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S Grandjouan

Publications and source records attributed to S Grandjouan.

At least 19 recordsLinked to original sources
PubMed2006

[Identification and management of HNPCC syndrome (hereditary non polyposis colon cancer), hereditary predisposition to colorectal and endometrial adenocarcinomas].

BACKGROUND: The HNPCC syndrome (hereditary nonpolyposis colon cancer) is an inherited condition defined by clinical and genealogical information, known as Amsterdam criteria. In about 70% of cases, HNPCC syndrome is caused by germline mutations in MMR genes, leading to microsatellite instability of tumor DNA (MSI phenotype). Patients affected by the disease are at high risk for colorectal and endometrial carcinomas, but also for small intestine, urothelial, ovary, stomach and biliary tract carcinomas. HNPCC syndrome is responsible for 5% of colorectal cancers. Identification and management of this disease are part of a multidisciplinary procedure. METHODS: Twelve experts have been mandated by the French Health Ministry to analyze and synthesize their consensus position, and the resulting document has been reviewed by an additional group of 4 independent experts. MAIN RECOMMENDATIONS: The lack of sensitivity of Amsterdam criteria in recognizing patients carrying a MMR germline mutation led to an enlargement of these criteria for the recruitment of possible HNPCC patients, and to a 2-steps strategy, asking first for a tumor characterization according to MSI phenotype, especially in case of early-onset sporadic cases. The identification of germline MMR mutations has no major consequence on the cancer treatments, but influences markedly the long-term follow-up and the management of at-risk relatives. Gene carriers will enter a follow-up program regarding their colorectal and endometrial cancer risks, but other organs being at low lifetime risk, no specific surveillance will be proposed.

Adenocarcinoma↗
PubMed2005

[HNPCC syndrome (hereditary non polyposis colon cancer): identification and management].

BACKGROUND: The hereditary non-polyposis colon cancer (HNPCC) syndrome is an inherited condition defined by clinical and genealogical information, known as Amsterdam criteria. In about 70% of cases, HNPCC syndrome is caused by germline mutations in MMR genes, leading to microsatellite instability of tumor DNA (MSI phenotype). Patients affected by the disease are at high risk for colorectal and endometrial carcinomas, but also for other organs tumors. HNPCC syndrome is responsible for 5% of colorectal cancers. MAJOR ASPECTS: The lack of sensitivity of Amsterdam criteria in recognizing patients carrying a MMR germline mutation led to an enlargement of these criteria for the recruitment of possible HNPCC patients, and to a two-steps strategy, asking first for a tumor characterization according to MSI phenotype, especially in case of early-onset sporadic cases. FURTHER DEVELOPMENTS: The identification of germline MMR mutations has no major consequence on the cancer treatments, but influences markedly the long-term follow-up and the management of at-risk relatives. Gene carriers will enter a follow-up program regarding their colorectal and endometrial cancer risks; other organs being at low lifetime risk, no specific surveillance will be proposed.

Adolescent↗
PubMed2001

[Practical data on digestive tract oncogenetics].

Inherited conditions predisposing to cancers have long been recognized. Specific medical recommendations have more recently been proposed to avoid the development of advanced cancers in such high-risk families. The identification of the first genes involved in monogenic dominant cancer-prone conditions have opened the ways to their predictive diagnosis in asymptomatic members in at-risk families. The development of such procedures has required specific involvement for clinicians and molecular geneticians. The example of familial predispositions to colonic cancers has been chosen to illustrate the practical issues, and to help the physicians in charge of at-risk families to offer their patients an access to these emerging possibilities in cancer prevention. A table summarizes the practical issues requested to refer a family and initiate the procedure of molecular testing.

Digestive System Neoplasms↗
PubMed2000

Extensive molecular screening for hereditary non-polyposis colorectal cancer.

The genetic abnormalities underlying hereditary non-polyposis colorectal cancer (HNPCC) are germline mutations in one of five DNA mismatch repair genes or in the TGFbetaRII gene. The aim of our study was to evaluate the significance of simple tests performed on tumours to select appropriate candidates for germline mutational analysis. We studied three groups of patients, HNPCC kindreds fulfilling the International Collaborative Group (ICG) criteria (n = 10), families in which at least one of the criteria was not satisfied (n = 7) and sporadic colorectal cancer (CRC) diagnosed before the age of 50 (n = 17). We searched for microsatellite instability (MSI), presence of hMSH2 and hMLH1 germline mutations, expression of hMSH2, hMLH1 and p53 proteins in tumoural tissue samples by immunostaining. Fifteen out of 17 (88%) of HNPCC and incomplete HNPCC cases were MSI and eight pathogenic germline mutations in hMSH2 or hMLH1 were detected in these two groups (53%). All the 17 early-onset sporadic cases were MSS and no germline mutations were detected among the seven investigated cases. Thirteen out of 15 (81%) familial cases were MSI and p53 protein-negative, whereas 13/14 (93%) sporadic cases were MSS and strongly p53 protein-positive. This extensive molecular investigation shows that simple tests such as MS study combined with hMSH2 and hMLH1 protein immunostaining performed on tumoural tissues may provide valuable information to distinguish between familial, and probably hereditary, and sporadic CRC cases.

Adaptor Proteins, Signal Transducing↗
PubMed1997

5-Fluorouracil (5-FU) continuous intravenous infusion compared with bolus administration. Final results of a randomised trial in metastatic colorectal cancer.

The aim of this Phase III, balanced randomised trial was to compare continuous intravenous infusion (CVI) of 5-FU with bolus (B) administration for metastatic colorectal cancer (CRC). One hundred and fifty-five non-pretreated patients were randomised to receive CVI 5-FU at a dose of 750 mg/m2/day (d), 7 d every 21 d (n = 77), or bolus 5-FU 500 mg/m2/d x 5 d every 28 d (n = 78). Incremental dose escalation at 50 mg per step was recommended in the absence of toxicity. All the patients had measurable metastatic disease (M), particularly, liver and a good performance status (WHO grade 0-1). Dose intensity was significantly higher in CVI than in the bolus group: 1369 mg/m2/week versus 558 mg/m2/week (P = 0.0001). Grade II-IV stomatitis was more frequent in the CVI group (31% versus 9%; P < 0.0001) as was hand and foot syndrome (14% versus 3%; P < 0.001). Diarrhoea (22% versus 12%) and grade III granulocytopenia (2% versus 6%) were comparable. Responses were more frequent in the CVI (26%) than in the bolus group (13%) (P < 0.04); progression-free survival was higher for the CVI group (P = 0.04), but there was no statistical difference in overall survival (median: 10 months (m) compared to 9 m), and 1 year survival (SD) 42% (6%) versus 40% (6%). In the multivariate analysis, survival was better for patients with a good PS, well-differentiated adenocarcinomas and a primary tumour without serosal extension. In conclusion, with a higher dose intensity, CVI 5-FU improved tumour control, but not overall survival.

Antimetabolites, Antineoplastic↗
PubMed1995

Carcinomas of the colon with multidirectional differentiation. Report of two cases and review of the literature.

Two cases of colonic carcinomas with multidirectional differentiation are presented. Both tumors showed light microscopic and immunohistochemical evidence of areas of adenocarcinomatous, squamous cell carcinomatous, and neuroendocrine differentiation. Only six similar cases have been previously reported. These highly malignant tumors support the recent concept of a multipotential stem cell within the mucosa of the gastrointestinal tract capable of differentiation in several directions.

Adenocarcinoma↗
PubMed1995

Nonsteroidal anti-inflammatory drug-induced colonic strictures: two cases and literature review.

We report two patients with large bowel submucosal diaphragm disease associated with nonsteroidal anti-inflammatory drugs (slow release form of diclofenac and phenylbutazone) who were admitted in 1990 and 1991 because of iron deficiency. At colonoscopy, the lumen of the ascending colon was divided into compartments by multiple thin circumferential mucosal membranes. Barium enema showed two short strictures in one patient. Right hemicolectomy was carried out on one patient. The other patient was simply advised to discontinue taking diclofenac and remains well. Such lesions are rare (10 cases have been reported) and resemble those previously described in the small bowel.

Aged↗
PubMed1994

[Colorectal cancers at the time of molecular genetics].

One must always keep in mind the distinction between constitutional genetic mutation and acquired or somatic genetic mutation. Our knowledge of the syndromes resulting from germ line mutations and the detailed clinical description of the diseased patients have been the key to research into the field of susceptibility to colorectal cancer. Research has now entered a new era due two major advances. First it is now possible to identify persons at risk, carriers of constitutional defects involving genes responsible for colorectal cancer. Secondly, it is now possible to better identify high risk lesions based on histological examination and use of molecular markers. In the future, further progress will allow us to analyse acquired mutations. These advances open the way to new diagnostic approaches and raise a considerable number of questions concerning the ethics of molecular diagnosis and treatment.

Biomarkers, Tumor↗
PubMed1991

[Colonic polyposis and cancers of the colon. Molecular markers, predisposition and diagnosis of familial forms].

Five to 10% of colorectal carcinomas are obvious inherited familial syndromes. The inherited molecular basis of the predisposition is uniformly present in normal cells of such patients. The identification of the genes underlying cancers, performed with the intent to clone, would first serve as a basis for a pre-symptomatic diagnosis. The APC gene, located on the long arm of chromosome 5, is the only molecular target already identified as involved in the predisposition to familial adenomatous polyposis. Other genes are involved in the progression of sporadic colorectal neoplasias. Their identification would help in the comprehension of colonic carcinogenesis. Molecular analysis of these markers determines improvements in the management of a frequent and most severe disease, in which progress in screening and treatment has been very slow over the past twenty years.

Adenomatous Polyposis Coli↗