Maria Antonietta Pistoia

Increased Enterocyte Apoptosis and Fas-Fas Ligand System in Celiac Disease

Our aim was to evaluate whether increased enterocyte apoptosis was responsible for mucosal flattening in celiac disease (CD), and, since the mechanisms responsible for tissue injury in this condition are unknown, we studied the possibility that the Fas-Fas ligand (FasL) system may be involved. Endoscopic duodenal biopsy specimens from 12 patients with untreated and 12 with treated CD and 12 control subjects were evaluated for enterocyte apoptosis by the terminal deoxynucleotidyl transferase-mediated digoxigenin-deoxyuridine triphosphate nick-end labeling assay and for Fas and FasL expression by immunohistochemistry. A coculture of isolated enterocytes (targets) and purified lamina propria mononuclear cells (LPMCs) (effectors) was performed in the absence or presence of an antagonistic ZB4 anti-Fas antibody. We found a significant correlation between the degree of villous atrophy, morphometrically evaluated, and the level of enterocyte apoptosis, suggesting that mucosal flattening is a consequence of exaggerated epithelial cell death. Most celiac enterocytes express Fas, and LPMCs express FasL. The abolishment of enterocyte apoptosis observed in the presence of ZB4 antibody suggests that enterocytes are potential targets of lymphocyte infiltrate. These results directly demonstrate that FasL-mediated apoptosis is a major mechanism responsible for enterocyte death in CD.

Cytolytic mechanisms of intraepithelial lymphocytes in coeliac disease (CoD)

The effector arm of the mucosal immune system comprises lymphocytes scattered at intraepithelial and lamina propria levels. Intraepithelial lymphocytes (IEL) are a large population of oligoclonal resting cells which exhibit phenotypic and functional characteristics of cytolytic T cells when activated. Several mechanisms have been demonstrated to account for their cytotoxicity. Among them, one is mediated by perforin and granzyme molecules, another is mediated by Fas ligand (FasL) which delivers apoptotic signals through Fas receptor on target cells. There is good evidence that a flat intestinal mucosa may be produced by activated T cells. The aim of our study was to evaluate FasL and perforin expression by IEL, and its possible correlation with the increased enterocyte apoptosis in coeliac mucosa. Endoscopic duodenal biopsy specimens from 10 untreated coeliac patients, 10 treated coeliac patients, and 10 biopsied controls were evaluated for enterocyte apoptosis by terminal deoxynucleotidyl transferase‐mediated digoxigenin‐deoxyuridine triphosphate nick end label method, for perforin expression by immunohistochemistry, and for FasL expression by immunocytochemistry. In untreated CoD there was a significant increase of percentage of both FasL+ and perforin+ IEL which positively correlated with enterocyte apoptosis in comparison with controls. All these parameters were significantly lower in treated CoD, even though they did not normalize. Our study demonstrates that in untreated CoD FasL and perforin expression by IEL is increased, and significantly correlates with the level of enterocyte apoptosis.

Prospective randomized evaluation of preoperative endoscopic vital staining using CH-40 for lymph node dissection in gastric cancer

AbstractBackground: CH-40 is a suspension of activated carbon particles that was developed in Japan to carry anticancer drugs to regional nodes and peritoneal seedings of gastric cancer. Methods: Forty-five consecutive patients who had surgical resection and D2 lymph node dissection for gastric cancer over a 2-year period were randomly assigned to preoperative endoscopic submucosal injection of CH-40 (group A) or no staining (group B). A total of 21 patients in group A and 24 in group B were available for analysis. Results: The number of resected nodes per patient was significantly higher (t=6.06; 40df; P<.0001) in group A (mean±S.E.=35.3±1.24) than in group B (mean±S.E.=25.5±1.02). The rate of metastatic nodes resected was significantly higher (χ2=6.903 ; 1df; P=.009) in stained (22.5%) than in non-stained (14.7%) nodes of group A and also (χ2=6.906 ; 1df; P=.009) in stained nodes of group A than in group B (15.8%). Conclusions: Preoperative endoscopic vital staining with CH-40 proved to be rapid, safe, and effective in all cases in this series. Its use allowed surgeons to resect a higher number of lymph nodes, and to identify and examine more metastatic nodes. It also permitted identification of nodal micrometastases on routine histopathologic examination.

Ulcerated ectopic gastric mucosa of the rectum

curvature of the antrum.• The clinical presentation is commonly with epigastric pain and overt or occult gastrointestinal bleeding. Symptoms of gastric outlet obstruction may be a feature during the development of the fistula. Symptoms may abate with the formation of the fistulous double pylorus.• Treatment has primarily been conservative medical management with H2-blockers and antacids. Surgery has only been reported in a few patients. The long-term results of either therapeutic approach have not been recorded. Malignant antroduodenal fistula with formation of a double pylorus appears to be extremely rare. Only one instance of double pylorus associated with carcinoma has been reported,t and in this case the double pylorus was not due to a fistula but resulted from the partitioning of the lumen of the pylorus by a large neoplastic fold. In the present case the endoscopic appearances suggest that a malignant antroduodenal bulb fistula had indeed developed. It is perhaps surprising that carcinoma of the distal antrum is not more frequently complicated by a duodenal fistula since one study reports that, overall, 18% of antral carcinomas extend into the duodenum1o and, if the lesion is less than 1 cm from the pylorus, extension into the duodenum may occur in up to 35 to 40%. It is a curiosity that malignant gastrointestinal fistulas are quite uncommon. l1

Evaluation of Carcinoembryonic Antigen Levels in Gastric Juice, Stomach Mucosa and Plasma in High-Risk and Gastric Cancer Patients

The aim of this study is to compare the levels of carcinoembryonic antigen (CEA) in the gastric juice, stomach mucosa and plasma of gastrectomy patients at risk of developing cancer with those in normal controls and gastric cancer subjects. Blood samples, gastric juices and biopsy material were taken from 52 patients (8 normal, 10 gastric carcinomas, 24 gastroresected according to Billroth II and 10 according to Billroth I). No significant correlation was found between age, sex or smoking habits and CEA levels in plasma, gastric juice or stomach mucosa. A significant correlation between CEA levels in gastric secretion and those in tissue emerged from out data (n = 52; r = 0.67; p less than 0.01). A minor correlation was found between tissue and plasma CEA values (r = 0.34; p less than 0.05). The mean levels of CEA in plasma did not show significant differences between controls and neoplastic risk subjects. The average level of CEA in gastric secretions and in tissue were significantly lower in normal controls than in neoplastic and gastroresected patients; in this latter group, we have observed a correlation between the severity of the histological lesions and the levels of CEA in the biopsy specimens; no correlation was found with the type of operation (Billroth I or Billroth II). The level of CEA in gastric juices and in biopsy material, therefore, appears to be more useful than in plasma in recognizing cancer risk subjects.

Imaging in digestive Videoendoscopy

This paper surveys the performances of a particular computer assisted digital sub-system for adding digital image processing and analysis capabilities to existing digestive videoendoscopy systems. The main clinical features offered by this system in particular are its compatibility with all existing videoendoscopes and its ability to work interactively with the endoscopist during the examination as well as after.

Vidéo-endoscopie: au-delà de I'image

RésuméDans ce travail sont illustrées les prestations d’un systeme électronique d’analyse et d’elaboration de I’image appliquees a la vidéo-endoscopie digestive.Le principal avantage clinique offert par ce système est représenté par son fonctionnement interactif durant l’examen endoscopique.SummaryThe performance of an electronic system for image processing and analysis in digestive videoendoscopy are illustrated in this paper.The main clinical advantage offered by this system is its interactivity during the endoscopic examination.

Phytobezoar and duodenal ulcer as complication of Duodopa therapy in a patient affected by Parkinson’s disease

Continuous duodenal infusion of levodopa/carbidopa intestinal gel (LCIG) is an established treatment to control motor fluctuations in Parkinson’s disease. Duodenal infusion allows a steady absorption of the drug in the small bowel, reducing plasmatic fluctuations of levodopa. Some complications may occur during the treatment, often related to intrajejunal percutaneous endoscopic gastrostomy (PEG-J). We report a case of duodenal ulcer associated with a phytobezoar involving the end of jejunal probe, in a patient who underwent PEG-J for LCIG infusion. In the last 2 weeks, the patient suffered from abdominal pain and dyspepsia. Oesophagogastroduodenoscopy showed an ulcerative lesion of the duodenum due to traction of the jejunal tube; the end of the jejunal tube was wrapped in a phytobezoar. This case is interesting because of the extension of the ulcerative lesion due to PEG-J dislocation and because of the subtle symptoms associated with it.

Utilisation de la vidéoendoscopie avec traitement et analyse de l’image dans le diagnostic du cancer gastrique précoce

RésuméCe document passe en revue les possibilités de diagnostic du cancer gastrique au début au moyen de la vidéoendoscopie assistée d’un système informatique pour le traitement et l’analyse de l’image. Les principales fonctions du traitement de l’image du système sont le grossissement, l’étirement des contrastes et l’amélioration des contours. Les fonctions analytiques incluent la mesure des dimensions réelles (longueurs, périmètres et surfaces).L’utilisation de vidéendoscopes électroniques couplés à ce système digital de traitement d’image et d’analyse se sont avérés cliniquement très utiles dans notre service d’endoscopie, améliorant la précision du diagnostic pré-opératoire du cancer gastrique de 30 % durant la période comprise entre 1987 et 1989 et de 70,60 % de 1990 à 1993. Nous avons en particulier noté un taux plus élevé de diagnostics préopératoires précis pour les cancers gastriques précoces de petite taille.Les fonctions d’analyse ont été utilisées pour mesurer les dimensions du cancer gastrique au début. On a pu enregistrer un taux de précision très important des mesures prises sous endoscopie assistée par ordinateur. En fait, aucune différence significative n’a été démontrée entre les valeurs mesurées en préopératoire et celles relevées en post-opératoire sur les biopsies.SummaryThis paper surveys the performance in early gastric cancer diagnosis of videoendoscopy assisted by a computer system for image processing and analysis. The main image processing functions of the system are magnification, stretch contrast and edge enhancement. The analytical functions include the measure of real dimensions (lengths, perimeters and areas).The use of electronic videoendoscopes connected to this digital system for image processing and analysis proved clinically useful, improving the accuracy of our Endoscopic Unit in the preoperative diagnosis of early gastric cancer from 30 per cent in the period 1987–1989 to 70.6 per cent in the period 1990–1993. In particular a higher rate of accurate preoperative diagnoses of small early gastric cancer was registered.The analysis functions were used to measure early gastric cancer dimensions. A high degree of accuracy in computer-aided endoscopic measurements was detected. In fact, no significant difference was demonstrated between the values measured preoperatively and those detected postoperatively in the fresh specimen.