The role of immunoinflammatory markers in the prognosis and resectability of pancreatic adenocarcinoma / O papel dos marcadores imunoinflamatórios no prognóstico e ressecabilidade do adenocarcinoma pancreático

ABSTRACT Background: Pancreatic adenocarcinoma has a high mortality rate. A prognostic tool is essential for a better risk stratification. The neutrophil/lymphocyte ratio and adaptations and the platelet/lymphocyte ratio seem promising for this purpose. Aim: Evaluate the prognostic value of neutrophil/lymphocyte ratio, derived neutrophil/lymphocyte ratio and platelet/lymphocyte ratio, analyze the ideal cutoff values and investigate their utility in predicting resectability. Methods: Data were collected of patients with pancreatic adenocarcinoma in Hospital de Clínicas de Porto Alegre between 2003 and 2013. The studied ratios were determined by blood count collected at hospital admission and after two cycles of palliative chemotherapy. Results: Basal neutrophil/lymphocyte ratio, derived neutrophil/lymphocyte ratio and platelet/lymphocyte ratio did not have prognostic impact in survival (p=0.394, p=0.152, p=0.177 respectively). In subgroup analysis of patients submitted to palliative chemotherapy, neutrophil/lymphocyte ratio, derived neutrophil/lymphocyte ratio and platelet/lymphocyte ratio determined after two cycles of chemotherapy were prognostic for overall survival (p=0.003, p=0.009, p=0.001 respectively). The ideal cutoff values found were 4,11 for neutrophil/lymphocyte ratio (sensitivity 83%, specificity 75%), 2,8 for derived neutrophil/lymphocyte ratio (sensitivity 87%, specificity 62,5%) and 362 for platelet/lymphocyte ratio (sensitivity 91%, specificity 62,5%), Neutrophil/lymphocyte ratio, derived neutrophil/lymphocyte ratio and platelet/lymphocyte ratio were not able to predict resectability (p=0.88; p=0.99; p=0.64 respectively). Conclusions: Neutrophil/lymphocyte ratio, derived neutrophil/lymphocyte ratio and platelet/lymphocyte ratio are useful as prognostic markers of overall survival in patients with pancreatic adenocarcinoma submitted to palliative chemotherapy. Its use as resectability predictor could not be demonstrated.

RESUMO Racional: O adenocarcinoma pancreático apresenta alta taxa de mortalidade. Uma ferramenta que possa predizer adequadamente o seu prognóstico é fundamental para melhor estratificação de risco. A razão neutrófilos/linfócitos e suas adaptações e a razão plaquetas/linfócitos tem se mostrado promissores para este fim. Objetivo: Avaliar o valor prognóstico das razões neutrófilos/linfócitos, neutrófilos/linfócitos derivada e plaquetas/linfócitos, analisar os pontos de corte mais adequados e investigar sua utilidade como fator preditivo de ressecabilidade. Métodos: Foram coletados dados de pacientes com adenocarcinoma pancreático atendidos no Hospital de Clínicas de Porto Alegre entre 2003 e 2013. As razões estudadas foram determinadas com base nos hemogramas coletados na internação e após dois ciclos de quimioterapia paliativa. Resultados: As razões neutrófilos/linfócitos basal, neutrófilos/linfócitos derivada basal e plaquetas/linfócitos basal não tiveram impacto prognóstico na sobrevida (p=0,394, p=0,152, p=0,177 respectivamente). No subgrupo submetido a quimioterapia paliativa, as razões neutrófilos/linfócitos, neutrófilos/linfócitos derivada e plaquetas/linfócitos após dois ciclos de tratamento mostraram-se fatores prognósticos para sobrevida global (p=0,003, p=0,009 e p=0,001 respectivamente). Os pontos de corte encontrados foram 4,11 para neutrófilos/linfócitos (sensibilidade 83% e especificidade 75%), 362 para plaquetas/linfócitos (sensibilidade 91% e especificidade 62,5%) e 2,8 para neutrófilos/linfócitos derivada (sensibilidade 87% e especificidade 62,5%). As razões neutrófilos/linfócitos, neutrófilos/linfócitos derivada e plaquetas/linfócitos não se mostraram estatisticamente significativas como preditores para ressecabilidade (p=0,88; p=0,99 e p=0,64 respectivamente). Conclusões: As razões neutrófilos/linfócitos, neutrófilos/linfócitos derivada e plaquetas/linfócitos são úteis como marcadores prognósticos de sobrevida global em pacientes com adenocarcinoma pancreático submetidos à quimioterapia paliativa. Seu uso como preditor de ressecabilidade não foi demonstrado.

Identification of Pancreatic Cancer-Associated Tumor Antigen from HSP-Enriched Tumor Lysate-Pulsed Human Dendritic Cells

PURPOSE: Vaccine strategies utilizing dendritic cells (DCs) to elicit anti-tumor immunity are the subject of intense research. Although we have shown that DCs pulsed with heat-treated tumor lysate (HTL) induced more potent anti-tumor immunity than DCs pulsed with conventional tumor lysate (TL), the underlying molecular mechanism is unclear. In order to explore the molecular basis of this approach and to identify potential antigenic peptides from pancreatic cancer, we analyzed and compared the major histocompatibility complex (MHC) ligands derived from TL- and HTL-pulsed dendritic cells by mass spectrophotometry. MATERIALS AND METHODS: Human monocyte-derived dendritic cells were pulsed with TL or HTL prior to maturation induction. To delineate differences of MHC-bound peptide repertoire eluted from DCs pulsed with TL or HTL, nanoflow liquid chromatography-electrospray ionization-tandem mass spectrometry (nLC-ESI-MS-MS) was employed. RESULTS: HTL, but not TL, significantly induced DC function, assessed by phenotypic maturation, allostimulation capacity and IFN-gamma secretion by stimulated allogeneic T cells. DCs pulsed with TL or HTL displayed pancreas or pancreatic cancer-related peptides in context of MHC class I and II molecules. Some of the identified peptides had not been previously reported as expressed in pancreatic cancer or cancer of other tissue types. CONCLUSION: Our partial lists of MHC-associated peptides revealed the differences between peptide profiles eluted from HTL-and TL-loaded DCs, implying that induced heat shock proteins in HTL chaperone tumor-derived peptides enhanced their delivery to DCs and promoted cross-presentation by DC. These findings may aid in identifying novel tumor antigens or biomarkers and in designing future vaccination strategies.

Clinicopathological Aspects of 542 Cases of Pancreatic Cancer: a Special Emphasis on Small Pancreatic Cancer

Small pancreatic cancers (longest diameter < or =2 cm) have been regarded as preliminary to early pancreatic cancer, which was thought to be highly curable. During our experience since 1989, we evaluated 542 cases of pancreatic cancer. Among them we found 74 cases of tumors < or =2 cm in diameter, small pancreatic cancer (TS1 pancreatic cancer). Well-differentiated adenocarcinomas (18.9%) and absence of symptoms (8.1%) were more frequent in patients with TS1 than in those with larger pancreatic tumors. Only 16 of the 74 patients (21.6%) with small pancreatic cancers had T1 tumors. According to the International Union Against Cancer (UICC) staging, only 11 patients (14.9%) were stage IA: their 5-yr survival rate was 23.3% and their median survival was 30.0 months. Among these 11 patients, 3 had tumors <1 cm; their median survival time was 30.0 months and their 5-yr survival rate was 50.0%. These findings may indicate that 'small' pancreatic cancer is not equivalent to 'early' pancreatic cancer.

Elementos semiológicos para o diagnóstico diferencial dos tumores pancreáticos / Imaging findings to differentiate pancreatic tumors

Resumo: O pâncreas pode ser acometido por neoplasias de origem epitelial, de células de ilhotas pancreáticas, tumores exócrinos, linfomas metástases. O objetivo deste trabalho é apresentar as principais características deste grupo de tumores, com intúito de diferenciá-los.

Introduçäo de um novo marcador laboratorial para câncer de pâncreas (CA 19.9): experiência atual / A new laboratory marker for cancer of the pancreas (CA 19.9): current experience

Apresenta-se um novo marcador tumoral, o CA 19.9. Os estudos envolveram inicialmente 29 pacientes portadores de adenocarcinoma gastrintestinal e de mama aonde näo se demonstrou qualquer tipo de especificidade, sendo os resultados obtidos no entanto superiores aos valores normais. Onze pacientes com câncer de pâncreas apresentaram os valores mais elevados do estudo, ao contrário de pacientes com doenças que estäo no diagnóstico diferencial de afecçöes pancreáticas. Um estudo comparativo entre o CEA e o CA 19.9 neste grupo de pacientes mostrou ser o CA 19.9 superior ao CEA na monitorizaçäo do câncer de pâncreas. Dos estudos pode-se ver que o CEA 19.9 se mostrou altamente específico para o diagnóstico de adenocarcinoma de pâncreas e altamente sensível para o diagnóstico de adenocarcinoma. Provou ser também, no carcinoma de pâncreas, um melhor marcador que o CEA