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Les cancers colorectaux (CCR) constituent un véritable problème de santé publique. En France, en 2015, ils se situent au 3ème rang des cancers et au 2ème rang des décès par cancer, en raison d’un diagnostic souvent tardif et de réponses variables aux thérapeutiques. L’amélioration des tests de dépistage ces vingt dernières années n’a pas significativement réduit la morbi/mortalité liée au CCR et une meilleure caractérisation des différents sous-types moléculaires reste importante pour l’identification de nouveaux biomarqueurs. Les tumeurs colorectales sont hétérogènes tant sur le plan clinico-pathologique que moléculaire, issues de différentes voies de cancérogenèse. Les tumeurs de la voie festonnée représentent 20 à 30% des CCR. Elles sont caractérisées par une instabilité épigénétique (CpG Island Methylation Phenotype, CIMP), une instabilité microsatellitaire (MSI) et des mutations fréquentes du gène BRAF. Sur le plan phénotypique, ce sont des tumeurs volontiers mucisécrétantes surexprimant les mucines MUC2 et MUC5AC. L’identification précoce de leurs précurseurs reste actuellement un enjeu, d’autant que la séquence carcinogénétique des tumeurs festonnées serait particulièrement rapide.Dans cette étude, nous avons déterminé les caractéristiques clinico-pathologiques et moléculaires d’une série de cancers et polypes colorectaux et évalué l’intérêt des gènes de mucines MUC2 et MUC5AC pour classer les polypes festonnés et identifier les lésions précurseurs des cancers CIMP/MSI.L’étude a porté sur 418 CCR et 330 polypes coliques, incluant 218 polypes festonnés et 112 adénomes conventionnels, dont nous avons déterminé le profil moléculaire (mutations KRAS/BRAF, MSI, CIMP, méthylation MGMT, MLH1), ainsi que le profil d’expression et de méthylation des gènes de mucines MUC2 et MUC5AC. Les résultats ont été comparés aux données cliniques et anatomo-pathologiques.Nous montrons que l’hypométhylation du gène MUC5AC est un marqueur spécifique des CCR CIMP/MSI, indépendant des données clinico-pathologiques. De plus, nous montrons que l’hypométhylation de MUC5AC est un évènement précoce qui est spécifiquement associé aux polypes hyperplasiques de type microvésiculaire (MVHP) et adénomes festonnés sessiles (SSA), suggérant une filiation entre ces deux lésions, qui seraient les précurseurs des CCR CIMP/MSI. L’hypométhylation de MUC5AC était par ailleurs très spécifique des lésions festonnées mutées BRAF, CIMP ou MSI.En conclusion, nos résultats suggèrent un rôle de la mucine MUC5AC dans le développement des tumeurs coliques de la voie festonnée. L’hypométhylation du gène MUC5AC est un évènement précoce qui pourrait avoir un intérêt pour le diagnostic des polypes festonnés, en particulier lorsque la morphologie est ambiguë, et pour l’identification précoce des lésions à potentiel malin. De plus, nos résultats suggèrent que certains MVHP pourraient progresser en SSA et en CCR CIMP/MSI, d’où l’importance de réaliser des biopsies des polypes festonnés lors de l'endoscopie afin de repérer le sous-type microvésiculaire parmi les polypes hyperplasiques colorectaux, qui pourrait, bénéficier d’une surveillance minimale. / Colorectal cancer (CRC) is a major public health problem yet it remains the third most common and the second deadliest cancer for both men and women in the United States and in Europe, owing to diagnosis at advanced stage and variable response to the treatments. However, the incidence and mortality appear to be steadily declining in countries with programmatic screening and it remains critical to characterize CRC molecular subtypes to identify new biomarkers. CRC display a wide clinicopathological and molecular heterogeneity and arise from different carcinogenesis pathway. Approximately 20% to 30% of CRC occur by the means of the serrated neoplasia pathway. CRC from the serrated pathway are associated with frequent epigenetic instability (CIMP, CpG island methylator phenotype) which causes most sporadic microsatellite instability (MSI) CRC through epigenetic inactivation of MLH1 and frequent BRAF mutation. CRC from the serrated pathway frequently display a mucinous pattern and are prone to express secreted mucins MUC2 and MUC5AC. Early identification of serrated pathway precursor lesions is currently challenging since the progression to adenocarcinoma in this pathway is particularly brief.We assessed in this study clinicopathological and molecular features of colorectal carcinomas and polyps and we analyzed the interest of mucin genes MUC2 and MUC5AC to classify serrated polyps and to identify the precursor lesions of CIMP/MSI carcinomas._x000D_A series of 418 CRC and 330 polyps was included in the study, with 218 serrated polyps and 112 conventional adenomas. We assessed the molecular profile (KRAS/BRAF mutations, MSI, CIMP, MGMT methylation, MLH1) and the expression and methylation profile of MUC2 and MUC5AC genes and further correlation with clinical and pathological data were performed.We show that MUC5AC hypomethylation is a specific marker of CIMP/MSI CRC, independently of other clinical or pathological factors. We show moreover than MUC5AC hypomethylation is an early event of carcinogenesis, specific to microvesicular hyperplastic polyps (MVHP) and sessile serrated adenoma (SSA) suggesting a filiation between these two lesions and also a progression of MVHP to SSA, SSA with dysplasia, and then to MSI/CIMP CRC. MUC5AC hypomethylation was moreover highly specific of BRAF mutated, CIMP or MSI serrated lesions.In conclusion, our results suggest that the MUC5AC mucin is involved/plays a role in the development/progression of colorectal tumors of the serrated pathway. MUC5AC hypomethylation occurs early during carcinogenesis and may be of interest for the diagnosis of serrated polyp especially in the presence of ambiguous morphology and to early detection of polyps carrying a malignant potential. Our results suggest moreover that some MVHP may progress to SSA and CIMP/MSI CRCs highlighting the importance to perform biopsy of serrated polyps during endoscopy to identify microvesicular subtype among colorectal hyperplastic polyps, which could require a minimal surveillance.

A Candida é um microrganismo dimórfico encontrado comumente no trato gastrointestinal, na pele e nas membranas mucosas dos seres humanos. Na forma de levedura, o fungo permanece em equilíbrio e não é patogênico, podendo estar presente na cavidade oral de indivíduos saudáveis. A candidíase oral geralmente é classificada em quatro grandes grupos, e a candidíase crônica hiperplásica (CCH) é representada por uma infecção crônica, caracterizada pela hiperplasia epitelial do hospedeiro. Especificamente, essas lesões são difíceis de serem diferenciadas de leucoplasias e têm sido associadas com o aumento da chance de desenvolvimento de displasias e lesões malignas. O objetivo deste trabalho foi realizar um levantamento dos casos diagnosticados no Serviço de Patologia Cirúrgica da FOUSP, com vistas a demonstrar a ocorrência dessas infecções em boca e avaliar seus aspectos histológicos característicos. Os casos foram selecionados utilizando o sistema Laudo e Imagem do Serviço de Patologia Cirúrgica da FOUSP e para caracterização das amostras, os dados clínicos do paciente e os aspectos da lesão foram coletados. A análise histopatológica das lâminas foi realizada posteriormente através da observação em microscópio de luz, e as colorações de hematoxilina-eosina (HE) e do ácido periódico de Schiff (PAS) foram utilizadas para avaliação das características microscópicas e a presença de Candida, respectivamente. Os profissionais que realizaram as biópsias foram contatados para obter informações a respeito da evolução da lesão e do paciente. De um total de 58675 biópsias realizadas entre janeiro de 2002 e dezembro de 2017, 36 casos foram diagnosticados como CCH. As mulheres foram mais afetadas, havendo predileção pela raça branca e pela quinta e sexta décadas de vida. De um modo geral, clinicamente, as lesões se apresentavam como um nódulo ou placa branca assintomática localizada em língua ou mucosa jugal. Histologicamente, significância estatística foi notada na presença de projeções epiteliais, exocitose, infiltrado inflamatório discreto e mononuclear. Hifas de Candida foram vistas em todas as amostras, distribuídas perpendicularmente à superfície epitelial. Dos 36 diagnósticos realizados, apenas 11 \"follow-ups\" foram obtidos e desses, apenas cinco pacientes tiveram melhoras quando tratados com antifúngico tópico ou sistêmico. Conclui-se que as lesões de CCH correspondem a uma mínima fração dos diagnósticos realizados no Serviço de Patologia da FOUSP e apresentam geralmente aspectos histológicos característicos. Entretanto, a infecção pelo microrganismo como causa da lesão ou sua presença como organismo oportunista em algumas lesões pode ser esclarecida com mais estudos, principalmente prospectivos. / Candida is a dimorphic microorganism commonly found in the gastrointestinal tract, skin and mucous membranes of humans. In the yeast phase, the fungus is not pathogenic and may be present in the oral cavity of healthy individuals. Oral candidiasis is generally classified into four groups, and the hyperplastic variant is represented by a chronic infection, characterized by an epithelial hyperplasia of the host. Specifically, these lesions are difficult to differentiate from leukoplakias and they also have been associated with an increased chance of developing dysplasias and malignant lesions. The aim of this work was to analyze the incidence of CHC diagnosed at the Oral Pathology Service of FOUSP, intending to demonstrate the occurrence of these infections in the oral cavity as well as to evaluate the histology of the specimens to define the anatomopathological aspects that characterize them. The cases were accessed through the \"Laudo e Imagem\" system and for the characterization of the samples, the clinical data of the patients and the aspects of the lesions were collected. Subsequently, the histopathological analysis of the sections was performed under light microscopy, and the hematoxylin-eosin and periodic acid Schiffer staining were used to evaluate the microscopic characteristics and the presence of Candida, respectively. The professionals who performed the biopsies were contacted to obtain information about the evolution of the lesion and the patient. Out of 58675 diagnoses done between January 2002 and December 2017, 36 cases were of CHC. Women were the most affected and there was a predilection for the white race as well as for the fifth and sixth decades of life. In general, clinically, the lesions appeared as an asymptomatic nodule or white plaque on the tongue or buccal mucosa. Histologically, statistical significance was noted in the presence of epithelial hyperplasia, exocytosis and mononuclear inflammatory infiltrate. Candida hyphae, arranged perpendicular to the epithelial surface, were seen in all samples. Of the 36 diagnoses, only 11 \"follow-ups\" were obtained and of these, only 5 patients had improvement when treated with topical or systemic antifungal drugs. It was concluded that the CHC lesions correspond to a minimal fraction of the diagnoses performed at the Oral Pathology Service of FOUSP, and although their histological characteristics is suggestive of infection by Candida, further studies, mainly prospective, are needed to better understand the lesion.

En este trabajo se ha estudiado el efecto de la temperatura de incubación y cultivo sobre el desarrollo y el crecimiento muscular de lubina, Dicentrarchus labrax, Atlántica y Mediterránea. Durante la fase de alimentación endógena el empleo de alta temperatura incrementa preferiblemente la hipertrofia, observándose una fuerte disminución de la tasa hiperplásica en la fase prelarvaria, con independencia de la temperatura. Con el inicio de la alimentación viva comienza una etapa de rápido crecimiento en la que las altas temperaturas de cultivo (17 y 19ºC) incrementan principalmente la hiperplasia fibrilar. Los lotes Atlántico y Mediterráneo mostraron un comportamiento semejante frente a la temperatura durante las fases de rápido crecimiento (larvario y postlarvario). Sin embargo, al final de cada estadío de desarrollo se apreciaron diferencias entre ambas poblaciones. La aplicación de pequeños incrementos de temperatura durante la incubación aumentó el crecimiento larvario posterior, manifiestándose principalmente al final de la metamorfosis larvaria. / The effect of incubating and rearing temperatures was studied on the development and muscle growth of both Atlantic and Mediterranean populations of D. labrax. During the endogenous feeding stage the higher temperature preferently increased muscle fibres hypertrophy. In the prelarval stage the muscle fibre hyperplasia almost ceased, and this fact was hardly modified by the temperature. Later on, during the rapid growth stage of external feeding, the hyperplastic growth of the myotome was significantly higher in the warm reared fishes (17 and 19 ºC). Muscle growth dynamics were very similar in the Atlantic and Mediteranean stocks during most of the larval and early stages of the postlarval phase (rapid muscle growth periods). However, at the end of each developmental stage both stocks showed significant differences. The application of small increases of temperature during the short incubating period of D. Labrax resulted in a gradual higher growth rate at the end of the larval development.

Σκοπος της μελέτης είναι να συγκρίνει τις απλές μεταλλικές ενδοπροθέσεις (stents) με τις εσωτερικά και εξωτερικά επικαλυπτόμενες μεταλλικές ενδοπροθέσεις σε πειραματόζωο χοίρο. Τοποθετήθηκαν μεταλλικά stents σε 9 θηλυκούς χοίρους που ζύγιζαν 25-30 κιλά. Τοποθετήθηκαν stent σε 18 ουρητήρες είτε στον δεξιό είτε στον αριστερό ουρητήρα. Σε έξι ουρητήρες τοποθεητήθηκε ενδοπρόθεση Wallstent (Schneider,Zurich,Switzerland)σε έξι τοποθετήθηκε Passager stent (Βoston Scientific, Natick,MA,USA)και σε έξι Corvita endoluminal graft- CEG(Boston Scientific, Natick, MA, USA). Εγινε έλεγχος της βατότητας με νεφροστομογραφία 24ώρες και 21ημέρες μετά την τοποθέτηση. Σε τεσσερεις περιπτώσεις το Passager stent μετανάστευσε στην ουροδόχο κύστη με αποτέλεσμα την ουρητηρική απόφραξη. Σε όλες τις άλλες περιπτώσεις η ροή των ούρων ήταν φυσιολογική. Το Wallstent stent προκάλεσε ήπια φλεγμονώδη αντίδραση και μεταπλασία του ουροθηλίου; Το CEG stent πιο έντονη αντίδραση και τέλος την πίο έντονη φλεγμονώδη αντίδραση προκάλεσε το Passager stent με συνοδό νέκρωση του ουροθηλίου. Τα επικαλλυμένα stents δεν εμφάνισαν ουροθηλιακή υπερπλασία στην έσω επιφάνεια του stent. Τα πειραματικά αποτελέσματα δείχνουν ότι το απλό Wallstent stent προκαλεί λιγότερη φλεγμονώδη αντίδραση των παρακείμενων ιστών σε σύγκριση με τα επικαλλυμένα stents. Απο την αλλη πλευρά τα επικαλυπτόμενα stents περιορίζουν σημaντικά την ουροθηλιακή υπερπλασία αλλα έχουν την τάση να μεταναστεύουν προς την ουροδόχο κύστη. / We report out experience with the use of metallic self expandable and balloon expandable stents for the treatment of malignant ureteral obstruction. We treated 12 consecutive patients with malignant ureteral obstruction, for a total of 14 ureters with stents placed. We placed metallic balloon exspandable stents in 6 patients and self-expandable metallic stents in the remaining 6. mean patient age was 65 years and mean followup was 9 months.(range 8 to 16). Of the ureters 11 were patent without any additional manipulations during the followup of 8 to 16 months. Secondary interventions were needed in 3 cases because of obstructive urothelial hyperplastic reaction,tumor ingrowth and local recurrence of the primary cancer invading the upper end of the stent. Two patients died 2 and 10 months after placement of the stent. Both types of metal stents have advantages and disadvantages that must be balanced against each other when choosing the ideal device for the treatment of obstruction. Implantation of a metal self-expanding or balloon expanding stent is safe and effective for the palliative treatment of malignant ureteral obstruction in late stage cancer patient.