Elevated hepatocyte paraffin 1 and neprilysin expression in hepatocellular carcinoma are correlated with longer survival.

Hepatocyte paraffin 1 (Hep Par 1) and neprilysin (CD10) are well-known markers of hepatocellular carcinoma (HCC). To assess their potential prognostic role, we conducted a retrospective analysis of 97 formalin-fixed and paraffin-embedded HCC from patients treated by surgery with curative intent, using standard immunohistochemical procedures and semiquantitative analysis. Strong Hep Par 1 expression and canalicular CD10 staining pattern were significantly correlated with smaller tumor size (p=0.007 and 0.04, respectively). On univariate analysis, longer overall survival was observed in patients with strong Hep Par 1 expression (p=0.0005) and in patients with a CD10can staining pattern (p=0.02). On multivariate analysis, the combined immunohistochemical score (CIS) obtained by addition of Hep Par 1 and CD10can scores and subtraction of cytoplasmic CD10 score was retained as the single most important prognostic factor (p=0.001). Patients with a CIS <4 had a 3.5-fold increased risk of death, as compared to those with a CIS >or=4. In conclusion, strong Hep Par 1 expression, presence of CD10can labeling, and absence of CD10cyt staining are favorable prognostic factors in HCC, which can be easily combined into a single immunohistochemical score for routine clinical use

The effect of lower body negative pressure on phase 1 cardiovascular responses at exercise onset in healthy humans

We tested the hypothesis that vagal withdrawal and increased venous return interact in determining the rapid cardiac output response (Phase I) at exercise onset. We used lower body negative pressure (LBNP) to increase blood dislocation to the heart by muscle pump action and simultaneously reduce resting vagal activity. At exercise start, we expected larger response amplitude for stroke volume and smaller for heart rate at progressively stronger LBNP levels, so that the cardiac output response would remain unchanged. Ten subjects performed 50 W exercise supine in Control condition and during -45 mmHg LBNP exposure. On single beat basis, we measured heart rate (HR), stroke volume (SV), and we calculated cardiac output (CO). We computed Phase I response amplitudes (A1) using an exponential model. SV A1 was higher under LBNP than in Control (p < 0.05). Conversely, the A1 of HR, was 23 ± 56 % lower under LBNP than in Control (although NS). Since these changes tended to compensate each other, the A1 for CO was unaffected by LBNP. The rapid SV kinetics at exercise onset is compatible with an effect of increased venous return, whereas the vagal withdrawal conjecture cannot be dismissed for HR kinetics. The rapid CO response may indeed be the result of two independent yet parallel mechanisms, as hypothesized, one acting on SV, the other on H

Selectivity of the photosensitiser Tookad® for photodynamic therapy evaluated in the Syrian golden hamster cheek pouch tumour model

The response to photodynamic therapy (PDT) with the photosensitiser (PS) Tookad was measured in the Syrian hamster cheek pouch model on normal mucosae and chemically induced squamous cell carcinoma. This PS is a palladium-bacteriopheophorbide presenting absorption peaks at 538 and 762 nm. The light dose, drug dose and drug injection-light irradiation times (DLI), ranging between 100 and 300 J cm(-2), 1-5 mg kg(-1) and 10-240 min respectively, were varied and the response to PDT was analysed by staging the macroscopic response and by the histological examination of the sections of the irradiated cheek pouch. A fast time decay of the tissular response with drug dose of 1-5 mg kg(-1) was observed for DLI ranging from 10 to 240 min and for light doses of 100-300 J cm(-2) delivered at a light dose rate of 150 mW cm(-2). A significantly higher level of tissular response was observed for squamous cell carcinoma compared to normal tissue. Nevertheless, the threshold level of the drug-light dose for a detectable response was not significantly different in the tumoral vs normal tissue. The highest response at the shortest DLIs and the absence of measurable response at DLI larger than 240 min at light dose of 300 J cm(-2) and drug dose of 5 mg kg(-1) reveals the predominantly vascular effect of Tookad. This observation suggests that Tookad could be effective in PDT of vascularised lesions

Rôle de la biopsie dans le diagnostic et le traitement de l'hépatite chronique C

La biopsie hépatique joue un rôle essentiel dans la prise en charge des patients avec hépatite chronique C. Elle est le gold standard actuel pour quantifier les lésions inflammatoires et la fibrose qui conditionnent les traitements antiviraux. Elle permet d'établir un pronostic, de rechercher d'éventuelles maladies associées et d'exclure des complications telles que cirrhose ou carcinome hépatocellulaire. La classification actuelle de l'hépatite chronique C est basée sur l'évaluation du grade et du stade histologiques. Le compte rendu de pathologie dans la routine d'un laboratoire est descriptif et semi-quantitatif. Le score numérique, en principe réservé à des spécialistes dans le cadre de protocoles ou d'études contrôlées, ne doit pas être utilisé sans que les éléments qui le constituent soient clairement détaillés

Endoscopic mucosal resection in the esophagus with a new rigid device: an animal study1

BACKGROUND AND STUDY AIMS:: There is a growing trend toward the use of minimally invasive endoscopic methods to treat early esophageal cancers. Although there is continuing controversy regarding the management of Barrett's esophagus and the value of surveillance programs continues to be debated, the ultimate goal is to eradicate all of the foci of intestinal metaplasia and hence the risk of developing an adenocarcinoma. A number of ablative techniques have so far been applied, but none has yet been shown to be superior and entirely satisfactory. The present study evaluates the feasibility, efficacy, and safety of a promising new method of endoscopic mucosal resection (EMR) in a sheep model, based on the use of a modified rigid esophagoscope. MATERIALS AND METHODS: The resectoscope consists of a rigid esophagoscope with a distal transparent window through which the mucosa and part of the submucosa are sucked in and then resected with a wire loop. The sheep model was chosen because of its similarities to human anatomy with regard to the thickness and histological structure of the esophagus. Fifty-five separate hemicircumferential resections and 11 circumferential resections were carried out in 21 and 11 animals, respectively. Mitomycin C, an agent inhibiting fibroblast proliferation, was administered at different time intervals after eight circumferential resections to prevent the development of esophageal strictures. Results : All of the specimens of hemicircumferential resections were obtained as single distinct pieces and were easily examined histologically. The surface of the specimen correlated with the size of the window and ranged from 6 to 12 cm (2). In circumferential resections, the specimens were obtained in two pieces. An accurate resection depth through the submucosa was achieved in 58 of 65 resected specimens. No complications occurred after hemicircumferential resections. Complications after circumferential resections (stenosis or perforation, or both) were minimized after appropriate timing of mitomycin C administration. CONCLUSIONS: This EMR method offers a promising approach in comparison with other options currently available. It appears to be superior in terms of the size of the resected specimen, the precision and regularity of the resection depth, and the accuracy of histological diagnosis with safety margins. Hemicircumferential EMRs have been shown to be safe in the sheep model. This new technique warrants further animal studies before being used for circumferential EMR in human

Histoplasmose disseminee a Histoplasma capsulatum chez un patient presentant un syndrome d'immunodeficience acquise (SIDA). [Disseminated histoplasmosis due to Histoplasma capsulatum in a patient with acquired immunodeficiency syndrome (AIDS)]

Very commonly encountered in the United States, histoplasmosis is rare in Europe, where only 27 patients have so far been infected by this mycosis. In Africa, two varieties of histoplasmosis have been observed: those due to H. capsulatum and H. duboisii. Histoplasmosis due to H. capsulatum is one of the twelve secondary infectious diseases listed in the surveillance definitions of AIDS. This complication has been described only in approximately 20 patients with AIDS; all patients had stayed on the American Continents. We report the case of a 30-year-old African male who lived in Switzerland and in Zaire. With AIDS and multiple Kaposi's sarcoma, the patient died from disseminated histoplasmosis due to H. capsulatum; a peripheral blood smear obtained a few hours before death revealed numerous typical yeast forms of H. capsulatum inside polymorphonuclear leukocytes. Post-mortem examination and cultures confirmed the diagnosis of disseminated histoplasmosis. Histoplasmosis should be suspected in AIDS patients even in Europe, especially where they have stayed in endemic areas. Examination of blood smears and bonemarrow aspirate may allow early recognition of the disease and permit appropriate treatment with amphotericin B and ketoconazole

Apport de l'imagerie par résonance magnétique et de la tomodensitométrie dans les cancers avancés de la cavité buccale. Etude comparative clinique, radiologique, morphologique [Magnetic resonance imaging and x-ray computed tomography in advanced cancer of the oral cavity. A comparative clinical, radiological and morphological study]

The objective of this prospective study is to assess the impact of magnetic resonance imaging (MRI) and computed tomography (CT) as compared to physical examination in the choice of type of surgery for advanced intraoral cancers (with or without resection of the mandibula). From 1990 to 1993, we operated on 21 intraoral malignant tumors with segmental resection of the mandibula followed by a histological examination. The preoperative evaluation consisted of an MRI (n = 8), a CT (n = 8) or both (n = 5). MRI suspected an infiltration of the bone in 9 cases, CT in 4 and physical examination in 16. This was histologically confirmed in 6 of the 21 patients only. MRI and CT both have a high sensitivity, as does physical examination, but neither have a good specificity (physical examination: 5 true positive, 4 true negative, 11 false positive, 1 false negative; MRI: 4 true positive, 4 true negative, 5 false positive, 0 false negative; CT: 3 true positive, 7 true negative, 3 false positive, 0 false negative). In conclusion, the decision of a mandibular resection can only be taken after a careful physical examination, including palpation under general anesthesia in a fully relaxed patient. This is best accomplished during the pretherapy bronchoesophagoscopy, routinely performed for the detection of synchronous second primary tumors using toluidin blue as a vital staining method. If this initial evaluation gives a suspicion of a massive infiltration of the mandible, an MRI, rather than a CT, should be performed to determine the extent of the resection because of a high rate of artefacts with CT

La nouvelle classification de Savary des oesophagites de reflux [Savary's new endoscopic classification of reflux oesophagitis]

Comme la classification de Savary-Miller dont elle adopte l'essentiel, la classification de l'oesophagite par refluxen 5 types de Savary-Monnier repose sur une analyse rigoureuse et précise des lésions endoscopiques. Ses principales qualités sont d'être simple, complète, logique et souple. Son impact sur la pratique est certain puisqu'elle a une excellente valeur pronostique et qu'elle permet de choisir la bonne stratégie thérapeutique. De plus, en isolant les cicatrices cylindriques (seules précancéroses à surveiller à long terme) elle permet de les utiliser pour préciser la topographie des oesophagites de reflux

Monoallelic methylation of the APC promoter is altered in normal gastric mucosa associated with neoplastic lesions

Adenomatous polyposis coli (APC) promoter hypermethylation has been reported frequently in normal gastric mucosa, but it remained to be clarified whether this occurs in every individual. In this study, methylation of the APC promoter was analyzed in histologically normal-appearing gastric mucosa samples by methylation-sensitive single-strand conformation analysis and by a methylation-sensitive dot blot assay. Epithelial cell samples were collected by microdissection from tissue sections. Equal amounts of methylated and unmethylated APC alleles were found in all gastric mucosa samples from patients without any gastric lesions (20 samples). Allele-specific methylation analysis showed that the methylation of the APC promoter was monoallelic; however, which allele was methylated depended on the cell type. Increased or decreased methylation was found in 10 of 36 (28%) normal gastric mucosa samples adjacent to a gastric or esophageal adenocarcinoma. No allelic loss was found at the APC locus. Modification of the methylation status was also found in 3 of 21 (14%) normal-appearing gastric mucosa samples adjacent to intestinal metaplasia. In contrast, all normal mucosa samples in cases with chronic gastritis but without metaplasia or dysplasia showed a monoallelic methylation pattern. Our results indicate the following: (a) In normal gastric mucosa, the APC promoter shows monoallelic methylation, which is not due to imprinting but most likely due to allelic exclusion; (b) the excluded allele differs between foveolar and glandular epithelial cells; (c) the APC methylation pattern is frequently altered in normal-appearing gastric mucosa of gastric or esophageal adenocarcinoma patients; and (d) such alterations also occur in normal gastric mucosa adjacent to intestinal metaplasi