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Biomedical subjects

J F Fléjou

Publications and source records attributed to J F Fléjou.

At least 19 recordsLinked to original sources
PubMed2006

Ciliated hepatic foregut cyst with extensive squamous metaplasia: report of a case.

Ciliated hepatic foregut cysts (CHFC) are rare cystic lesions of the liver composed of a ciliated pseudostratified columnar epithelium with mucous cells, connective tissue, and smooth muscles bundles. We report the first case of CHFC with extensive squamous metaplasia without dysplasia or carcinoma. A unilocular, avascular, hypoechoic 60-mm liver lesion located in segment IV was detected by ultrasonography in a 31-year-old woman. The cyst was surgically removed and was lined mainly by a regular squamous epithelium without keratin formation. After extensive sampling, a ciliated pseudostratified columnar epithelium with some alcian blue-positive goblet cells was identified. The lesion was totally examined and there was no epithelial dysplasia or carcinoma. Squamous epithelium is very rare in hepatic foregut cysts and may degenerate into squamous carcinoma. Squamous epithelium is also described in biliary cysts. When squamous epithelium is identified in a liver cyst, an extensive sampling is recommended to identify possible foci of squamous carcinoma and to classify more precisely the histological type of the lesion. Because some cases of squamous carcinoma have been described in CHFC, surgical removal of the lesion may be more appropriate than close follow-up or sclerosing therapy.

Adult↗
PubMed2006

Induction of the adenoma-carcinoma progression and Cdc25A-B phosphatases by the trefoil factor TFF1 in human colon epithelial cells.

TFF1 is overexpressed in inflammatory diseases and human cancers of the digestive and urogenital systems. To examine the transforming potential of TFF1 in human colon epithelial cells, premalignant PC/AA/C1 adenoma cells (PC) derived from a patient with familial adenomatous polyposis (FAP) were transformed by the TFF1 cDNA and used as a model of the adenoma-carcinoma transition. Constitutive expression of TFF1 increased anchorage-independent cell growth in soft agar, and induced or potentiated the growth of colon PC-TFF1 and kidney MDCKts.src-TFF1 tumor xenografts in athymic mice. This resulted in reduction of thapsigargin-induced apoptosis and promotion of collagen type I invasion through several oncogenic pathways. Using the differential display approach to identify TFF1 target genes, we found that the dual specific phosphatases Cdc25A and B implicated in cell cycle transitions are strongly upregulated under active forms in both PC-TFF1 and HCT8/S11-TFF1 colon cancer cells. Accordingly, TFF1 expression is absent in normal human colon crypts but is induced in correlation with Cdc25a and b transcript levels and tumor grade in familial and sporadic colon adenomas and carcinomas. We propose that TFF1 and Cdc25A-B cooperate with other dominant oncogenic pathways to induce the adenoma and adenocarcinoma transitions. Agents that target TFF1/Cdc25 signaling pathways may be useful for treating patients with TFF1-positive solid tumors.

Adenoma↗
PubMed2001

Regression of liver fibrosis after biliary drainage in patients with chronic pancreatitis and stenosis of the common bile duct.

BACKGROUND: Chronic obstruction of the common bile duct may cause hepatic fibrosis and secondary biliary cirrhosis. METHODS: We studied liver-biopsy specimens from 11 patients with chronic stenosis of the common bile duct due to chronic pancreatitis; all the patients had undergone liver biopsy before or at the time of surgical biliary decompression and underwent a subsequent liver biopsy for various clinical reasons. The patients were followed as part of a prospective study of 501 patients who had been treated for chronic pancreatitis. Two pathologists, who were unaware of the sequence of specimens, graded fibrosis on a scale of 0 (none) to 3 (cirrhosis). RESULTS: The 11 patients were all men. Chronic pancreatitis was due to alcohol abuse in 10 of the men; 1 had idiopathic disease. The median age at diagnosis was 38 years. The median interval between the first and second liver biopsies was 2.5 years (range, 0.3 to 9.0). The two patients who had restenosis of the biliary anastomosis were excluded from the analysis of fibrosis. In the group of nine patients without restenosis, the second specimen showed significant improvement in fibrosis (P=0.01). The fibrosis improved by two grades in two patients and by one grade in four patients; in three patients, the grade did not change. The pathologists agreed on the grading of specimens from 10 of the 11 patients. CONCLUSIONS: In patients with chronic pancreatitis and stenosis of the common bile duct, liver fibrosis may regress after biliary drainage.

Adult↗
PubMed2001

There are some benefits for eradicating Helicobacter pylori in patients with non-ulcer dyspepsia.

BACKGROUND: The relationship between Helicobacter pylori infection and non-ulcer dyspepsia is not established. AIM: To determine whether eradication of H. pylori might be of benefit in non-ulcer dyspepsia patients. METHODS: We randomly assigned 129 H. pylori infected patients with severe epigastric pain, without gastro-oesophageal reflux symptoms, to receive twice daily treatment with 300 mg of ranitidine, 1000 mg of amoxicillin, and 500 mg of clarithromycin for 7 days and 124 such patients to receive identical-appearing placebos. RESULTS: Treatment was successful (decrease of symptoms at 12 months) in 62% of patients in the active-treatment group and in 60% of the placebo group (N.S.). At 12 months, the rate of eradication of H. pylori was 69% in the active-treatment group and 18% in the placebo group (P < 0.001). Complete relief of symptoms occurred significantly more frequently in patients on the active treatment (43%) than in placebo-treated patients (31%, P=0.048). Within the active-treatment group, therapeutic success was significantly more frequent in the non-infected patients (84% vs. 64%, P=0.04). CONCLUSIONS: Although eradicating H. pylori is not likely to relieve symptoms in the majority of patients with non-ulcer dyspepsia, a small proportion of H. pylori-infected patients may benefit from eradication treatment.

Adolescent↗
PubMed2001

A randomized comparison of four omeprazole-based triple therapy regimens for the eradication of Helicobacter pylori in patients with non-ulcer dyspepsia.

BACKGROUND: Helicobacter pylori eradication rates in France after therapy with omeprazole, amoxicillin and clarithromycin are among the lowest in Europe. This study evaluated alternative eradication regimens. METHODS: Helicobacter pylori-positive patients (n=323) with non-ulcer dyspepsia were randomized to receive one of four 1-week regimens consisting of omeprazole, 20 mg b.d., plus either: amoxicillin, 1000 mg b.d., and clarithromycin, 500 mg b.d. (OAC); bacampicillin, 1200 mg b.d., and clarithromycin, 500 mg b.d. (OBC); clarithromycin, 250 mg b.d., and metronidazole, 500 mg b.d. (OCM); or amoxicillin, 1000 mg b.d, and azithromycin, 500 mg on day 1 and 250 mg on days 2-5 (OAAz). Eradication was confirmed by urea breath test 4-6 weeks after treatment. Susceptibility testing was performed in the case of eradication failure. RESULTS: The eradication rate with OAAz was 38% (95% CI, 25.6-49.4) on intention-to-treat analysis, which was lower (P < 0.05) than with the other regimens [OCM, 61% (50.0-72.8); OBC, 65% (54.0-76.5); OAC, 72% (61.8-81.8)]. Of the strains isolated following treatment failure with OAC, OBC or OCM, 84% were clarithromycin resistant. CONCLUSIONS: OAC remains the reference treatment for H. pylori eradication in France, although bacampicillin offers a useful alternative to amoxicillin. Susceptibility testing should be considered after unsuccessful eradication therapy.

Administration, Oral↗
PubMed2001

Familial multiple gastrointestinal stromal tumours with associated abnormalities of the myenteric plexus layer and skeinoid fibres.

AIMS: Multiple familial gastrointestinal stromal tumours are rare. We report the third family with two cases of multiple gastrointestinal stromal tumours showing skeinoid fibres. Associated abnormalities of the myenteric plexus layer are described and new hypotheses for the histogenesis of gastrointestinal stromal tumours are formulated. METHODS AND RESULTS: Multiple gastrointestinal stromal tumours developed in the duodenum and proximal jejunum were removed from mother and son. No history of a specific syndrome or of mastocytosis was known. Light microscopy revealed typical gastrointestinal stromal tumours with skeinoid fibres. An unusual abnormality of the myenteric plexus layer, showing a diffuse spindle cell hyperplasia, was noted in the macroscopically normal digestive wall. No abnormalities of the ganglion cells were associated. Tumours and the spindle cell hyperplasia showed similar morphological and immunohistochemical features with expression of CD34 and CD117 antigens. Follow-up revealed recurrences in the mother. CONCLUSION: The morphological characteristics of these two cases of familial gastrointestinal stromal tumours and of the associated abnormalities of the myenteric plexus layer, help to better explain the histogenesis of multiple familial gastrointestinal stromal tumours. The hyperplasia of the myenteric plexus could be considered a risk factor for recurrent tumours.

Actins↗
PubMed2001

Cytokeratin immunoreactivity of intestinal metaplasia at normal oesophagogastric junction indicates its aetiology.

BACKGROUND AND AIMS: Cytokeratin (CK) 7 and 20 patterns are specific for long and short segments of Barrett's oesophagus but their use has not been assessed in intestinal metaplasia arising in macroscopically normal gastro-oesophageal junction (GOJ). PATIENTS AND METHODS: This study was carried out in a large prospective series of 254 patients who underwent upper endoscopy, had normal gastro-oesophageal anatomy, and who had biopsies of the antrum, fundus, cardia, GOJ, and lower oesophagus. Intestinal metaplasia of the GOJ was typed by histochemistry with high iron diamine-alcian blue staining and by immunohistochemistry using CK7 and CK20 antibodies. Results were correlated with clinical, endoscopic, and pathological data. RESULTS: Sixty (23.6%) of our patients presenting with a normal GOJ had intestinal metaplasia. The CK7/CK20 pattern identified two groups of patients: one highly correlated with Barrett's and the other with characteristics of Helicobacter pylori gastritis. The Barrett's type CK7/CK20 pattern was related to a high frequency of gastro-oesophageal reflux symptoms (p<0.02) and normal endoscopic appearance of the stomach (p<0.03). In contrast, the gastric type CK7/CK20 pattern was linked to atrophic (p<0.02) or erythematous (p<0.05) appearance of the stomach (p<0.03), high frequency of H pylori infection (p<0.04), antral inflammation (p<0.006) with atrophy (p<0.02), and intestinal metaplasia (p<0.02). CONCLUSION: In patients presenting with intestinal metaplasia in normal appearing GOJ, the cytokeratin pattern identifies two groups of patients, one with features identical to those of long segment Barrett's oesophagus and one with features seen in H pylori gastritis. These data may be used by clinicians and should result in improved endoscopic surveillance strategies targeted specifically at patients at increased risk of Barrett's oesophagus and thus cancer.

Adolescent↗
PubMed2001

Inducible nitric oxide synthase attenuates chronic colitis in human histocompatibility antigen HLA-B27/human beta2 microglobulin transgenic rats.

Rats transgenic for HLA-B27/human beta2-microglobulin develop a spontaneous multisystem inflammatory disorder that closely mimics human spondyloarthropathies. Prominent features of this disorder are gut inflammation that predominates in the colon, and arthritis. Several mediators such as IFN-gamma, IL-1beta, TNF-alpha, and inducible nitric oxide synthase (iNOS) have been found increased in the inflamed colonic mucosa. In the colon of HLA-B27 transgenic rats, iNOS is predominantly expressed by epithelial cells, and iNOS transcripts are detected in the hip cartilage of those rats, but not in nontransgenic littermates. The role of iNOS in this disorder was evaluated by administering the corticosteroid dexamethasone, or the NOS inhibitor L-N6-(1-iminoethyl)lysine (L-NIL) to HLA-B27 transgenic rats with established disease. Treatment with dexamethasone attenuated some aspects of gut inflammation, although it had no effect on iNOS expression. In contrast, treatment with L-NIL effectively inhibited iNOS activity, and resulted in an increase in colitis. Cytokine transcripts in the colon were modified by these treatments: IFN-gamma and IL-1beta were decreased after dexamethasone treatment, whereas administration of L-NIL resulted in decreased IFN-gamma, and TNF-alpha. A trend towards increased IL-1b expression was observed which could have contributed to the L-NIL pro-inflammatory effect. These results suggest that iNOS exerts a protective effect on colitis, in the inflammatory disorder of HLA-B27 transgenic rats.

Animals↗
PubMed2001

[CagA status and virulence of Helicobacter pylori strains. Results of a French multicentric prospective study].

UNLABELLED: Previous experimental and epidemiological studies with few patients suggested that the presence of the cagA gene was a virulence factor for Helicobacter pylori (H. pylori). AIM: To establish in this large epidemiological cohort study the relationship between the histological virulence of H. pylori infection and the cagA status of the bacteria. METHODS: This prospective cohort study (6 month follow-up) was conducted on adult patients undergoing endoscopy for upper gastrointestinal symptoms. The cagA status of H. pylori-positive patients was established using the polymerase chain reaction (PCR) method on an antral biopsy. A score of histological virulence (inflammation, activity) was recorded on the basis of the Sydney system (on antral, angular and fundic biopsies). Eradication treatment given was not imposed and a clinical follow-up was performed at 3 and 6 months. H. pylori eradication was verified by a 13C urea breath test at 3 months. RESULTS: Four hundred and twenty two centers recruited 652 patients (mean age: 51 +/- 15 years, 55% female). Upper GI endoscopy was abnormal in 80% of the patients of whom 68% had a gastritis aspect; 38% were infected by H. pylori, and among them 51% were cagA-positive. The histological virulence scores associated with the cagA-positive strains were significantly higher than those associated with the cagA-negative strains, globally (P = 0.0035), in the antrum (P = 0.0063), and in the angulus (P = 0.046), but not in the fundus (P = 0.05). The cagA status was correlated neither with the symptom severity at inclusion and at 6 months (P > 0.05), nor with the H. pylori eradication rate at 3 months (75% in cagA-positive and 70% in cagA-negative strains, P = 0.52). CONCLUSION: This study on a large cohort of patients confirms the greater histological virulence of H. pylori cagA-positive strains. However, this virulence was not associated with more severe symptoms nor with an increase in resistance to H. pylori eradication treatment.

Adult↗
PubMed2000

Angiogenesis in the neoplastic sequence of Barrett's oesophagus. Correlation with VEGF expression.

The purpose of this study was to determine the angiogenic profile of human oesophageal adenocarcinoma. This study was carried out on a large series of surgically resected Barrett's adenocarcinomas and associated preneoplastic lesions. Vascularization was quantified by microvessel counting and measurement of the percentage microvessel surface area after immunohistochemistry using the CD34 antibody. The expression of vascular endothelial cell growth factor (VEGF) was also examined by immunohistochemistry. Results were correlated with clinico-pathological data and prognosis. Vascularization, assessed by both microvessel counting and measurement of the microvessel surface, was statistically higher in superficial cancers than in others. Higher vascularization was correlated with a lower rate of lymph node and distant metastasis, as well as with better survival. However, when superficial carcinomas were excluded from the study, microvessel count failed to provide any significant prognostic information. Irrespective of the inclusion or exclusion of superficial tumours, the expression of VEGF was correlated with a higher vascularisation but did not provide prognostic significance. It is concluded that high angiogenic properties are acquired in precancerous lesions and early cancers in Barrett's oesophagus. Vascularization as assessed by both microvessel counting and measurement of the microvessel surface is not informative for prognosis in infiltrative Barrett's adenocarcinomas. The expression of VEGF is correlated with vascularization, but has no independent prognostic relevance.

Adenocarcinoma↗
PubMed2000

Chromosomal numerical aberrations are frequent in oesophageal and gastric adenocarcinomas: a study using in-situ hybridization.

AIMS: (i) To investigate and compare the numerical aberrations of chromosomes 7, 8, 11, 17 and Y in a series of 60 adenocarcinomas of the oesophagus, gastric cardia and gastric antrum; and (ii) to specify the sequence of chromosomal aberrations occurring during the neoplastic progression of Barrett's oesophagus. METHODS AND RESULTS: Chromosomal in-situ hybridization was performed on deparaffinized tissue sections from 20 Barrett's adenocarcinomas, 20 adenocarcinomas of the cardia and 20 adenocarcinomas of the antrum, with centromeric alpha satellite DNA probes specific for chromosomes 7, 8, 11, 17 and Y, labelled with digoxigenin. Signals were detected by immunoperoxidase staining. The copy number for each chromosome was counted in 200 tumour cells nuclei and 100 lymphocytes as controls. In parallel, the DNA content of the nuclear suspensions was measured by flow cytometry. Numerical abnormalities of the five chromosomes (loss of the Y chromosome, monosomy, trisomy, and tetrasomy) were frequently observed in the three groups of adenocarcinomas (from 40% to 65% of the cases). Sixty per cent to 75% of oesophagus and gastric adenocarcinomas were DNA-aneuploid. Chromosomal aberrations progressively increased with advancing degrees of dysplasia in Barrett's mucosa, with an increasing frequency of trisomy and loss of the Y chromosome from non-dysplastic Barrett's mucosa to invasive adenocarcinoma, and with monosomy and tetrasomy present only in invasive cancers. CONCLUSION: Our study confirms the high frequency of chromosomal numerical aberrations in oesophageal and gastric adenocarcinomas, without differences between adenocarcinomas of the gastric cardia and antrum. We have shown that these alterations occur early during the neoplastic transformation of Barrett's mucosa.

Adenocarcinoma↗
PubMed2000

Intraductal papillary mucinous tumors of the pancreas confined to secondary ducts show less aggressive pathologic features as compared with those involving the main pancreatic duct.

Intraductal papillary mucinous tumors (IPMTs) of the pancreas are rare tumors characterized by a malignant potential. Because of the progress of imaging procedures, smaller cystic pancreatic lesions are now detected and some of them correspond to IPMTs that involve ectatic pancreatic branch ducts but spare the main pancreatic duct. To investigate differences in morphology and clinical behavior of branch and main duct types of IPMT, a surgical series of 43 cases was studied. All pathologic specimens of IPMT, surgically resected in our institution between October 1987 and July 1998, were analyzed. In all cases, the entire pancreatic specimen was systematically examined. IPMT of the branch type was found in 13 (30%) patients, whereas IPMT of main pancreatic duct type that involved the main pancreatic duct and branch ducts was observed in 30 (70%) patients. Patients with IPMT of the branch type were younger (median age, 55 yrs vs 64 yrs), and all but one of the lesions were located in the head and neck of the pancreas (vs 17 of 30 patients with the main duct type). The size of the cysts ranged from 4 to 55 mm, and the major duct showed a mild dilation in most cases. In contrast to the main pancreatic duct type, which showed invasive carcinoma and in situ carcinoma in 11 (37%) of 30 patients and 6 (20%) of 30 patients, respectively, IPMT of the branch type showed significantly less aggressive histologic lesions with five (39%) patients with simple hyperplasia, six (46%) patients with atypical hyperplasia, and two (15%) patients with in situ carcinoma. No invasive carcinoma was observed in this group. IPMT of the branch type occurs in younger patients and is associated with less aggressive histologic features than is the main pancreatic duct type. Our findings raise the difficult issue of clinical management of IPMT of the branch type as a distinctive group.

Adult↗
PubMed2000

The Vienna classification of gastrointestinal epithelial neoplasia.

BACKGROUND: Use of the conventional Western and Japanese classification systems of gastrointestinal epithelial neoplasia results in large differences among pathologists in the diagnosis of oesophageal, gastric, and colorectal neoplastic lesions. AIM: To develop common worldwide terminology for gastrointestinal epithelial neoplasia. METHODS: Thirty one pathologists from 12 countries reviewed 35 gastric, 20 colorectal, and 21 oesophageal biopsy and resection specimens. The extent of diagnostic agreement between those with Western and Japanese viewpoints was assessed by kappa statistics. The pathologists met in Vienna to discuss the results and to develop a new consensus terminology. RESULTS: The large differences between the conventional Western and Japanese diagnoses were confirmed (percentage of specimens for which there was agreement and kappa values: 37% and 0.16 for gastric; 45% and 0.27 for colorectal; and 14% and 0.01 for oesophageal lesions). There was much better agreement among pathologists (71% and 0.55 for gastric; 65% and 0.47 for colorectal; and 62% and 0.31 for oesophageal lesions) when the original assessments of the specimens were regrouped into the categories of the proposed Vienna classification of gastrointestinal epithelial neoplasia: (1) negative for neoplasia/dysplasia, (2) indefinite for neoplasia/dysplasia, (3) non-invasive low grade neoplasia (low grade adenoma/dysplasia), (4) non-invasive high grade neoplasia (high grade adenoma/dysplasia, non-invasive carcinoma and suspicion of invasive carcinoma), and (5) invasive neoplasia (intramucosal carcinoma, submucosal carcinoma or beyond). CONCLUSION: The differences between Western and Japanese pathologists in the diagnostic classification of gastrointestinal epithelial neoplastic lesions can be resolved largely by adopting the proposed terminology, which is based on cytological and architectural severity and invasion status.

Adenoma↗
PubMed1999

Deletion mapping of the tumor suppressor locus involved in colorectal cancer on chromosome band 8p21.

Several somatic genetic alterations have been described in colorectal carcinoma (CRC). Recurrent chromosomal deletions have suggested the presence of tumor suppressor genes (TSG) specifically involved in colorectal carcinogenesis. For one of them, two non-overlapping regions have been proposed on the short arm of chromosome 8, encompassing the LPL and NEFL genes. The short arm of chromosome 8 has been extensively studied in colorectal cancer and in other cancer types. Both regions have been reported as candidate loci for a TSG. In order to delineate a reliable region of deletional overlap on chromosome arm 8p in CRC, a series of 365 CRC samples was selected for the absence of microsatellite instability (RER, replication error); tumor and normal matched DNAs were studied for 54 microsatellite polymorphisms distributed on 8p using multiplex-PCR amplification. After purification of tumor nuclei by flow cytometry based on either the abnormal DNA index or the presence of a high expression of cytokeratin, complete allelic losses on 8p were observed in 48% of cases. Measurement of the DNA index showed that 88% of RER tumors were hyperploid. Complete allelic losses of only part of the short arm were observed on 26 occasions. These data allowed us to define a 1 cM interval of common deletion, flanked by the loci D8S1771 and NEFL, where a putative TSG may be localized.

Animals↗
PubMed1999

Squamous cell carcinoma and lipomatous pseudohypertrophy of the pancreas.

A 68-year-old woman who had been treated for non-insulin-dependent diabetes mellitus for the past 20 years was admitted to hospital because of abdominal pain and weight loss. Radiological investigation revealed a tumour in the body of the pancreas and numerous intraductal calcifications in both the tail and the head of the pancreas. Left-sided pancreatectomy was performed to remove the tumour. The resection specimen showed fatty enlargement of the parenchyma and numerous intraductal calcifications in the tissue adjacent to the tumour, which was 7 cm in diameter and was found to be a primary squamous cell carcinoma with a spindle cell component. There was also lipomatous pseudohypertrophy.

Aged↗