ORIGINAL ARTICLE
AG-2018-13 dx.doi.org/10.1590/S0004-2803.201800000-59
Pancreatic cancer in Brazil: mortality trends and projections until 2029 Isabelle Ribeiro BARBOSA, Camila Alves dos SANTOS and Dyego Leandro Bezerra de SOUZA Received 8/2/2018 Accepted 31/7/2018
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 20002004, 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. HEADINGS – Pancreatic neoplasms. Mortality. Forecasting. Demography.
INTRODUCTION
Pancreatic cancer is one of the main cancer-related causes of death in developed countries, and one of the most lethal malignant neoplasms in the world(1). Considering the year 2012, 337 thousand people were diagnosed with pancreatic cancer in the world, while 330 thousand people died because of this disease. This type of cancer is classified as the ninth most frequent in the world, despite its rarity. Due to its high mortality rates, pancreatic cancer is the seventh cancer-related cause of death in the world(2). The symptoms of pancreatic cancer are initially insidious and gradually progress over time, including epigastric pain with or without posterior irradiation, weight loss, discomfort, nausea and fatigue. Jaundice is a characteristic sign of cancers in the head of the pancreas, due to the compression of the common bile duct. Sometimes a tumor can extend to the duodenum or stomach, leading to the obstruction of the gastric outlet(3). The two main types of pancreatic cancer are adenocarcinoma (responsible for 85% of cases) and pancreatic endocrine tumors (which represent less than 5% of cases)(1). Only 10%-10% of patients are diagnosed in initial stages, when surgical resection can be an option. More than 90% of individuals are diagnosed in advanced stages. Due to the bad prognosis and late treatment, the survival rates during the first year of diagnosis is very low (10%-20%) and decreases to 5% in the fifth year(4). Currently there are no adequate, safe, effective and sensible monitoring strategies in terms of costs, to be implemented for the
general population, even for those with significant risk factors, such as exposure to tobacco and advanced age(5). Moreover, environmental and genetic factors contribute to the etiology of pancreatic cancer. Individuals with family history of pancreatic cancer have a higher risk of developing the disease and this risk increases with the number of first-degree relatives affected. Family history is related to germinal mutations in genes CDKN2A, BRCA2, PALB2, STK11 and PRSS1, which have been demonstrated to increase the risk of developing pancreatic cancer(6). The consumption of tobacco is the most consistently risk factor established for pancreatic cancer, contributing to 25% of cases. Other suspected risk factors include the excessive consumption of alcohol, chronic pancreatitis, and dietary-endocrine factors(7). Emerging molecular studies suggest that the carcinogenic effect of hyperglycemia, the mitogenic effect of hyperinsulinemia associated with obesity and chronic inflammation in diabetes can be considered as risk factors involved in the proliferation and metastasis of pancreatic cancer(8). Pancreatic cancer occurs at all ages, but the incidence peak occurs between 60 and 80 years of age. Less than 10% of cases occur in individuals under the age of 55, and the average onset age is 71 years(3). Pancreatic cancer rates are considerably higher in the Afro-American population than in any other racial group. Men present higher incidence rates than women(9). As a disease with remarkable mortality, comprehension of the geographic distribution of pancreatic cancer and the behavior of rates throughout time is important, as the analysis of the epidemiological situation is necessary to support the planning of public
Declared conflict of interest of all authors: none Disclosure of funding: no funding received Universidade Federal do Rio Grande do Norte, Departamento de Saúde Coletiva, Programa de Pós-Graduação em Saúde Coletiva, Natal, RN, Brasil. Corresponding author: Dyego Leandro Bezerra de Souza. Orcid: 0000-0001-8426-3120. E-mail:
[email protected].
230 • Arq Gastroenterol • 2018. v. 55 nº 3 jul/set
Barbosa IR, Santos CA, Souza DLB. Pancreatic cancer in Brazil: mortality trends and projections until 2029
health measures for vulnerable groups. To this date, few studies have examined the epidemiology of pancreatic cancer in South America, especially in Brazil. Therefore, the objective of the study presented herein is to analyze the temporal trends of pancreatic cancer in Brazil and its geographic regions in the period 2000-2014 and calculate mortality projections for the period 2015-2029. METHODS
A temporal series, ecological study was carried out, based on secondary data registered by the Brazilian Mortality Information (SIM), made available by the Informatics Department of the Unified Health System (Brazil’s publicly funded healthcare system). Analysis included deaths due to pancreatic malignant neoplasms (C25) categorized from the International Statistical Classification of Diseases and Related Health Problems – 10th revision (ICD-10) occurred in Brazil in the period 2000-2014, and analyzed according to sex, age group and Brazilian geographic regions. Although within recent years it is recognized that SIM experimented a significant improvement in quality, the utilization of secondary data on mortality is subject to under-registry. For the correction of under-registered deaths by pancreatic cancer, information was obtained from the Redistribution of the Deaths per Chapters, corrected by Active Search Investigation, an initiative of the Ministry of Health, with data provided by the Informatics Department of the Unified Health System. The correction factor was calculated for each age group, period, region and sex, from the percentage difference between the amount of deaths reported to SIM and redistributed deaths, based on Chapter II (Neoplasms) of ICD-10. The difference (D) was expressed in decimal values with 1 corresponding to a 100% change, with the possibility of obtaining values higher than 1 as some locations presented redistributed values above those reported to SIM (Equation 1). When the redistributed value was less than what was reported to SIM, a negative difference was obtained. D=
NR − NS NS
In Equation 1, NR is the number of redistributed deaths by neoplasms, and NS is the number of neoplasm-related deaths reported to SIM. The difference obtained (D) was added to the value 1 to establish a correction value (F, in agreement with Chapter II - neoplasms), as the number 1 represents a neutral factor in a multiplication, according to Equation 2: F= 1 + D Factor F was then multiplied by the number of deaths by suicide. It was assumed that the correction factor for Chapter II was applicable to pancreatic cancer, as shown by Equation 3: OC= F x NOS In equation 3, OC is the corrected number of deaths due to pancreatic cancer, and NOS is the number of deaths due to pancreatic cancer reported to SIM. With information on the readjusted number of deaths, standardized mortality rates were calculated, adjusted to the world population, per 100,000 inhabitants(10). Population data by region, sex and age were obtained from demographic censuses and inter-
census projections, available at the website of the Brazilian Institute of Geography and Statistics. The temporal trends of pancreatic cancer mortality in Brazil and its geographic regions were analyzed, and projections were made until 2029 in five-year periods (2015-2019, 2020-2024 and 2025-2029). Analysis of mortality trends utilized Joinpoint regression, with software Joinpoint Regression Program (National Cancer Institute, Bethesda, Maryland, USA), version 4.4.0. The objective of the analysis is to identify the occurrence of possible joinpoints, where significant changes in trends occurred. The applied method identified joinpoints based on the model with up to three change points. The final model selected was the most adjusted method, with Annual Percentage Change (APC) based on the trend of each segment, estimating whether these values were statistically significant to a 0.05 level. The significance tests utilized were based on the Monte Carlo permutation method and on the calculation of the annual percentage variation of the ratio, utilizing the logarithm of the ratio. In the description of trends, the terms “significant increase” or “significant decrease” mean that the slope of the trend is statistically significant (P
