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Background: Surgery remains the only curative option for the treatment of pancreatic adenocarcinoma (PDAC). The goal of this study was to investigate the clinical outcome and prognostic factors in patients after resection for ductal adenocarcinoma of the pancreatic head. Methods: The data from 195 patients who underwent pancreatic head resection for PDAC between 1993 and 2011 in our center were retrospectively analyzed. The prognostic factors for survival after operation were evaluated using multivariate analysis. Results: The head resection surgeries included 69.7% pylorus-preserving pancreatoduodenectomies (PPPD) and 30.3% standard Kausch-Whipple pancreatoduodenectomies (Whipple). The overall mortality after pancreatoduodenectomy (PD) was 4.1%, and the overall morbidity was 42%. The actuarial 3- and 5-year survival rates were 31.5% (95% CI, 25.04%-39.6%) and 11.86% (95% CI, 7.38%-19.0%), respectively. Univariate analyses demonstrated that elevated CEA (p = 0.002) and elevated CA 19–9 (p = 0.026) levels, tumor grade (p = 0.001) and hard texture of the pancreatic gland (p = 0.017) were significant predictors of a poor survival. However, only CEA >3 ng/ml (p < 0.005) and tumor grade 3 (p = 0.027) were validated as significant predictors of survival in multivariate analysis. Conclusions: Our results suggest that tumor marker levels and tumor grade are significant predictors of poor survival for patients with pancreatic head cancer. Furthermore, hard texture of the pancreatic gland appears to be associated with poor survival.

Backround: Oxidative stress (OS) has been implicated in pathogenesis of human disorders such as depressive disorder, sepsis, cardiovascular disease, acute and chronic pancreatitis, and cancer. Increased OS is result of imbalance between increased reactive oxygen and nitrogen species (RONS) production and / or insufficient activity of antioxidant defence system. Antioxidant system, which is composed of antioxidant enzymes such as superoxide dismutase, catalase, glutathione peroxidases (GPX), glutathione reductase (GR) and non- enzymatic antioxidant reduced glutathione (GSH) plays an important role in the protection of cells against enhanced OS. The aim of this study was to assess the OS markers and antioxidant enzymes in different pathophysiological states. Materials and methods: Activities of erythrocyte glutathione peroxidase (GPX1), GR and concentration of GSH as well as levels of OS markers were analysed in six different pathophysiologic states. These parameters were measured in 35 women with depressive disorder (DD), 40 patients with metabolic syndrome (MetS), 30 septic patients (S) followed up in the course of sepsis; 15 non-septic critically ill patients (NC), 13 patients with acute pancreatitis (AP), 50 with chronic pancreatitis (CP) and 50 patients with pancreatic cancer (PC), compared to...

Introduction: Intraperitoneal tumor seeding is a common form of recurrence after surgery for GI tumours. Early diagnosis and treatment may influence the course of disease. Hypothesis and objectives of the work The finding of free tumor cells and / or elevation of tumor markers in peritoneal fluid predicts intraperitoneal tumor recurrence. The results of these tests can be used to indicate HIPEC. Aim of this work is to determine the sensitivity and specificity of cytology and tumor markers levels and importance of these tests for early diagnosis and prognosis of recurrence. Another objective was to confirm the applicability of RT PCR for identification of free tumor cells. Patients and methods . Materials are sourced both during initial surgery (220 patients) and by the dispensary controls (25 patients). The peritoneal fluid was examined cytologically and biochemically too. 50 samples was exemined by RT PCR. Results Elevation of tumor markers or finding of free intraperitoneal tumor cells predicts recurrence. The prognosis of these patients corresponds to stage IV TNM classification, regardless of other parameters TNM. Low sensitivity of these tests (34% for cytology, 53% for tumor markers) does not allow its use as an indicator of HIPEC. Due to degradation of RNA we did not confirm the value of RT...

Introdução: A escolha da via de acesso para tratamento paliativo da obstrução biliar nos tumores da confluência biliopancreática (TCBP) permanece incerta para os pacientes com baixo risco anestésico-cirúrgico ou longa expectativa de vida. Objetivo: Estudar a influência da derivação biliar mediante abordagem laparotômica e endoscópica nos resultados assistenciais e nos custos do tratamento paliativo dos TCBP. Método: Estudo coorte retrospectivo de prontuários dos pacientes portadores de TCBP submetidos ao tratamento paliativo endoscópico ou cirúrgico no Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto da Universidade de São Paulo (HCFMRP-USP), no período de 2002 a 2013, com análise de variáveis epidemiológicas, clínicas e assistenciais e dos custos. Resultados: Dentre os 150 pacientes com TCBP estudados, 92 (61,33%) foram submetidos à derivação das vias biliares por laparotomia (TL) e 58 (38,66%) por via endoscópica (TE), onde a prótese plástica foi utilizada na maioria dos casos (N = 38, 65,51%). Os grupos foram homogêneos para a maioria das variáveis epidemiológicas e clínicas antes dos procedimentos. As taxas de complicações precoces foram equivalentes na comparação dos grupos (55,17% para TE e 40,1% para TL), porém as complicações tardias foram mais frequentes no grupo TE (20,68% para TE e 10,34% para TL), o que se associou principalmente às recorrências das obstruções biliares. As curvas de sobrevida foram menores para TE. Não houve diferença significativa entre o custo mediano por procedimento no grupo TE (R$2.861,00) e TL (R$3.427,00) (p=0,3253). Por outro lado, o custo mediano total para o grupo TE (R$8.586,00) foi menor que o do grupo TL (R$12.810,00) (p=0,0001). Conclusão: a combinação das vantagens das duas modalidades de tratamento paliativo para os TCBP (maior sobrevida e eficácia na redução da colestase no grupo TL e menores tempo de internação e custo global no grupo TE) é uma meta a ser atingida e o acesso videolaparoscópico é uma alternativa a ser explorada. / Introduction: the advanced tumors of the biliopancreatic confluence (TCBP) often present with biliary obstruction, which can receive palliative treatment, through laparotomy, laparoscopic or endoscopic. Objective: to study the influence of laparotomy and endoscopic approaches in care results and costs of the palliative treatment of TCBP. Method: retrospective coorte study of medical records of patients with TCBP undergoing to the endoscopic and / or laparotomic palliation at the Hospital of Clinics of the Faculty of Medicine of Ribeirão Preto, University of São Paulo (HCFMRP-USP), from 2002 to 2013 with analysis of epidemiological variables, clinical, care and treatment costs. Results: among the 150 patients with TCBP studied, 92 (61.33%) underwent biliary bypass by laparotomy (TL) and 58 (38.66%) endoscopically (TE). The groups were homogeneous for most of the epidemiological and clinical variables before the procedures. The rates of early complications were similar between the groups (55.17% for TE and 40.1% for TL), but late complications were more frequent in the TE group (20.68% for TE and 10.34% for TL), which was mainly associated with the recurrence of biliary obstruction. The survival curves were lower for TE. The median cost of the procedure in the TE group (R$ 2,861.00) wasn´t different from TL (R$ 3,427.00) (p = 0,3253). On the other hand, the median total cost for the TE group (R$ 8,586.00) was lower than the TL group (R$ 12,810.00) (p = 0,0001). Conclusion: the combination of the advantages of the two methods of palliative treatment for TCBP (greater efficacy in reducing cholestasis in the TL group and lower length of stay and the overall costs in the TE group) is a goal to be achieved, and the laparoscopic access is an alternative to be explored.

Le pronostic est depuis longtemps un concept de base de la médecine. Hippocrate envisageait déjà le pronostic des maladies par l’étude des circonstances passées, l’établissement des faits présents, et enfin la prédiction des phénomènes à venir. Pour lui, tout l’art du pronostic était de savoir interpréter intelligemment ces informations, et ainsi moduler le pronostic en fonction de leur valeur relative. Une recherche à visée pronostique consiste toujours actuellement en l’examen des relations entre un état de santé connu au moment de l’investigation et un évènement futur. L’augmentation de l’espérance de vie implique que de plus en plus de personnes vivent avec une ou plusieurs maladies ou problèmes altérant leur santé. Dans ce contexte, l’étude du pronostic n’a jamais été aussi importante. Cependant, contrairement au domaine des essais cliniques randomisés dans lequel les recommandations CONSORT sont appliquées depuis plus de 20 ans et garantissent une recherche de qualité, la recherche pronostique commence seulement à se doter d’initiatives similaires. En effet, des recommandations TRIPOD ont été élaborées en 2015 et un groupe de travail, PROGRESS, s’est constitué en 2013 au Royaume-Uni et a fait le constat que les recherches a visée pronostique sont réalisées de façon très hétérogènes et malheureusement ne respectent pas toujours des standards de qualité nécessaires pour supporter leurs conclusions et garantir la reproductibilité des résultats (...) / Prognosis is historically a basic concept of medicine. Hippocrates already considered the prognosis of disease as the study of the past circumstances, the establishment of the present state of health and finally the prediction of future events. He presented the prognosis as the ability to interpret these elements and to adapt the prognosis regarding their relative values. Currently, the prognostic research is still based on the examination of the relationship between a well-established health condition at the time of the investigation and the occurrence of an event. The increase in life expectancy implies that more and more people are living with one or more diseases or with problems that can impair their health status. In this context, the study of the prognosis has never been more important. However, in comparison with the field of randomized clinical trials in which the CONSORT statement recommendations are implemented for more than 20 years in order to guarantee quality research, the prognostic research only begins to develop similar initiatives. Indeed, in 2015 the TRIPOD statement recommendations were provided and in 2013 a working group called PROGRESS was constituted in the United Kingdom and its members made the observation that prognostic researches are developed with considerable heterogeneity in the methodology used and unfortunately do not always meet the quality standards required to support their conclusions and their reproducibility (...)

Background: Surgery remains the only curative option for the treatment of pancreatic adenocarcinoma (PDAC). The goal of this study was to investigate the clinical outcome and prognostic factors in patients after resection for ductal adenocarcinoma of the pancreatic head. Methods: The data from 195 patients who underwent pancreatic head resection for PDAC between 1993 and 2011 in our center were retrospectively analyzed. The prognostic factors for survival after operation were evaluated using multivariate analysis. Results: The head resection surgeries included 69.7% pylorus-preserving pancreatoduodenectomies (PPPD) and 30.3% standard Kausch-Whipple pancreatoduodenectomies (Whipple). The overall mortality after pancreatoduodenectomy (PD) was 4.1%, and the overall morbidity was 42%. The actuarial 3- and 5-year survival rates were 31.5% (95% CI, 25.04%-39.6%) and 11.86% (95% CI, 7.38%-19.0%), respectively. Univariate analyses demonstrated that elevated CEA (p = 0.002) and elevated CA 19–9 (p = 0.026) levels, tumor grade (p = 0.001) and hard texture of the pancreatic gland (p = 0.017) were significant predictors of a poor survival. However, only CEA >3 ng/ml (p < 0.005) and tumor grade 3 (p = 0.027) were validated as significant predictors of survival in multivariate analysis. Conclusions: Our results suggest that tumor marker levels and tumor grade are significant predictors of poor survival for patients with pancreatic head cancer. Furthermore, hard texture of the pancreatic gland appears to be associated with poor survival.

Objective: The aim of this study was to develop an immunomagnetic/real-time reverse transcriptase polymerase chain reaction (RT-PCR) assay and assess its clinical value for the molecular detection of circulating tumor cells (CTCs) in peripheral blood of pancreatic cancer patients. Methods: The presence of CTCs was evaluated in 34 pancreatic cancer patients before systemic therapy and in 40 healthy controls, through immunomagnetic enrichment, using the antibodies BM7 and VU1D9 [targeting mucin 1 and epithelial cell adhesion molecule (EpCAM), respectively], followed by real-time RT-PCR analysis of the genes KRT19, MUC1, EPCAM, CEACAM5 and BIRC5. Results: The developed assay showed high specificity, as none of the healthy controls were found to be positive for the multimarker gene panel. CTCs were detected in 47.1% of the pancreatic cancer patients before the beginning of systemic treatment. Shorter median progression-free survival (PFS) was observed for patients who had at least one detectable tumor-associated transcript, compared with patients who were CTC negative. Median PFS time was 66.0 days [95% confidence interval (CI) 44.8–87.2] for patients with baseline CTC positivity and 138.0 days (95% CI 124.1–151.9) for CTC-negative patients (p = 0.01, log-rank test). Conclusion: Our results suggest that in addition to the current prognostic methods, CTC analysis represents a potential complementary tool for prediction of outcome in pancreatic cancer patients. / Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich.

Souvent diagnostiqué à un stade avancé, le cancer du pancréas (CP) est un cancer particulièrement létal pour lequel il n’y a, à ce jour, que très peu de possibilités de traitement et de diagnostic anticipé. L’identification de facteurs de risque modifiables pourrait fournir des données épidémiologiques nécessaires au soutien de la mise en place de mesures préventives. Cette thèse a pour but d’étudier l’étiologie du CP en évaluant le rôle de la consommation d’alcool et du mode de vie dans l’étude prospective européenne sur le cancer et la nutrition (EPIC), cohorte multicentrique de plus de 500,000 sujets provenant de 10 pays européens. La consommation d’alcool a d’abord été évaluée en regard du risque de CP. Les rôles des différents types d’alcools ainsi que du tabagisme dans la relation entre l’alcool et le CP ont été examinés. Cette évaluation a montré qu’une consommation d’alcool élevée était associée à une augmentation du risque de CP. Ensuite, la relation entre le Healthy Lifestyle Index, un indicateur combinant le passé tabagique, la consommation d’alcool, l’alimentation, l’anthropométrie et l’activité physique, et le risque de CP a été étudiée. Pour quantifier l’impact de l’amélioration de ces facteurs, des fractions de CP attribuables ont été estimées en considérant des scénarios hypothétiques où les participants adopteraient des modes de vie plus sains. L’adhérence à des habitudes saines était fortement et inversement associée au risque de CP. Ces travaux ont apporté des connaissances informatives sur l’étiologie du CP, et soutiennent le développement de mesures de santé publique promouvant la prévention du CP par l’adoption de modes de vie sains / Commonly diagnosed at late stage, pancreatic cancer (PC) is a highly fatal cancer with limited opportunities for early detection and effective treatment. The identification of modifiable risk factors may offer relevant scientific evidence for PC prevention. This doctoral research program investigated PC etiology through a comprehensive examination of the role of alcohol consumption and other lifestyle determinants in the occurrence of PC within the European Prospective Investigation into Cancer and nutrition (EPIC) study, a multi-center cohort involving more than 500,000 participants from 10 European countries. Alcohol intake was evaluated with respect to the risk of PC. The role of different alcoholic beverages and potential effect modification by smoking habits on PC risk were also examined. Findings from this evaluation provided epidemiological evidence that large intakes of alcohol were associated with an increased risk of PC.The association between the healthy lifestyle index, a score combining information on smoking history, alcohol intake, diet, obesity, and physical activity and the risk of PC was examined. To quantify the impact of modifying several lifestyle factors, population attributable fractions were estimated assuming counterfactual scenarios whereby study participants hypothetically moved towards healthier behaviors. Adherence to healthy lifestyle habits was strongly inversely related to PC. This comprehensive evaluation provides informative insights on the etiology of PC and supports the development and implementation of public health guidelines to promote individuals’ adoption of healthy lifestyle habits for PC prevention

Indiana University-Purdue University Indianapolis (IUPUI). / The abysmal five year pancreatic cancer survival rate of less than 6% highlights the need for new treatments for this deadly malignancy. Cytotoxic drugs normally target rapidly dividing cancer cells but unfortunately often target stem cells resulting in toxicity. This warrants the development of compounds that selectively target tumor cells. An inhibitor of the mitotic kinase, MPS1, which has been shown to be more selective towards cancer cells than non-tumorigenic cells, shows promise but its effects on stem cells has not been investigated. MPS1 is an essential component of the Spindle Assembly Checkpoint and is proposed to be up-regulated in cancer cells to maintain chromosomal segregation errors within survivable limits. Inhibition of MPS1 kinase causes cancer cell death accompanied by massive aneuploidy. Our studies demonstrate that human adipose stem cells (ASCs) and can tolerate higher levels of a small molecule MPS1 inhibitor than pancreatic cancer cells. In contrast to PANC-1 cancer cells, ASCs and telomerase-immortalized pancreatic ductal epithelial cells did not exhibit elevated chromosome mis-segregation after treatment with the MPS1 inhibitor for 72hrs. In contrast, PANC-1 pancreatic cancer cells exhibited a large increase in chromosomal mis-segregation under similar conditions. Furthermore, growth of ASCs was minimally affected post treatment whereas PANC-1 cells were severely growth impaired suggesting a favorable therapeutic index. Our studies, demonstrate that MPS1 inhibition is selective towards pancreatic cancer cells and that stem cells are less affected in vitro. These data suggest MPS1 inhibition should be further investigated as a new treatment approach in pancreatic cancer.