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Aim Subtotal colectomy is the treatment of last resort in patients with severe colonic inertia (SCI) refractory to laxatives. Some studies have reported hypoplasia of the interstitial cells of Cajal (ICC) using a semi-quantitative analysis. The aims of this study were first to investigate if semi-quantitative or morphometry is better at the quantification of colonic ICC and secondly to determine whether there is a relationship between the number of ICC and the severity of constipation. Method Clinical and pathological data from patients with subtotal colectomy for SCI were collected. Quantification of ICC using CD117 immunohistochemistry and morphometric methods was performed at three different colonic sites in patients and controls. Results Twenty patients had a colectomy for SCI. All were considered to have failed maximal medical treatment and 45 % were hospitalized at least once for colonic obstruction due to faecaloma. Using a semi-quantitative methodology, 30 % of patients displayed ICC hypoplasia (< 7 per high power field (HPF)) and all controls had normal ICC. Using morphometry, the percentage of colonic ICC was significantly less in patients compared with controls with no significant differences between the ascending, transverse and descending colonic segments. Overall 60 % of patients had ICC hypoplasia (< 1% vs. 20 % of controls [p = 0.009]). The severity of constipation was not related to the quantity of ICC. Conclusion In patients with SCI, morphometric analysis is more sensitive than semi-quantitative analysis in the detection of ICC hypoplasia. The severity of constipation was not related to the quantity of ICC. This article is protected by copyright. All rights reserved.

Purpose To determine the rate of negative appendectomy and clarify the causes of negative appendectomy in patients with clinically suspected acute appendicitis who had surgery after 64-section helical computed tomography (CT). Material and Methods A retrospective analysis of 1057 patients who had appendectomy after 64-section helical CT was performed to determine the rate of negative appendectomy. The 64-section helical CT examinations obtained with submillimeter and isotropic voxels in the patients with negative appendectomy were analyzed by two readers and compared to clinical, operative and histopathological reports, discharge summaries and original radiology reports. Results The negative appendectomy rate was 1.7% (18/1057). Appendix enlargement (> 6 mm) and fat stranding were present in 17 (17/18; 94%) and 6 patients (6/18; 33%), respectively. In 13 patients (13/18; 72%) 64-section helical CT findings were consistent with acute appendicitis. Interpretive errors in original imaging reports were identified in five patients (5/18; 28%). Conclusion The preoperative use of 64-section helical CT results in a very low rate of negative appendectomy. Patients with negative appendectomy have 64-section helical CT findings consistent with a diagnosis of acute appendicitis in the majority of cases. Interpretive errors are less frequent.

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 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.

Patients with Crohn's disease are at increased risk for small bowel adenocarcinoma. We report herein two cases of Crohn's disease-related ileal adenocarcinoma, which were investigated by means of magnetic resonance (MR)-enterography. Two different patterns were observed. In one case, the tumor presented as long circumferential, asymmetric and heterogeneous thickening of the ileum with visible nodule on free induction echo stimulated acquisition images. In the other case, the malignant lesion presented as a tumor mass of the terminal ileum, extending onto the cecum, and showed restricted diffusion on diffusion-weighted MR imaging. In both cases, the tumors were diagnosed preoperatively. Histopathological analysis after surgical resection confirmed T4N1 poorly differentiated mucinous adenocarcinoma of the ileum in association with findings consistent with active in one case and inactive Crohn's disease in the other case. Our observations suggest that MR-enterography may be a useful imaging test for the detection of small bowel adenocarcinoma in patients with Crohn's 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 CD3ɛ/CD8 double immunohistochemistry and PCR-based clonality analysis of the rearranged T cell receptor (TCR) genes. Results An aberrant immunophenotype (CD3ɛ + CD8 − IELs ≥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 ≥80% CD3ɛ + 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.

In short bowel syndrome (SBS), although a remaining colon improves patient outcome, there is no direct evidence of a mucosal colonic adaptation in humans. This prospective study evaluates morphology, proliferation status, and transporter expression level in the epithelium of the remaining colon of adult patients compared with controls. The targeted transporters were Na+/H+exchangers (NHE2 and 3) and oligopeptide transporter (PepT1). Twelve adult patients with a jejuno-colonic anastomosis were studied at least 2 yr after the last surgery and compared with 11 healthy controls. The depth of crypts and number of epithelial cells per crypt were quantified. The proliferating and apoptotic cell contents were evaluated by revealing Ki67, PCNA, and caspase-3. NHE2, NHE3, PepT1 mRNAs, and PepT1 protein were quantified by quantitative RT-PCR and Western blot, respectively. In patients with SBS compared with controls, 1) hyperphagia and severe malabsorption were documented, 2) crypt depth and number of cells per crypt were 35% and 22% higher, respectively ( P < 0.005), whereas the proliferation and apoptotic levels per crypt were unchanged, and 3) NHE2 mRNA was unmodified; NHE3 mRNA was downregulated near the anastomosis and unmodified distally, and PepT1 mRNA and protein were unmodified. We concluded that, in hyperphagic patients with SBS with severe malabsorption, adaptive colonic changes include an increased absorptive surface with an unchanged proliferative/apoptotic ratio and well-preserved absorptive NHE2, NHE3, and PepT1 transporters. This is the first study showing a controlled nonpharmacological hyperplasia in the colon of patients with SBS.

Chronic intestinal pseudoobstruction (CIPO) is classified into enteric visceral myopathies, neuropathies, and/or mesenchymopathies. Although the histology usually permits to highlight pathologic abnormalities of CIPO, it fails in almost a third of cases. The yield of a systematic immunohistochemistry needs to be evaluating.Twenty-one adult patients with idiopathic CIPO [11 females/10 males, median age 23.1 (0.3 to 57) y] were included and compared with 27 control and 10 with mechanical obstruction patients. Comparison between standard histology (hematoxylin and eosin-stained sections) and systematic immunohistochemistry using muscular (smooth muscle alpha-actin, desmin, and smoothelin-A/B), nervous (Hu C/D, Bcl-2, and S100 protein), and mesenchymal (CD117) markers was carried out.Histology showed neuromuscular abnormalities in 13 out of 21 (62%) patients, consisting of enteric visceral myopathy in 9 (43%) patients, enteric visceral neuropathy in 2 (9.5%), and mixed neuromyopathy in 2 (9.5%). Among the 8 patients who had no histologic structural abnormality, 6 patients (75%) had underlying abnormalities detected with immunohistochemistry: immunostain with Hu C/D detected a hypoganglionosis (50 ganglion cells/cm) in 6 out of 21 (29%) patients, 4 of them undiagnosed on standard histology; CD117 (c-kit) detected a interstitial cells of Cajal defect in 10 out of 21 (48%) patients, 2 of them with no histologic structural abnormality. Smoothelin-A/B and desmin were useless as normally expressed in all patients with no myopathy; although it was not relevant in ileal samples (86% of abnormal expression in control patients), smooth muscle alpha-actin showed an abnormal expression in 2 CIPO patients (2/21).Immunohistochemistry using Hu C/D and CD117 antibodies combined to the standard histology increased the yield of detection of neuromuscular abnormalities in idiopathic CIPO patients.

Refractory celiac disease (RCD) was recently subdivided into 2 subtypes (RCD I and II) based on a normal or abnormal phenotype of intraepithelial lymphocytes (IELs), respectively. It is not clear, however, if these 2 entities differ in their presentation at diagnosis or long-term outcome. We compared the clinical and biological characteristics of RCD I and RCD II at diagnosis, the risk of developing an overt lymphoma, and the predictive factors of survival.Medical files of 14 patients with RCD I and 43 with RCD II were analyzed retrospectively. Predictive factors of overt lymphoma and survival were studied in univariate and multivariate analyses.At diagnosis, malnutrition, ulcerative jejunitis, and lymphocytic gastritis were more common in patients with RCD II than RCD I (P.05). Overt lymphomas occurred in 2 patients with RCD I and 16 with RCD II. In the univariate analysis, abnormal IEL phenotype and increased age at diagnosis of RCD were predictive factors for overt lymphoma. Abnormal IEL phenotype (P.01), clonality (P= .01), and overt lymphoma (P= .001) predicted short survival time. Only abnormal IEL phenotype (P= .03) and overt lymphoma (P= .04) were predictive in the multivariate analysis. The 5-year survival rate was 93% in patients with RCD I and 44% with RCD II.RCD II has a much more severe presentation and prognosis than patients with RCD I;44% of patients with RCD II survive 5 years after diagnosis. Abnormal IEL phenotype is a predictive factor but not a necessary condition for the development of overt lymphoma.

Resume La pseudo-obstruction intestinale chronique (POIC) est une maladie rare, caracterisee par des symptomes chroniques et/ou recidivants, suggerant une obstruction intestinale sans obstacle organique. Elle est caracterisee par une incapacite intestinale a propulser le bol alimentaire, d’origine neurogene et/ou myogene. Elle se manifeste par des tableaux cliniques varies, associant des signes d’occlusion intestinale et des signes generaux. Chez l’adulte, la POIC est le plus souvent secondaire a une maladie systemique. Les pathologies les plus frequemment incriminees etant une connectivite, certains toxiques, une endocrinopathie, une amylose, une enterite radique ou un syndrome paraneoplasique. Plusieurs cas de POIC, en rapport avec un syndrome paraneoplasique, ont ete rapportes en association a des anticorps anti-Hu. Il s’agit d’anticorps circulants, diriges contre une nucleoproteine neuronale du systeme nerveux central et/ou peripherique (Anna-1). Leur recherche doit etre systematique en cas de POIC, notamment apres 40 ans (association a un cancer bronchopulmonaire a petites cellules dans 75 % des cas). De facon recente et exceptionnelle, l’association anti-Hu et POIC a ete rapportee en l’absence de neoplasie. Nous rapportons, ici, le cas d’un patient atteint de POIC et d’un syndrome des anti-Hu, en l’absence de neoplasie sous-jacente avec un recul de 13 ans.

Purpose Microsatellite instability (MSI) due to mismatch repair (MMR) deficiency has been reported to occur at variable frequencies in inflammatory bowel disease–associated intestinal neoplasias (IBD-Ns). We investigated a large series of IBD-N for associations between MSI and several biologic and clinical parameters related to tumors, patients, and their treatment. Patients and Methods A total of 277 IBD-Ns in 205 patients were screened for MSI. Biologic and clinical variables of patients with high levels of DNA microsatellite instability high (MSI-H) were collected and compared with those associated with 33 MSI-H non-IBD colorectal cancers (CRCs). Results A total of 27 IBD-Ns from 17 patients were found to be MSI-H. Compared with sporadic MSI-H CRCs, patients presented with a younger age at diagnosis, and there was no female predominance and no right-sided predominance. Unlike sporadic MSI-H CRCs, MSI-H IBD-Ns presented with heterogeneous mismatch repair defects involving MLH1, MSH2, MSH6, or PMS2, and a low frequency of MLH1 promoter methylation. They exhibited frequent BRAF mutations and frameshift mutations in genes containing coding repeat sequences. Conclusion The mechanisms underlying MMR deficiency in MSI-H IBD-Ns are different from those in sporadic MSI-H tumors and seem to be more related to those observed in hereditary MSI-H tumors. However, BRAF mutations were observed in MSI-H IBD-Ns, similar to sporadic MSI-H tumors, but unlike hereditary MSI-H tumors. Finally, the mutational events in target genes for instability are the same in MSI-H IBD-N tumors as in non-IBD sporadic and hereditary colorectal MSI-H cancers, indicating a colon-related repertoire of target gene alterations.

Chronic intestinal pseudo-obstruction (CIPO) is a disease characterized by episodes resembling mechanical obstruction in the absence of organic, systemic, or metabolic disorders. Pseudo-obstruction is an uncommon condition and can result from primary (40%) or secondary (60%) causes. The most common symptoms are nausea, vomiting, abdominal distension, abdominal pain and constipation or diarrhea. These symptoms are usually present many years before CIPO diagnosis. They can lead to severe electrolyte disorders and malnutrition. Principles for management of patients with CIPO are: to establish a correct clinical diagnosis in excluding mechanical obstruction; to perform a symptomatic and physiologic assessment of the gastrointestinal tract involved; to look for extra-intestinal manifestations, especially for myopathy and neuropathy; to discuss in some cases a surgery for full-thickness intestinal biopsies, and/or a neuromuscular biopsy in case of mitochondrial cytopathy suspicion. The management is primarily focused on symptom control and nutritional support to prevent weight loss and malnutrition. Treatment of CIPO includes prokinetic agents which may help to reduce gastrointestinal symptoms Courses of antibiotics may be needed in patients with symptoms suggestive of bacterial overgrowth. When necessary, enteral nutrition is preferred. In carefully selected patients, feeding jejunostomy with or without decompression gastrostomy may be tried. Long term parenteral nutrition should be reserved for patients who can not tolerate enteral nutrition. Intestinal transplantation can be discussed in selected patients.

This prospective study was designed to identify factors that could predict conversion in patients undergoing first laparoscopic ileocecal resection for Crohn's disease.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.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; P0.05). 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.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.

Gastrointestinal stromal tumors (GIST) are the most frequent mesenchymal tumors of the digestive tract and respond poorly to chemotherapy. A tyrosine kinase inhibitor treatment, imatinib mesylate, was recently shown to have antitumor effects in metastatic patients. However, this drug is a substrate for multidrug resistance (MDR) proteins. Therefore, we investigated the expression of ABCB1 (P-glycoprotein), ABCC1 (MRP1), and ABCG2 (BCRP) by Western blotting in 21 GISTs and 3 leiomyosarcomas. All the GISTs were positive for either ABCB1 (86% of cases) or ABCC1 expression (62%), but negative for ABCG2. ABCB1 was expressed in all gastric GISTs, but in only 67% of nongastric GISTs. By contrast, ABCC1 expression was more common in nongastric tumors (78% versus 42%). The levels of these MDR proteins in gastric GISTs were higher for ABCB1 (P = 0.007) and lower for ABCC1 (P = 0.004) compared with nongastric GISTs. We found no correlation between MDR protein expression and the risk assessment. None of the six patients treated with imatinib was resistant, although all were positive for at least one MDR protein. These results confirm that gastric and nongastric GISTs have different biological characteristics and suggest that MDR proteins do not impair the initial response of the tumor to imatinib.

The persistence of gastric lymphoma after Helicobacter pylori eradication may be difficult to evidence on endoscopic and histological examination. The aims of the study were to evaluate the detection of monoclonal immunoglobulin H (IgH) gene rearrangement in endoscopically infiltrated and normal mucosa at diagnosis and during follow-up in order to determine its clinical and prognostic impact. We studied 60 gastric marginal zone lymphomas of mucosa-associated lymphoid tissue (MALT), and IgH monoclonality was detected at diagnosis in 52 patients (87%). The endoscopically normal mucosa contained clonal lymphomatous cells in 69% of cases before remission. A complete histological remission (HR) was observed in 28 patients (47%). Among them, 23 were followed for molecular remission (MR). The median delay was 10 months to achieve HR and 18 months to achieve MR. Interestingly, patients with HR but not MR had a longer delay to achieve HR (21 months) (P=0.0006) and a more frequent clonal normal mucosa at diagnosis (88%) than patients with both HR and MR (10 months and 39%, respectively). The presence of monoclonal B cells at both infiltrated and normal sites may therefore identify patients with a longer delay to achieve complete response, suggesting that molecular dissemination may require therapeutic intensification.

Summary 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.

e risque de cancer colo-rectal est augmente au cours de la RCH [1] Selon une meta-analyse recente, ce risque est de 2 %, 8 % et 18 % apres respectivement 10, 20 et 30 ans d’evolution de la maladie [2]. Le risque est surtout marque en cas de pancolite ; en cas de colite gauche, le risque est plus faible et debute plus tardivement. En cas de rectite ou de recto-sigmoidite, le risque n’est pas augmente. L’existence d’une cholangite sclerosante primitive et d’un antecedent familial de cancer colo-rectal majore egalement le risque [1].

Variability in the frequency of KIT mutations in gastrointestinal mesenchymal tumors has been reported in the literature, and their prognostic value remains uncertain. This retrospective multicenter study included 276 patients with gastrointestinal mesenchymal tumors.We detected c-kit and CD34 protein expression by immunohistochemistry. Mutations in exons 11 and 9 of KIT and exons 12 and 18 of PDGFR were detected by length analysis of polymerase chain reaction products and direct DNA sequencing.Eighty-seven percent of the tumors analyzed were c-kit positive, with gastric tumors expressing CD34 more frequently than other tumors (86% vs. 52%; P0.001). KIT exon 11 mutations were detected in 90 of 179 (50.3%) of c-kit-positive and 12% of c-kit-negative tumors. These mutations showed variation in their length and location. Mutations were heterozygous in 94% of cases. Mutations were more frequent in CD34( +) tumors than in CD34( -) tumors ( P0.01), and 9% of tumors had a second mutation in exon 11. Mutations in exon 9 of KIT were present in 5.1% of the gastrointestinal stromal tumors, and mutations of the PDGFR were present in 11% of the KIT -nonmutated tumors. Patient's age, the primary location, size, necrosis, and mitotic counts of tumors were associated with metastases in c-kit-positive tumors. However, mitotic activity was the only independent factor identified in multivariate analysis ( P0.001). KIT mutations were slightly more frequent in metastatic than in nonmetastatic tumors (61% vs. 46%; P = 0.06). Deletions of codons 562-579 were more strongly associated with metastases than were deletions of codons 550-561 ( P = 0.0001).Mutations in KIT or PDGFR were detected in 58.4% of the c-kit-positive and also in some c-kit-negative tumors.

Most gastrointestinal stromal tumors (GISTs) contain activating mutations of the proto-oncogene c-kit. The GNNK− isoform of c-kit has a greater oncogenic potential than the GNNK+ isoform. We studied tumors from 29 patients with GIST, 19 of whom had c-kit mutations, and compared them to normal cells and HMC-1 mast cell line. c-kit transcripts were quantified by real-time PCR. The ratios of GNNK−/+ isoforms and of wild-type/mutant alleles were determined by RT-PCR and fluorometric quantification. On average, GISTs contained 1.9 times more c-kit transcripts than the HMC-1 cell line and GISTs with c-kit mutations contained 2.8 times more c-kit transcripts than those without (P=0.003). The median GNNK−/+ isoform ratios in GISTs with and without c-kit mutations were 4.4 and 4.1, respectively, and there was no difference in the GNNK−/+ ratios between the GISTs and the control samples. Both mutant and wild-type alleles of c-kit were expressed in similar amounts in 13/15 mutant GISTs. The oncogenic effects of KIT in GISTs are not related to the higher expression level of the GNNK− isoform. The high expression level of both mutated and wild-type allele transcripts of c-kit suggests that interactions between spontaneously activated and normal c-kit receptors are important in GIST tumorigenesis.

We have previously shown that H. pylori increases the passage of intact protein across the digestive epithelium, in vitro and in vivo in mice. The aim of this study was to test whether H. pylori can alter gastric permeability to a food-type antigen in humans.Antral and corpus gastric biopsies obtained from H. pylori-positive and H. pylori-negative patients suffering from nonulcer dyspepsia with normal esogastroduodenal endoscopy were mounted in adapted Ussing chambers to measure gastric permeability. Electrical resistance (R, an index of epithelial integrity) and fluxes of 14C-mannitol (JMan, a marker of paracellular permeability) and 3H-horseradish peroxidase (HRP, a test protein of antigen transport and processing) under intact (JHRPi) and degraded (JD) form, across the biopsies, were measured.At the corpus level, biopsies obtained from H. pylori-positive patients, as compared to H. pylori-negative patients, presented significantly higher intact--but not degraded--HRP fluxes (JHRPi = 446 +/- 297 and 219 +/- 265 ng/h cm2, p0.05; JD = 4,247 +/- 3,884 and 3,575 +/- 2,594 ng/h x cm2, respectively), and an increase in paracellular permeability (Jman = 0.35 +/- 0.1 vs 0.24 +/- 0.08 micromol/h x cm2, p0.02, respectively). At the antrum level, a tendency to increased intact HRP fluxes in H. pylori-positive patients, as compared to H. pylori-negative patients, was observed (JHRPi = 284 +/- 250 vs 207 +/- 203 ng/h x cm2, p0.09), without modifications of paracellular permeability.H. pylori infection increases absorption of an intact food antigen across the corpus gastric mucosa. This phenomenon may contribute to the maintenance of gastric inflammation and could play a role in the development of allergic sensitization to dietary antigens in susceptible individuals.

For the assessment of colonic Crohn's disease (CCD) attacks, no clinicobiological and/or morphological (endoscopic, radiological) criteria of severity have been validated in relation to anatomical criteria of severity (ACS) as a gold standard obtained from colectomy specimen examination. Our objective was to assess the accuracy of colonoscopy in predicting the anatomical severity grading of CCD.Colectomy specimens from 78 consecutive patients operated between 1982 and 1996 for CCD resistant to medical treatment were analyzed and classified into two groups according to the presence (ACS+) or absence (ACS-) of ACS. These were defined as either deep ulcerations eroding the muscle layer, or mucosal detachments or ulcerations limited to the submucosa but extending to more than one third of one defined colonic segment (right, transverse, left colon). Three endoscopic criteria of severity (ECS) were then defined: 1) deep ulcerations eroding the muscle layer (ECS1), 2) deep ulcerations not eroding the muscle layer but involving more than one third of the mucosal area (ECS2), and 3) mucosal detachment on the edge of ulcerations (ECS3).According to colectomy specimen examination, 68 and 10 patients belonged to ACS+ and ACS- groups, respectively. ECS1, ECS2, and/or ECS3 were found in 70 patients. Positive predictive values of ECS1, ECS2, and ECS3 for the presence of ACS were 90%, 98%, and 92%, respectively. Negative predictive values were 43%, 72%, and 23% respectively. However, at least one ECS (ECS1, ECS2, or ECS3) was found in 95% of patients with ACS. The extent of ulcerations at colonoscopy was correlated to the results of colectomy specimen examination (p0.001). Taking into account only patients with ACS, 88% of those with at least one ECS were diagnosed through left side colonoscopy. Usual clinical and biological severity criteria were not different in ACS + and ACS- groups. Two cases of toxic megacolon and toxic shocks were observed after the colonoscopy.In experienced hands, colonoscopy can be useful in severe CCD attacks. When at least one ECS is found, colonoscopy predicts the anatomical severity of the colitis with a high probability. Conversely, when none of the three ECSs is found, colonoscopy can reasonably exclude the diagnosis of severe anatomical CCD.

Background Colonoscopy with pan-chromoendoscopy (CE) is superior to standard colonoscopy in detecting neoplasia in patients with IBD. Performing random biopsies in unsuspicious mucosa after CE remains controversial. Methods Consecutive patients with IBD who underwent surveillance colonoscopy using CE were prospectively included. The standardised procedure used CE, performed targeted biopsies or endoscopic resection on suspicious lesions and then quadrant random biopsies every 10 cm. A panel of five expert pathologists reviewed histological slides with dysplasia. Logistic regression model was used to evidence the factors associated with neoplasia in any or in random biopsies. Results 1000 colonoscopes were performed in 1000 patients (495 UC, 505 Crohn9s colitis). In 82 patients, neoplasia was detected from targeted biopsies or removed lesions, and among them dysplasia was detected also by random biopsies in 7 patients. Importantly, in 12 additional patients dysplasia was only detected by random biopsies. Overall, 140 neoplastic sites were found in 94 patients, 112 (80%) from targeted biopsies or removed lesions and 28 (20%) by random biopsies. The yield of neoplasia by random biopsies only was 0.2% per-biopsy (68/31 865), 1.2% per-colonoscopy (12/1000) but 12.8% per-patient with neoplasia (12/94). Dysplasia detected by random biopsies was associated with a personal history of neoplasia, a tubular appearing colon and the presence of primary sclerosing cholangitis (PSC). Conclusions Despite their low yield, random biopsies should be performed in association with CE in patients with IBD with a personal history of neoplasia, concomitant PSC or a tubular colon during colonoscopy. Trial registration number IRB 001508, Paris 7 University.

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.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.In univariate analysis, the following were significantly associated with a high risk of tumor recurrence: male patients (P = 0.006), bowel obstruction (P0.001), weight loss5 Kg (P = 0.03), circumferential tumor (P = 0.02), macroscopic or microscopic pericolic organ invasion (T4 stage; P0.001), perineural invasion (P = 0.02), vascular invasion (P = 0.045), poor tumor differentiation (P = 0.005), mesocolic invasion1 cm (P = 0.009), less than 14 uninvolved nodes on the specimen (P = 0.03), and visceral peritoneal invasion (T4; P0.001). 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.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.

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 IE1 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. Copyright © 2000 John Wiley & Sons, Ltd.

Three cases of apparent primary villous atrophy of the terminal ileum in women with chronic diarrhoea are reported. Eight cases have previously been reported in the literature. Clinical characteristics are the presence of severe chronic secretory diarrhoea with episodes of hypokalaemia combined with signs of ileal malabsorption and/or efficacy of cholestyramine. Diagnosis is based on ileoscopy and histology. An association with microscopic colitis was present in the three patients and in four cases in the literature. The pathogenesis of primary ileal villous atrophy remains unknown and may involve dysimmunity. Its association with microscopic colitis may indicate a common pathogenesis or support the hypothesis that the faecal stream or bile salts play a role in the pathogenesis of microscopic colitis.

International audience; PURPOSE:To describe CT features of inflammatory bowel disease (IBD)-related colorectal cancer and correlate the imaging findings with histopathological findings.MATERIALS AND METHODS:CT imaging findings in 17 patients with IBD-related colorectal cancer were retrospectively evaluated. Imaging findings were correlated with surgical and histopathological findings. Univariate and multivariate analyses explored the relationships between CT and histopathological variables.RESULTS:Two different CT patterns were individualized including clearly visible soft tissue mass (8/17; 47%) (Type 1 tumor) or stenosis with marked circumferential thickening resembling inflammation (9/17; 53%) (Type 2 tumor). At univariate analysis, thickness of tumor-free colorectal wall at CT was greater in Crohn disease (median, 13 mm) than in ulcerative colitis (median, 7 mm) (P = 0.011). Significant association was found between presence of signet ring cells and Type 2 tumor at CT (6/9, 67% P = 0.009) and colonic dilatation proximal to tumor (5/6, 83%; P = 0.035). At multivariate analysis, free-fluid effusion was the single independent CT variable predictive for the presence of signet ring cells (odds ratio = 50; 95% CI 2.56-977.02; P = 0.01).CONCLUSION:Colorectal cancer in IBD displays two main features on CT. Type 2 tumors and free-fluid effusion correlate with presence of signet ring cells. Knowledge of these findings is critical to help suggest the diagnosis.

Introduction Alkalization of gastric fluids could inhibit plasmin-mediated and/or pepsin-mediated fibrinolysis. We evaluated the gastric antifibrinolytic effect of proton pump inhibitors in a live porcine model. Material and methods Six pigs were randomly assigned to treatment with proton pump inhibitors vs no treatment. After endoscopic mucosal resection, 8 μm sections were incubated on fibrin films. Fibrinolytic activity was assessed through focal lysis time. One-hundred-and-forty-two mucosal sections and 129 submucosal sections were analysed. Twenty-four additional sections were analysed on plates containing tranexamic acid to explore pepsin-mediated fibrinolysis. Results Focal lysis times in treated vs control groups were 21.0 min vs 21.2 min ( p = 0.39) in the mucosa, and 22.2 min vs 20.2 min ( p = 0.56) in the submucosa. No lysis could be seen on the plasmin-inhibited fibrin plates. Conclusion Only plasmin-mediated fibrinolysis was observed. Proton pump inhibitors had no significant plasmin-dependant antifibrinolytic effect. They may enhance haemostasis through different pathways.

International audience; AIM: To evaluate whether crypt abscesses from inflammatory bowel disease (IBD) patients contain bacteria and to establish their nature. METHODS: We studied 17 ulcerative colitis patients, 11 Crohn's disease patients, 7 patients with acute self-limited colitis (ASLC) and normal colonic biopsies from 5 subjects who underwent colonoscopy for colon cancer screening. A fluorescent in situ hybridization technique was applied to colonic biopsies to assess the microbiota composition of the crypts and crypt abscesses. RESULTS: Crypts colonized by bacteria were observed in 42.9% and 3.6% of ASLC and IBD patients, respectively (P = 0.019). Crypt abscesses colonized by bacteria were observed in 28.6% and 0.0% of ASLC and IBD patients, respectively (P = 0.035). CONCLUSION: These results do not support the hypothesis that crypt abscesses in IBD are the result of localized dysbiosis arising from persistence of living bacteria colonizing the crypts.

OBJECTIVE. The purpose of this article is to present the MDCT enteroclysis features of the multiple complications of celiac disease and illustrate why this technique is helpful to adult patients with celiac disease.CONCLUSION. MDCT enteroclysis findings can suggest the diagnosis in adult patients with unknown celiac disease, and many complications of celiac disease can be recognized because of their characteristic appearance. Familiarity with these signs can help in appropriate planning of further diagnostic procedures.

Chronic intestinal pseudo-obstruction (CIPO) is a disease characterized by episodes resembling mechanical obstruction in the absence of organic, systemic, or metabolic disorders. Pseudo-obstruction is an uncommon condition and can result from primary (40%) or secondary (60%) causes. The most common symptoms are nausea, vomiting, abdominal distension, abdominal pain and constipation or diarrhea. These symptoms are usually present many years before CIPO diagnosis. They can lead to severe electrolyte disorders and malnutrition. Principles for management of patients with CIPO are: to establish a correct clinical diagnosis in excluding mechanical obstruction; to perform a symptomatic and physiologic assessment of the gastrointestinal tract involved; to look for extra-intestinal manifestations, especially for myopathy and neuropathy; to discuss in some cases a surgery for full-thickness intestinal biopsies, and/or a neuromuscular biopsy in case of mitochondrial cytopathy suspicion. The management is primarily focused on symptom control and nutritional support to prevent weight loss and malnutrition. Treatment of CIPO includes prokinetic agents which may help to reduce gastrointestinal symptoms Courses of antibiotics may be needed in patients with symptoms suggestive of bacterial overgrowth. When necessary, enteral nutrition is preferred. In carefully selected patients, feeding jejunostomy with or without decompression gastrostomy may be tried. Long term parenteral nutrition should be reserved for patients who can not tolerate enteral nutrition. Intestinal transplantation can be discussed in selected patients.

Intervention studies of colorectal adenoma recurrence have demonstrated the need for surrogate markers of the cancer risk. Short-chain fructo-oligosaccharides (sc-FOS) have protective actions on colon carcinogenesis in animal models. We investigated differences in biological markers between adenoma and adenoma-free subjects, before and after 3 mo of daily intake of 10 g sc-FOS, within a multicenter study. After a full colonoscopy, 3 groups were studied at baseline and after 3 mo: 26 subjects with small colorectal adenoma(s), 18 with large adenoma(s), and 30 with no adenoma. At baseline, the mean fecal butyrate concentration was significantly lower in the adenoma groups than in the adenoma-free group (12.01 +/- 5.08 vs. 17.28 +/- 7.34 mmol/g dry weight) but was significantly increased in that group after 3-mo ingestion of sc-FOS (15.7 +/- 8.0 mmol/g; P = 0.02). In subjects without adenoma, sc-FOS ingestion was associated with a decrease in fecal lithocholic acid (P = 0.02) and an increase in cholic acid (P = 0.02), chenodeoxycholic acid (P = 0.04), total primary bile acids (P = 0.03), and ursodeoxycholic acid (P = 0.05). Fecal pH, blood parameters, and crypt cell proliferation were not significantly modified by sc-FOS ingestion in either group. In subjects with and without adenoma, sc-FOS affects some aspects of the colonic environment, which may be involved in prevention of colorectal neoplasia.

Cerebellar syndromes and radiologic cerebellar atrophy after hyperpyrexia have occasionally been reported, mostly in neuroleptic malignant syndromes, but neuropathologic studies are extremely rare. We studied 3 patients (a 74-year-old woman, a 63-year-old man, and an 80-year-old man) who had heat stroke during heat waves in France. One patient had generalized seizures and died 28 hours after admission. The other patients survived one month and 2 months after admission; both had palatal myoclonus, and in one case, magnetic resonance imaging showed high signal intensity in the cerebral peduncles. The main neuropathology in the 3 cases was severe diffuse loss of Purkinje cells associated with heat shock protein 70 expression by Bergmann glia. In situ end labeling was negative in surviving Purkinje cells, suggesting that the mechanism of neuronal death was not apoptosis. Degeneration of Purkinje cells axons resulted in myelin pallor of the white matter of the folia and of the hilum of the dentate nuclei. DNA internucleosomal breakages were identified by in situ end labeling in the dentate nuclei and centromedian nuclei of the thalamus and were associated with degeneration of the cerebellar efferent pathways: superior cerebellar peduncles, decussation of the superior cerebellar peduncles (Wernekinck commissure), and dentatothalamic tract. These findings suggest that the mechanisms of neuronal death in the dentate nuclei and centromedian nuclei of the thalamus was different from that in Purkinje cells and more likely resulted from deafferentation. Ammon's horn and other areas susceptible to hypoxia were spared. These observations confirm the selective vulnerability of Purkinje cells to heat-induced injury and involvement of the cerebellar efferent pathways in palatal myoclonus.

Background Management of severe acute colitis (SAC) complicating inflammatory bowel disease remains a challenge despite significant advances in medical therapy. The aim of this study was to report a 20-year experience with subtotal colectomy (STC) performed for SAC. Study design A total of 164 consecutive patients with a mean age of 37 ± 15 years (range 16 to 86 years) underwent STC for SAC defined according to the criteria of Truelove and Witts. The decision for surgical treatment was based on clinical, biologic, radiologic, and endoscopic severity criteria both at entry and during hospitalization after failure to improve under medical treatment. A Brooke ileostomy was made to the right iliac fossa and a sigmoidostomy was made to the midline incision. All complications before discharge were recorded as in-hospital morbidity or mortality. Results Colonoscopy was performed in 153 patients and endoscopic diagnosis of SAC was confirmed by pathologic examination in 84% of the cases. STC was performed on an emergency basis in 40 patients with complications and only after failure of medical treatment in the remaining 124 patients. The mortality rate was 0.6%. The overall morbidity rate was 33%; 24 patients required reoperation, including 8% undergoing reoperation during followup for small bowel obstruction. Definitive pathologic diagnosis changed in one half of the patients; the final diagnosis was Crohn's disease in 110 cases, ulcerative colitis in 35, and indeterminate colitis in 19. Conclusions Our results demonstrated the safety of STC performed in a tertiary care center for patients with SAC who presented with complications or failed to respond to intensive medical therapy.

t(11;18)(q21;q21) is a specific chromosomal translocation associated with mucosa-associated lymphoid tissue (MALT) lymphoma. It fuses the amino terminal of the API2 gene to the carboxyl terminal of the MALT1 gene and generates a chimeric fusion product. Although the translocation is frequently detected in gastric and pulmonary MALT lymphoma, its incidence in MALT lymphomas from other sites is largely unknown. It also remains unknown whether the occurrence of the translocation is influenced by the nature of preceding diseases associated with MALT lymphomas. We screened for t(11; 18)(q21;q21) in 417 cases of MALT lymphoma from 8 major sites by reverse transcription-polymerase chain reaction. t(11;18)(q21;q21) was found at highest frequencies in MALT lymphomas from the lung (38%) and stomach (24%), and at moderate frequencies in those from the conjunctiva (19%) and orbit (14%). However, the translocation was found only rarely in MALT lymphomas from the salivary gland (1%) and was absent in those from the thyroid, skin, liver, and other rare sites, and in immunoproliferative small intestinal disease (IPSID). In gastric MALT lymphoma, t(11;18)(q21;q21) was significantly associated with infection by CagA-positive strains of Helicobacter pylori. As CagA-positive strains of H pylori are much more potent in induction of host inflammatory responses, including activation of neutrophils, which release highly genotoxic oxygen reactive species, we therefore examined neutrophil infiltration in recognized precursors of MALT lymphoma including H pylori-associated gastritis, lymphoepithelial sialadenitis, and Hashimoto thyroiditis. Neutrophil infiltration was prominent in H pylori-associated gastritis but not in lymphoepithelial sialadenitis and Hashimoto thyroiditis. Our results demonstrate that t(11;18)(q21; q21) occurs at markedly variable frequencies in MALT lymphoma of different sites and suggest that the occurrence of the translocation is influenced by the nature of premalignant diseases associated with MALT lymphoma. Oxidative damage might play a role in development of t(11;18)(q21; q21).

20-30% of gastric mucosa-associated lymphoid tissue (MALT) lymphoma associated with Helicobacter pylori do not regress after antibiotic therapy. Regression can be assessed only by extended follow-up. To assess whether t(11;18, q21;q21), which results in a chimeric transcript between the AP12 and MLT genes, predicts lymphoma resistance to antibiotic therapy, we screened for the fusion transcript with RT-PCR in ten responsive and 12 non-responsive gastric MALT lymphomas. The AP12-MLT transcript was detected in nine (75%) of 12 patients non-responsive to antibiotic therapy but not in responsive patients. Most H pylori-associated gastric MALT lymphomas that do not respond to antibiotic therapy are associated with t(11;18, q21;q21).

As only a handful of lymphoma cases have been reported in conjunction with primary intestinal lymphangiectasia, it is not yet clear if this association is merely fortuitous or related to primary intestinal lymphangiectasia induced immune deficiency. We report on two female patients, 50 and 58 years old, who developed small intestinal high grade B cell lymphoma a long time (45 and 40 years, respectively) after the initial clinical manifestations of primary intestinal lymphangiectasia. They presented with a longstanding history of fluctuating protein losing enteropathy, multiple cutaneous plane warts, and markedly dilated mucosal and submucosal lymphatic channels in duodenal biopsies. One had a large ulcerated tumour of the proximal ileum and the other diffuse ileal infiltration. In both, histological examination showed centroblastic high grade B cell lymphoma associated with duodenojejuno-ileal mucosal and submucosal lymphangiectasia. They were subsequently successfully treated with surgery and postoperative chemotherapy (AVmCP: adriamycin, cyclophosphamide, Vm26, and prednisolone), and chemotherapy alone (PACOB: adriamycin, cyclophosphamide, vincristine, bleomycine, and prednisolone), respectively. A three year follow up in both cases showed persistent diffuse lymphangiectasia without evidence of lymphoma. The present findings support the hypothesis that primary intestinal lymphangiectasia is associated with lymphoma development. Keywords: protein losing enteropathy; immune deficiency; intestinal lymphangiectasia; malignant lymphoma; Waldmann disease