We report two cases of familial juvenile polyposis coli. SMAD4 gene mutation was found in our two patients, leading to the definite diagnosis. Colonic cancer occurred in the first patient. Long-term outcome was favorable after colectomy. In the second patient, prophylactic total colectomy was performed. Rectal bleeding, diarrhea, stomach obstruction and vomiting developed during the follow-up. Proctectomy, distal partial gastrectomy and total gastrectomy were successively performed.

Androgens play a crucial role in the development, maintenance and regulation of male phenotype and reproductive physiology through the androgen receptor, a transcription factor. Testosterone or dihydrotestosterone binding induces a trans-conformation of the androgen receptor and allows its translocation into the nucleus, where it recognizes specific DNA sequences. Recent developments in molecular genetics, as well as structural analysis of the androgen receptor, allow a better understanding of the structure/function relationship of this nuclear receptor. Molecular analyses of androgen insensitivity syndrome, as well as hormone-resistant prostate cancer, Kennedy's disease and isolated male infertility, have been proved useful as privileged models for this purpose. In the absence of identified AR receptor mutations in androgen insensitivity syndromes, abnormalities of transcriptional cofactor should be considered. Finally, identification of androgen-dependent genes will be helpful for evaluating the degree of the molecular defect of androgen action within target cells.

To report the case of significant growth of a myoma in a premenopausal woman with a suspicion of BRCA1 and BRCA2 mutation, treated by tamoxifen for a hormonodependent breast cancer and to point out the carcinologic ovarian risks with a mutation BRCA1-BRCA2 in this context. Case. Four months after surgical treatment, chemotherapy and the beginning of tamoxifen, an explosive growth of the abdomen justified pelvic echography and laparoscopy confirming the diagnosis of uterine myoma. A polymyomectomy by laparotomy was performed.

Diagnosis of haematological malignancies is based on multiparametric analysis such as morphology, phenotype and genotype studies. Some entities are only defined by one of these approach. Flow-cytometry (FCM) is useful to determined the normal counterpart of the tumoral process and its differentiation status within the involved lineage. Furthermore, FCM is able to detect clonality in B or T proliferations and criteria for malignancies such as abnormal phenotype. Finally it also specifies prognosis criterias. Among the different haematological malignancies, acute lymphoblastic leukaemia (ALL) can be diagnosed using FCM, whereas acute myeloblastic leukaemia diagnosis is only confirmed by this methodology, which could moreover determine prognosis factors. A scoring system (EGIL) determine the normal counterpart of tumoral cells using a panel of different markers. Immunophenotyping is also useful in chronic lymphoproliferative disorders, such as chronic lymphocytic leukaemia (CLL) by using a similar scoring system (so-called Matutes scoring). Since FCM is able to detect simultaneously numerous cell markers it could be more accurate than immunohistochemistry for the diagnosis of follicular lymphoma, mantle cell lymphoma or hairy cell leukaemia. Finally, during treatment follow-up, minimal residual disease characterised by the detection of rare specific events, may be examined using FCM, in some situations.

The "Standards, Options and Recommendations" (SOR) project, started in 1993, is a collaboration between the Federation of French cancer centers (FNCLCC), the 20 French cancer centers, and specialists from French public universities, general hospitals and private clinics. The main objective is the development of clinical practice guidelines to improve the quality of health care and the outcome of cancer patients. The methodology is based on a literature review and critical appraisal by a multidisciplinary group of experts, with feedback from specialists in cancer care delivery.

The authors report a case of familial pyoderma gangrenosum following a mammoplasty reduction. This disease should be known by all surgeons, because its occurrence may follow all surgical procedure. The only efficient treatment is based on steroids and large surgical excisions must be contraindicated.

Through a national retrospective study, the authors report the clinical and hematological characteristics of 124 acute lymphoblastic leukemia of the adult diagnosed during 5 years (1993-1997). The national prevalence is of 0.28/100.000 inhabitants/year. The sex-ratio is of 1.3. Sixty six per cent of patients were 16-35 years of age, and only 10% of them were more than 60 years of age. A tumoral syndrome was present at 71% of the cases with peripheral adenopathies in 55%, splenomegaly in 40%, hepatomegaly in 19% and a mediastinal tumor in 18% of the cases. The bone pain were rarely signaled (10%) and neuro-meningeal affection was found in only 3% of cases. There was no testicular lesions. The white blood cells count was less than 30.000/mm3 in 60% whereas an important hyperleucocytosis superior than 100.103/mm3 was observed in 20% of the cases. Anemia and thrombopenia were noted in 94% and 90% of the cases respectively. Acute lymphoblastic leukemia typing by cytological study of Bone marrow according to the Fransh-American-Britain criteria (FAB) had found 43%, 48% and 4% for type 1,2 and 3 respectively. In 5% of the cases the type of the acute lymphoblastic leukemia was not precised (diagnosis based on the Bone biopsy).

Prostate cancer (CaP) is the most frequent cancer among men over 50 and its frequency increases with age. It has become a significant public health problem due to the ageing population. Epidemiologists report familial aggregation in 15 to 25% of cases and inherited susceptibility with autosomal dominant or X-linked model in 5 to 10% of cases. Clinical and biological features of familial CaP remain controversial.

Our team was at the origin of the discovery of the relationship between rearrangements in genes encoding the retinoic acid receptors and tumorigenesis in human. Studying the molecular basis for hepatitis B virus (HBV)-associated liver cancer, we demonstrated that the viral DNA can behave as an insertional mutagen. This work also led to the identification of the first gene (RAR beta) encoding a receptor for the active derivative of vitamin A, retinoid acid. In collaboration with L. Degos, we then demonstrated the existence a systematic alteration of another retinoic acid receptor, RAR alpha, in acute promyelocytic leukemia (APL). Most recent work allowed us to involve a novel subnuclear organelle, the so-called PML Nuclear Bodies, in APL pathogenesis, underlying the major role played by the functional organization of the nucleus both in the normal and the pathological cell.

Molecular biology studies have led to the identification of two different types of colorectal carcinomas. The first group, called LOH (for loss of heterozygosity), represents 80% of colorectal cancers and is characterised by aneuploidy, allelic losses and a location in the distal colon. The second group displays phenotypic microsatellite instability (MSI-positive tumours), has a near-diploid karyotype and a relatively low frequency of allelic losses. It accounts for 15% of all colorectal cancers and for about 30% of right-sided cancers. Four different pathways have been identified as responsible for tumour progression: the WNT/Wingless, the K-ras, the Transforming growth factor (TGF) and the P53 pathways. The involvement of these pathways depends on the tumour type. In LOH-positive tumours, the WNT/Wingless pathway is activated through an APC mutation, whereas MSI+ tumours do so through a catenin stabilising mutation. The TGFb growth inhibitory pathway is altered either by mutations in the signal transduction molecules SMAD2 and SMAD4 in LOH positive tumours or by mutations of TGFbRII in MSI+ tumours. In the p53 pathway, mutations in BAX may contribute to the adenoma-carcinoma transition just as p53 mutations may do in LOH positive tumours. Until now, cancer phenotype determination has had no clinical implications. However, the predictive value of the MSI status was recently stressed as a predictive factor for response to chemotherapy. Immunohistochemistry could represent a complementary strategy to molecular biology in assessing MSI status. This simple test would allow to screen all colorectal carcinomas for MSI status, which would provide valuable management information in addition to the histological assessment for tumour stage and grade.

Gastrointestinal stromal tumors (GISTs) are non differentiated sarcoma of the gastrointestinal tract and have for a long time been confused with well differentiated tumors and classified as leiomyosarcoma. These tumors are characterized immunohistochemically by CD 117 staining. This marker represents the expression of c-kit which is a receptor for growth factor with enzymatic activity (tyrosine kinase). Recent studies have found that an inhibitor of specific tyrosine kinase is effective in the treatment of GIST with an estimated response rate of more than 60%. This new drug could significantly improve the prognosis of these aggressive chemoresistant tumors.

Familial Multiple Polyposis Coli is an autosomal dominant hereditary illness characterized by the appearance in childhood of hundreds of colorectal polyps which inexorably undergo malignant transformation. It is accompanied by extracolonic manifestations some of which may also be life-threatening. Total colectomy should not be postponed beyond age 20 except in rare cases of an attenuated form of the disease (AAPC). Subtotal Colectomy with ileorectal anastomosis is a well-tolerated procedure with quite acceptable functional results, but the need for eventual proctectomy is about 30% at 20 years and the risk of rectal cancer is about 10% at 20 years even with close endoscopic surveillance. Total colectomy with ileal pouch-anal anastomosis is therefore the intervention of choice since it eliminates the risk of late rectal carcinoma albeit with more serious morbidity and less good functional results. Desmoid tumors are the leading cause of death in patients who have undergone total colectomy. NSAID's, tamoxifen, and chemotherapy are used preventively and therapeutically; surgical excision is sometimes required. Duodenal adenomas are present in almost 100% of these patients post-colectomy and the risk of duodenal cancer is 200 times higher than in the general population. Endoscopic surveillance of the duodenum is essential and prophylactic duodenal resection should be considered when duodenal polyposis is extensive.

Bourneville's disease, first described in 1862, is a phacomatosis that is either autosomal dominant or sporadic. Its typical clinical signs include mental retardation, epilepsy and cutaneous adenomas. The pulmonary form is rare, less than 1%, and is secondary to occlusion of the bronchus, vascular and lymphatics by immature smooth muscle cells. Chylothorax may appear in more than 50% of all cases. No guidelines currently exist for treatment of recurrent chylothorax. However, several possibilities are described in the literature.

Retrocervical cystic hygroma is a congenital defect associated to chromosomic anomalies. We report a retrospective study about 35 cystic hygroma autopsies colliged in C.M.N.T in 10 years. Antenatal sonography has a sensibility 94.5%. Genetic abnormalities dominated by trisomie 13 Turner syndrome dad found in 11.5%. Medical abortion has done in 48.5%. A multidisciplinary management autorized to understand etiopathogeny of this defect.

A better knowledge of fundamental mechanisms of carcinogenesis allows the development of novel therapeutic tools specifically targeting the cancer cell. Our understanding of cellular and molecular mechanisms controlling cellular cycle and cell survival is an important step for new anti-cancer treatments. This review will focus on new therapeutic's strategies in advanced pancreatic cancer.