Gallbladder Cancer In Chile Research Articles

Epigenome-Wide Analysis of Methylation Changes in the Sequence of Gallstone Disease, Dysplasia, and Gallbladder Cancer.

Gallbladder cancer (GBC) is a highly aggressive malignancy of the biliary tract. Most cases of GBC are diagnosed in low-income and middle-income countries, and research into this disease has long been limited. In this study we therefore investigate the epigenetic changes along the model of GBC carcinogenesis represented by the sequence gallstone disease → dysplasia → GBC in Chile, the country with the highest incidence of GBC worldwide. To perform epigenome-wide methylation profiling, genomic DNA extracted from sections of formalin-fixed, paraffin-embedded gallbladder tissue was analyzed using Illumina Infinium MethylationEPIC BeadChips. Preprocessed, quality-controlled data from 82 samples (gallstones n=32, low-grade dysplasia n=13, high-grade dysplasia n=9, GBC n=28) were available to identify differentially methylated markers, regions, and pathways as well as changes in copy number variations (CNVs). The number and magnitude of epigenetic changes increased with disease development and predominantly involved the hypermethylation of cytosine-guanine dinucleotide islands and gene promoter regions. The methylation of genes implicated in Wnt signaling, Hedgehog signaling, and tumor suppression increased with tumor grade. CNVs also increased with GBC development and affected cyclin-dependent kinase inhibitor 2A, MDM2 proto-oncogene, tumor protein P53, and cyclin D1 genes. Gains in the targetable Erb-B2 receptor tyrosine kinase 2 gene were detected in 14% of GBC samples. Our results indicate that GBC carcinogenesis comprises three main methylation stages: early (gallstone disease and low-grade dysplasia), intermediate (high-grade dysplasia), and late (GBC). The identified gradual changes in methylation and CNVs may help to enhance our understanding of the mechanisms underlying this aggressive disease and eventually lead to improved treatment and early diagnosis of GBC.

Need for Prophylactic Cholecystectomy in Silent Gall Stones in North India

One of the criteria for recommending cholecystectomy for silent gall stones, is gall stones in regions with high incidence of gall bladder cancer. Both gall stones and gall bladder cancer are common in North India. All tertiary care centres in India report high rates of gall bladder cancer (GBC) incidence and poor treatment outcomes in the majority of cases due to advanced stage of presentation. Csendes of Chile has reported very high incidence of gallbladder cancer in Chile and Bolivia and advocated prophylactic cholecystectomy in asymptomatic patients. Incidence rate of gall bladder cancer in Indian males is equal to that of Chile, whereas in females, the rates are almost double the rates of Chile. Indians have also been found to have high concentrations of heavy metals in gall bladder wall, and antibodies to tumor suppressor genes. In India, gall bladder cancer is the commonest GI cancer in women and fourth commonest cancer overall in the female population. In view of the epidemiology and clinical scenario of gall bladder cancer and proven safety of laparoscopic cholecystectomy, there is a need to act before it is too late in the current rates of gall bladder cancer. This study looks at the evidence correlating gall stones and gall bladder cancer, in relation to India. There is pressing evidence today to justify a strategy of prophylactic cholecystectomy in silent gall stones in North India. Data for this study was selected through an internet based search for literature concerning gall stones and gall bladder cancer in India, and for prophylactic cholecystectomy.

Association of aflatoxin with gallbladder cancer in Chile.

Association of aflatoxin with gallbladder cancer in Chile.

Gallbladder cancer in Chile: what have we learned?

Gallbladder cancer (GBC) should be considered an orphan disease in oncology and represent a unique carcinogenetic model. This review will analyse some of the current aspects of GBC. Chile has the highest incidence and mortality of GBC in the world. Most patients are diagnosed in advanced stages with few treatment options. During the last two decades, little progress has been made in early diagnosis and treatment. At the molecular level, recent access to next-generation sequencing and other techniques for detecting the mutations of multiple genes have made advances in this area. The use of therapies targeted according to the detection of specific molecular alterations is in the early stages of evaluation and could represent a significant advance in the treatment of a large number of patients from developing countries.

Tu1947 Circulating Immune-Related Markers and Gallbladder Cancer in Chile

Tu1947 Circulating Immune-Related Markers and Gallbladder Cancer in Chile

Gallbladder Cancer in Chile

To explore gallbladder cancer (GBC), the second leading cause of cancer-related death in women in Chile. Analysis of macroscopic and microscopic variables, morphometry, and survival in 1,366 patients with GBC. Patients comprised 1,138 women and 228 men; diagnoses included 213 (15.6%) cases of mucosal carcinoma, 132 (9.7%) cases of muscular carcinoma, 316 (23.1%) cases of subserosal carcinoma, 382 (28.0%) cases of serosal carcinoma, and 323 (23.6%) cases beyond the serosa. Women older than 55 years with a gallbladder length greater than 9.5 cm had a five-times-greater relative risk of cancer. Those with a gallbladder wall thickness less than 7 mm had a better 5-year survival rate than those with a gallbladder wall thickness greater than 10 mm (P = .0001). Patients who had cholesterolosis of the gallbladder had 9.2 times less probability of having cancer. The infiltration level of the gallbladder wall was the most important independent prognostic factor (P < .001), followed by differentiation and lymphatic involvement (P < .001 and P = .05, respectively). Vascular infiltration had a mortality rate of 100%. Morphologic features are strongly associated with the prognosis of GBC and must be taken into consideration when supplementary treatment is recommended.

Cancer: scenario and relationship of different geographical areas of the globe with special reference to North East-India.

Cancer is becoming the most important public health burden around the globe. As per the GLOBOCAN 2008 estimates, about 12.7 million cancer cases and 7.6 million cancer deaths were estimated to have occurred in 2008. The burden of cancer cases for India in the year 2020 is calculated to be 1,148,757 (male 534,353; female 614,404) compared to 979,786 in 2010. The pattern of cancer incidence is varying among geographical regions, esophageal cancer for example being high in China, lung cancer in USA, and gallbladder cancer in Chile. The question remains why? Is it due to the diversity in genome pool, food habits, risk factor association and role of genetic susceptibility or some other factors associated with it? In India, the North East (NE)-India region is seeing a marked increase in cancer incidence and deaths, with a very different cancer incidence pattern compared to mainland India. The genome pool of the region is also quite distinct from the rest of India. Northeastern tribes are quite distinct from other groups; they are more closely related to East Asians than to other Indians. In this paper an attempt was made to see whether there is any similarity among the pattern of cancer incidence cases for different sites of NE-India region to South or East-Asia. Principal Component Analysis (PCA), Hierarchical Cluster Analysis (HCA), Pearson Correlation coefficient test was assessed to evaluate the linkage of North-East India region to other regions. A p value <0.05 was considered as statistically significant. The results clearly shows that there are similarities in occurrence of cancer incidence patterns for various cancer sites of NE-India with South and East-Asian regions, which may lead to the conclusion that there might be a genetic linkage between these regions.

Geographic variation of gallbladder cancer mortality and risk factors in Chile: a population-based ecologic study.

Chile's gallbladder cancer rates are among the highest in the world, being the leading cause of cancer deaths among Chilean women. To provide insights into the etiology of gallbladder cancer, we conducted an ecologic study examining the geographical variation of gallbladder cancer and several putative risk factors. The relative risk of dying from gallbladder cancer between 1985 and 2003 was estimated for each of the 333 Chilean counties, using a hierarchical Poisson regression model, adjusting for age, sex and geographical location. The risk of gallbladder cancer mortality was analyzed in relation to region, poverty, Amerindian (Mapuche) population, typhoid fever and access to cholecystectomy, using logistic regression analysis. There were 27,183 gallbladder cancer deaths, with age and sex-adjusted county mortality rates ranging from 8.2 to 12.4 per 100,000 inhabitants. Rates were highest in inland and southern regions. Compared to the northern-coast, the northern-inland region had a 10-fold risk (95% of confidence interval (95% CI): 2.4-42.2) and the southern-inland region had a 26-fold risk (95% CI: 6.0-114.2). Independent of region, other risk factors for gallbladder cancer included a high Mapuche population (Odds ratio (OR):3.9, 95% CI 1.8-8.7), high typhoid fever incidence (OR:2.9, 95% CI 1.2-6.9), high poverty (OR:5.1, 95% CI 1.6-15.9), low access to cholecystectomy (OR:3.9, 95% CI 1.5-10.1), low access to hospital care (OR:14.2, 95% CI 4.2-48.7) and high urbanization (OR:8.0, 95% CI 3.4-18.7). Our results suggest that gallbladder cancer in Chile may be related to both genetic factors and poor living conditions. Future analytic studies are needed to further clarify the role of these factors in gallbladder cancer etiology.

Cáncer de vesícula biliar: Tendencia y distribución del riesgo en Chile

Gallbladder cancer (GBC) is the first cause of death by cancer among Chilean women and mortality has not improved in the last 20 years. To study GBC mortality trend from 1985-2002, analyze risk differentials by age, sex, geographic region and accessibility to surgery. Mortality data was obtained from death certificate databases. Population data was obtained from the census and biliary surgery information, from Ministry of Health registries. Standardized Mortality rates were based in the world population; trend was analyzed with point of change methods. From 1985 to 2002, 27,183 GBC deaths occurred, 1,510 per year. The absolute number of deaths increased in 65% but standardized mortality rates remained unchanged at 11.3 per 100,000. These were higher among women than men (15.6 and 7.0, respectively, with a risk ratio of 2.2). Sex ratio peaked at ages 35-54 with risk ratio of 4.1. Death risk increased from North to South, peaking in poorer areas, especially in places with rural population and Mapuche ethnic admixture. Mortality appear to correlate with the rate of people waiting for gallbladder surgery, but not reaching statistical significance (r(2) 0.27, ns). Compared with other countries, Chile has a higher rate of GBC deaths in relation to its gross domestic product per capita. There is a high and persistent persistent risk for GBC in Chile, particularly among women, from the Southern regions where gallbladder surgery is insufficient for the needs, as reflected by the rates of people waiting for biliary surgery. GBC rates could be dropped by offering gallbladder surgery to everyone waiting for it and to those incident cases with gallstones.

Gallbladder cancer in Chile and selected countries

Se presenta un trabajo descriptivo que analiza la mortalidad por cáncer vesicular en países seleccionados por presentar una gran magnitud y tendencia al aumento como Chile, Japón y Suecia. Se ha considerado además a otros países como Estados Unidos y algunos escandinavos para apreciar contrastes. El período de estudio comprende desde 1953 hasta 1987 y los datos provienen de publicaciones existentes, particularmente un estudio efectuado en Japón en 1992 con respaldo de la Organización Mundial de la Salud. Las tasas están separadas por sexo y ajustadas a la población mundial para una adecuada comparabilidad. Se observa que Estados Unidos, al igual que la mayoría de los países desarrollados, tiene tasas de mortalidad por cáncer vesicular bajas, además de decrecientes en las cuatro décadas estudiadas. Es llamativo que su población blanca tiene tasas más elevadas en forma inicial, particularmente en mujeres, pero la tendencia al descenso se presenta en los dos grupos raciales (más marcadamente en población blanca) y en ambos sexos. Esta evolución conduce a un acercamiento de las magnitudes para estos cuatro grupos poblacionales en la década del 80. En los países escandinavos, Suecia tiene las tasas más elevadas, seguido por Finlandia, pero las magnitudes para este último son inferiores en la década del 80 además de tender a una estabilización tanto en hombres como en mujeres. Se aprecia que las tasas para hombres en Suecia y Japón (Aoki et al. 1992) ascienden desde 1,4 y 1,5 por 100.000 en el quinquenio 1958-62 hasta 2,5 y 5,3 por 100.000 respectivamente, en el quinquenio 198387, mientras que en Chile se elevan desde un mismo valor inicial de 1,3 hasta alcanzar 5,8 por 100.000 en 1983-87, una magnitud bastante más alta que en Suecia pero poco superior a la de Japón. Las tasas para mujeres en Suecia y Japón ascienden desde 2,5 y 1,5 por 100.000 en 195 8-62 (según Aoki et al. ob.cit.) a 4,3 y 5,3 por 100.000 respectivamente, en 1983-87. En Chile, las magnitudes son muy superiores y además ascendentes desde 6,2 en 1968-72 hasta alcanzar 13,1 por 100.000 en 1983-87, condición que ratifica una situación de preeminencia mundial marcada que había sido descrita. Se plantea la hipótesis de que la evolución señalada para la mortalidad por cáncer vesicular en diferentes países puede estar correlacionada con sus tasas de colecistectomía, hipótesis que ha sido postulada por diversos autores. Será necesario efectuar estudios actualizados, en particular para Suecia y Japón que no han publicado datos recientes o no los tienen disponibles, para ratificar o rechazar esta hipótesis.

Gallbladder cancer in Chile: A report on 54 potentially resectable tumors

Fifty-four patients with potentially resectable gallbladder tumors, chosen from 205 cases diagnosed at the Pathologic Unit of the authors' institution, were included in a prospective protocol of management. Of the potentially resectable tumors, only four were indicated before cholecystectomy (7.4%). Inconspicuous tumors were frequently observed, explaining in part the poor results of ultrasonogram for diagnosis. Poorly differentiated tumors were related to a greater rate of metastasis and shorter survival. Likewise, younger patients were associated with a worse prognosis. Patients with tumor confined to the mucosal layer were followed-up only during their postoperative courses. Patients with tumor involvement of the subserosa or muscular layer were offered treatment of a second operation, which included a lymphadenectomy and a liver wedge resection. For patients with serosal involvement, a more aggressive approach was proposed. Metastatic lymph node involvement was found in 9 of the 25 (36%) patients in whom dissection was performed. However, tumor invasion of the liver was seen in 10 of the 24 (41.6%) patients who underwent a liver resection. Patients who had a curative resection had a significantly longer survival in comparison with those who had a palliative resection or simple cholecystectomy.