Search

A continuing flow of new scientific developments concerning coeliac disease in the last decade asks for the formulation of new concepts of pathophysiology and clinical considerations. Immunogenetic studies have shown a correlation of the disease to the HLA region on the short arm of chromosome 6, immunological research has led to the concept of a T-cell driven immunologic response of the small intestine, with the identification of highly sensitive and specific antibodies. The understanding of the histopathology of coeliac disease has changed dramatically, initiated by the proposition of a spectrum of gluten sensitive enteropathy by Marsh in 1992. Clinical studies report a significant change in patient characteristics and epidemiology. The incidence of the disease has shifted to a majority of adult coeliacs, the disease may present with less severe symptoms of malabsorption and the screening studies suggest an overall prevalence of up to 1 in 200–300. Histopathology has been standardized; lymphocytic enteritis (Marsh I), lymphocytic enteritis with crypthyperplasia (Marsh II), and villous atrophy, subdivided in partial, subtotal and total (Marsh IIIABC). Special attention is given to a subgroup of ‘refractory coeliacs’, including the identification of pre-malignant T-cells in the intestinal mucosa. The management of coeliacs primarely consists of monitoring for compliance and complications. Dietetic and medical associations need to establish protocols and offer additional training to undergraduetes, internships, general practitioners and other allied health professionals. It might be relevant to have a low threshold for intestinal biopsies. However, screening asymptomatics may be harmful for individuals. Research is needed to assess the benefits of mass-screening in the future. HLA analysis can contribute towards recognising populations at increased risk.

BACKGROUND AND STUDY AIMS The aim of this study was to evaluate the feasibility, safety, and clinical impact of push-and-pull enteroscopy (PPE) in patients with suspected or documented small-bowel diseases, in a prospective multicenter trial in three European medical centers. PATIENTS AND METHODS A total of 100 patients (mean age 56 +/- 16 years; range 13 - 90) were included at the three institutions between July and November 2004. The leading symptoms were: acute recurrent or chronic gastrointestinal bleeding (n = 64), polyposis syndrome (n = 8), chronic abdominal pain (n = 7), chronic diarrhea (n = 7), and others (n = 14). RESULTS No major PPE-associated complications such as perforation, bleeding, or relevant injury to the small-bowel tissue or mesentery were encountered. Minor complications occurred in 12 %. The mean time required to carry out the procedure from the oral and anal approaches was 75 +/- 19 min (32 - 150 min). The average insertion depths into the small bowel were 200 +/- 70 cm per PPE session (220 +/- 90 cm with the oral approach and 130 +/- 80 cm with the anal approach). The average radiation exposure (including diagnostic and therapeutic interventions) was 2.1 +/- 2.4 min and 155 +/- 159 dGy/cm2. PPE was fully diagnostic in 72 % of cases. The majority of the patients (34 %) were suffering from angiodysplasias; ulcerations and erosions of various etiologies were seen in 16 %, and polyps and tumors in 13 %. The PPE findings played a role in the subsequent treatment in 62 % of the patients. Endoscopic treatments, including argon plasma coagulation, polypectomy, dilation, and foreign-body extraction, were carried out in 42 %. Medical treatment was given in 12 %, and patients were referred for surgery in 8 % of cases. CONCLUSIONS This prospective analysis shows that PPE is safe and has a high diagnostic and therapeutic yield in patients with suspected or known small-bowel disease.

The hypothesis of a defect in the intestinal transport and processing of toxic (31-49) or immunostimulant (57-68 and the 33-mer 56-89) gliadin peptides was tested in patients with active celiac disease (ACD), patients with treated celiac disease (TCD), and controls.Using duodenal biopsy specimens mounted in Ussing chambers, we measured electrical resistance, mucosal-to-serosal radiolabeled-peptide fluxes, and peptide processing during transport using radio-reverse-phase high-performance liquid chromatography.Peptide 31-49 fluxes (24.7 microg x 3 h(-1). cm(-2)) were increased in patients with ACD compared with controls and patients with TCD (12.7 and 12.3 microg x 3 h(-1). cm(-2); P0.01). In contrast, no increase was observed for peptide 57-68 or 56-89 (33-mer). Electrical resistance was decreased in patients with ACD versus controls (15.3 vs. 23.9 ohms. cm(2); P0.001). Peptide 57-68 was partially degraded by brush-border peptidases in controls but not in patients with celiac disease. However, it was totally degraded after intestinal transport both in controls and patients with celiac disease. Peptides 31-49 and 56-89 were resistant to brush-border peptidases in all groups of patients but were totally degraded during intestinal transport in controls and patients with TCD. In patients with ACD, however, 50% of peptide 31-49 was delivered intact into the serosal compartment and only partial degradation of the 33-mer was observed. These abnormalities were not related to a nonspecific paracellular leakage.Our data indicate that gliadin peptides, although poorly or not digested by intraluminal enzymes, can be fully digested by enterocytes in controls and patients with TCD. In patients with ACD, incomplete degradation of the 33-mer and protected transport of the peptide 31-49 might favor their respective immunostimulatory and toxic effects.

Background & aims: Refractory celiac sprue, a low-grade intraepithelial lymphoma characterized by expansion of clonal intraepithelial lymphocytes with intracellular CD3ϵ but no surface CD3-T-cell receptor complexes, can be an intermediary step between celiac disease and overt T-cell lymphoma. To gain insight into the mechanisms of lymphomagenesis in celiac disease, we have performed the first cytogenetic study in refractory celiac sprue. Methods: Karyotypes were performed on: (1) 7 cell lines derived from clonal intraepithelial lymphocytes of patients with refractory celiac sprue; (2) 14 control T-cell lines, either from 4 of 7 patients with refractory celiac sprue or from 10 patients with uncomplicated celiac disease; and (3) bone marrow and peripheral blood lymphocytes in 1 of 7 patients with refractory celiac sprue. Rearrangements were confirmed by in situ hybridization using whole-chromosome painting probes and by comparative genomic hybridization in one patient. Results: A recurrent structural chromosomal aberration leading to partial trisomy of the long arm of chromosome 1 was found in 6 of 7 cell lines from patients with refractory celiac sprue but in none of the control T-cell lines. In one patient with circulating abnormal intraepithelial lymphocytes, the partial trisomy 1q was confirmed on cells freshly isolated from bone marrow and blood. Conclusions: Refractory celiac sprue is strongly associated with partial trisomy of the 1q region. Gain of chromosome 1q, recently found in 16% of enteropathy-type T-cell lymphoma, may be an early event in lymphomagenesis related to celiac disease and provides a key to investigating molecular mechanisms of lymphoid transformation in this disease.

BACKGROUND AND STUDY AIMS: Little is known of the long-term outcome in patients with gastrointestinal bleeding of obscure origin, who undergo investigation by means of push enteroscopy. The aim of this study was to assess the rate of recurrent bleeding and its predictive factors in patients with gastrointestinal bleeding of obscure origin, after exploration by push enteroscopy. PATIENTS AND METHODS: 105 patients with gastrointestinal bleeding of obscure origin (iron-deficiency anemia: n = 56; overt bleeding: n = 49) underwent exploration by push enteroscopy from December 1994 to December 1998. They were classified into three groups according to enteroscopy findings: no lesion found (group A; 56 patients), arteriovenous malformations (group B; 18 patients), and other gastrointestinal lesions (group C; 31 patients). Actuarial rates of rebleeding during follow-up were calculated and factors associated with rebleeding were assessed by means of univariate and multivariate analysis. RESULTS: Follow-up data were obtained for 101 patients (96 %). The mean follow-up was 29 months (6 - 54 months). The 2-year actuarial rate of rebleeding was 31 % in the overall population, and 27.6 %, 56 % and 24 % in groups A, B, and C, respectively (P = 0.13). The number of previous bleeding episodes and the number of packed red cell units transfused were two independent factors predictive of recurrent bleeding. The modality of recurrent bleeding (anemia or overt bleeding) was similar to that of the initial episode in 94 % of cases. In group A, a gastrointestinal lesion was found after rebleeding in one of the 12 patients with iron-deficiency anemia, and in four of the five patients with overt bleeding. CONCLUSION: Recurrent bleeding occurs in about one-third of patients who undergo investigation by push enteroscopy for gastrointestinal bleeding of obscure origin, with a trend towards more frequent rebleeding in patients with arteriovenous malformations. Frequent previous bleeding episodes and transfusion requirements are predictive of recurrent bleeding.

Background & Aims Little is known about intestinal CD4+ T-cell lymphoma; this rare malignancy is misdiagnosed frequently. We evaluated diagnostic criteria and factors that might affect its development and outcome. Methods In a retrospective analysis, we analyzed medical records and intestinal specimens from 10 patients diagnosed with intestinal CD4+ T-cell lymphoma among 115 consecutive patients examined for severe enteropathy with villous atrophy. Samples were analyzed by histology, flow cytometry, and comparative genomic hybridization. Results Small-intestine epithelial and lamina propria tissues from patients who presented with chronic diarrhea and malnutrition had variable levels of infiltration of CD3+ CD4+ T cells. Flow cytometry showed a high frequency of CD4+ intraepithelial cells, which frequently expressed a specific Vβ chain. T-cell receptor β clonality was confirmed by DNA sequencing. Two patients had HLA and serology results compatible with celiac disease and autoimmune enteropathy, respectively. Two patients were found to have antibodies against human T-cell leukemia virus and 2 patients had signs of a recent infection with the herpes viruses. Comparative genomic hybridization analyses showed heterogeneous chromosomal abnormalities. Symptoms were reduced in patients treated with steroids (n = 5), but not in patients given purine analogues or chemotherapy. Antibodies against CD52 produced clinical and histologic responses in 2 of 2 patients, whereas severe adverse effects developed in 1 patient. At the latest follow-up evaluation, all patients were alive. Conclusions There is much heterogeneity in the onset and genetic features of intestinal CD4+ T-cell lymphomas, despite their common presentation as indolent lymphoproliferations of the intestinal mucosa. Patients should be treated with steroids, and possibly antibodies against CD52 (for the most aggressive forms of this disorder).

Probiotics are nonpathogenic microorganisms that, when ingested, exert a positive influence on the health or physiology of the host. They can influence intestinal physiology either directly or indirectly through modulation of the endogenous ecosystem or immune system. The results that have been shown with a sufficient level of proof to enable probiotics to be used as treatments for gastrointestinal disturbances are 1) the good tolerance of yogurt compared with milk in subjects with primary or secondary lactose maldigestion, 2) the use of Saccharomyces boulardii and Enterococcus faecium SF 68 to prevent or shorten the duration of antibiotic-associated diarrhea, 3) the use of S. boulardii to prevent further recurrence of Clostridium difficile-associated diarrhea, and 4) the use of fermented milks containing Lactobacillus rhamnosus GG to shorten the duration of diarrhea in infants with rotavirus enteritis (and probably also in gastroenteritis of other causes). Effects that are otherwise suggested for diverse probiotics include alleviation of diarrhea of miscellaneous causes; prophylaxis of gastrointestinal infections, which includes traveler's diarrhea; and immunomodulation. Trials of gastrointestinal diseases that involve the ecosystem are currently being performed, eg, Helicobacter pylori infections, inflammatory bowel disease, and colon cancer.

Introduction Enteropathy-associated T-cell lymphoma (EATL) is an intestinal tumor of intraepithelial T lymphocytes. The 2008 WHO classification distinguishes two types of EATL: the first type of EATL (type I), the most frequent (80-90%) is strongly associated with celiac disease (CD) and the HLA-DQ2/DQ8 haplotypes. The tumor cells are CD3+CD8-/+CD4-CD56- and contain cytotoxic granules. In almost all cases, a varying proportion of the tumor cells express CD30. The second type of EATL (type II), the monomorphic form, has a distinct immunophenotype (CD3+CD4-CD8+CD56+). In two types, TCRgamma genes are often clonally rearranged. EATL may be preceded by refractory celiac disease (RCD), corresponding to CD refractory to gluten free diet (GFD). RCD is divided in two types based on the absence (type I) or presence (type II) of abnormal intraepithelial lymphocytes (IEL) showing down-regulation of CD8 and often TCRgamma genes rearrangement. RCD II is now considered as a small cell intraepithelial T-cell lymphoma that could be an intermediate stage between CD and EATL. The aim of the present study was to establish the pattern of CD30 expression in EATL. This could have therapeutic implications with the use of anti-CD30 monoclonal antibody like brentuximab vedotin (BV). Methods Consecutive adult patients (pts) diagnosed with EATL between 2007 and 2013 in two university hospitals in Paris (Necker University Hospital and Georges Pompidou European Hospital) were eligible for this study. Diagnosis was confirmed after histopathologic and immunohistochemical review. For the purpose of the present study, two expert hematopathologists (V.V. and N.B.) reviewed all EATL and extended the phenotypic analysis to reclassify them according to the 2008 WHO classification. A panel of antibodies directed against CD20, CD3, CD4, CD5, CD8, CD56, granzyme B and ALK1 was used. CD30 staining was performed with Monoclonal Mouse Anti-Human CD30, Clone Ber-H2 (Dako). Consecutive RCDI and RCDII cases with complete phenotype and clonality analyses diagnosed in the same period were used as control. Diagnosis of CD was based on HLA-DQ2/8 typing, detection of celiac specific antibodies and of villous atrophy with increased counts of IEL on normal diet. Pts were further classified in RCDI or II depending on their clinical and histological response to a GFD and the presence of abnormal IEL. Results Twenty five adults were diagnosed with EATL on consensus review (median age 53 years [range 34-76], M/F ratio 12/13). Twenty five RCDI pts (median age 51 years [range 16-75], M/F ratio 6/19) and 20 RCDII pts (median age 62 years [range 29-81], M/F ratio 7/13) were used as control. A clinical history of CD was found in 17/20 (85%) evaluable EATL pts. Histological features of CD/RCD were seen in all cases (20/20) of EATL in which the mucosa adjacent to the tumor could be investigated (half of these were RCDII). Primary sites of EATL were small intestine (20/25), mesenteric lymph nodes (3/25), peritoneal nodules (1/25) and spleen (1/25). Phenotypic analysis showed that EATL cases were all WHO type I (25/25). ALK1 was constantly negative. IEL were CD3+ in all 70 cases. CD8 was normally expressed in all RCDI IEL and downregulated in all RCDII IEL and 35% of EATL. In all cases of EATL (25/25), CD30 was strongly expressed by all large tumor cells. In RCDI and II, CD30 was negative in most cases (∼90%), and was rarely expressed by dispersed atypical lymphocytes (IEL or in lamina propria) in some cases. TCRgamma genes were clonally rearranged in 11/14 (79%) EATL, 3/25 (12%) RCDI and 18/20 (90%) RCDII. Based on these results, we initiated in 2012 a pilot study combining BV with chemotherapy followed by autologous stem-cell transplantation (ASCT) as frontline treatment of EATL. Five pts have currently been treated. The associated chemotherapy regimen was IVE/MTX (Sieniawski M, Blood 2010) for the first two pts. After presentation at ASH 2012 Annual Meeting of preliminary results of a phase 1 study combining BV with CHP regimen as frontline treatment of systemic ALCL and other CD30-positive mature T–cell and NK–cell lymphomas (Fanale MA, Abstract #60), we replaced IVE/MTX by CHP regimen, and treated 3 other pts. The treatment was well tolerated, and the 5 pts reached CR and underwent ASCT. Conclusion CD30 is strongly expressed in EATL type I. Promising results of the combination of BV with CHP led us to plan a phase 2 study of BV and CHP followed by ASCT as frontline treatment of EATL. Disclosures: Off Label Use: Brentuximab vedotin was used in enteropathy-associated T-cell lymphoma (EATL).

Background: The aim of this study was to evaluate the diagnostic and therapeutic yield of intraoperative enteroscopy in patients with obscure gastrointestinal (GI) bleeding. Methods: Complete intraoperative enteroscopy was performed in 25 patients with GI bleeding (overt hemorrhage 21, occult blood loss 4). The cause of GI bleeding was unknown before intraoperative enteroscopy in 20 patients and presumed in 5 (colon 4, duodenum 1). Results: Complete inspection of the small bowel was achieved in all cases. Mucosal-based lesions of the small bowel were identified in 16 of the 20 patients in whom the source of bleeding was unknown preoperatively (angiodysplasia 12, other causes 4). These lesions were treated by segmental small bowel resection (15) or medical therapy (1). With a mean 19-month follow-up, the rebleeding rate was 30% (6 of 20), and 2 of them in whom enteroscopy was negative died of massive hemorrhage. Intraoperative enteroscopy was normal in the 5 patients with bleeding of presumed GI origin preoperatively. Conclusions: Intraoperative enteroscopy remains a valuable tool for exploring obscure GI bleeding in selected patients.

Background & Aims: Celiac disease is a gluten-induced enteropathy characterized by the presence of gliadin-specific CD4 + T cells in the lamina propria and by a prominent intraepithelial T-cell infiltration of unknown mechanism. The aim of this study was to characterize the subset(s) of intraepithelial lymphocytes (IELs) expanding during active celiac disease to provide insights into the mechanisms involved in their expansion. Methods: Flow-cytometric analysis of isolated IELs and/or immunohistochemical staining of frozen sections were performed in 51 celiac patients and 50 controls with a panel of monoclonal antibodies against T-cell and natural killer (NK) receptors. In addition, in vitro studies were performed to identify candidate stimuli for NK receptor expression. Results: In normal intestine, different proportions of IELs, which were mainly T cells, expressed the NK receptors CD94/NKG2, NKR-P1A, KIR2D/3D, NKp46, Pen5, or CD56. During the active phase of celiac disease, the frequency of CD94 + IELs, which were mostly αβ T cells, was conspicuously increased over controls. In contrast, the expression of other NK markers was not modified. Furthermore, expression of CD94 could be selectively induced in vitro by T-cell receptor activation and/or interleukin 15, a cytokine produced by intestinal epithelial cells. Conclusions: The gut epithelium favors the development of T cells that express NK receptors. In active celiac disease, there is a specific and selective increase of IELs expressing CD94, the HLA-E–specific NK receptor that may be related to T-cell receptor activation and/or interleukin 15 secretion. GASTROENTEROLOGY 2000;118:867-879

The VIPoma syndrome is rare. It is usually caused by a neuroendocrine tumor located in the pancreas. Somatostatin analogs and interferon-a can be helpful in the symptomatic control of the disease, but the efficacy of chemotherapy in metastatic disease is limited. We report the case of a 32-yr-old patient who had a primary intestinal VIPoma with peritoneal carcinomatosis and hepatic metastases. Somatostatin analogs and conventional chemotherapy regimens were not effective on VIPoma syndrome and tumor progression. The combination of 5- fluorouracil and interferon-alpha was associated with a major clinical improvement and tumor regression. Further investigations should evaluate the place of such a combination as a first line treatment for patients with metastatic neuroendocrine tumors.

The immune system protects vertebrates against various infections and tumors. It recognizes foreign antigens and microorganisms, and reacts to protect the host. Situations of immunodeficiency expose the host to an increased risk of infections and tumors. On the other hand, situations of excessive immune response can also be detrimental. Biotherapeutic agents (BTA) have been defined as microorganisms with therapeutic properties (1). They include lactic acid bacteria (LAB), Bifidobacteria, and yeasts, especially Saccharomyces. This chapter reviews the basic mechanisms of immunity, evidence for immunomodulating activities of BTA, and the mechanisms involved, and summarizes the current and future applications in this field.

Objective: An increase in the number of intraepithelial lymphocytes (IEL) in the rectal epithelium of patients with active celiac disease has been described. No data are available about how they vary during a gluten-free diet. The aim of the study was to assess the effect of a gluten-free diet on T-cell activation in the rectal mucosa of adult patients with celiac disease. Methods: Frozen duodenal and rectal biopsies were available in four celiac patients (one male, three female, mean age 39 yr) both before and after 7 to 24 months on a gluten-free diet. Biopsy samples were stained using monoclonal antibodies directed against CD3, βF1, TcRδ1, CD25, and HLADR. Numbers of IEL were estimated by counting the peroxidase-stained cells per 100 epithelial cells. Four patients without histological abnormalities were used as control subjects. Results: In the four patients with active celiac disease but in none of the controls, CD25 was expressed by both duodenal and rectal lamina propria cells and HLADR was expressed by duodenal (4/4) and rectal (2/4) epithelial cells. In addition, two patients with active celiac disease had features of lymphocytic colitis, i.e., >20 IEL per 100 epithelial cells. After a gluten-free diet, the mean number of rectal CD3+βF1+ IEL decreased (9% vs 21%) and the expression of CD25 and HLADR was no longer present. These changes mirrored those found in the small intestinal biopsies. Conclusion: These results suggest that in celiac disease, gluten-driven T-cell activation is not restricted to the proximal part of the intestine but is present on the whole intestinal length. Assessment of the effectiveness of a gluten-free diet through rectal biopsies warrants investigation, as it could lessen discomfort for patients and prove more cost-effective.

Background : Few data are available on the accuracy of preoperative imaging or on long-term outcome after surgery for intraductal papillary and mucinous tumors of the pancreas. The aims of this study were to assess the following: (1) the accuracy of preoperative computed tomography, endoscopic retrograde pancreatography, and endoscopic ultrasonography for determination of tumor invasion and pancreatic extension as compared with surgical findings; (2) the long-term outcome after surgery. Methods : Forty-seven patients who underwent surgery between 1980 and 1995 for pathologically diagnosed intraductal papillary and mucinous tumors were included in this study. The findings of available computed tomography (n = 25), endoscopic retrograde pancreatography (n = 29), and endoscopic ultrasonography (n = 21) were reviewed by experienced clinicians blinded to pathologic diagnosis to assess tumor invasion and pancreatic extension. Pathologic specimens were reviewed by experienced pathologists. Postoperative follow-up data were analyzed. Results : Histologic features of invasive carcinoma were found in 43% of patients, severe dysplasia in 21%, and mild or moderate dysplasia in 36%. The overall accuracy of computed tomography, endoscopic retrograde pancreatography, and endoscopic ultrasonography in distinguishing between invasive and noninvasive tumors were, respectively, 76%, 79%, and 76%. The overall 3-year disease-free survival rate was 63%, but it was 21% among patients with invasive carcinoma at surgery ( p Conclusions : This study emphasizes the need for early surgical resection in patients with suspected intraductal papillary and mucinous tumors of the pancreas because of the high frequency of invasive carcinoma and the inadequacy of preoperative imaging for assessing malignancy. (Gastrointestinal Endosc 1998;47:42-9.)

Double balloon enteroscopy is a new method allowing the exploration of the whole intestine by the oral or anal route,1 with the possibility of endoscopic intervention. We describe here the first case of enduring paralytic ileus following this technique. A 47 old woman was referred to our unit for chronic and obscure undiagnosed gastrointestinal bleeding. Unremarkable conventional upper and lower endoscopies were performed twice. Small bowel follow through studies, abdominal computed tomography (CT), and pushed enteroscopy were also normal. A capsule enteroscopy was performed showing three angiodysplasias in the distal jejunum, all measuring 2–3 mm. To reach them, we performed a double balloon enteroscopy which showed two of the three lesions. Electrocoagulation with an argon plasma coagulator (50 W, 1.5 l/min) was performed …

AIM: To investigate the feasibility of small bowel polypectomy using double balloon enteroscopy and to evaluate the correlation with capsule endoscopy (CE). METHODS: This is a retrospective review of a single tertiary hospital. Twenty-five patients treated by enteroscopy for small bowel polyps diagnosed by CE or other imaging techniques were included. The correlation between CE and enteroscopy (correlation coefficient of Kendall for the number of polyps, intra-class coefficient for the size and coefficient of correlation kappa for the location) was evaluated. RESULTS: There were 31 polypectomies and 12 endoscopic mucosal resections with limited morbidity and no mortality. Histological analysis revealed 27 hamartomas, 6 adenomas and 3 lipomas. Strong agreement between CE and optical enteroscopy was observed for both location (Kappa value: 0.90) and polyp size (Kappa value: 0.76), but only moderate agreement was found for the number of polyps (Kendall value: 0.47). CONCLUSION: Double balloon enteroscopy is safe for performing polypectomy. Previous CE is useful in selecting the endoscopic approach and to predicting the difficulty of the procedure.

tients with human immunodeficiency virus (HIV) infection. Am J Gastroenterol 1994;89:2276-7. 11. Revuz J, Guillame J-C, Janier M, et al. Crossover study of thalidomide vs. placebo in severe recurrent aphthous stomatitis. Arch Dermatol 1990;126:923-7. 12. Grinspan D, Blanco GF, Agiiero S. Treatment of aphthae with thalidomide. J Am Acad Dermatol 1989;20:1060-3. 13. Gibbels E. Die thalidomide-polyneuritis. Stiittgart:Georg Thieme, 1968. 14. Florence AL. Is thalidomide to blame? [letter]. BMJ 1960;2: 1954.

Large granular lymphocyte leukemia (LGL) is characterized by clonal expansion of CD3+ T cells or CD3(-) natural killer cells and frequently is associated with autoimmune diseases. We describe 2 patients with celiac disease who no longer responded to gluten-free diets after they developed T-cell LGL, with intestinal localization of malignant lymphocytes. Flow cytometry phenotyping of isolated intestinal intraepithelial and lamina propria cells eliminated type II refractory celiac disease, identifying large-sized CD8(+)CD57(+) T cells. Treatment with a combination of cyclosporine and methotrexate restored the patients' sensitivity to gluten-free diets. LGL therefore might be a cause of refractory celiac disease that is sensitive to immunosuppressive therapy.

BACKGROUND & AIMS: The transferrin receptor (CD71) is up-regulated in duodenal biopsy samples from patients with active celiac disease and promotes retrotransport of secretory immunolglobulin A (SIgA)-gliadin complexes. We studied intestinal epithelial cell lines that overexpress CD71 to determine how interactions between SIgA and CD71 promote transepithelial transport of gliadin peptides. METHODS: We analyzed duodenal biopsy specimens from 8 adults and 1 child with active celiac disease. Caco-2 and HT29-19A epithelial cell lines were transfected with fluorescence-labeled small interfering RNAs against CD71. Interactions among IgA, CD71, and transglutaminase 2 (Tgase2) were analyzed by flow cytometry, immunoprecipitation, and confocal microscopy. Transcytosis of SIgACD71 complexes and intestinal permeability to the gliadin 3H-p3149 peptide were analyzed in polarized monolayers of Caco-2 cells. RESULTS: Using fluorescence resonance energy transfer and in situ proximity ligation assays, we observed physical interactions between SIgA and CD71 or CD71 and Tgase2 at the apical surface of enterocytes in biopsy samples and monolayers of Caco-2 cells. CD71 and Tgase2 were co-precipitated with SIgA, bound to the surface of Caco-2 cells. SIgACD71 complexes were internalized and localized in early endosomes and recycling compartments but not in lysosomes. In the presence of celiac IgA or SIgA against p3149, transport of intact 3H-p3149 increased significantly across Caco-2 monolayers; this transport was inhibited by soluble CD71 or Tgase2 inhibitors. CONCLUSIONS: Upon binding to apical CD71, SIgA (with or without gliadin peptides) enters a recycling pathway and avoids lysosomal degradation; this process allows apicalbasal transcytosis of bound peptides. This mechanism is facilitated by Tgase2 and might be involved in the pathogenesis of celiac disease.

Enteropathy-associated T-cell lymphoma (EATL) is a rare non-Hodgkin lymphoma frequently associated with celiac disease. We report a case of EATL complicating adult autoimmune enteropathy (AIE). Analysis of phenotype, rearrangements in T-cell receptor genes, and chromosome alterations by high-resolution comparative genomic hybridization identified features distinct from those described for types I and II EATL. Furthermore, EATL arose from a single T-cell clone that had been present for several years in AIE-associated, oligoclonal, intestinal T-cell infiltrate. Emerging T-cell clones should be monitored in patients with AIE who receive long-term immunosuppressive therapy.

for patients with EGC that fulfilled the expanded criteria: mucosal cancer without ulcer findings irrespective of tumor size; mucosal cancer with ulcer findings ≤3 cm in diameter; and minute submucosal invasive cancer ≤3 cm in size. 780 patients with 806 EGC lesions were enrolled. The patients underwent ESD and then received periodic endoscopic followup andmetastatic surveys for 0-66months (median, 16months). Themain outcomemeasures were en bloc resection rate, and complete resection rate. Complications were assessed, and factors related to each were analyzed statistically. The disease-free survival rates were estimated. Also we compared treatment outcomes between the standard and expanded indication groups. Results: En bloc resection was achieved in 97% (782/806). Tumor of middle or upper stomach was at higher risk of piecemeal resection. 750 of 806 lesions (93.1%) were deemed to have undergone curative resection. En bloc resection, tumor site, and tumor size were the significant contributors to curative ESD. During follow-up period, one local and ten metachronous recurrences occurred. There was no cancer related death and 3-year recurrence-free survival rate was 96.7%. The complete resection rate of standard indication group was superior to expanded indication group. (97.1% and 81.5%, respectively) but there was no significant difference in recur free survival rate between two groups. (p=0.776) Conclusion: Expanded indication of ESD should be applied carefully to properly selected patients with EGC. The prognosis of EGC patients treated by ESD is likely to be excellent, though further longer follow-up studies are warranted.

To the Editor: X-linked agammaglobulinemia is characterized by a profound defect in the production of antibodies of all isotypes; the defect is related to impaired B-lymphocyte differentiation resulting from mutations in the gene for B tyrosine kinase.1 Immunity against viral infections is generally intact in patients with X-linked agammaglobulinemia, with the exception of an unusual susceptibility to enteroviral infection.1 Chronic intestinal inflammation mimicking Crohn's disease has been described in a few patients with X-linked agammaglobulinemia.2,3 Its origin, however, is unknown. A 22-year-old man with X-linked agammaglobulinemia that had been diagnosed at the age of 9 was referred for chronic . . .

Abstract 2937 Poster Board II-913 Enteropathy-associated T-cell Lymphoma (EATL) may complicate celiac disease (CD), refractory celiac disease type I (RCD I) characterized by normal intraepithelial lymphocytes (IEL) or refractory celiac disease type II (RCD II) defined by abnormal IEL (CD3s-,CD3i+ and CD8-) and a clonal rearrangement of the gamma or delta chain of the T cell receptor (TCRγ/δ). It remains unknown whether the type of the associated enteropathy, non clonal (CD or RCD I) or clonal (RCD II), may be a prognostic factor in EATL. We aimed to assess the prognosis of EATL according to the type of the associated enteropathy. Medical files of 29 patients with EATL were retrospectively studied. The type of associated enteropathy was confirmed by immunohistochemistry analysis in all cases and by flow cytometry phenotyping analysis of freshly isolated IEL and search for a TCR γ or δ clonal rearrangement by Multiplex PCR whenever possible. Kaplan-Meier curves and Logrank test were used to compare survival of EATL in the 2 groups of enteropathy (clonal or not). Mean age at EATL (13 women / 16 men) onset was 57 years. The associated enteropathy was CD (n=10) or RCD I (n=2) in 12 patients and RCD II in 17 patients. No statistical difference was found in lymphoma staging with localized (IE and IIE) versus disseminated stages (IV) found in 42% and 58% of patients with CD or RCD I and in 53% and 47% of patients with RCD II, respectively. Diagnostic or therapeutic surgery was practiced in 83% and 47% of patients with CD or RCD I and with RCD II, respectively and chemotherapy in 92% and 82% of the same groups of patients, respectively (n.s). Considering all the EATL, the two-year and five-year survival rates of EATL were 34.1% and 20.2%, respectively. In subgroup analysis, the two-year and five-year survival rates of EATL were 66.7% and 53.3% in case of CD and/or RCD I and 11.8% and 0% in case of RCD II, respectively (p=0.0007). In conclusion, the type of enteropathy significantly impacts the prognosis of EATL with a particular short survival in case of associated RCD II enteropathy. Disclosures: No relevant conflicts of interest to declare.

Introduction En France, la strategie de depistage des polypes et du cancer colorectal (CCR) repose sur la combinaison de la recherche de sang dans les selles et de la coloscopie. La video-capsule specifique du colon (VCC), pourrait etre une alternative a cette strategie [1, 2]. Le but de cette etude prospective, multicentrique francaise etait de comparer les performances diagnostiques de la VCC a celles de la coloscopie dans une population a risque moyen ou eleve de CCR. (analyse intermediaire planifiee apres 105 inclusions/550 prevues). Patients et Methodes Les patients a risque moyen de CCR (50-74 ans) ou a risque eleve (antecedents personnels ou familiaux de neoplasie colique) ont ete inclus dans l’etude. Les criteres d’exclusion etaient une symptomatologie evocatrice de stenose intestinale, une diverticulose colique recemment compliquee et une insuffisance cardiaque et/ou renale evoluee. La VCC et la coloscopie ont ete realisees, chez le meme patient, a 24 heures d’intervalle, selon une methodologie publiee (1, 2). Les donnees ont ete interpretees (niveau de preparation, presence de lesion,…), en double insu, par l’endoscopiste ayant realise la coloscopie et le lecteur de la VCC. En cas de discordance entre les deux interpretations, un comite d’adjudication tranchait. Resultats 105 patients (39 femmes et 66 hommes), âges en moyenne de 60 ± 10 ans ont ete inclus de mai 2007 a fevrier 2008. Trente patients (29 %) etaient a risque moyen de CCR et 75 patients (71 %) a risque eleve. 90 % des VCC etaient excretees dans les 10 heures apres l’ingestion. La preparation du colon etait jugee bonne ou excellente dans 55 % des cas en VCC et 87 % des cas en coloscopie. La prevalence de polype significatif (≥ 6 mm) etait de 25 % pour la VCC et la coloscopie. Les performances de la VCC pour le diagnostic de polype ≥ 6 mm etaient : Sensibilite 55 %, Specificite 87 %, Valeur Predictive Positive 52 % et Valeur Predictive Negative 88 %. Chez les patients ayant une preparation bonne ou excellente, les performances etaient respectivement de 69 %, 84 %, 56 %, et 90 %. Apres adjudication des cas discordants, les performances etaient respectivement de 73 %, 93 %, 73 % et 93 %. Cinq evenements secondaires ont ete observes, en rapport avec la preparation (2 fois) ou la coloscopie (3 fois). La VCC a ete mieux appreciee que la coloscopie (echelle visuelle analogique : 8,80 vs 8,27 p Conclusion Ces resultats montrent l’excellente acceptabilite et tolerance de la VCC pour le depistage et le suivi de lesions neoplasiques colo-rectales. Cependant la preparation etait jugee insuffisante chez pres d’un malade sur deux et a conduit a modifier le protocole de preparation. De plus, les resultats apres adjudication confirment l’importance d’un apprentissage prealable a l’utilisation de cette technique. Malgre ces reserves, la combinaison d’une sensibilite de 73 % et d’une VPN de 93 % pour la detection de polypes de plus de 6 mm semble particulierement prometteuse.

To the Editor: We have read with interest the report by Carbonnel et al[1][1]which suggests that complicated celiac disease (CD) is a form of cryptic T-cell lymphoma in four patients. We have recently published a similar study of six patients with complicated CD, which we classified as refractory