121 research outputs found
Tumor budding in colorectal cancers
Le « tumor budding » est dĂ©fini comme la prĂ©sence, au niveau du front dâinvasion de la tumeur, de cellules isolĂ©es ou groupĂ©es en petits amas de 5 cellules tumorales au maximum se dĂ©tachant du reste de la tumeur. On peut traduire en français ce terme par celui de bourgeonnement tumoral, mais nous emploierons dans cette mise au point le terme anglais consacrĂ© dans la littĂ©rature. Cette caractĂ©ristique morphologique, qui sâobserve dans un grand nombre de cancers colorectaux (CCR), est considĂ©rĂ©e comme la traduction morphologique du phĂ©nomĂšne de transition Ă©pithĂ©liomĂ©senchymateuse (TEM), Ă©tape-clĂ© dans le processus dâinvasion tumorale et dans la dissĂ©mination mĂ©tastatique. Au cours de ces derniĂšres annĂ©es, le « tumor budding » est clairement apparu comme un facteur pronostique pĂ©joratif dans le CCR, en particulier le CCR de stade II (i.e. sans mĂ©tastase ganglionnaire), raison pour laquelle lâUnion Internationale Contre le Cancer (UICC), dans sa derniĂšre version, a proposĂ© dâinclure ce critĂšre pour porter lâindication dâun traitement adjuvant. Cependant, il apparaĂźt que les mĂ©thodes de dĂ©termination et de quantification du « tumor budding » varient considĂ©rablement dâune Ă©tude lâautre. Câest pourquoi un effort important doit ĂȘtre fait dans ce sens, de la part des pathologistes, avant dâinclure ce critĂšre dans la dĂ©cision thĂ©rapeutique pour les malades atteints de CCR.âTumor buddingâ is defined by the presence, at the invasive tumor front, of isolated neoplastic cells or clusters of up to 5 neoplastic cells, detaching from the rest of the tumor. The term âtumor buddingâ is also used in French. This morphological feature, which is observed in a large number of colorectal cancers (CRC), is closely related to the epithelial-mesenchymal transition (EMT), a key component of the tumoral invasion process and of metastatic scattering. During the past years, strong, consistent evidence shows that âtumor buddingâ is an adverse prognostic factor, mostly in stage II CRC (i.e. without lymph node metastasis). That is why the International Union against Cancer (UICC) in its last version suggested to include this criteria for the management of adjuvant chemotherapy. Nevertheless, the scoring systems of âtumor buddingâ are still lacking standardization and inter-observer reproducibility. Consensus has to be reached by pathologists before this feature can be implemented as part of the therapeutic decisionmaking
MiRNA Genes Constitute New Targets for Microsatellite Instability in Colorectal Cancer
Mismatch repair-deficient colorectal cancers (CRC) display widespread instability at DNA microsatellite sequences (MSI). Although MSI has been reported to commonly occur at coding repeats, leading to alterations in the function of a number of genes encoding cancer-related proteins, nothing is known about the putative impact of this process on non-coding microRNAs. In miRbase V15, we identified very few human microRNA genes with mono- or di-nucleotide repeats (nâ=â27). A mutational analysis of these sequences in a large series of MSI CRC cell lines and primary tumors underscored instability in 15 of the 24 microRNA genes successfully studied at variable frequencies ranging from 2.5% to 100%. Following a maximum likelihood statistical method, microRNA genes were separated into two groups that differed significantly in their mutation frequencies and in their tendency to represent mutations that may or may not be under selective pressures during MSI tumoral progression. The first group included 21 genes that displayed no or few mutations in CRC. The second group contained three genes, i.e., hsa-mir-1273c, hsa-mir-1303 and hsa-mir-567, with frequent (â„80%) and sometimes bi-allelic mutations in MSI tumors. For the only one expressed in colonic tissues, hsa-mir-1303, no direct link was found between the presence or not of mono- or bi-allelic alterations and the levels of mature miR expression in MSI cell lines, as determined by sequencing and quantitative PCR respectively. Overall, our results provide evidence that DNA repeats contained in human miRNA genes are relatively rare and preserved from mutations due to MSI in MMR-deficient cancer cells. Functional studies are now required to conclude whether mutated miRNAs, and especially the miR-1303, might have a role in MSI tumorigenesis
Aspects anatomopathologiques des lĂ©sions prĂ©cancĂ©reuses survenant dans le cadre des maladies inflammatoires chroniques de lâintestin (MICI)
Les malades atteints de rectocolite hémorragique et de maladie de Crohn présentent un risque accru de développer un cancer
colorectal (CCR). Ces cancers compliquant une maladie inflammatoire chronique de lâintestin (MICI) sont prĂ©cĂ©dĂ©s dâune lĂ©sion prĂ©cancĂ©reuse,
la dysplasie (ou nĂ©oplasie intra-Ă©pithĂ©liale), qui offre la possibilitĂ© dâun traitement prĂ©ventif. En dĂ©pit des limites de la surveillance
coloscopique, la dysplasie reste le meilleur marqueur de la prise en charge du risque de CCR dans le cadre des MICI. A la différence des
adĂ©nomes qui prĂ©cĂšdent les CCR sporadiques, la dysplasie survenant dans un contexte de MICI a pour particularitĂ© dâĂȘtre trĂšs hĂ©tĂ©rogĂšne
dâun point de vue macroscopique et histologique. Or, la bonne connaissance de ces lĂ©sions est indispensable pour une prise en charge optimale
de ces malades, le type de dysplasie diagnostiquée conditionnant une prise en charge différente
OncogenĂšse des cancers colorectaux (CCR) au cours des maladies inflammatoires chroniques de l'intestin (MICI)
Les maladies inflammatoires chroniques de l intestin (MICI), qui comprennent la rectocolite hĂ©morragique (RCH) et la maladie de Crohn (MC), se compliquent de cancers colorectaux (CCR). Les CCR sont prĂ©cĂ©dĂ©s d une lĂ©sion prĂ©cancĂ©reuse, la dysplasie. Contrairement Ă la cancĂ©rogenĂšse colorectale sporadique, les mĂ©canismes molĂ©culaires et les altĂ©rations gĂ©nĂ©tiques sous-tendant la cancĂ©rogenĂšse colorectale compliquant les MICI sont mal connus. De plus, les donnĂ©es existant dans la littĂ©rature concernent essentiellement la RCH. L objectif de cette thĂšse a Ă©tĂ© de mieux caractĂ©riser, d un point de vue anatomo-pathologique et molĂ©culaire, les nĂ©oplasies intestinales compliquant les MICI. Nous avons observĂ© des frĂ©quences respectives de la dysplasie adjacente et de la dysplasie Ă distance des CCR identiques dans la MC et dans la RCH. Nous avons montrĂ© que le phĂ©notype d instabilitĂ© des microsatellites (MSI), dĂ» Ă des altĂ©rations des gĂšnes de rĂ©paration de mĂ©sappariement des bases (gĂšnes MMR), Ă©tait impliquĂ© dans une fraction significative de ces nĂ©oplasies. Les mĂ©canismes sous-tendant la dĂ©ficience MMR dans ce contexte Ă©taient diffĂ©rents de ceux observĂ©s dans les tumeurs MSI sporadiques et semblaient plus proches de ceux observĂ©s dans les tumeurs MSI hĂ©rĂ©ditaires. En revanche, les mĂ©canismes de progression tumorale semblaient identiques Ă ceux des autres tumeurs MSI. Enfin, nous avons montrĂ© qu un dĂ©faut de champ impliquant la MGMT (O6 mĂ©thylguanine-DNA mĂ©thyltransfĂ©rase), un gĂšne de rĂ©paration n appartenant pas au systĂšme MMR, pourrait ĂȘtre une Ă©tape initiatrice-clĂ© intervenant avant la dĂ©ficience MMR dans les CCR MSI (sporadiques, hĂ©rĂ©ditaires et compliquant une MICI).Inflammatory bowel disease (IBD), both ulcerative colitis (UC) and Crohn s disease (CD), face an increased risk of colorectal cancer (CRC). CRC develop from a precursor lesion, dysplasia. In contrast to sporadic colorectal carcinogenesis, less is known about molecular mechanisms and genetic alterations underlying colorectal carcinogenesis complicating IBD. Moreover, most data in the literature are focused on UC. The aim of this work was to better characterize intestinal neoplasias complicating IBD from a pathological and molecular point of view. We observed similar frequencies of dysplasia adjacent to and distant from CRC in both CD and UC. We showed that the microsatellite instability (MSI) phenotype, a phenotype due to mismatch repair (MMR) genes defects, was involved in a significant part of these neoplasias. The mechanisms underlying MMR deficiency in the setting of IBD were different from those in sporadic MSI CRC and seemed to be more related to those observed in hereditary MSI CRC. In contrast, the mechanisms of tumoral progression seemed to be similar to those of other MSI tumors. At least, we showed that MGMT (O6 methylguanine-DNA methyltransferase) field defect, a repair gene not belonging to the MMR system, may be a crucial initiating step prior to MMR deficiency in the development of MSI CRC arising in different clinical contexts (sporadic, inherited, and IBD-associated CRC).PARIS-BIUSJ-Physique recherche (751052113) / SudocSudocFranceF
Etude du profil d'expression protéique des cancers coliques de stade II et III par technique de Tissue microarray (impact sur la récidive aprÚs chirurgie)
PARIS6-Bibl. St Antoine CHU (751122104) / SudocSudocFranceF
Primary Resistance to Immune Checkpoint Inhibitors in Metastatic Colorectal CancerâBeyond the MisdiagnosisâIn Reply
International audienceNo abstract availabl
Epidemiology, Risk Factors and Diagnosis of Small Bowel Adenocarcinoma
Adenocarcinomas of the small intestine are rare tumors but their incidence is increasing. There is a slight male predominance. The median age at diagnosis is the 6th decade. The most frequent primary location is the duodenum. There is no clearly identified environmental risk factor, but adenocarcinomas of the small intestine are associated in almost 20% of cases with predisposing diseases (Crohn’s disease, Lynch syndrome, familial adenomatous polyposis, Peutz–Jeghers syndrome and celiac disease)
Lâautopsie de NapolĂ©on Bonaparte. Mise au point anatomo-pathologique pour le bicentenaire de la mort de NapolĂ©on Ier sur lâĂźle de Sainte-HĂ©lĂšne en 1821
International audienceNapoleon Bonaparte died on 5 May 1821 on the island of St Helena after almost six years of exile. The next day, Dr Francesco Antommarchi, a Corsican doctor chosen by the Bonaparte family to treat the exiled emperor, performed the autopsy in the presence of sixteen people, including seven British doctors. Two hundred years after the event of 6 May 1821, the cause of Napoleon's death is still a mystery. Various hypotheses, such as arsenic intoxication, cardiac arrhythmia or, more recently, anaemia caused by gastrointestinal haemorrhage associated with chronic gastritis, have been put forward in the medical-historical literature. The main reasons for all these debates and misunderstandings are the presence of several autopsy reports, their often unscientific interpretation, as well as a certain taste for mystery. However, from a scientific point of view, the question arises as to whether autopsy reports are really conclusive as to the real cause of death. Thus, on the occasion of the bicentenary of Napoleon I's death in St. Helena, an international group of anatomo-pathologists specialising in digestive pathology set themselves the goal of analysing Napoleon I's autopsy reports according to their level of medical evidence (high, moderate and low). The autopsy reports of 1821 support the hypothesis of advanced malignant neoplasia of the stomach associated with gastric haemorrhage as the immediate cause of Napoleon I's death on 5 May 1821.NapolĂ©on Bonaparte est mort le 5 mai 1821 sur lâĂźle de Sainte-HĂ©lĂšne aprĂšs presque six annĂ©es dâexil. Le lendemain, le docteur Francesco Antommarchi, mĂ©decin corse choisi par la famille Bonaparte pour soigner lâempereur exilĂ©, procĂ©da Ă lâautopsie en prĂ©sence de seize personnes, dont sept mĂ©decins britanniques. Deux cents ans aprĂšs cet Ă©vĂ©nement du 6 mai 1821, des mystĂšres entourent encore la cause de la mort de NapolĂ©on. DiffĂ©rentes hypothĂšses, telle quâune intoxication Ă lâarsenic, une arythmie cardiaque ou, plus rĂ©cemment, une anĂ©mie causĂ©e par une hĂ©morragie gastro-intestinale associĂ©e Ă une gastrite chronique, ont Ă©tĂ© avancĂ©es dans la littĂ©rature mĂ©dico-historique. Les principales raisons de tous ces dĂ©bats et malentendus sont la prĂ©sence de plusieurs rapports dâautopsie, de leur interprĂ©tation souvent peu scientifique, de mĂȘme quâun certain goĂ»t pour le mystĂšre. Toutefois, dâun point de vue scientifique, la question de savoir si les rapports dâautopsie permettent vraiment de conclure quant Ă la cause rĂ©elle du dĂ©cĂšs se pose. Ainsi, Ă lâoccasion du bicentenaire de la mort de NapolĂ©on 1er Ă Sainte HĂ©lĂšne, un groupe international dâanatomo-pathologistes spĂ©cialisĂ©s en pathologie digestive sâest donnĂ© pour objectif dâanalyser les rapports dâautopsie de NapolĂ©on 1er selon leur niveau dâĂ©vidence mĂ©dicale (Ă©levĂ©, modĂ©rĂ© et faible). Les rapports dâautopsie de 1821 sont en faveur de lâhypothĂšse dâune nĂ©oplasie maligne avancĂ©e de lâestomac associĂ©e Ă une hĂ©morragie gastrique comme cause immĂ©diate de la mort de NapolĂ©on Ier le 5 mai 1821
The gastric disease of Napoleon Bonaparte: brief report for the bicentenary of Napoleonâs death on St. Helena in 1821
Item does not contain fulltextAfter the defeat at the battle of Waterloo on June 18, 1815, Napoleon Bonaparte was sent into exile to the Island of St. Helena where he died 6 years later on May 5, 1821. One day after his death, Napoleon's personal physician, Dr. Francesco Antommarchi, performed the autopsy in the presence of Napoleon's exile companions and the British medical doctors. Two hundred years later, mysteries still surround the cause of his death and different hypotheses have been postulated in the medical and historical literature. The main reasons seem to be the presence of several autopsy reports, their interpretation and perhaps the greed for thrill and mystery. Therefore, for the bicentenary of Napoleon's death, an international consortium of gastrointestinal pathologists assembled to analyse Napoleon's autopsy reports based on the level of medical evidence and to investigate if the autopsy reports really do not allow a final statement
305âClinical Significance of Pseudopolyps for Patients With Inflammatory Bowel Disease
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