Epidemiologia do câncer de pâncreas na América Latina e no Brasil / Epidemiology of pancreatic cancer in Latin America and Brazil

Introdução: O câncer de pâncreas é um tumor de alta letalidade, é o décimo segundo tipo mais comum e a sétima causa de morte, em ambos os sexos, no mundo. Estima-se que o câncer de pâncreas terá um aumento contínuo de incidência e mortalidade nos próximos 20 anos e isso causará um enorme ônus econômico para as populações em todo o mundo. Para o monitoramento e vigilância epidemiológica em câncer, pode-se apoiar em dados secundários como no Sistema de Informação em Mortalidade e dos registros de câncer (de base populacional e hospitalares) e estimativas a partir destes dados; por essa razão, investigou-se a epidemiologia do câncer de pâncreas na América Latina e no Brasil. Métodos: A tese compreende três manuscritos: (i) tendências de incidência, mortalidade e anos de vida ajustados por incapacidade (DALYs), bem como a fração de mortes por câncer de pâncreas atribuíveis a fatores de risco comportamentais e metabólicos em países da América Latina e Caribe (LAC) entre 1990 e 2019 (Global Burden Disease, 2019); (ii) mortalidade por câncer de pâncreas no Brasil e unidades da federação entre 1979 e 2019, dados do Sistema de Informação em Mortalidade (SIM); (iii) comparabilidade, validade, completude e pontualidade para cinco tumores gastrointestinais, câncer de esôfago, estômago, colorretal, fígado e pâncreas, em Registros de Câncer de Base Populacional (RCBPs) brasileiros. Resultados: Observou-se um aumento na incidência, mortalidade e DALYs para o câncer de pâncreas em ambos os sexos na maioria dos países da América Latina e Caribe; as maiores taxas de incidência e mortalidade foram observadas no Uruguai e as menores no Haiti. Redução na fração de mortes atribuíveis ao tabagismo entre 1990 e 2019, para ambos os sexos nos países da LAC; entretanto, aumento dentre os fatores metabólicos. No Brasil, entre 1979 e 2019, foram notificados um total de 209.425 óbitos por câncer de pâncreas, com tendência de aumento de 1,5% ao ano em homens e 1,9% em mulheres. Houve tendência de aumento da mortalidade na maioria dos estados brasileiros, com maiores tendências nas regiões Norte e Nordeste, e correlação positiva entre o índice de desenvolvimento humano e a tendência de aumento da mortalidade por câncer de pâncreas. Dentre os dezesseis RCBPs brasileiros estudados, todos atenderam aos critérios de comparabilidade, porém metade apresentou índices abaixo do esperado para validade e completude para tumores de fígado e pâncreas. Para pontualidade, os dezesseis registros apresentaram mais de 48 meses de atraso na divulgação dos dados em relação ao ano calendário de 2023. Considerações finais: O câncer de pâncreas representa um desafio para a saúde pública nos países da América Latina e no Brasil, diante do desafio na redução da incidência e da mortalidade, assim como na vigilância epidemiológica em câncer através dos RCBPs brasileiros que necessitam de suporte para continuidade do monitoramento da incidência do câncer.

Introduction: Pancreatic cancer is a tumor of high lethality, is the twelfth most common type and the seventh cause of death, in both sexes, in the world. It is estimated that pancreatic cancer will have a continuous increase in incidence and mortality over the next 20 years and this will cause a huge economic burden for populations around the world. For epidemiological monitoring and surveillance in cancer, it is possible to use on secondary data such as the Mortality Information System and cancer registries (population-based and hospital) and estimates from these data, for this reason the epidemiology of pancreatic cancer in Latin America and Brazil was investigated. Methods: The thesis comprises three manuscripts: (i) trends in incidence, mortality and disability-adjusted life years (DALYs) as well as the fraction of pancreatic cancer deaths attributable to behavioral and metabolic risk factors in Latin American and Caribbean (LAC) countries between 1990 and 2019 (Global Burden Disease, GBD 2019); (ii) mortality from pancreatic cancer in Brazil and federal units between 1979 and 2019, data from the Mortality Information System (SIM); (iii) comparability, validity, completeness and timeless for five gastrointestinal tumors, esophageal, stomach, colorectal, liver and pancreatic cancers, in the Brazilian Population-Based Cancer Registries (PBCRs). Results: An increase in the incidence, mortality and DALYs of pancreatic cancer was observed in most countries in Latin America and the Caribbean, the highest incidence and mortality rates were observed in Uruguay and the lowest in Haiti. The fraction of pancreatic cancer deaths attributable to smoking reduced between 1990 and 2019 for both sexes in LAC countries, however, it increased for metabolic risk factors. In Brazil, between 1979 and 2019, a total of 209,425 deaths from pancreatic cancer were reported, with a trend of increase of 1.5% per year in men and 1.9% in women. There was an increase in mortality in most Brazilian states, higher in the North and Northeast regions with a positive correlation between the improvement of the human development index and the trend of increased mortality from pancreatic cancer. Among the sixteen Brazilian PBCRs studied, all agreement the criteria of comparability, but half have lower than expected indices for validity and completeness for liver and pancreatic tumors, and as for timeless the sixteen records are more than 48 months late in the release of data in relation to the calendar year 2023. Conclusions: Pancreatic cancer represents a challenge for public health in LAC and Brazil, given the challenge in reducing incidence and mortality, as well as in epidemiological surveillance in cancer through Brazilian PBCRs to ensure the activity and stability for continued monitoring of cancer incidence.

Duodenopancreatectomia com ressecção venosa: análise de morbidade e mortalidade em 30 dias / Pancreaticoduodenectomy with venous resection: an analysis of 30-day morbidity and mortality

ABSTRACT BACKGROUND: Pancreaticoduodenectomy (PD) with the resection of venous structures adjacent to the pancreatic head, even in cases of extensive invasion, has been practiced in recent years, but its perioperative morbidity and mortality are not completely determined. OBJECTIVE: To describe the perioperative outcomes of PD with venous resections performed at a tertiary university hospital. METHODS: A retrospective study was conducted, classified as a historical cohort, enrolling 39 individuals which underwent PD with venous resection from 2000 through 2016. Preoperative demographic, clinical and anthropometric variables were assessed and the main outcomes studied were 30-day morbidity and mortality. RESULTS: The median age was 62.5 years (IQ 54-68); 55% were male. The main etiology identified was ductal adenocarcinoma of the pancreas (82.1%). In 51.3% of cases, the portal vein was resected; in 35.9%, the superior mesenteric vein was resected and in the other 12.8%, the splenomesenteric junction. Regarding the complications, 48.7% of the patients presented some type of morbidity in 30 days. None of the variables analyzed was associated with higher morbidity. Perioperative mortality was 15.4% (six patients). The group of individuals who died within 30 days presented significantly higher values for both ASA (P=0.003) and ECOG (P=0.001) scores. CONCLUSION: PD with venous resection for advanced pancreatic neoplasms is a feasible procedure, but associated with high rates of morbidity and mortality; higher ASA e ECOG scores were significantly associated with a higher 30-day mortality.

RESUMO CONTEXTO: A duodenopancreatectomia (DP) com ressecção de estruturas venosas adjacentes à cabeça do pâncreas, mesmo em casos de invasão extensa, tem sido praticada nos últimos anos, mas sua morbidade e mortalidade perioperatórias não são completamente determinadas. OBJETIVO: Descrever os resultados perioperatórios de DP com ressecções venosas realizadas em um hospital terciário universitário. MÉTODOS: Foi realizado estudo retrospectivo, classificado como coorte histórica, envolvendo 39 indivíduos submetidos à DP com ressecção venosa entre 2000 e 2016. Foram estudadas variáveis demográficas, clínicas e antropométricas pré-operatórias e os desfechos principais foram a morbidade e mortalidade em 30 dias. RESULTADOS: A mediana de idade foi 62,5 anos (IQ 54-68), sendo 55% dos indivíduos do sexo masculino. A principal etiologia identificada foi o adenocarcinoma ductal de pâncreas (82,1%). Em 51,3% dos casos, a veia porta foi submetida à ressecção; em 35,9%, a veia mesentérica superior foi ressecada e nos outros 12,8%, a junção esplenomesentérica. Em relação às complicações, 48,7% dos pacientes apresentaram algum tipo de morbidade em 30 dias. Nenhuma das variáveis analisadas associou-se à maior morbidade. A mortalidade perioperatória foi 15,4% (seis pacientes). O grupo de indivíduos que cursou com mortalidade em 30 dias apresentou escores significativamente mais altos de ASA (P=0,003) e ECOG (P=0,001). CONCLUSÃO: A DP com ressecção venosa para neoplasias avançadas do pâncreas é um procedimento factível, porém que se acompanha de altos índices de morbidade e mortalidade; escores de ASA e ECOG altos são fatores significativamente associados à maior mortalidade.

Granuloma anular, pronóstico de diabetes mellitus. A propósito de un caso / Annular granuloma, prognosis of diabetes mellitus. On the purpose of a case

RESUMEN El granuloma anular es una dermatosis de relativa frecuencia en niños, jóvenes y adultos. Está caracterizado por lesiones cutáneas eritemato-pápulo-nodulares, que adoptan una disposición anular. Su etiopatogenia es desconocida, pero con numerosos factores predisponentes, desencadenantes o asociados a ella; como es la diabetes mellitus y/o procesos neoplásicos o paraneoplásicos. Resulta importante el estudio de pacientes con este diagnóstico por su asociación con entidades como las antes mencionadas. Se realizó el reporte de un caso en adulto mayor de 65 años, con diagnóstico de granuloma anular, diabetes mellitus y neoplasia de páncreas.

ABSTRACT Annular granuloma is a dermatosis relatively frequent in children, young and adult people. It is characterized by erythematous-papular-nodular skin lesions adopting annular disposition. Its etio-pathogenesis is unknown, but there are many predisposal, unleashing factors, or associated to this disease, like diabetes mellitus and/or neoplastic or paraneoplastic processes. It is important to study the patients diagnosed with the disease due to its association with entities like those before mentioned. The reported case is the case of a patient elder than 65 years, diagnosed with annular granuloma, diabetes mellitus and pancreas neoplasia.

Pancreaticoduodenectomy: impact of the technique on operative outcomes and surgical mortality / Duodenopancreatectomia: impacto da técnica nos resultados operatórios e mortalidade cirúrgica

ABSTRACT Background: Pancreaticoduodenectomy (PD) is a procedure associated with significant morbidity and mortality. Initially described as gastropancreaticoduodenectomy (GPD), the possibility of preservation of the gastric antrum and pylorus was described in the 1970s. Aim: To evaluate the mortality and operative variables of PD with or without pyloric preservation and to correlate them with the adopted technique and surgical indication. Method: Retrospective cohort on data analysis of medical records of individuals who underwent PD from 2012 through 2017. Demographic, anthropometric and operative variables were analyzed and correlated with the adopted technique (GPD vs. PD) and the surgical indication. Results: Of the 87 individuals evaluated, 38 (43.7%) underwent GPD and 49 (53.3%) were submitted to PD. The frequency of GPD (62.5%) was significantly higher among patients with pancreatic neoplasia (p=0.04). The hospital stay was significantly shorter among the individuals submitted to resection due to neoplasias of less aggressive behavior (p=0.04). Surgical mortality was 10.3%, with no difference between GPD and PD. Mortality was significantly higher among individuals undergoing resection for chronic pancreatitis (p=0.001). Conclusion: There were no differences in mortality, surgical time, bleeding or hospitalization time between GPD and PD. Pancreas head neoplasm was associated with a higher indication of GPD. Resection of less aggressive neoplasms was associated with lower morbidity and mortality.

RESUMO Racional : A duodenopancreatectomia (DP) é procedimento associado com significativa morbimortalidade. Inicialmente descrita como gastroduodenopancreatectomia (GDP), a possibilidade de preservação do antro gástrico e piloro foi descrita na década de 1970. Objetivo : Avaliar a mortalidade e variáveis operatórias da DP com ou sem preservação pilórica e correlacioná-las com a técnica adotada e indicação cirúrgica. Método: Estudo de coorte histórica, baseado em análise de dados de registros médicos de indivíduos submetidos à DP entre os anos de 2012 a 2017. Foram analisadas variáveis demográficas, antropométricas e operatórias e correlacionadas com a técnica adotada (GDP vs. DP) e a indicação cirúrgica. Resultados : Dos 87 indivíduos avaliados, 38 (43,7%) foram submetidos à GDP e 49 (53,3%) à DP. A frequência de realização da GDP (62,5%) foi significativamente maior entre os pacientes com neoplasia de pâncreas (p=0,04). O tempo de internação total foi significativamente menor entre os indivíduos submetidos à ressecção por neoplasias de comportamento menos agressivo (p=0,04). A mortalidade cirúrgica foi de 10,3%, não havendo diferença entre GDP e DP. A mortalidade foi significativamente maior entre os indivíduos submetidos à ressecção por pancreatite crônica (p=0,001). Conclusão : Não houve diferenças na morbimortalidade, tempo cirúrgico, sangramento ou tempo de internação entre GDP e DP. A neoplasia de cabeça de pâncreas associou-se mais com indicação de GDP. A ressecção de neoplasias menos agressivas associou-se a menor morbimortalidade.

Câncer pancreático no Brasil: tendências e projeções da mortalidade até 2029. Arq Gastroenterol / Pancreatic cancer in brazil: mortality trends and projections until 2029

ABSTRACT BACKGROUND: Pancreatic cancer is one of the main cancer-related causes of death in developed countries, and one of the most lethal malignant neoplasms. This type of cancer is classified as the ninth most frequent in the world. OBJECTIVE: Analyze temporal trends for pancreatic cancer in Brazil in the period 2000-2014 and calculate mortality projections for the period 2015-2029. METHODS: Ecological study, with temporal series, based on information provided by the Brazilian Mortality Information System. Analysis included deaths due to pancreatic malignant neoplasms in Brazil in the period 2000-2014, and analyzed according to sex, age group and Brazilian geographic regions. Projections were made until 2029 in five-year periods, calculated in Nordpred (within the R software). Mortality trends were analyzed by Joinpoint regression. RESULTS: Between 2000 and 2014, there were 112,533 deaths due to pancreatic cancer in Brazil. Age-standardised rates was 5.1 deaths/100,000 men and 3.81 deaths/100,000 women. The highest rates were registered for the Midwest region, for both genders. Projections indicated that for the five-year period 2025-2029 there will be increased mortality rates for men in the Northeast and Midwest regions. Joinpoint analysis for Brazil did not reveal significant increases for women (APC=0.4%; 95% CI: -0.2; 1.0), however, there was a significant increasing mortality trend for men (APC= 3.7%; 95% CI: 0.6-7.0) in the period 2000-2004, followed by a stable period, an then another period of significant increases after 2010. These figures are mostly explained by variations in the Brazilian demographic structure. CONCLUSION: Pancreatic cancer mortality is unequally distributed across Brazilian regions and genders, and during the next two decades the differences will be accentuated.

RESUMO CONTEXTO: O câncer de pâncreas é uma das principais causas de morte relacionadas ao câncer em países desenvolvidos, e uma das neoplasias malignas mais letais. Este tipo de câncer é classificado como o nono mais frequente do mundo. OBJETIVO: Analisar as tendências temporais do câncer de pâncreas no Brasil no período de 2000-2014, e calcular as projeções de mortalidade para o período de 2015-2029. MÉTODOS: Estudo ecológico, de séries temporais, baseado em informações advindas do Sistema de Informações sobre Mortalidade brasileiro. A análise incluiu os óbitos por neoplasias malignas pancreáticas no Brasil, no período de 2000 a 2014, avaliados segundo sexo, faixa etária e regiões geográficas brasileiras. As projeções foram feitas até 2029, em períodos de cinco anos, calculados no Nordpred (no software R). E as tendências de mortalidade foram analisadas por regressão Joinpoint. RESULTADOS: Entre 2000 e 2014, ocorreram 112.533 mortes por câncer de pâncreas no Brasil. A taxa padronizada foi de 5,1 mortes /100.000 homens e 3,81 mortes /100.000 mulheres. As maiores taxas foram registradas para a região Centro-Oeste, para os dois gêneros. As projeções indicaram que, para o quinquênio 2025-2029, haverá aumento nas taxas de mortalidade de homens nas regiões Nordeste e Centro-Oeste. A análise do joinpoint para o Brasil não revelou aumento significativo para as mulheres (APC=0,4%; IC95%: -0,2; 1,0), entretanto, houve um aumento significativo da tendência de mortalidade para homens (APC=3,7%; IC95%: 0,6-7,0) no período 2000-2004, seguido de um período de estabilidade e, em seguida, aumento significativo após 2010. Esses resultados são explicados principalmente por variações na estrutura demográfica brasileira. CONCLUSÃO: A mortalidade por câncer de pâncreas está distribuída de forma desigual nas regiões e gêneros brasileiros e, nas próximas duas décadas, as diferenças serão acentuadas.

Utilidad pronóstica del PET/CT en cáncer de páncreas / Prognostic value of PET/CT in pancreatic cancer

Background: Pancreatic cancer is the tenth most prevalent cancer in world, and represents the fourth cause of cancer death. It has a five year-survival of 5%. Aim: To assess the prognostic value of PET/CT in pancreatic cancer. Material and Methods: Sixty-nine patients with pancreatic adenocarcinoma who underwent staging 18F-fluorodeoxyglucose (FDG) PET/CT between December 2008 and July 2016 were selected. Gender, age, body-mass index, laboratory tests (Ca 19-9, hemoglobin, erythrocyte sedimentation rate, liver enzymes, lactate dehydrogenase), histological differentiation of tumor, American Joint Committee on Cancer (AJCC) stage, size and 18F-FDG uptake (maximal stan-dardized uptake value [SUVmax]) of the primary tumor, nodal involvement and distant metastasis detected by PET/CT were registered. Survival was assessed using Kaplan-Meier curves, Log Rank test and Cox multivariable analysis. Results: Mortality was 66.7%, during a mean observation time of 18 months (range 20 days-66 months). Curative surgery, lack of metastases detected by PET/CT, histologically well differentiated tumors, and SUVmax ≤ 4.3 were significantly associated with a better specific survival, determined by the Log Rank test. Histological differentiation was the only variable that had a statistically significant prognostic value in the multivariable analysis. Conclusions: The detection of distant metastases and the intensity of primary tumor 18F-FDG uptake during PET/CT provide useful prognostic information in pancreatic cancer patients.

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.

Twelve years of experience using cholecystojejunal by-pass for palliative treatment of advanced pancreatic cancer / Derivação colecistojejunal para o tratamento paliativo do câncer de pâncreas avançado

ABSTRACT Background: The cholecistojejunal bypass is an important resource to treat obstructive jaundice due to advanced pancreatic cancer. Aim: To assess the early morbidity and mortality of patients with pancreatic cancer who underwent cholecystojejunal derivation, and to assess the success of this procedure in relieving jaundice. Method: This retrospective study examined the medical records of patients who underwent surgery. They were categorized into early death and non-early death groups according to case outcome. Results: 51.8% of the patients were male and 48.2% were female. The mean age was 62.3 years. Early mortality was 14.5%, and 10.9% of them experienced surgical complications. The cholecystojejunostomy procedure was effective in 97% of cases. There was a tendency of increased survival in women and patients with preoperative serum total bilirubin levels below 15 mg/dl. Conclusion: Cholecystojejunal derivation is a good therapeutic option for relieving jaundice in patients with advanced pancreatic cancer, with acceptable rates of morbidity and mortality.

RESUMO Racional: A derivação colecistojejunal é um importante recurso para o tratamento de pacientes com icterícia obstrutiva secundária ao câncer de pâncreas avançado. Objetivo: Avaliar a morbimortalidade precoce dos doentes com câncer de pâncreas submetidos à derivação colecistojejunal, assim como avaliar o alivio da icterícia. Método: Estudo retrospectivo de prontuários de pacientes que foram operados. Eles foram categorizados de acordo com a resolução dos casos em: morte precoce e sem morte precoce. Resultados: 51,8% dos pacientes eram homens e 48,2% mulheres. A média etária foi de 62,3 anos. A mortalidade precoce foi de 14,5%. 10,9% evoluíram com complicações cirúrgicas. A colecistojejunostomia foi efetiva em 97% dos casos. Houve tendência à maior sobrevida em mulheres e pacientes com níveis séricos de bilirrubina total pré-operatório menor do que 15mg/dl. Conclusão: A derivação colecistojejunal constitui boa opção terapêutica para alívio da icterícia em pacientes com câncer de pâncreas avançado, apresentando morbimortalidade aceitável.

Evaluation of microvessel density and p53 expression in pancreatic adenocarcinoma

OBJECTIVE: To evaluate the prognostic significance of microvessel density and p53 expression in pancreatic cancer. METHODS: Between 2008 and 2012, 49 patients with pancreatic adenocarcinoma underwent resection with curative intention. The resected specimens were immunohistochemically stained with anti-p53 and anti-CD34 antibodies. Microvessel density was assessed by counting vessels within ten areas of each tumoral section a highpower microscope. RESULTS: The microvessel density ranged from 21.2 to 54.2 vessels/mm2. Positive nuclear staining for p53 was found in 20 patients (40.6%). The overall median survival rate after resection was 24.1 months and there were no differences in survival rates related to microvessel density or p53 positivity. Microvessel density was associated with tumor diameter greater than 3.0 cm and with R0 resection failure. CONCLUSIONS: Microvessel density was associated with R1 resection and with larger tumors. p53 expression was not correlated with intratumoral microvessel density in pancreatic adenocarcinoma.

Tendência da mortalidade por câncer de pâncreas em Salvador - Brasil, 1980 a 2012 / Mortality trends from pancreatic cancer in Salvador - Brazil, 1980 to 2012 / Tendencia de mortalidad por cáncer de páncreas en Salvador - Brasil, 1980 y 2012

Introdução: O câncer de pâncreas apresenta taxas de letalidade que se aproximam de 100%, com cerca de 250 mil mortes anuais em todo mundo. Objetivo: Descrever a tendência da taxa de mortalidade por câncer de pâncreas no Estado da Bahia e na cidade de Salvador, de 1980 a 2012. Método: Estudo de agregados de série temporal, cujos dados sobre os óbitos e sobre a população foram obtidos no Sistema de Informação sobre Mortalidade e no Instituto Brasileiro de Geografia e Estatística, respectivamente. Para a análise da tendência temporal, utilizou-se a regressão de Poisson, com a avaliação de superdispersão. Resultados: Observou-se uma redução anual média nas taxas padronizadas de mortalidade por câncer de pâncreas de 0,83% entre os homens e de 0,31% entre as mulheres em Salvador. Já no Estado da Bahia, o aumento foi de 2,40% e de 1,97% entre homens e mulheres, respectivamente. Conclusão: O crescimento das taxas no Estado da Bahia evidencia a importância das ações de prevenção primária direcionadas especialmente para o combate ao tabagismo e ao consumo de álcool, principais fatores de risco associados à incidência dessa neoplasia.

Introduction: The pancreatic cancer presents lethality rates approaching 100%, with about 250,000 annual deaths worldwide. Objective: The aim of this paper is to describe the mortality rate trends of pancreatic cancer in the State of Bahia and Salvador city, from 1980 to 2012. Method: Aggregate study, whose data on deaths and on population were obtained from the Mortality Information System and from the Brazilian Institute of Geography and Statistics, respectively. For the analysis of time trends we used Poisson regression with overdispersion assessment. Results: There was an annual average reduction in standardized mortality rates from pancreatic cancer of 0.83% among men and 0.31% among women in Salvador. In the state of Bahia, the rates increased 2.40% and 1.97% among men and women, respectively. Conclusion: The increasing rates in the State of Bahia, indicating the importance of primary prevention actions against tobacco use and alcohol consumption, the main risk factors associated with the incidence of this neoplasm.

Introducción: El cáncer de páncreas presenta tasas de letalidad que se aproximan al 100%, con cerca de 250.000 muertes anuales en todo el mundo. Objetivo: Describir la tendencia de la tasa de mortalidad por cáncer de páncreas en el Estado de Bahia y en la ciudad de Salvador, entre los años 1980 y 2012. Método: se trata de un estudio de agregados de serie temporal cuyos datos sobre los óbitos y la población han sido obtenidos del Sistema de Información sobre Mortalidad y del Instituto Brasileño de Geografía y Estadística, respectivamente. Para el análisis de la tendencia temporal se ha utilizado la regresión de Poisson, con la evaluación de sobredispersión. Resultados: Se observó una reducción anual media de las tasas estandarizadas de mortalidad por cáncer de páncreas del 0,83% entre los hombres y 0,31% entre las mujeres en Salvador. En el Estado de Bahía, se encontró una tendencia creciente, siendo que ese aumento fue de 2,40% y del 1,97% para los hombres y mujeres, respectivamente. Conclusión: El crecimiento de las tasas indica la importancia de las acciones de prevención primaria dirigidas contra el consumo de tabaco y alcohol, los principales factores de riesgo asociados con la incidencia de esta neoplasia.

Higher overall survival in metastatic pancreatic cancer: the impact of where and how treatment is delivered / Maior sobrevida global em pacientes com câncer pancreático metastático: o impacto de onde e como o tratamento é realizado

Objective To determine the overall survival of patients with advanced pancreatic cancer and evaluate factors that impact prognosis in a private cancer center.Methods Data from the Hospital Cancer Registry at Hospital Israelita Albert Einstein were retrospectively collected. The patients enrolled had metastatic cancer at diagnosis or earlier staging and subsequent recurrence. Cases of neuroendocrine tumors were excluded.Results A total of 65 patients were evaluated, including 63 with adenocarcinoma. The median overall survival for patients in all stages was 20.7 months (95%CI: 15.6-25.7), while the overall survival of metastatic disease was 13.3 months. Among the 33 cases with stage IV cancer, there was no evidence of a statistically significant association between median survival and CA19-9 dosage (p=0.212), tumor location (p=0.482), first treatment performed (p=0.337), lymphovascular invasion (p=0.286), and age (p=0.152). However, the number of lines of chemotherapy was significantly associated with survival (log-rank p=0.013), with an estimated median survival of 10.2 months for patients who received up to two lines of treatment and 23.5 months for those receiving more than two lines of chemotherapy.Conclusion The survival of patients treated was longer than that reported in the literature. The only statistically significant factor related to increased survival was higher number of lines of chemotherapy received. We believe that the higher socioeconomic status of patients surveyed in this study, as well as their greater access to treatment options, may have influenced their overall survival.

Objetivo Determinar a sobrevida global dos pacientes com câncer pancreático avançado e avaliar fatores com impacto prognóstico em um centro de câncer privado.Métodos Foram coletados retrospectivamente os dados do Registro de Câncer do Hospital Israelita Albert Einstein. Os pacientes incluídos apresentaram câncer metastático ao diagnóstico ou em estádio mais precoce com recorrência subsequente. Os casos de tumores neuroendócrinos foram excluídos.Resultados Foram avaliados 65 pacientes, incluindo 63 com adenocarcinoma. A sobrevida global mediana dos pacientes em todos os estádios foi 20,7 meses (IC95%: 15,6-25,7), enquanto a sobrevida global de doença metastática foi de 13,3 meses. Entre os 33 casos com câncer em estádio IV, não houve evidência de associação estatisticamente significativa entre a sobrevida mediana e CA19-9 ao diagnóstico (p=0,212), localização do tumor (p=0,482), primeiro tratamento realizado (p=0,337), invasão vasculo-linfática (p=0,286) e idade (p=0,152). No entanto, o número de linhas de quimioterapia foi significativamente associado com a sobrevida (log-rankp=0,013), com uma sobrevida mediana estimada de 10,2 meses para os pacientes que receberam até duas linhas de tratamento e de 23,5 meses para os que receberam mais de duas linhas.Conclusão A sobrevida dos pacientes tratados foi maior do que o relatado na literatura. O único fator estatisticamente significativo relacionado à maior sobrevida foi maior número de linhas de quimioterapia recebidas. Acreditamos que o nível socioeconômico dos pacientes pesquisados neste estudo, assim como seu maior acesso a opções de tratamento, pode ter influenciado em sua sobrevivência global.

Auditory Brainstem Response in Term and Preterm Infants with Neonatal Complications: The Importance of the Sequential Evaluation

Introduction Literature data are not conclusive as to the influence of neonatal complications in the maturational process of the auditory system observed by auditory brainstem response (ABR) in infants at term and preterm. Objectives Check the real influence of the neonatal complications in infants by the sequential auditory evaluation. Methods Historical cohort study in a tertiary referral center. A total of 114 neonates met inclusion criteria: treatment at the Universal Neonatal Hearing Screening Program of the local hospital; at least one risk indicator for hearing loss; presence in both evaluations (the first one after hospital discharge from the neonatal unit and the second one at 6 months old); all latencies in ABR and transient otoacoustic emissions present in both ears. Results The complications that most influenced the ABR findings were Apgar scores less than 6 at 5 minutes, gestational age, intensive care unit stay, peri-intraventricular hemorrhage, and mechanical ventilation. Conclusion Sequential auditory evaluation is necessary in premature and term newborns with risk indicators for hearing loss to correctly identify injuries in the auditory pathway. .

Influence of surgical technique in the peritoneal carcinomatosis surgical wound implant: experimental model in mice / Influência da técnica cirúrgica na implantação da carcinomatose peritoneal em ferida operatória: modelo experimental em camundongos

BACKGROUND: The number of malignancies increased alarmingly. Surgery constitutes one of the most efficient therapeutic modalities for the treatment of solid tumors. The neoplastic implant in surgical wound is a complication whose percentage of occurrence reported in the literature is variable, but sets with high morbidity and therapeutic difficulties. Protecting the wound is one of the recommended principles of oncologic surgery. AIM: To evaluate the influence of wound protection in the development of tumor implantation. METHODS: Sarcoma 180 tumor cells were used, with intraperitoneal inoculation in Swiss mice. After the establishment of neoplastic ascites, animals were randomized into two groups of 10, each group consisting of five males and five females. In both groups, laparotomy and manipulation of intra-abdominal organs was performed. In a group laparotomy was performed using the protection of the abdominal wound and the other group without it. On the 9th postoperative day macroscopic evaluation of the operative scar was performed, which was later removed for microscopic evaluation. RESULTS: There was microscopic infiltration of tumor cells in the wound of all animals. However, the group that held the protection, infiltration was less intense when compared to the group without it. The infiltration was also more severe in females than in males of the same group. CONCLUSION: Tumor infiltration into the wound was more intense in the group in which the protection of the surgical site was not performed, and in females when compared to males of the same group. .

RACIONAL: O número de neoplasias vem aumentando de maneira preocupante. O tratamento cirúrgico constitui-se em uma das modalidades terapêuticas mais eficientes para os tumores sólidos. O implante neoplásico em ferida operatória é complicação cujo percentual de ocorrência relatado na literatura é variável, porém configura alta morbidade e grande dificuldade terapêutica. A proteção da ferida operatória é um dos princípios de cirurgia oncológica recomendados, entretanto pouco estudado. OBJETIVO: Avaliar a influência da proteção de ferida operatória no desenvolvimento de implante tumoral na ferida operatória. MÉTODOS: Foram utilizadas linhagens de células tumorais do Sarcoma 180, com inoculação intraperitoneal em camundongos Swiss. Após o estabelecimento da ascite neoplásica, os animais foram randomizados em dois grupos de 10, cada grupo composto por cinco machos e cinco fêmeas. Nos dois grupos foi realizada laparotomia e manipulação de órgãos intra-abdominais. Em um grupo a laparotomia foi realizada utilizando a proteção da ferida abdominal e no outro grupo sem proteção. No 9º dia pós-operatório foi realizada avaliação macroscópica da cicatriz operatória, sendo esta removida posteriormente para avaliação microscópica. RESULTADOS: Houve infiltração microscópica de células tumorais na ferida operatória em todos animais. Porém, no grupo em que se realizou a proteção da ferida a infiltração foi menos intensa quando comparado ao grupo sem proteção. A infiltração também foi mais intensa nas fêmeas do que nos machos do mesmo grupo. CONCLUSÃO: A infiltração tumoral na ferida operatória foi mais intensa no grupo em que não foi realizada a proteção da ferida operatória e nas fêmeas quando comparadas aos machos do mesmo grupo. .

Role of neoadjuvant concurrent chemoradiation in locally advanced unresectable pancreatic cancer: A feasibility study at tertiary care centre.

BACKGROUND: Pancreatic cancer has an extremely poor prognosis and prolonged survival is achieved only by resection with macroscopic tumor clearance. There is a strong rationale for a neoadjuvant approach, since a relevant percentage of pancreatic cancer patients present with non‑metastatic but locally advanced disease. The objective of the present study was to assess the effect of neoadjuvant chemoradiation therapy (NACRT) on tumor response, down staging and resection, toxicity and any survival advantage. MATERIALS AND METHODS: A prospective pilot study was carried out from January 2009 to June 2011 in which 15 patients of locally advanced unresectable pancreatic cancer were included. All patients were treated with NACRT protocol with oral Capecitabine and 3D conformal radiotherapy (3DCRT) of 30 Gy in 10 fractions. The patients were restaged 3 to 4 weeks after the completion of NACRT and explored for resection. RESULTS: Out of 15 patients, fourteen were evaluable. Four patients underwent surgery, 5 had partial response but remained unresectable, 2 patients had stable disease and 3 had progressive disease. Most of the toxicities were slight and were in grade 1 to 2. None of the patients developed grade 3 or 4 gastrointestinal or hematological toxicity. The median survival was 15 months for resected patients and 8.6 months for unresected patients, respectively. The 2 year actuarial overall survival was 34.6%. CONCLUSION: All patients with locally unresectable pancreatic cancer should be offered chemoradiation therapy, in hopes of down staging the tumor for possible resection and achieving higher survival.

LOW MORTALITY RATE IN 97 CONSECUTIVE PANCREATICODUODENECTOMIES: the experience of a group / Baixa mortalidade em 97 duodenopancreatectomias consecutivas: a experiência de um grupo

Context Pancreaticoduodenectomy is the procedure of choice for resectable cancer of the periampullary region. These tumors account for 4% of deaths from cancer, being referred to as one of the lowest survival rates at 5 years. Surgery remains a complex procedure with substantial morbidity and mortality. Despite reports of up to 30% mortality rates, in centers of excellence it have been identified as less than 5%. Recent studies show that pancreaticojejunostomy represents the “Achilles’ heel” of the procedure. Objective To evaluate the post-operative 30 days morbidity and mortality rates. Methods Retrospective analysis of 97 consecutive resected patients between July, 2000 and December, 2012. All patients were managed by the same group, and data were obtained from specific database service. The main objective was to evaluate the 30-day mortality rate, but we also studied data of surgical specimen, need for vascular resection and postoperative complications (gastric stasis, pancreatic fistula, pneumonia and reoperation rate). Results Thirty-day mortality rate was 2.1% (two patients). Complete resection with no microscopic residual tumor was obtained in 93.8% of patients, and in 67.3% of cases pathology did not detected metastatic nodes. Among postoperative complications were reported 6% of prolonged gastric stasis, 10.3% of pneumonia, 10.3% of pancreatic fistula and 1% of infection in the drain pathway. Two patients underwent reoperation due to bleeding and infected hematoma caused by pancreatic fistula, and another for intestinal obstruction because of adhesions at postoperative day 12. Conclusions The pancreaticoduodenectomy as treatment procedure for periampullary cancers has a low morbidity and mortality rate in services with experience in Hepato-Pancreato-Biliary surgery, remaining as first-line treatment in resectable patients. .

Contexto A duodenopancreatectomia é o procedimento de escolha para neoplasias ressecáveis da região periampolar. Estes tumores representam 4% dos óbitos por câncer, sendo referida como uma das mais baixas taxas de sobrevida em 5 anos. A cirurgia continua sendo um procedimento complexo com substancial morbi-mortalidade. Apesar dos relatos de até 30% de mortalidade, em serviços de excelência tem sido apontada como inferior a 5% e estudos recentes mostram que a pancreatojejunostomia representa o “tendão de Aquiles” do procedimento. Objetivo Avaliar a morbi-mortalidade em 30 dias nesta série de pacientes ressecados. Métodos Analisamos até o momento dados de 97 pacientes consecutivos submetidos à duodenopancreatectomia de julho de 2000 a dezembro de 2012. Todos os pacientes foram manejados pelo mesmo grupo e os dados obtidos de banco de dados específico do serviço. O objetivo principal era avaliar a mortalidade em 30 dias, mas também foi reportado os dados referentes ao espécime cirúrgico, a necessidade de ressecção vascular e complicações pós-operatórias (estase gástrica, fístula pancreática, pneumonia e taxa de reoperação). Resultados A mortalidade em 30 dias foi 2.1% (dois pacientes). Em 93.8% dos pacientes a ressecção foi completa com margem microscópica tumoral negativa e em 67.3% dos casos não se detectou linfonodos metastáticos ao estudo anatomopatológico. Entre as complicações pós-operatórias, foram relatadas 6% de estase gástrica prolongada, 10.3% de pneumonia, 10.3% de fístula pancreática e 1% de infecção no trajeto do dreno. Dois pacientes foram submetidos a reoperação devido a sangramento e hematoma infectado decorrente de fístula pancreática. Um paciente foi reoperado por ...

Tumores neuroendocrinos del páncreas: resultados quirúrgicos y sobrevida alejada / Pancreatic neuroendocrine tumors: surgical outcomes and overall survival

Background: pancreatic neuroendocrine tumors (PNET) account for 1-2percent of pancreatic neoplasms. Its incidence has increased in recent years probably due to improved imaging studies. Aim: to analyze the clinical characteristics, surgical outcomes and overall survival of patients with PNET who underwent resective surgery. Methods: case series study. Data was collected from the central database and clinical records from patients with biopsy-proven PNET's who underwent surgical resection from june 2005 to june 2012. Results: twenty patients were included (10.6 percent of all pancreatic resections), 12 female, with a median age of 44 [20-77] years. Abdominal pain was the most common symptom. Two patients had a type 1 multiple endocrine neoplasia (MEN-1) syndrome. Pre-operative work up included CT, MR and/or PET/CT. Five patients had functional tumors. Five Whipple procedures, 14 distal pancreatectomies and 1 enucleation were performed. Among the postoperative complications, there were 5 type B and 1 type C pancreatic fistulas. There was no mortality. At 31 [5-90] month median follow-up, overall survival was 100%. Conclusion: PNETs represent an increasing reason for pancreatic resection in our center. Surgical resection of the tumor with negative microscopic margins is the treatment of choice.

Introducción: los tumores neuroendocrinos del páncreas (TNEP) representan el 1-2 por ciento de las neoplasias pancreáticas. Su incidencia ha aumentado en los últimos años debido probablemente a la mayor capacidad diagnóstica de los estudios por imágenes. Objetivos: analizar las características clínicas, resultados quirúrgicos y sobrevida alejada de los pacientes con TNEP operados en nuestro centro. Material y Métodos: estudio descriptivo de una serie de casos. Análisis de base de datos y registros clínicos de los pacientes con diagnóstico histológico de TNEP sometidos a cirugía resectiva en nuestro centro entre junio de 2005 y junio de 2012. Resultados: serie compuesta por 20 pacientes (10,6 por ciento de las resecciones pancreáticas), 12 de sexo femenino, con una mediana de edad de 44 (20-77) años. El dolor abdominal fue el síntoma de presentación más frecuente. Dos pacientes eran portadores del síndrome de neoplasia endocrina múltiple tipo 1 (NEM-1). La evaluación diagnóstica se realizó con CT, RM y/o PET/CT. Los tumores fueron funcionantes en 5 enfermos. Se realizaron 5 pancreatoduodenectomías (PD), 14 pancreatectomías corporocaudales (PC) y 1 enucleación. Entre las complicaciones postoperatorias, hubo 5 fístulas pancreáticas tipo B y una tipo C. No hubo mortalidad. En el seguimiento (mediana de 31 [5-90] meses), ningún paciente falleció por progresión de la enfermedad. Conclusión: los TNEP representan una patología en aumento en nuestro centro. La cirugía resectiva con márgenes microscópicos negativos es la alternativa terapéutica de elección.

Técnica y resultados con reconstrucción pancreato-gástrica ducto-mucosa en pancreatoduodenectomy / Duct-to-mucosa pancreaticogastrostomy after pancreatoduodenectomy: experience in 37 patients

Background: Pancreatic reconstruction in pancreatoduodenectomy (PD) has many technical options. Evidence shows no difference in pancreatic fistula rate or mortality between pancretogastrostomy and pancrea-ticojejunostomy reconstruction. Aim: To report the results of the technique used by our team to perform duct-to-mucosa pancreaticogastrostomy (DMPG) in PD. Material and Methods: Follow up of 37 patients aged 53 +/- 12 years (59 percent women), subjected to pancreatoduodenectomy, using DMPG. Perioperative complications were reported using the Dindo-Clavien classification. Results: All patients had a pancreatic cancer. The tumor was located in the head or ampulla of Vater in 38 percent of patients. The most common histological type was adenocarcinoma in 33 patients (89 percent). Seventy three percent of patients did not have regional lymph node involvement (NO). Two patients died (5 percent). Postoperative complications were registered in 35 percent of patients. Two patients developed pancreatic fistulas, that were type A and B I one patient each, according to the classification of the International Study Group on Pancreatic Fistula. Conclusions: The morbidity and mortality associated with DMPG in PD in the reported cohort are comparable to those reported by other local studies.

Introducción: Para la reconstrucción pancreática en pancreatoduodenectomía (PD) existen diversas técnicas; la evidencia científica no demuestra diferencia en el porcentaje de fístulas pancreáticas ni morbi-mortalidad entre la reconstrucción con pancreatogastrostomía y pancreatoyeyunostomía. Nuestro objetivo es describir la técnica de pancreato-gastro anastomosis ducto-mucosa (PGADM) y los resultados en términos de morbimortalidad de esta técnica utilizada para la reconstrucción pancreática en PD. Material y Método: Estudio de serie de casos con seguimiento. Se incluyeron pacientes mayores de 15 años que fueron sometidos a PD y en los cuales se realizó reconstrucción pancreática con PGADM por el equipo de cirugía hepatopancreática y biliar del Hospital Regional de Temuco desde 1996 hasta 2010. Se reportó morbilidad perioperatoria según la clasificación de Dindo-Clavien. Se aplica estadística descriptiva. Resultados: La cohorte está constituida por 37 pacientes, la edad promedio fue 53 +/- 12 años y el 59 por ciento género masculino. Todos los pacientes tienen confirmación histopatológica de neoplasia, siendo los orígenes más frecuentes la cabeza del páncreas y ampolla de Vater con un 38 por ciento. El tipo histológico más frecuente fue el adenocarcinoma en 33 pacientes (89 por ciento). El 73 por ciento de los pacientes no tenía compromiso de ganglios linfáticos regionales (N0). La morbilidad peri operatoria fue de 35 por ciento. Dos pacientes presentaron fístulas pancreáticas (5,4 por ciento), uno tipo A y otra tipo B según la clasificación de la ISGPF. La mortalidad perioperatoria es de 2 pacientes (5 por ciento). Conclusiones: La morbi-mortalidad asociada a PD con reconstrucción pancreática con PGADM es comparable a la reportada por series nacionales.

Resultados actuales de la pancreatoduodenectomía para el tratamiento de los tumores periampulares y análisis de factores pronósticos de sobrevida / Results of pancreaticoduodenectomy in the treatment of periampullary tumors

Background: The diagnosis and treatment of periampullary tumors represents a challenge for current medicine. Aim: To review the results of pancreaticoduodenectomy (PDD) in the treatment of periampullary tumors and to identify risk factors that impact the long-term survival. Patients and Methods: We performed a retrospective study of patients who underwent a PDD for periampullary tumors between 1993 and 2009. We reviewed perioperative results and long term survival. We performed a multivariate analysis for long-term survival. Results: A PDD was performed in 181 patients aged 58 ± 12 years (98 females). Piloric preservation was done in 53 percent and a pancreatogastric anastomosis was used in 94 percent of cases. Morbidity was 62 percent and postoperative mortality was 5.5 percent. Pancreatic cancer was the most frequent pathological finding in 41 percent, followed by ampullary cancer in 28 percent and distal bile duct cancer in 16 percent. Median survival was 17 months, with a five years survival of 24 percent. Survival for ampullary tumors was 28 months with a five years survival of 32 percent. The median and five years survival were 14 months and 16 percent for bile duct cancer and 11 months and 14 percent for pancreatic cancer. Multivariate analysis identified tumor type (pancreas /bile duct) and lymph node dissemination as independent predictors of mortality. Conclusions: One quarter of patients experienced long term survival. Mortality predictors were tumor type and lymph node dissemination.