Despite progress in treatment strategies, only ~24% of pancreatic ductal adenocarcinoma (PDAC) patients survive >1 year. Our goal was to elucidate deregulated pathways modulated by microRNAs (miRNAs) in PDAC and Vater ampulla (AMP) cancers. Global miRNA expression was identified in 19 PDAC, 6 AMP and 25 paired, histologically normal pancreatic tissues using the GeneChip 4.0 miRNA arrays. Computational approaches were used for miRNA target prediction/identification of miRNA-regulated pathways. Target gene expression was validated in 178 pancreatic cancer and 4 pancreatic normal tissues from The Cancer Genome Atlas (TCGA). 20 miRNAs were significantly deregulated (FC≥2 and p <0.05) (15 down- and 5 up-regulated) in PDAC. miR-216 family (miR-216a-3p, miR-216a-5p, miR-216b-3p and miR-216b-5p) was consistently down-regulated in PDAC. miRNA-modulated pathways are associated with innate and adaptive immune system responses in PDAC. AMP cancers showed 8 down- and 1 up-regulated miRNAs (FDR p <0.05). Most enriched pathways ( p <0.01) were RAS and Nerve Growth Factor signaling. PDAC and AMP display different global miRNA expression profiles and miRNA regulated networks/tumorigenesis pathways. The immune response was enriched in PDAC, suggesting the existence of immune checkpoint pathways more relevant to PDAC than AMP.

. Mentor, designed the protocol and critical review. ABSTRACT PURPOSE:To study the effect of alcoholism on intestinal healing and postoperative complications in rats. METHODS:One hundred and sixty rats were divided into two groups: control and treated. The control group received water and the treated group 30% ethanol. After 180 days, colotomy with anastomosis were performed. After, the groups were divided into four subgroups: 20 rats for study at the following moments: 4 th , 7 th , 14 th and 21 st postoperative. The analyzed parameters were: weight gain, breaking strength, tissue hydroxyproline, postoperative complications and histopathological study. RESULTS:Weight gain was greater in the control group (p<0.05). When all the subgroups were clustered, breaking strength was significantly greater in the control (p<0.05). Histopathology and hydroxyproline dosage did not show differences. There were five surgical site infections in the treated group while the control group showed two (p>0.05). Nine fistulas occurred in the treated group whereas the control group two (p<0.05). There were three deaths in the control group and seven in the treated group (p>0.05). CONCLUSIONS:Treated group undergo a malnutrition process that is revealed by lower weight gain. Impaired intestinal healing as indicated by smaller breaking strength. There were a larger number of postoperative complications in the treated animals.Key words: Wound Healing. Alcoholism. Ethanol. Tensile Strenght. Hydroxyproline. Rats. RESUMO OBJETIVO:Estudar o efeito do alcoolismo no processo de cicatrização intestinal e suas complicações pós-operatórias em ratos. MÉTODOS:Cento e sessenta ratos foram divididos em dois grupos: tratado e controle. O controle recebeu água, enquanto o tratado etanol a 30%. Após 180 dias foram realizadas colotomia, seguida de anastomose. Após os animais foram divididos em quatro subgrupos de 20 ratos para estudo nos seguintes momentos: 4º, 7º, 14º e 21º pós-operatório. Os parâmetros analisados foram: ganho de peso, força de ruptura, hidroxiprolina tecidual, complicações pós-operatórias e estudo histopatológico. RESULTADOS:O ganho de peso foi superior no grupo controle (p<0,05). Após agrupamento dos momentos a força de ruptura foi superior no controle (p<0,05). Não houve diferença quanto à histopatologia e hidroxiprolina. Houve cinco infecções de incisão no grupo tratado, enquanto no controle ocorreram duas (p>0,05). Houve nove fístulas no grupo tratado, enquanto no controle duas (p<0,05).Ocorreram sete mortes no grupo tratado e apenas três no controle (p>0,05). Intestinal healing in rats submitted to ethanol ingestionActa Cirúrgica Brasileira -Vol. 27 (3) 2012 -237 CONCLUSÕES:No grupo tratado ocorreu um processo de subnutrição evidenciado pelo menor ganho de peso. Piora na cicatrização intestinal, indicada pela menor força de ruptura. Ocorreu um maior número de complicações pós-operatórias no grupo tratado.Descritores: Cicatrização. Alcoolismo. Etanol. Resistência à Tração. Hidroxiprolina. Ratos.

F. G. Romeiro et al. 287bined approach is cautiously performed on an individualized schedule. Our results suggest that the Child-Pugh classification should not be a limitation to this combined treatment.

Background. Hepatocellular carcinoma is a relevant cause of mortality worldwide, mainly among patients who have a prior liver disease. In spite of clear recommendations regarding surveillance and screening methods, most patients are still diagnosed only when they are no longer candidates to curative treatment modalities, while others do not achieve the goals of such treatments, thus increasing the need of anticancer drugs. Moreover, when cirrhotic patients begin to receive these drugs, many types of adverse events are seen as a reason to withdrawal, even when there are findings suggesting a good response to the treatment. Case Summary. This case report is about a cirrhotic patient who received many types of treatment, from surgery and chemoembolization during early stages to first- and second-line systemic therapy when the disease turned to be advanced. Since he had no signs of liver dysfunction and suffered tumor progression during sorafenib treatment, regorafenib was initiated. The main findings that make this case important are the adverse events after taking this second-line agent, which would certainly be considered unacceptable and would lead to the drug withdrawal. The reasons why regorafenib was maintained are explained based on clinical and imaging findings, showing how this decision led to an excellent response. Conclusions. The knowledge of the main adverse events described in the pilot clinical trials can avoid unnecessary withdrawal of regorafenib. In addition, some clinical and imaging findings can be deemed as predictors of good response to tyrosine kinase inhibitors.