio, 15; 95 percent confidence interval, 4-78) were the two independent risk factors for conversion. CONCLUSIONS: This prospective study demonstrated that the severity of the disease increased significantly the conversion rate of the first laparoscopic ileocecal resection. Knowledge of these risk factors for conversion could be helpful in preoperative preparation and counseling of patients.

A prospective assessment of cytomegalovirus infection in active inflammatory bowel disease.

BACKGROUND: The prevalence and clinical significance of cytomegalovirus infection is reportedly high in patients with refractory inflammatory bowel disease but is unknown in unselected patients with active disease. METHODS: In patients admitted for active inflammatory bowel disease, we prospectively studied the presence and significance of cytomegalovirus infection using anti-cytomegalovirus antibodies, cytomegalovirus viraemia and antigenaemia and cytomegalovirus inclusions and cytomegalovirus immunochemistry staining in ileocolonic biopsies. RESULTS: A total of 64 patients were included (ulcerative colitis, n = 23; Crohn's disease, n = 41), 18 of whom had been on high-dose oral steroids and 11 on immunosuppressants. Anti-cytomegalovirus IgG and IgM were positive in 42 (66%) and 3 (5%) patients respectively. Blood or urine cytomegalovirus replication markers were found in 4 (6%) patients, all of whom had ulcerative colitis. Three patients had cytomegalovirus viraemia and received anti-viral treatment with ganciclovir. Only one of these patients had cytomegalovirus antigenaemia and also associated biopsy-proven cytomegalovirus colitis, probably as a primary cytomegalovirus infection. This patient is the only one who benefitted from anti-viral therapy. CONCLUSIONS: Cytomegalovirus infection is infrequent in in-patients with active inflammatory bowel disease. Systematic search of cytomegalovirus replication markers should not be performed. Isolated viraemia without associated antigenaemia or direct demonstration of cytomegalovirus in ileocolonic biopsies does not warrant anti-viral therapy.

Identifying patients with T3-T4 node-negative colon cancer at high risk of recurrence.

PURPOSE: Adjuvant chemotherapy is effective for node-positive colon cancer patients. In node-negative patients, it could be justified in high-risk patients. The purpose of this study was to determine clinical and pathological findings associated with tumor recurrence in T3-T4 node-negative colon cancer patients. METHODS: From 1974 to 1993, 108 patients undergoing colectomy for T3-4N0M0 colon cancer, without adjuvant chemotherapy, followed until death or for a minimum of five years, were divided into two groups: patients without recurrence (n = 74) and those dead from colon cancer or alive with recurrence (n = 34). Thirty-three clinical and pathological findings were studied. RESULTS: In univariate analysis, the following were significantly associated with a high risk of tumor recurrence: male patients (P = 0.006), bowel obstruction (P < 0.001), weight loss >5 Kg (P = 0.03), circumferential tumor (P = 0.02), macroscopic or microscopic pericolic organ invasion (T4 stage; P < 0.001), perineural invasion (P = 0.02), vascular invasion (P = 0.045), poor tumor differentiation (P = 0.005), mesocolic invasion >1 cm (P = 0.009), less than 14 uninvolved nodes on the specimen (P = 0.03), and visceral peritoneal invasion (T4; P < 0.001). In multivariate analysis, the following were independent prognostic factors of recurrence: male patients (P = 0.005), bowel obstruction (P = 0.002), pericolic organ invasion (i.e., T4 tumor; P = 0.02), and less than 14 uninvolved nodes on a specimen (P = 0.01). On the other hand, preoperative carcinoembryonic antigen serum level, size and tumor location, blood transfusion, and mucin production were not associated with higher risk of tumor recurrence. CONCLUSION: Our study identifies a subgroup of patients with node-negative colon cancer at high risk of recurrence, who could be included in priority trials of adjuvant chemotherapy.

Long-term results of ileal pouch-anal anastomosis for colorectal Crohn's disease.

INTRODUCTION: The aim of this study is to report ten-year results of ileal pouch-anal anastomosis in selected patients with colorectal Crohn's disease for whom coloproctectomy and definitive end ileostomy was the only alternative. METHODS: 41 patients (22 females/19 males) with a mean age of 36 +/- 13 (range, 16-72) years underwent ileal pouch-anal anastomosis for colorectal Crohn's disease between 1985 to 1998. None had past or present history of anal manifestations or evidence of small-bowel involvement. Diagnosis of Crohn's disease was established preoperatively in 26 patients, on the resected specimen after ileal pouch-anal anastomosis, or after occurrence of Crohn's disease-related complication in 15 patients. RESULTS: Follow-up was 113 +/- 37 months, (18-174) 20 patients having been followed for more than 10 years. There was no postoperative death. Eleven (27 percent) patients experienced Crohn's disease-related complications, 47 +/- 34 months (8-101) after ileal pouch-anal anastomosis: 2 had persistent anal ulcerations with pouchitis and granulomas on pouch biopsy and were treated medically; 2 experienced extrasphincteric abscesses and 7 presented pouch-perineal fistulas which were treated surgically. Among them, 3 patients with persistent perineal fistula despite surgery required definitive end-ileostomy. Of the 20 patients followed for more than 10 years, 7 (35 percent) experienced Crohn's disease-related complications which required pouch excision in 2 (10 percent). CONCLUSIONS: Ten years after ileal pouch-anal anastomosis for colorectal Crohn's disease, rates of Crohn's disease-related complications and pouch excision were 35 and 10 percent, respectively. These good long-term results justify for us to propose ileal pouch-anal anastomosis in selected patients with colorectal Crohn's disease (i.e., no past or present history of anal manifestations and no evidence of small-bowel involvement) for whom the only alternative is definitive end ileostomy.

Histological and immunological parameters to predict treatment outcome of Helicobacter pylori eradication in low-grade gastric MALT lymphoma.

Helicobacter pylori eradication is generally accepted as the first choice of treatment for stage IE low-grade gastric MALT lymphoma (mucosa-associated lymphoid tissue-type lymphoma). Treatment failure may be attributed to the extent of the disease and to progression into an antigen-independent phase. This study assessed the value of morphological grading and the expression of the co-stimulatory markers CD40, CD80 and CD86 and their ligands to predict clinical outcome in 23 consecutive low-grade MALT lymphoma patients treated with H. pylori eradication. Complete regression was achieved in 13/23 patients (56%), partial regression in two (9%), and no response in eight (35%). Histological grading was highly predictive of clinical response, especially in stage IE(1) patients, with complete remissions in 10/12 tumours with purely low-grade (type A) morphology and 1/8 tumours with increased numbers of blasts (type B) (p=0.0046) and was related to the expression of costimulatory markers (p=0.0061). Moreover, CD86 as a single marker proved to be of predictive value for treatment outcome (p=0.0086). These results suggest that morphological grading and immunological criteria can be defined to recognize the transition into the antigen-independent phase of gastric MALT-NHL. In addition to clinical stage, these critera may in future serve as a practical pathological guide to the choice of therapy.