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Biomedical subjects

G Monges

Publications and source records attributed to G Monges.

At least 19 recordsLinked to original sources
PubMed2002

A phase II single institutional experience with preoperative radiochemotherapy in pancreatic adenocarcinoma.

BACKGROUND: Resection of pancreatic adenocarcinoma has a limited impact on survival. We hypothesized that delivering preoperative radiochemotherapy (RTCT) might enhance local control of the cancer and improve survival. METHODS: Nineteen patients with localized pancreatic cancer (14 head and 5 body) were treated during the past 4 years with an intramural protocol consisting of continuous infusion of fluorouracile (5-FU: 650 mg/m(2)/D1-D5 and D21-D25 and Cisplatin 80 mg/m(2)/bolus D2 and D22 with preoperative external beam radiotherapy (RT) (30Gy split course RT or 45 Gy standard fractionation RT). RESULTS: Four patients did not have surgical resection: Three patients were noted to have liver metastases and 1 patient developed peritoneal carcinomatosis. The remaining 15 patients had potentially curative resection (12 Whipple procedure and 3 distal subtotal pancreatectomy). There was no postoperative death. Pathologic findings showed five major responses including 2 patients with complete pathologic response. The overall median survival for the 19 study patients was 20 months. The median disease free and 2-year overall survival for the group with resection were 30 months and 52.3%. CONCLUSIONS: Preoperative RTCT followed by resection is well-tolerated and safe for patients with localized pancreatic cancer. Major histological response occurred for 25% of patients. This approach could offer improvement in patient survival.

Adenocarcinoma↗
PubMed2001

Genetic alterations associated with hepatocellular carcinomas define distinct pathways of hepatocarcinogenesis.

BACKGROUND & AIMS: To evaluate how characterization of genetic alterations can help in the elucidation of liver carcinogenesis pathways, 137 tumors were analyzed. METHODS: High-density allelotype, p53, Axin1, and beta-catenin gene mutations were determined. Alterations were analyzed according to clinical parameters. RESULTS: Tumors could be divided into 2 groups according to chromosome stability status. In the first group, demonstrating a chromosome stability, beta-catenin mutation associated with chromosome 8p losses were frequently found as the single genetic alterations. beta-catenin mutations were associated with large tumor size and with negative hepatitis B virus status. In the second group, demonstrating a chromosome instability, the most frequent allelic losses were on chromosome 1p, 4q, 6q, 9p, 13q, 16p, 16q, and 17p; Axin1 and p53 were frequently mutated. All of these alterations, except losses on 6q and 9p, were associated with hepatitis B virus infection. P53 mutations, 17p, 13q losses, and a high value of the fractional allelic loss index were associated with poor differentiated tumors, independently of risk factors. Finally, in the whole series, chromosome 9p and 6q losses were associated with poor prognosis. CONCLUSIONS: Two main pathways defined by genetic alterations show different risk factors and clinical characteristics. Furthermore, loss of chromosome 9p or 6q is an independent prognostic indicator.

Adolescent↗
PubMed2001

MSH2 and MLH1 immunodetection and the prognosis of colon cancer.

MSH2 and MLH1 are proteins involved in DNA reparation. They are mutated in some forms of colon cancer, i.e. hereditary non-polyposis carcinomas and a subset of sporadic carcinomas. We have studied the expression of MSH2 and MLH1 in a retrospective series of 225 colorectal carcinomas by immunohistochemistry. The results were compared to molecular tests of microsatellite instability using amplification by PCR of BAT-25 and BAT-26 repeated sequences and to histoclinical data. Positivity of both proteins was never associated with MSI phenotype. MSH2 and/or MLH1 negative tumors were frequently tumors of the proximal colon; in this subpopulation or proximal tumors, MSH2 and/or MLH1 negativity was associated with a longer disease-free survival.

Adaptor Proteins, Signal Transducing↗
PubMed2001

[Adenocarcinomas of the distal esophagus. Adenocarcinomas of the cardia].

Adenocarcinomas of the distal esophagus and the gastric cardia have many similar characteristics and common risk factors. Gastric cardia tumors are more closely related to esophageal adenocarcinomas than to distal gastric carcinomas. Adenocarcinomas of the distal esophagus and gastric cardia should be regarded as one clinical entity. However the two types of tumor differed in prevalence of molecular characteristics that are interesting to analyze, to identify the risk factors specially associated with each entities.

Adenocarcinoma↗
PubMed2000

Increased expression of the mRNA encoding the somatostatin receptor subtype five in human colorectal adenocarcinoma.

Numerous studies have suggested that the antiproliferative potency of somatostatin (SS) analogues may be an efficient tool to improve the prognosis of colorectal cancer. In order to facilitate current efforts to design potent antitumour SS analogues, we studied the distribution of human SS receptors (hsst1-5) mRNAs in a large set of tumoural and normal colonic tissues. Localisation of hsst1-5 mRNAs in normal and tumoural tissues was performed by in situ hybridisation using radioactive antisense or sense riboprobes. Semi-quantitative analysis of hsst5 mRNA was performed using a computerised image analysis system. Hsst binding sites were characterised by studying the relative potency of SS14, SS28 or SS analogues in displacing [(125)I]Tyr degrees -d-Trp(8)-SS14 bound to HT29-D4 cells. Hsst5 mRNA was by far the most expressed subtype in both normal and transformed epithelial cells as well as in the HT29-D4 cell line. An increased expression of hsst5 mRNA was found in tumours. Hsst1 mRNA was expressed preferentially as clusters in immune cells in lamina propria and in stroma close to the tumour. A low expression of hsst4, hsst3 and hsst2 was seen in normal and tumoural tissue. In HT29-D4, binding experiments with SS14 demonstrated the existence of one SS binding class (K(d)=524 nM, B(max)=1fmol/10(6 )cells). In competition binding studies, SS28 and BIM23268 (an analogue that shows preferential specificity towards hsst5) effectively inhibited binding of [(125)I]Tyr degrees -d-Trp(8)-SS14 (IC(50)=15 and 157 nM respectively), while BIM23197 (an analogue that shows preferential affinity for hsst2) was ineffective. Our results show a high expression of hsst5 mRNA in human tumoural colonic tissue, while hsst5 protein is the predominant hsst protein subtype in a tumoural colonic cell line.

Adenocarcinoma↗
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

Distribution of heme oxygenase 2 in nerves and c-kit(+) interstitial cells in human stomach.

Different populations of interstitial cells (ICs) may serve as gut pacemakers or as intermediaries between enteric nerves and smooth muscle cells. However, very little is known about the substances that ICs might use to communicate with other cells and no data are available in humans. Because carbon monoxide (CO) is emerging as a putative mediator in the regulation of gastrointestinal motility, this study examined the presence of heme oxygenase (HO2), the constitutive form of the enzyme for CO production, in human stomach with particular attention to ICs. The distribution of HO2 in nerves and ICs in human antrum was studied using specific antibodies. The immunostaining was observed using confocal laser scanning microscopy. HO2 immunoreactivity was found in myenteric neurons and nerve fibers supplying the circular muscle layer and in intramuscular c-kit(+) ICs, but not in c-kit(+) ICs surrounding the myenteric ganglia. The presence of HO2 in different cell types suggests that CO may serve as an intercellular messenger between myenteric neurons and ICs and between ICs and smooth muscle cells in human stomach.

Adult↗
PubMed1999

Distant lymph node metastases in esophageal cancer: impact of endoscopic ultrasound-guided biopsy.

BACKGROUND AND STUDY AIMS: The aim of this retrospective study was to evaluate the impact of endoscopic ultrasound (EUS)-guided biopsy in patients with esophageal carcinoma where distant lymph nodes which were possibly metastatic were visualized using EUS. PATIENTS AND METHODS: Out of 198 patients (150 men, mean age 66 years) examined over a 4-year period by EUS for local staging of esophageal cancer (121 squamous cell carcinomas and 77 adenocarcinomas), there was EUS visualization of distant lymph nodes in 40 (20%). EUS-guided biopsy was carried out in the latter patients, of cervical nodes with mediastinal tumors (n = 19), of celiac nodes with cervical tumors (n = 2) or superior mediastinal tumors (n = 9), and upper mediastinal lymph nodes in the case of distal adenocarcinomas (n = 10). RESULTS: On EUS-guided biopsy, results were positive in 31 patients, eight were correctly negative (as confirmed by surgery), and in one patient there was a technical failure, with positive findings on subsequent surgery. The sensitivity and specificity of the diagnosis of malignant lymph nodes were therefore 97% and 100% respectively. The positive results of EUS-guided biopsy modified the tumor staging in 31 of these cases (77.5%), proving distant lymph node metastasis which is classified as stage M1. With regard to actual clinical management, surgery was withheld from 24 patients (60% of 40 cases) who were then treated with concomitant radiotherapy and chemotherapy. CONCLUSION: EUS-guided biopsy of distant lymph nodes was indicated in 20% of patients with esophageal cancers, and the biopsy results led to upgrading of the tumor stage in about 80% of cases and influenced the treatment decision in about 60%.

Adenocarcinoma↗
PubMed1999

Endoscopic mucosal resection (EMR): results and prognostic factors in 21 patients.

BACKGROUND AND STUDY AIMS: The aim of this study was to evaluate the efficacy of endoscopic mucosectomy (EM), and to present our experience with the endoscopic removal of superficial tumors of the gastrointestinal tract. PATIENTS AND METHODS: A total of 21 patients were included in the study (16 men, 5 women), between September 1995 and May 1997. In 16 cases the site of the lesions was an esophageal carcinoma, in two cases a gastric carcinoma, and in three cases a sessile polyp of the duodenum with severe dysplasia. Surgery was not recommended for the patients with esophageal or gastric tumors (on account of cardiac disease, cirrhosis or poor health). All patients underwent an endoscopic ultrasound (EUS) examination. The lesions were classified as usT1N0 in 20 cases, and usT0N0 in one case, according to the pretreatment EUS findings. We used the technique of polypectomy after submucosal injection of 10-15 ml of saline serum. RESULTS: Complications were encountered in 2/21 patients (9.5 %). Bleeding occurred in one case, but hemostasis was achieved endoscopically. In the other case, the patient presented with a thoracic pain and was treated by morphine injection. Endoscopic resection was considered to be complete in 19/21 patients (90.4%). In the other two cases, both involving esophageal tumors, histologic examination indicated only a partial tumor removal. However, these two patients had survived with negative EUS and endoscopic biopsy findings at 18 and 22 months later, respectively. None of the patients whose resections were considered complete presented with local recurrence, but three patients developed another superficial esophageal cancer, which was also treated by endoscopic mucosal resection (EMR). The mean follow-up was 20 months. CONCLUSIONS: EMR is a safe and efficient treatment of early gastrointestinal tumors. The development of high-frequency EUS probes may further improve the results of this technique in the future.

Adult↗
PubMed1999

Detection of telomerase in hepatocellular carcinomas using a PCR ELISA assay: comparison with hTR expression.

BACKGROUND: While telomerase is undetectable in most normal somatic tissues, telomerase activation has been detected in many immortal cell lines and various cancers. AIM: To investigate telomerase expression in hepatocellular carcinoma, and to assess the expression of the RNA component of telomerase, hTR. METHODS: 39 hepatocellular carcinomas were studied using a telomerase polymerase chain reaction (PCR) enzyme linked immunosorbent assay, which does not require radioactive PCR amplification and yields a semiquantitative measurement. Expression of hTR was also assessed by a non-radioactive in situ hybridisation procedure. The correlations between these two markers and the clinicopathological data were analysed. RESULTS: Telomerase activity was detected in 23 of 39 hepatocellular carcinoma specimens (59%). Comparison of hepatocellular carcinoma with and without telomerase expression, or with high and low telomerase (10 cases v 13 cases), showed no differences in the principal clinicopathological data. Although median survival was lower in the group with detectable telomerase activity than in that with undetectable activity (510 v 720 days) the difference was not significant (log-rank test, p = 0.08). hTR expression was detected in 11 of 14 cases of hepatocellular carcinoma tested (78%) and in four of 12 samples of adjacent non-cancerous tissue (33%). Five tumours and four non-cancerous tissues were positive for hTR, whereas no telomerase activity was detected in these. CONCLUSIONS: The presence of telomerase activity in hepatocellular carcinomas is confirmed. No correlation was observed between clinicopathological data and telomerase expression in hepatocellular carcinoma, but survival seemed better in the absence of telomerase expression. hTR seems to be more widely expressed than telomerase.

Adult↗
PubMed1999

No loss of sst receptors gene expression in advanced stages of colorectal cancer.

As demonstrated by several studies, the pan-inhibitory peptide somatostatin (SS) is implicated in a large variety of physiological processes in the gastrointestinal tractus. SS inhibits hormonal and gastric acid secretions, and decreases gastric and intestinal motility, mesenteric blood flow and intestinal absorption. In vitro and in vivo studies showed also that the antiproliferative potency of SS analogs may be a target to improve the prognosis of colorectal cancer. Here we report the expression profile of the five SS receptor subtypes (hsst1-5) mRNAs in a large set of tumoral and normal colon. Using reverse transcription-PCR, we showed that hsst5, hsst1 and hsst2 mRNA subtypes were the most frequently expressed hsst mRNA subtypes in normal and pathological colon. Interestingly, we found that the frequency of hsst5 mRNA expression in the left colon was significantly higher in tumors than in normal samples: 81. 2% (13/16) and 36.4% (4/11) respectively (0.025>P>0.01, chi2 test with Yates' correction). We did not find any influence of Dukes' stage on hsst mRNAs expression. Of interest, no loss of hsst2 and hsst5 mRNA expression in advanced stages was noted. Some differences in the frequency of expression of hsst mRNAs according to the origin of the tissue (left or right colon) were evident. The expression of hsst5 and hsst2 mRNA in advanced colorectal carcinoma associated with the development of new SS analogs boost the relevance of colorectal cancer treatment by somatostatin analogs.

Aged↗
PubMed1999

[Semi-automated quantitative method for detecting the loss of heterozygosity at the long arm of chromosome 4 in hepatocellular carcinoma].

OBJECTIVES: Chromosomal deletions are the most frequent genetic alterations observed in hepatocellular carcinoma. Loss of heterozygosity on chromosome 4q has been observed in 40% of hepatocellular carcinomas suggesting the presence of a tumor suppressor gene which has not yet been identified. METHODOLOGY: We developed a semi-automated quantitative genotyping method which allowed us to characterize 119 hepatocellular carcinomas with 22 fluorescent microsatellite markers distributed on chromosome 4q. RESULTS: 4q loss was observed in 40% of cases. Among these deletions, 19 cases of partial or interstitial loss made it possible to define two common minimal regions of deletion of 25.1 and 37.6 centimorgans localized between markers D4S414 and D4S430 and between markers D4S3033 and D4S408, respectively. CONCLUSION: This work represents the first step towards the identification and characterization of new genes involved in hepatic carcinogenesis.

Adult↗
PubMed1999

[Reporting of resected colonic carcinomas. Assessment of practices in 8 French counties in 1995].

OBJECTIVES: The objective of this work was to study the reporting of resected colonic carcinomas and to compare them with Consensus Guidelines published in January 1998. METHODS: The study included 535 colonic carcinomas collected in 8 French registries in 1995, and chosen by drawing lots. For each report, the presence of the information requested by the Guidelines was looked for. Three synthetic variables were built: 2 scores and one qualitative at 2 classes. The influence of patients, tumour and health care system's characteristics was analysed on the 3 dependent variables. RESULTS: Some important variations were observed for information's percents in reporting. In monovariate analysis, scores were significantly influenced by cancer's sub-location, area of patient's residence, surgical center, type of laboratories and pathologist case volume. In multivariate analysis, significant heterogeneity in practices remained between geographical areas. Types of laboratories and pathologist case volume affected differently dependent variables. CONCLUSION: This study shows the necessity to assess the practices before consensus because of the impact of pathological forms in therapeutic decisions and variations observed.

Aged↗
PubMed1998

Value of endoscopic ultrasonography for assessment of patients presenting elevated tumor marker levels after surgery for colorectal cancers.

BACKGROUND AND STUDY AIMS: This prospective study was undertaken to evaluate the role of endoscopic ultrasound (EUS) in patients presenting with elevated tumor marker levels (CEA, CA 19-9) after surgery for colorectal cancer. PATIENTS AND METHODS: During a 26-month period, colonic EUS was performed in 21 patients who had undergone surgical treatment for colorectal cancers. All patients presented with elevated tumor marker levels at the time of examination but all other diagnostic procedures (US, CT scan of the abdomen and thorax, bone scintigraphy and colonoscopy) did not demonstrate recurrence. Colonic EUS was performed using a linear convex probe (echoendoscopes Pentax: FG 32 UA, 36 U, 38 UX). In cases with normal findings on colonic EUS, upper gastrointestinal tract EUS was also performed. RESULTS: 21 colonic EUS and six upper gastrointestinal tract EUS examinations were performed. Of 21 colonic EUS examinations, 15 showed either local recurrence (n = 9) or peritoneal carcinomatosis (n = 6) and six EUS-guided biopsies were performed. Of these 15 patients, 13 were operated on and results were confirmed in 12 of 13 patients, namely in 8/9 cases with suspected anastomotic recurrence and in all four operated cases with presumed peritoneal carcinomatosis. EUS-guided biopsy had diagnosed three of the four cases before. Upper GI EUS was performed in the six cases with normal colonic EUS; two cases showed mediastinal lymph nodes and one showed celiac lymph nodes. EUS-guided biopsy confirmed the malignancy of these nodes. For the diagnosis of recurrence, sensitivity, specificity and accuracy of lower plus upper gastrointestinal EUS were 94.4%, 66.6% and 90.4% respectively. CONCLUSION: EUS of the colon and--in selected cases--also of the upper gastrointestinal tract is quite useful in this clinical setting. Further studies are needed to evaluate the impact of EUS on outcome in larger patient numbers.

Adult↗