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Biomedical subjects

J Y Scoazec

Publications and source records attributed to J Y Scoazec.

At least 19 recordsLinked to original sources

[High intensity focused ultrasonic destruction of hepatic parenchyma].

OBJECTIVE: High intensity focused ultrasound (HIFU) is an effective and precise method of focal tumoral destruction since it is associated with imagery. This method is widespread for the endorectal treatment of prostatic adenocarcinomas. HIFU seem appropriate for the treatment of liver tumors but its use needs to be experimentally tested in vivo. The aim of the work is to study the feasibility, tolerance and effectiveness of the destruction of porcine liver by HIFU. MATERIAL AND METHODS: Ten pigs had liver destruction by HIFU after coeliotomy. Four to 5 2,3 cm(3) HIFU lesions were performed per animal under ultrasonographic control. The study included biological surveillance and an autopsy was performed 4 to 24 hours later for histological examination of the liver. RESULTS: The destruction of the liver was feasible in all cases and the 4 lobes of the liver could be treated. The general and biological tolerance of the procedure was excellent. Ultrasonographic features of the HIFU lesions were defined. The histological examination of the lesions showed well-circumscribed necrosis areas associated with cavitation or histological deficiencies of various degrees. CONCLUSION: This work demonstrated that liver destruction by HIFU is a feasible and effective method with low morbidity. A long-term experimental study is necessary before comtemplating its clinical use.

Animals↗

[Total pancreatectomy for mucinous pancreatic tumor].

AIM OF THE STUDY: To report our experience of total pancreatectomy (TP) in ten patients with mucinous pancreatic tumors (MPT), to discuss pre and peroperative investigations in the management of MPT, and operative, functional and carcinologic results after TP. PATIENTS AND METHODS: This retrospective study from January 1985 to January 2001 included ten patients, 5 men and 5 women (mean aged: 64 years). Six patients underwent one step TP for intraductal papillary mucinous tumor of the pancreas (IPMT) in 5 cases, and multifocal mucinous cystadenoma in one case. Four patients underwent a second step TP for tumor recurrence (2 IPMT, and 2 cystadenocarcinomas) which occurred 12 to 121 months post operatively (mean: 49 months). RESULTS: Post TP diabetes was controlled by insulinotherapy (3 injections a day), except in one patient who needed insulin administration through a pump. One patient, with cystadenocarcinoma, died from cancer recurrence 18 months after TP and 140 months after the initial pancreaticoduodenectomy. One patient died from heart disease 34 months postoperatively. The 8 other patients were alive with a mean follow-up of 33 months (range 11-61 months). CONCLUSION: Curative surgery for mucinous tumors of the pancreas may require TP, which is indicated preoperatively according to imaging, or intraoperatively following surgical findings and frozen section of the pancreatic margin. Totalization of a previous partial pancreatectomy is mandatory in case of tumoral persistence or recurrence in the pancreatic remnant. Postoperative diabetes can be managed successfully by a specialized team.

Adenocarcinoma, Mucinous↗

TP53 mutations, amplification of P63 and expression of cell cycle proteins in squamous cell carcinoma of the oesophagus from a low incidence area in Western Europe.

In Europe, high incidence rates of oesophageal squamous cell carcinoma (SCCE) are observed in western France (Normandy and Brittany) and in north-eastern Italy. Analysis of TP53 mutations in tumours from these regions has shown a high prevalence of mutations at A:T basepairs that may result from DNA damage caused by specific mutagens. However, the spectrum of TP53 mutations in regions of low incidence is unknown. We report here TP53 mutation analysis in 33 SCCE collected in Lyon, an area of low incidence. These tumours were also examined for MDM2 and P63 amplification, and for expression of p16(INK4a/CDKN2a), cyclin E, p27(Kipl)and Cox2. TP53 mutations were detected in 36% of the cases (12/33). In contrast with regions of high incidence, the mutation spectrum did not show a high prevalence of mutations at A:T base pairs. P63 was amplified in 5/32 cases tested (15.5%). No amplification of MDM2 was found. Expression studies revealed frequent loss of p16(INK4a/CDKN2a)(46%) and p27(Kipl)(25%) expression, and frequent overexpression of Cyclin E (70%) and Cox2 (42%). Overall, these results indicate that in Europe, SCCE from areas of high and low incidence present a similar pattern of molecular alterations but differ by the type of TP53 mutations.

Aged↗

Integrin up-regulation in chronic liver disease: relationship with inflammation and fibrosis in chronic hepatitis C.

In 94 patients with chronic hepatitis C, the pattern of integrin expression was correlated with firstly, the histological activity index, necro-inflammatory grade, and stage of fibrosis; secondly, the expression of inflammatory markers including ICAM-1; and thirdly, the extent and intensity of laminin deposition in the perisinusoidal matrix. Immunohistochemical results were evaluated according to a semi-quantitative scoring system or by image analysis. Increased beta1 expression was observed in 88.2% of cases. The expression of alpha1 and alpha5 was increased in 55% and 58.5% of cases, respectively. alpha6 chain was detected in 78.7% of cases. There were no statistically significant differences in integrin expression level according to Knodell's score, inflammatory grade, or stage of fibrosis. ICAM-1 expression was higher in patients with high scores for beta1 expression, but the differences were not statistically significant. There were significantly more patients with high scores for beta1 expression among those with continuous perisinusoidal deposition of laminin. Moreover, a close statistical correlation was observed between alpha6 induction and perisinusoidal laminin deposition (p<0.001). The results suggest that integrin up-regulation in chronic hepatitis C is more closely related to the fibrotic process than to the inflammatory lesions. This reinforces the idea that integrin induction in chronic liver disease is part of a coordinated process involved in the progression of liver fibrosis.

Adult↗

Differential upregulation of cellular adhesion molecules at the sites of oxidative stress in experimental acute pancreatitis.

BACKGROUND: Severe acute pancreatitis (AP)(2) is associated with exaggerated leukocyte adherence and activation. Endothelial cellular adhesion molecules (CAMs) can be induced by cytokines, but also directly by oxygen free radicals (OFRs), mediated by nuclear factor kappa-B (NF-kappa B). We investigated the behavior of inducible CAMs in relation to pancreatic oxidative stress. Our novel modification of cerium capture histochemistry (reaction of OFRs with cerium produces laser reflective Ce perhydroxide precipitates) combined with reflectance confocal laser scanning microscopy (CLSM) allows the histological codemonstration of in vivo OFR production and immunolabeled CAMs, or NF-kappa B. METHODS: Taurocholate AP was induced in rats; sham operated and normal animals served as controls. To achieve in situ, in vivo reaction of cerium with OFRs, animals were perfused with CeCl(3) solution at different time points (1, 2, 8, 24 h) and then sacrificed. E-selectin, P-selectin, ICAM-1, VCAM, and NF-kappa B p65 were labeled by immunofluorescence (IF) on frozen sections of cerium perfused pancreata. IF and Ce perhydroxide reflectance were simultaneously detected by CLSM. Pancreatic gene expression of the same CAMs was quantified by competitive RT-PCR (MIMIC internal control). RESULTS: Control pancreata showed negligible reflectance and minimal CAM expression. Early (1, 2 h) AP samples were characterized by intense, heterogeneous acinar OFR production, strong P-selectin, and increasing ICAM expression, with nuclear translocation of p65, histologically all colocalizing with the areas of acinar oxidative stress. Adherent polymorphonuclear leukocytes (PMNs) displayed weak OFR formation. Later (8, 24 h), a slowly declining P-selectin, but persisting ICAM-1 expression, was paralleled by widespread adherence of PMNs producing surprisingly large amounts of OFRs. VCAM and E-selectin showed a mild increase at 24 h. CAM gene activation was in good correlation with the protein expression. CONCLUSIONS: The early acinar oxidative stress is colocalized with NF-kappa B activation, preferential P-selectin, and ICAM upregulation in this AP model. Subsequently, adherent, activated PMNs become the major source of OFRs, thereby contributing to tissue damage.

Animals↗

Alteration of CD44 and cadherins expression: possible association with augmented aggressiveness and invasiveness of endometrial carcinoma.

Cadherins and CD44 isoforms are transmembrane glycoproteins with diverse functions in cell-cell and cell-matrix interactions and may be a determinant of invasive and metastatic behavior in carcinomas. The immunohistochemical expression of cadherins and CD44 in tissue samples from 15 normal endometrium and 33 endometrial adenocarcinomas were examined. The immunohistochemical analysis was performed using the monoclonal antibody HECD-1 against E-cadherin and the polyclonal antibody against N-cadherin. In addition, the monoclonal antibodies 2C5, which binds to CD44s and all of the variants encoded by exons 3-10; 3G5, which is specific for CD44v3; and 2F10, which is specific for CD44v6 were used. E-cadherin (P=0.0001) and N-cadherin (P<0.001) expressions were statistically lower in endometrial adenocarcinoma than in normal endometrium. In contrast, an overexpression of CD44 isoforms (P<0.01) and CD44v3 (P<0.01) expressions was found in endometrial adenocarcinomas compared with normal endometrium. No difference was noted for CD44v6. An association was found between a decrease in E-cadherin expression and the occurrence of local recurrent and nodal metastasis. An association was found between CD44 overexpression, lymph space involvement, and myometrial invasion. Our results suggest that cadherin and CD44 expressions in endometrial carcinomas may have a prognostic value. Alteration of CD44 seems to be related to local invasion, while alteration of E-cadherin seems to be associated with dissemination of the disease.

Adenocarcinoma↗

Molecular and clinical differences between adenocarcinomas of the esophagus and of the gastric cardia.

Adenocarcinoma of the esophagus (ADCE) with Barrett's mucosa and adenocarcinoma of the cardia (ADCC) are often reported as a single pathological entity. In this study we have used strict anatomical-pathological criteria to distinguish between these two lesions and we have investigated their differences in TP53 mutations, MDM2 gene amplification, and cytokeratin expression. DNA was extracted from the tumor areas of formalin-fixed, paraffin-embedded sections in 26 ADCC and 28 ADCE patients. TP53 mutations were detected by temporal temperature gradient electrophoresis and identified by sequencing. MDM2 amplification was assessed by differential polymerase chain reaction. The expression of cytokeratins 4, 7, and 13 was examined by immunohistochemistry. In ADCC, the male to female ratio was 1.8:1, compared to 27:1 in ADCE. Five ADCC patients had a history of other neoplasms, compared to only one ADCE patient. The two types of tumor differed in the prevalence of TP53 mutations (31% in ADCC and 50% in ADCE) and of MDM2 gene amplification (19% in ADCC and 4% in ADCE), and in the pattern of expression of cytokeratin 7 (positive in 100% of ADCE and in 41% of ADCC) and cytokeratin 13 (positive in 81% of ADCE and in 36.5% of ADCC). ADCE and ADCC differ in their clinical characteristics, in the prevalence of TP53 mutations and MDM2 amplifications, and in the patterns of cytokeratin expression. These results support the notion that ADCC and ADCE are distinct pathological entities.

Adenocarcinoma↗

Endothelial cell marker expression in dysplastic lesions of the liver: an immunohistochemical study.

BACKGROUNDS/AIMS: Hepatocellular carcinoma usually contains continuous capillary vessels lacking the differentiation markers specific for normal sinusoidal endothelial cells. We therefore aimed to search for alterations in endothelial cell marker expression in precancerous liver lesions. METHODS: Expression of the endothelial cell markers CD31, CD34 and BNH9 was analyzed in 138 dysplastic lesions from 40 cirrhotic patients (20 with and 20 without hepatocellular carcinoma). RESULTS: No expression of the three endothelial cell markers was detected in cirrhotic nodules and in non dysplastic regenerative macronodules. The three markers were detected in 29.8% of dysplastic lesions and 47% of hepatocellular carcinomas. At least one marker was detected in 75% of dysplastic lesions and 100% of hepatocellular carcinomas. The three markers were more frequently expressed in areas of small cell than of large cell change (34 vs 10%). No correlation was found with the grade of dysplasia, the occurrence of arterialization and the association with hepatocellular carcinoma. CONCLUSIONS: Alterations in the hepatic microcirculation comparable to those observed in hepatocellular carcinoma are present in a significant proportion of dysplastic lesions of the liver and may be indirect markers of the process of liver carcinogenesis.

Adult↗

Complete response of an HIV negative gastric Kaposi's sarcoma (KS) patient with peritoneal carcinomatosis by liposomal daunorubicin treatment.

We report the first case of an HIV negative patient with gastric Kaposi's sarcoma (KS) and peritoneal carcinomatosis in whom a complete response (CR) was obtained after liposomal daunorubicin administration. The patient presented with epigastric pain and hematemesis. Upper gastric endoscopy with multiple biopsies showed gastric involvement by KS. The whole physical examination and the thoraco-abdomino-pelvic CT scans showed no other localization. A total gastrectomy was performed. Histological examination confirmed the diagnosis of KS with involvement of regional lymph nodes and peritoneal lesions. Six cycles of liposomal daunorubicin were given. Post-treatment coelioscopic control was normal. The patient received another six adjuvant cycles of liposomal daunorubicin. The patient is in complete remission six months after the end of treatment. Liposomal daunorubicin is a promising treatment in the non HIV patient with visceral KS.

Adult↗

Expression of CD44 standard and isoforms V3 and V6 in uterine smooth muscle tumors: a possible diagnostic tool for the diagnosis of leiomyosarcoma.

Alterations of CD44 proteins, a family of cell adhesion molecule, have been linked with tumorigenesis, carcinogenesis, and prognosis in various neoplasms. Our aims were to evaluate and compare CD44 isoforms expression patterns in normal myometrium, uterine leiomyomas, and leiomyosarcomas and to correlate CD44 expression with clinicopathologic parameters. Fresh (n = 15) and formalin-fixed, paraffin-embedded (n = 76) tissues samples of myometrium, leiomyomas, and leiomyosarcomas were used for immunoblotting and immunohistochemistry, respectively. Semiquantitative evaluation was made after immunostaining. Monoclonal antibodies were used. By immunoblotting in myometrium and leiomyomas samples, we observed a band at 85 kd, corresponding to the apparent molecular weight of CD44s, and bands at 140 kd with the monoclonal antibodies against CD44v3 and CD44v6. In leiomyosarcomas, CD44s and CD44v6 were detected, but not CD44v3. By immunohistochemistry, decreased CD44s expression was found in leiomyomas and leiomyosarcomas (73.9% +/- 16.6% and 82.1% +/- 20.7%, respectively) compared with myometrium (97.3% +/- 6.2%; P < .0001). No CD44v6 staining was detected in myometrium, leiomyomas, and leiomyosarcomas. No CD44v3 expression was detected in leiomyosarcomas, whereas myometrium and leiomyomas expressed CD44v3. For the diagnosis of leiomyosarcoma, the absence of CD44v3 staining had a sensitivity, specificity, and positive and negative predictive values of 100%. In patients with recurrence of leiomyosarcomas, CD44s expression was decreased (P = .03). We conclude that CD44s immunostaining in leiomyosarcomas may have prognostic significance. The loss of CD44v3 expression could be used as a putative diagnostic tool for uterine leiomyosarcomas.

Adult↗

Orthotopic liver transplantation for idiopathic portal hypertension: indications and outcome.

BACKGROUND: Idiopathic portal hypertension is a rare clinical syndrome which may be associated with a spectrum of histological lesions, including nodular regenerative hyperplasia and incomplete septal cirrhosis. Here, we report eight adult patients with idiopathic portal hypertension who experienced an unusually severe clinical evolution characterized by the development of progressive hepatic failure requiring orthotopic liver transplantation. Our aims are: (a) to stress the distinctive clinical presentation of these patients, (b) to describe their biological and histopathological features, and (c) to evaluate the results of orthotopic liver transplantation in this rare indication. METHODS: Complete clinical charts and histological data were available in all patients. All patients were male. Their age at diagnosis ranged from 17 to 59 years. Complications of portal hypertension revealed the disease in all cases. Medical treatment was performed in all patients and portosystemic shunt in three. RESULTS: The development of progressive hepatic failure led to the indication of liver transplantation after a delay ranging from 3 to 10 years. Explanted livers showed pure nodular regenerative hyperplasia in three patients and incomplete septal cirrhosis in five. Recovery was uneventful. All patients are alive, without recurrence of the disease. CONCLUSIONS: This report points to the existence of severe cases of idiopathic portal hypertension occurring without underlying or associated systemic disease and characterized by a poor clinical course and requiring liver transplantation.

Adolescent↗

Cystic endocrine tumors of the pancreas: clinical, radiologic, and histopathologic features in 13 cases.

Cystic endocrine tumors of the pancreas are rare and raise difficult clinical problems. Our aims were to reevaluate the diagnostic and therapeutic strategy and to assess their histopathologic characteristics. Thirteen cystic endocrine tumors diagnosed in 10 patients were included. Clinical, radiologic, and pathologic data were reviewed. There were 6 male and 4 female patients (median age, 46 yrs). Six patients had evidence of multiple endocrine neoplasia type 1 (MEN1) disease. Four had a functional endocrine syndrome. Ten tumors were visible on imaging studies. The most suggestive radiologic features were the existence of a peripheral hypervascular rim (10 cases) and images of cyst into cyst (two cases). On gross and histologic examinations, two distinct types were present. Macrocystic tumors (six cases) were unilocular and limited by a thick wall containing nests of tumor cells. Microcystic tumors (seven cases) were characterized by the presence of multiple cystic spaces directly lined by tumor cells. Surgical resection was performed in all cases. Three patients had lymph node metastases at the time of diagnosis. One patient is dead with metastatic dissemination. The others are alive without recurrence or metastasis. The diagnosis of endocrine tumor must be considered for any pancreatic cyst discovered in a patient with a history of MEN1 syndrome or with clinical features suggestive of this syndrome. Cystic pancreatic endocrine tumors must be treated by surgical resection because of their possible malignant evolution.

Adult↗

Collagenous gastritis: a report of six cases.

Collagenous gastritis is an exceptional entity with eight cases documented to date characterized by the presence of a thick subepithelial collagen band associated with an inflammatory infiltrate of the gastric mucosa. The aim of our study was to describe the clinical and histologic characteristics of six new cases of collagenous gastritis. All cases showed a subepithelial collagen band that averaged 30 microm but often measured up to 120 microm. This finding was almost always accompanied by mixed chronic inflammation in the lamina propria and by surface epithelial damage of varying severity. Our study seems to delineate two subsets in patients with collagenous gastritis: 1) collagenous gastritis occurring in children and young adults presenting with severe anemia, a nodular pattern on endoscopy, and a disease limited to the gastric mucosa without evidence of colonic involvement, and 2) collagenous gastritis associated with collagenous colitis occurring in adult patients presenting with chronic watery diarrhea. These findings highlight the fact that subepithelial collagen deposition may be a generalized disease affecting the entire gastrointestinal tract.

Adult↗