Cáncer de vesícula biliar ¿la contaminación por bilis afecta el pronóstico? / Gallbladder Cancer: does bile contamination affect the prognosis?

Resumen Introducción: En algunas áreas el cáncer de la vesícula biliar se detecta en hasta el 3,5% de los pacientes intervenidos por colelitiasis. Con el objetivo de evaluar el rol de la ruptura de la vesícula y la consiguiente contaminación por bilis, se evaluó una serie de pacientes portadores de cáncer de vesícula diagnosticado posterior a la colecistectomía. Materiales y Método: El estudio se efectuó en 109 pacientes en quienes se diagnosticó un cáncer de vesícula posterior a la colecistectomía. El grupo a estudiar se dividió de acuerdo a la ocurrencia o no de contaminación por bilis al momento de la colecistectomía, como también de acuerdo a la magnitud de ésta. Resultados: De los pacientes estudiados, en 32 se documentó la ocurrencia de contaminación por bilis al momento de la colecistectomía. De estos, en 13 la contaminación fue considerada mayor. El tiempo promedio de seguimiento fue de 33 meses, 35 pacientes (32,1%) fallecieron durante el seguimiento. La sobrevida media de la totalidad de la serie que tuvo contaminación por bilis no se diferenció de los pacientes sin contaminación. Sin embargo, el grupo que tuvo una contaminación catalogada como mayor, presentó una sobrevida estadísticamente inferior al resto de los pacientes. Finalmente, se realizó un análisis mediante el modelo de regresión de COX que incluyó edad, género, nivel de invasión y tipo de contaminación, resultando la existencia de contaminación mayor por bilis un factor independientemente asociado al pronóstico. Conclusión: La presencia de ruptura vesicular y contaminación mayor por bilis debiera considerarse un factor pronóstico.

Background: Incidental gallbladder cancer is observed in up to 3.5% of patients undergoing laparoscopic cholecystectomy. To study the role of wall perforation on the prognosis, we evaluated a series of patients in whom perforation occurred during the cholecystectomy. Materials and Method: 109 patients who underwent a laparoscopic cholecystectomy in whom final diagnosis was gallbladder cancer were the focus of the study. We divided the patients according the occurrence of spillage. Furthermore, patients with spillage were divided into two categories according the spillage magnitude. Results: Of the patients, spillage was documented in 32 (29.3%). In 13 patients spillage was considered major. The median follow-up of patients was 36 months, while 35 (32.1%) patients died during the follow-up. Five-year survival of all patients with spillage was not statistically different from the group without spillage. However, the group with major spillage had a statistically worse survival than the rest. A Cox regression analysis including age, gender, level of invasion and spillage category showed that major spillage was independently associated with a worse prognosis.

Mortalidad por cáncer de vesícula y egresos hospitalarios por patología biliar en Chile 2002-2014, en relación a la garantía GES colecistectomía preventiva / Changes in gallbladder cancer mortality and hospital discharges due to preventive cholecystectomy in Chile

Background: Gallbladder cancer is a relevant public health problem in Chile. Aim: To analyze the mortality trend due to gallbladder cancer and hospital discharges due to biliary disease between 2002 and 2014. To analyze the effect on these parameters of the new health system called explicit guaranties in health whose acronym in Spanish is GES. Material and Methods: Mortality and hospital discharge databases available at the website of the Ministry of Health were analyzed. Changes in crude and adjusted rates were evaluated, analyzing data by geographical regions, sex and age. The standardization was carried out using the direct method and using as reference the Chilean population in 2002. The trends were evaluated through the Poisson regression method. Results: There is a 4.5% trend towards a decreasing mortality at a national level, as compared with the figures before GES came into force. Mortality among people aged 35 to 49 decreased by 4% before GES, and by 8% after GES. The trend of hospital discharges varied from −1% before GES, to a 2% increase after GES. Discharges among people aged 35-49 years increased from 0.1% to 2.9%. Conclusions: The discharge rate increase after GES, does not yet show a break in the reduction of mortality at the national level, although it does benefit the group of 35 to 49 years.

Carcinoma epidermoide puro-combinado de vesícula biliar / Gallbladder epidermoid carcinoma

Background: Gallbladder epidermoid carcinoma is rare and more common in women over 55 years of age. Aim: To report the features of 15 patients with gallbladder epidermoid carcinoma. Material and Methods: Review of medical records of patients with gallbladder cancer in an oncology service. Results: Of 207 patients with gallbladder cancer, 15patients aged 53-72years, 93% women had an epidermoid component in their cancer. Forty percent were diabetic and 33% had cholelithiasis. All had locoregional extension of the tumor. A cholecystectomy was done in nine patients (using open surgery in six). In six patients, only a biopsy was done. Median survival was 4.2 months. Conclusions: Gallbladder epidermoid carcinoma is uncommon and has a bad prognosis.

Cáncer de la vesícula biliar: análisis preliminar del programa GES para prevención de esta enfermedad / Gallbladder cancer: preliminary evaluation of the GES program to prevent the disease

Objetivo: Analizar datos relacionados con el programa «Colecistectomía como prevención del cáncer de vesícula biliar¼. Método: Se analizan los resultados obtenidos de la página web del DEIS del Ministerio de Salud chileno. Resultados: El año 2006, fecha de inicio del programa, fueron egresados 42.780 pacientes entre 20 y 64 años con diagnósticos correspondientes a los códigos CIE-10, K80-K83. El año 2012, el número de egresos fue de 58.818, lo que significó que desde el año 2006 fueron egresados 39.419 pacientes más que si se hubiesen mantenido los números del año 2006. Por otra parte, desde antes de la puesta en práctica del programa, se aprecia una disminución de la mortalidad ajustada por edad del cáncer de vesícula. Conclusión: Aunque desde la puesta en marcha del programa de prevención del cáncer de vesícula se observa un aumento en el número de casos intervenidos, especialmente durante los años 2011 y 2012, la caída de la tasa de mortalidad parece deberse a factores diferentes al aumento de las colecistectomías.

Goal: To evaluate published data related to the program ‘Cholecystectomy as prevention of Gallbladder Cancer’. Method: Analysis of the results obtained from the DEIS web page (Ministry of Health of Chile). Results: Since 2006, The Chile Ministry of Health began a program to reduce the number of gallbladder cancer cases in Chile. To accomplish the above, Chile Government has guarantied the execution of a cholecystectomy program under parameters of quality, opportunity and financial support between the ages of 35 and 49 years old. During 2006, 42,780 patients corresponding to the ICD 10 codes, K80-K83 between 20 and 64 years old were discharged from Chilean Hospitals. In 2012, six years after the beginning of the program, 58,818 were discharged. The program would make done possible to discharge approximately 39,419 extra patients. On the other hand, during the last ten years, a decrease in the mortality rate of gallbladder cancer has been observed in Chile. Conclusion: Although since the beginning of the program an increase in the number of patients discharged is observed, the decrease in the gallbladder cancer mortality seems not to have relation with the program.

Effects of Surgical Methods and Tumor Location on Survival and Recurrence Patterns after Curative Resection in Patients with T2 Gallbladder Cancer

BACKGROUND/AIMS: Extended cholecystectomy is generally recommended for patients with T2 gallbladder cancer. However, few studies have assessed the extent of resection relative to T2 gallbladder tumor location. This study analyzed the effects of surgical methods and tumor location on survival outcomes and tumor recurrence in patients with T2 gallbladder cancer. METHODS: Clinicopathological characteristics, extent of resection, survival rates, and recurrence patterns were retrospectively analyzed in 88 patients with pathologically confirmed T2 gallbladder cancer. RESULTS: The 5-year disease-free survival rate was 65.0%. Multivariate analysis showed that lymph node metastasis was the only independent risk factor for poor 5-year disease-free survival rate. Survival outcomes were not associated with tumor location. Survival tended to be better in patients who underwent extended cholecystectomy than in those who underwent simple cholecystectomy. Recurrence rate was not affected by surgical method or tumor location. Systemic recurrence was more frequent than local recurrence without distant recurrence. Gallbladder bed recurrence and liver recurrence were relatively rare, occurring only in patients with liver side tumors. CONCLUSIONS: Extended cholecystectomy is the most appropriate treatment for T2 gallbladder cancer. However, simple cholecystectomy with regional lymph node dissection may be appropriate for patients with serosal side tumors.

¿Cuál es el rol de la cirugía en el tratamiento de un paciente con cáncer de la vesícula biliar estadio IIIb? / What is the role of surgery in the treatment of a patient with stage IIIb gallbladder cancer

El cáncer de la vesícula biliar (CaVB), es una neoplasias frecuente en nuestro país. La supervivencia (SV) global no supera el 40% a 5 años. La invasión de la túnica serosa y el estadio IIIB, se asocian a menor SV por considerarse una etapa avanzada de la enfermedad; por ello no hay consenso respecto del rol de la cirugía en estos casos. El objetivo de este artículo es analizar la evidencia existente respecto del rol de la cirugía en el tratamiento de un paciente con CaVB estadio IIIb. Se realizó una búsqueda sistemática de la evidencia disponible en la bases de datos Clinical Evidence, National Health Service, Health Technology Assessment, Tripdatabase, Cochrane Library y PubMed. Se buscaron a documentos de resumen de la evidencia (overviews, guías de práctica clínica (GPC, tablas GRADE), artículos secundarios (revisiones sistemáticas/RS) y artículos primarios (ensayos clínicos/EC y estudios observacionales/EO). Posteriormente, la evidencia se clasificó según la propuesta de la CEBM 2009. Se encontró un total de 420 documentos relacionados: 25 overviews, 15 tablas GRADE, 30 GPC, 37 RS, 99 EC y 214 EO. Al examinar en detalle todos los documentos; Se comprobó que sólo 17 estaban relacionados con los resultados del tratamiento quirúrgico de la CaVB en etapa III; y 5 se refieren a esta (3 EO, 1 GPC y una recomendación del NCI), pero ninguno al estadio IIIb. Existen pocos estudios relacionados, la mayor parte de ellos son de tipo retrospectivo, con un pequeño número de pacientes incluidos, de población y procedimientos quirúrgicos heterogéneos; por ende, es muy sacar conclusiones y realizar recomendaciones basadas en la evidencia existente.

Gallbladder cancer (GBC), is a common neoplasm in our country. The overall survival rate (OSR) does not exceed 40% at 5 years. The invasion of the serosa and IIIB stage, are associated with lower OSR seen it are an advanced stage of the disease, so there is no consensus on the role of surgery in this type ofpatients. The aim of this study is to analyze the existing evidence concerning the role of surgery in the treatment of a patient with stage IIIb GBC. A systematic search of available evidence in the databases Clinical Evidence, National Health Service, Health Technology Assessment, Tripdatabase, Cochrane Library and PubMed search was performed. Evidence summary documents (overviews, GRADE tables, Clinical Guidelines/CG), secondary articles (systematic reviews) and primary articles (Clinical trials/CT) and observational studies/OS) were searched. Subsequently, evidence was classified as proposed by EMBC 2009. A total of 420 related documents were found: 25 overviews, 15 GRADE tables, 30 CG, 37 SR, 99 CT and 214 OS. In reviewing at length all documents; It was verified that only 17 were related to results of surgical treatment of GC that stage III was mentioned and 5 refer to this (3 OS, 1 CG and a recommendation from NCI), but none of them to the IIIb stage. There are few related studies, most of them are retrospective, with a small number of patients included, heterogeneous population and surgical procedures; thereby, it is difficult to draw conclusions and make recommendations based on the evidence.

Cáncer temprano de la vesícula biliar: tratamiento y sobrevida a largo plazo / Survival of patients with early gallbladder cancer

Background: Advanced gallbladder cancer has a high mortality. Therefore, this tumor should be diagnosed and treated in early stages. Aim: To analyze the survival rates of patients with an early gallbladder cancer. Material and Methods: Retrospective analysis of medical records of patients with early gallbladder cancer diagnosed until 2003. From that date, all patients with gastrointestinal cancer were registered in a prospective record. Patients with early gallbladder cancer defined as Tis (Carcinoma in situ), T1A (Tumor invades lamina propia) and T1B (Tumor invades muscular layer), were included in this analysis. Results: Eighty patients aged 31 to 87 years (74 percent women) were analyzed. The diagnosis was made during surgery in two patients and during the pathological study in the rest. All 24 patients with Tis tumors were alive after 96 months of follow up. Only one of 16 patients with T1A tumors died of unknown causes. Among the 40 patients with T1B tumors, 24 were re-operated and survival was over 90 percent. Conclusions: This group of patients with early gallbladder cancer had a five years survival over 90 percent. In patients with muscle involvement does not seem necessary to extend the surgery.

Introducción: Dada la elevada mortalidad del cáncer vesicular en etapas avanzadas, lo ideal es diagnosticarlo y tratarlo en una etapa temprana de la enfermedad. Objetivo: Analizar la sobrevida de pacientes con carcinoma temprano de la vesícula biliar y el impacto de una eventual re-operación. Material y Método: Se incluyen en el estudio 80 pacientes con cáncer temprano, siendo la mayoría (65 pacientes) parte de un estudio prospectivo desde mayo de 2004 hasta febrero de 2013. Fueron divididos en 3 grupos: a) carcinoma in situ T1s; b) carcinoma mucoso T1a; c) carcinoma muscular I1b. Seguimiento en el 100 por ciento de los casos. Resultados: El diagnóstico de carcinoma temprano se hizo en 2 pacientes durante la cirugía, en el resto fue un hallazgo del estudio histo-patológico. Los 24 pacientes con carcinoma in situ estaban vivos a los 96 meses de seguimiento. De los 16 pacientes con carcinoma mucoso, sólo 1 (6 por ciento) falleció sin conocerse la causa. Entre los 40 pacientes con cáncer muscular, hubo 24 que no se reoperaron y 16 reoperados. Los resultados anatomo patológicos fueron similares y la sobrevida de ambos grupos fue superior al 90 por ciento. Conclusión: En pacientes con carcinoma de la vesícula biliar in situ y hasta la mucosa, la colecistectomía logra sobrevida mayor del 95 por ciento a largo plazo. En pacientes con carcinoma muscular, ésta se acompaña de una sobrevida mayor a 90 por ciento a 5 años y no parece justificarse ampliar la cirugía.

Evaluation of P53, E-cadherin, Cox-2, and EGFR protein imunnoexpression on prognostic of resected gallbladder carcinoma / Avaliação da imuno-expressão das proteínas P53, E-caderina, Cox-2 e EGFR no prognóstico do carcinoma de vesícula biliar ressecado

BACKGROUND: Gallbladder carcinoma presents a dismal prognosis. Choice treatment is surgical resection that is associated a high levels of both morbidity and mortality. Best knowledgement of prognostic factors may result a better selection of patients either for surgical or multimodal treatment. AIM: To evaluate tecidual immunoexpression of P53, E-cadherin, Cox-2, and EGFR proteins and to correlate these findings with resected gallbladder adenocarcinoma survival. METHODS: Clinical, laboratorial, surgical, and anatomopathological reports of a series of gallbladder adenocarcinoma patients were collected by individualized questionary. Total sample was 42 patients. Median of age was 72 years (35-87). There were seven men and 35 women. Lesion distribuition in according TNM state was the following: T1 (n=2), T2 (n=5), T3 (n=31), T4 (n=4). Twenty-three patients underwent radical resection (R0), while 19 palliative surgery (R1-R2). A block of tissue microarray with neoplasic tissue of each patient was confected. It was performed evaluation of P53, E-Caderine, COX-2, and EGFR proteins imunoexpression. These findings were correlated with overall survival. RESULTS: Five-year survival was 28%. The median of global survival was eight months. Only immunoexpression of EGFR protein was considered independent variable at multivariated analysis. CONCLUSION: Final prognosis was influenced by over-expression of EGFR protein in tumoral tissue. .

RACIONAL: O carcinoma de vesícula biliar apresenta mau prognóstico. O tratamento de escolha é a ressecção cirúrgica que está associado à alta morbimortalidade. O melhor conhecimento de fatores prognósticos pode resultar em melhor seleção dos doentes para o tratamento cirúrgico e multimodal. OBJETIVOS: Avaliar a imunoexpressão tecidual das proteínas P53, E-caderina, Cox-2 e EGFR e correlacionar com a sobrevida do adenocarcinoma de vesícula biliar ressecado. MÉTODO: Os dados clínicos, laboratoriais, cirúrgicos e anatomopatológicos de uma série de doentes operados por adenocarcinoma de vesicula biliar foram coletados. A casuística total foi de 42 doentes. A mediana de idade foi de 72 anos (35-87). Foram sete homens e 35 mulheres. A distribuição da lesão de acordo com TNM foi a seguinte: T1 (n=2), T2 (n=5), T3 (n=31), T4 (n=4). Vinte três doentes realizaram ressecção radical (R0) enquanto 19 operação paliativa (R1-R2). Um bloco de tissue microarray foi confeccionado com tecido neoplásico de cada doente. para avaliação da imunoexpressão das proteínas P53, E-Caderina, COX-2 e EGFR. Esses achados foram correlacionados com prognóstico final dos doentes. RESULTADOS: A sobrevida estimada em cinco anos foi de 28%. A mediana de sobrevida global foi de oito meses. Apenas a imunoexpressão da proteína EGFR foi considerada variável independente no prognóstico dos doentes. CONCLUSÃO: Pior prognóstico teve relação com a imunoexpressão aumentada da proteína EGFR no tecido tumoral. .

Adjuvant chemoradiation for resected gallbladder cancer: Treatment strategies for one of the leading causes of cancer death in Chilean women.

BACKGROUND: Gallbladder cancer (GBC) is the second leading cause of cancer death in women in Chile. Even after curative surgery, prognosis is grim. To evaluate acute and late toxicity and efficacy of adjuvant chemoradiation (CRT) after curatively resected GBC. MATERIALS AND METHODS: We retrospectively analyzed the cohort of patients diagnosed between January 1999 and December 2009, treated with adjuvant CRT at our institution. Treatment protocol considered external beam radiation (RT) (45–54 Gy) to tumor bed and regional lymph nodes with or without concurrent 5-fluorouracil (5-FU) (500 mg/m2/day by 120-hours continuous infusion on days 1–5 and 29–33). Data was obtained from medical records, mortality from death certificates. Survival was estimated by Kaplan– Meier curves. RESULTS: 46 patients with curatively resected GBC received adjuvant CRT. Median age was 57 years (range 33–76); 39 patients were female. After diagnosis, a second surgery was performed in 42 patients. Cholecystectomy with hepatic segmentectomy and lymphadenectomy was the curative surgery in 41 patients. All patients received RT with a planned dose of 45 Gy in 25 fractions, 11 patients received a boost to the tumor bed up to 54 Gy and 34 patients had concurrent 5-FU. Therapy was well tolerated. Five patients experienced grade 3 toxicities. No grade 4 or 5 toxicity was observed. No grade >2 late toxicity was observed. Three- and 5-year overall survival (OS) were 57% and 51%, respectively. CONCLUSIONS: Adjuvant chemoradiation is well tolerated and might impact favorably on survival in patients with curatively resected GBC.

Adenocarcinoma da vesícula biliar: avaliação dos fatores prognósticos em 100 casos ressecados no Brasil / Gallbladder adenocarcinoma: evaluation of the prognostic factors in 100 resectable cases in Brazil

RACIONAL: A despeito da sua relativa raridade, o adenocarcinoma de vesícula biliar é neoplasia que apresenta comportamento biológico agressivo. O único tratamento curativo tem sido a ressecção cirúrgica radical com margem livre. Fatores prognósticos têm sido estudados por serem importantes para identificar pacientes que podem se beneficiar de ressecção cirúrgica agressiva. OBJETIVO: Avaliar preditores prognósticos em longo prazo de pacientes com câncer da vesícula biliar. MÉTODOS: Foram identificados e retrospectivamente revisados os prontuários médicos de todos os doentes submetidos a tratamento cirúrgico que apresentavam diagnóstico histológico confirmado de adenocarcinoma de vesícula biliar durante período de 14 anos. Os dados foram submetidos à análise estatística uni e multivariada. RESULTADOS: A amostra total foi de 100 doentes. A mediana de idade foi de 71 anos (34 a 93). Houve 17 mulheres e 83 homens. A distribuição das lesões de acordo com o sistema de estadiamento TNM foi: I (n=22), II (n=59), III (n=6), IV (n=4) e desconhecido (n=9). Cinquenta e dois doentes foram submetidos à ressecção radical (R0) enquanto 48 à cirurgia paliativa (R1-R2). A morbidade global foi de 14% enquanto que a mortalidade pós-operatória (até 30º dia do pós-operatório) foi de 12 %. A taxa de sobrevida em cinco anos foi de 28% enquanto a mediana de sobrevida foi de 10 meses. A análise multivariada identificou seis fatores prognósticos: estádio T, nível sérico de CA 19.9, perfuração da vesícula biliar, embolização linfática, coorte cirúrgico histórico e linfadenectomia hilar. CONCLUSÃO: O tratamento do câncer de vesícula biliar apresenta alta morbimortalidade. Os fatores prognósticos foram: estádio T, nível sérico de CA 19.9, perfuração da vesícula biliar, embolização linfática, coorte cirúrgico histórico e linfadenectomia hilar.

BACKGROUND: In spite its relative rarity, gallbladder adenocarcinoma is a neoplasm who presents an aggressive biologic behavior. The single curative treatment has been radical surgical resection with free margin. Prognostic factors has been studied because are very important to identify long-term survival patients which may benefit of aggressive surgical resection. AIM: To evaluate long-term prognostic predictors from gallbladder cancer. METHODS: The medical records of all patients that presented confirmed histological diagnosis of gallbladder adenocarcinoma operated over a 14 year period were identified and retrospectively reviewed. Uni and multivariate analysis was done. RESULTS: Total sample was 100 patients. Median age was 71 years (34 to 93). There were 17 men and 83 women. Lesion distribution according to TNM stage system was: I (n=22), II (n=59), III (n=6), IV (n=4) and unknown (n=9). Fifty two patients underwent radical resection (R0) while 48 to palliative surgery (R1-R2). Overall major morbidity was 14%, while postoperative surgical mortality rate (30th postoperative day) was 12 %. Five-year survival rate was 28% while median of survival was 10 months. Multivariate analysis identified six prognostic factors: T stage, serum level of CA 19.9, gallbladder perforation, lymphatic embolization, surgical historical cohort (after 2002) and hilar lymphadenectomy. CONCLUSION: Prognostic factors were: T stage, serum level of CA 19.9, gallbladder perforation, lymphatic embolization, surgical historical cohort and hilar lymphadenectomy.

Factores pronósticos en el cáncer vesicular subseroso / Prognostic factors in subserous gallbladder cancer

Introducción: Es importante identificar los factores pronósticos del cáncer vesicular subseroso para poder plantear distintas terapias dentro de este grupo tumoral. Objetivo: Evaluar qué factores pronósticos afectan la sobrevida en pacientes con cáncer vesicular subseroso. Material y métodos: Cohorte retrospectiva. Se analizan los pacientes con diagnóstico histopatológico de cáncer vesicular subseroso (T2), a partir de la biopsia de la pieza quirúrgica, operados en el Hospital Regional Valdivia (HRV) entre los años 2001-2005. Para caracterizar a la población se realizó estadística descriptiva. La sobrevida global se describió mediante curvas de Kaplan Meier. Para medir los factores pronósticos (reoperación, terapia adyuvante (quimioradioterapia), grado de diferenciación y el compromiso linfonodal), se realizó análisis bivariado mediante la prueba de Long Rank y análisis multivariado por medio de una regresión de Cox. Resultados: La cohorte incluyó 18 pacientes. Edad promedio 65 (39-86) años. Predominó el sexo femenino, 12 (66,66 por ciento). El diagnóstico preoperatorio "probable cáncer vesicular", se encontró en 5 pacientes (27,77 por ciento), colecistitis aguda en 8 (44,44 por ciento), colelitiasis sintomática en 3 (16,66 por ciento). Once pacientes (61,11 por ciento) fueron catalogados como N1 y 7 (38,88 por ciento) como N0. Cinco tumores (27,77 por ciento) se clasificaron como mal diferenciados, 9 (50,00 por ciento como moderadamente y 3 (16,66 por ciento) como bien diferenciados. Cuatro pacientes se reoperaron (22,22 por ciento). La sobrevida a 5 años fue 81,71 por ciento y 18,18 por ciento para los N0 y N1 respectivamente. Tanto el análisis bivariado (p=0.0049) como el multivariado (HR:18,34; IC 95 por ciento; 1,18-283, p=0.037) arrojó que el compromiso linfonodal es un factor de mal pronóstico. Conclusión: El compromiso linfonodal sería un factor pronóstico en el cáncer vesicular subseroso.

Introduction: It is important to identify the prognostic factors of the gallbladder cancer dye to be able to raise different therapies within this group tumor. Objective: To evaluate prognostic factors that affect the survival of patients with subserous gallbladder cancer. Material and methods: retrospective cohort study. We analyze the patients with histopathological diagnosis of subserous gallbladder cancer (T2) from the biopsy of the surgical specimen, operated in the Regional Hospital Valdivia (HRV) between the years 2001-2005. To characterize the population descriptive statistical analysis was carried out. Overall survival was described by Kaplan Meier curves. To measure the prognostic factors ( reoperation, adjuvant therapy (chemo), degree of differentiation and commitment linfonodal), bivariate analysis was performed using the Long rank test and multivariate analysis by means of a Cox's regression. Results: The cohort included 18 patients. Average age 65 (39-86) years. A predominance of females, 12 (66.66 percent. The preoperative diagnosis "vesicular likely cancer", was found in 5 patients (27.77 percent), acute cholecystitis in 8 (44.44 percent), symptomatic cholelithiasis in 3 (16.66 percent). Eleven patients (61.11 percent) were classified as N1 and 7 (38.88 percent) as N0. Five tumors (27.77 percent) were classified as poorly differentiated, 9 (50.00 percent) as moderately and 3 (16.66 percent) as well differentiated. Four patients surgery (22.22 percent). The survival at 5 years was 81.71 percent and 18.18 percent for the N0 and N1 respectively. Both the bivariate analysis (p=0.0049) as the multivariate (HR:18.34; 95 percent CI 1.18 -283, p=0,037) showed that the linfonodal involvement is a poor prognostic factor. Conclusion: The linfonodal involvement would be a prognostic factor in cancer subserous vesicular.

Letalidad del cáncer de vesícula biliar es independiente del lugar de atención o características sociodemográficas: Chile 2002-2005 / Mortality due to gallbladder cancer: Retrospective analysis in three Chilean hospitals

Background: Chile has the highest gallbladder cancer (GBC) death rate world-wide, affecting mainly Southern areas of the country. Aim: To compare the survival of GBC patients treated in hospitals located in areas with low and high risk for GBC. Material and Methods: Medical records of all patients with GBC admitted to one public hospital located in southern Chile, a public hospital and a private clinic, both located in Metropolitan Santiago, were reviewed. Cases were analyzed by age, sex, stage at diagnosis, ethnicity, socioeconomic status (SES) and rural residence. Survival was calculated using Kaplan Meier method. Results: A total of 598 cases (469 women), were analyzed. No differences in age or sex among hospitals were detected. At the moment of diagnosis, 75, 50 and 44 percent of cases from the hospital in southern Chile, the public hospital in Santiago and the private clinic in Santiago, were in stage IV, respectively. Five years survival was lower in the public hospital in southern Chile than in the public hospital in Santiago (10.7 and 14.4 percent respectively, p < 0.05) but not statistically different from the figure at the private clinic in Santiago (13.0 percent). However, when adjusting for stage at the moment of diagnosis, no difference in survival between the three hospitals, was found. The median days of survival were 1,559, 188, 70 and 69 for stages I, II, III and IV respectively. Conclusions: GBC mortality is high. The stage at the moment of diagnosis is only significant predictor of survival.

Survival of a cohort of patients with Intermediate and advanced gall bladder cancer treated with a prospective therapeutic protocol / Sobrevida de uma coorte de pacientes com câncer na vesícula intermédio e avançado tratados com um protocolo terapêutico de natureza prospectiva

PURPOSE: To evaluate the results of a prospective therapeutic protocol with long-term follow up in terms of survival rates in a cohort of patients treated with Intermediate and Advanced GBC (GBC). METHODS: Prospective cohort of patients with intermediate and advanced stages of GBC treated between 1996 and 2006. All cases were treated with a partial hepatic segmentectomy on segments IVb and V and a regional lymph node dissection and six cycles of out-patient chemotherapy (5-FU and leukovorin). With an average follow-up of 31.5 months, the morbidity, operative mortality, hepatic and lymphatic infiltration and actuarial survival were measured. Descriptive statistics were applied as well as bivariate analysis applying Fisher's exact test and non-parametrical tests and Kaplan Meier survival curves. Also logistic regression and proportional risk of Cox were applied. RESULTS: 40 patients were included in this protocol, with an average age of 59.5 years (40-85 years), of which 28 were women (70 percent). Depth of wall infiltration: muscular 8 patients (20 percent), subserosal 12 patients (30 percent), serosal 12 patients (30 percent) and perivesicular adipose tissue 8 patients (20 percent). The series morbidity was 27.5 percent. There was no operative mortality. The chemotherapy was well tolerated. The overall actuarial survival in the series was 50 percent at 60 months. CONCLUSION: Our protocol treatment has morbidity, mortality and survival rates similar to previously reported series.

OBJETIVO: Avaliar os resultados de resultados da aplicação de um protocolo terapêutico de natureza prospectiva, com seguimento em longo prazo nos termos de taxas de sobrevivência em uma coorte de pacientes operados com carcinoma vesícula biliar (CVB) intermédio e avançado. MÉTODOS: A coorte prospectiva de pacientes com estágios intermediários e avançados de CVB tratados entre 1996 e 2006. Todos os casos foram tratados com uma segmentectomia hepática parcial em segmentos IVb e V e uma dissecção linfonodal regional e seis ciclos de quimioterapia de ambulatório (5-FU e leukovorin). Com um tempo de seguimento médio de 31,5 meses, a morbidade, mortalidade operatória, hepático e infiltração linfática e atuarial de sobrevida foram medidas. Estatísticas descritivas foram aplicadas, bem como análise bivariada aplicando o teste exato de Fisher, testes não-paramétricos, curvas de sobrevida Kaplan Meier e técnica de regressão logística e risco proporcional de Cox. RESULTADOS: Foram incluídos 40 pacientes neste protocolo, com uma média de idade de 59,5 anos (40-85 anos), dos quais 28 eram mulheres (70 por cento). Profundidade de infiltração parede: muscular 8 pacientes (20 por cento), subserosal 12 pacientes (30 por cento), serosas 12 pacientes (30 por cento) e perivesicular no tecido adiposo, 8 pacientes (20 por cento). A série morbidade foi de 27,5 por cento. Não houve mortalidade operatória. A quimioterapia foi bem tolerada. A sobrevida global atuarial da série foi de 50 por cento em 60 meses. CONCLUSÃO: Nosso protocolo tem tratamento morbidade, mortalidade e taxas de sobrevivência semelhantes às relatadas anteriormente série.

Carcinoma subseroso de la vesícula biliar (pT2): valor pronóstico de la expresión de los genes supresores de tumores p53 y p27 en matrices de tejidos / p53 and p27 gene expression in subserosal gallbladder carcinoma

Background: Subserosal carcinoma is the stage that presents the greatest difficulty in the diagnosis therapeutic handling and prognosis evaluation. Aim To study the expression of p53 and p27 genes in subserosal gallbladder cancer. Material and methods: One hundred twenty seven tissue samples of subserosal gallbladder cancer (coming from 112 females aged 62 ± 13years and 15 men aged 67 ± 17years) and 50 control samples were selected to construct tissue arrays. p53 andp27genes were determined by immunohistochemistry. Results: Thirty eight percent of tumors were not detected at the macroscopic examination, 52 percent and 17 percent had lymph node and blood vessel involvement, respectively. Fifty six and 46 percent were positive for p53 and p27, respectively. No association between the expression of both genes and gender, degree of differentiation, lymph node or blood vessel involvement, was observed. Overall five years actuarial survival was 32 percent. Patients with positive or negative p53 expression had a 22 percent and 53 percent survival, respectively (p =0.05). No association between survival and p27 expression was observed. Conclusions: p53 gene expression is a prognostic factor for subserosal gallbladder cancer.

Cáncer vesicular en colecistectomías: análisis de sobrevida y factores pronósticos / Survival and prognostic factors in gallbladder cancer

Objetivos: Identificar si el sexo, compromiso en profundidad de la pared vesicular (T) compromiso linfonodal (N), grado histológico y localización del cáncer vesicular son factores pronósticos de supervivencia. Material y Métodos: Estudio de cohorte, retrospectivo, de pacientes sometidos a colecistectomía entre los años 2001 y 2005 diagnosticados de cáncer vesicular en anatomía patológica. Se revisaron los antecedentes anatomo-clínicos de los pacientes operados y se estableció su sobrevida a 5 años. Se efectuó análisis exploratorio de los datos describiendo la supervivencia según el método Kaplan Meier. Se utilizó supervivencia global y específica según sexo, componente T, N y grado de diferenciación. Se utilizó método log rank para determinar la comparación de las curvas de supervivencia. Resultados: Se realizaron 3069 colecistectomías. 95 pacientes presentaron cáncer vesicular (3,1 por ciento). El sexo femenino fue predominante. Edad promedio 64 años. 77 pacientes fueron sometidos a colecistectomía exclusiva y 8 pacientes a cirugía oncológica extendida. Dentro del T, el T3 fue el más frecuente (39,4 por ciento). El 31,9 por ciento de ellos se catalogó como NO. Según el grado de diferenciación el más frecuente fue el moderadamente diferenciado con un 44,7 por ciento. La sobrevida global a 5 años fue de un 29,2 por ciento. Se encontró que tanto el T, N, grado de diferenciación, y la localización del tumor son factores pronósticos en estos pacientes en forma estadísticamente significativa. Conclusión: la sobrevida a 5 años en el cáncer vesicular depende de la profundidad de invasión tumoral, compromiso linfonodal, grado de diferenciación y localización del tumor.

Background: Gallbladder cancer is the first cause of cancer death among chilean women. Aim: To determine prognostic indicators of survival in gallbladder cancer. Material and methods: Retrospective review of medical records of 95 patients aged 34 to 86 years (69 females) with gallbladder cancer diagnosed between 2001 and 2005 in a regional hospital. Pathological reports and clinical data of patients were reviewed. Five year survival was determined using Ufe tables. Results: Forty percent of tumors were classified as T3 and 32 percent as NO. Forty five percent of tumors were moderately differentiated. Five years survival was 29 percent. T and N classification, the degree of differentiation and the location of the tumor were prognostic factors for survival. Conclusions: Gallbladder cancer in this series of patients had a bad five years survival that depends on the degree of tumor invasion and differentiation.

Cáncer de vesícula biliar: Tendencia y distribución del riesgo en Chile / Gallbladder cancer: trend and risk distribution in Chile

Background: Gallbladder cancer (GBC) is the first cause of death by cancer among Chilean women and mortality has not improved in the last 20 years. Aim: To study GBC mortality trend from 1985-2002, analyze risk differentials by age, sex, geographic region and accessibility to surgery. Material and Methods: 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. Results: 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 (r2 0.27, ns). Compared with other countries, Chile has a higher rate of GBC deaths in relation to its gross domestic product per capita. Conclusions: 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.

Adjuvant radiation therapy in gall bladder cancers: 10 years experience at Tata Memorial Hospital.

INTRODUCTION AND PURPOSE: In gall bladder cancers, even after curative surgery, survivals are dismal and loco-regional failure accounts for 40-86%. Although these are considered radio-resistant, adjuvant radiation, with or without chemotherapy, has been tried to improve loco-regional control and overall survival rates. With an aim to evaluate the natural history of gall bladder cancers, role of radiation therapy (RT) and prognostication, a retrospective analysis was undertaken. MATERIALS AND METHODS: Between 1991-2000, 60 patients with gall bladder cancer, treated with radical intent, were evaluated. Patients details including history, physical examination, liver function tests, ultrasonography of the abdomen and chest X-ray; and CT scan Abdomen if done, were noted. In patients who underwent surgery, surgical details, histopathology and pathological staging, were recorded. The details of post-operative adjuvant treatment, including radiation therapy details, as well as chemotherapeutic agents, number of cycles and type of infusion [bolus/infusion], were noted. RESULTS: Sixty patients underwent surgery. On histopathological staging, 28 patients (46.5%) had stage II, 19 (32%) had stage III, 12 (20%) had stage-I and 1 patient had stage IV disease. Thirteen (21%) patents did not receive any adjuvant treatment, 32 (53%) patients received adjuvant RT alone, 8(14%) received post-operative CT+RT and 7 (12%) patients received CT alone. With a median follow-up of 18 months (12-124 months), 27 (45%) patients were disease free, 11 (19%) had local failures, 7 (11%) had loco-regional, 7 (11%) loco-regional+distant, 4 (7%) distant and 4 (7%) patients had local+distant failures. The Overall Disease Free Survival (DFS) and overall survival was 30% and 25%, at 5 years, respectively. Stage grouping ('P' = 0.007), Pathological T ('P' = 0.01) had significant impact on DFS on univariate analysis, where as histological grade ('P' = 0.06) showed trend towards significance. CONCLUSION: Gall bladder cancers are aggressive and lethal. Early diagnosis and curative surgery, followed by appropriate adjuvant radiation therapy, may improve survivals, with no established consensus till date. Following curative surgery, pathological T stage and stage grouping, are the significant prognostic factors for outcome.

Analysis of Prognostic Factors after Curative Resection for Gallbladder Carcinoma / 대한소화기학회지

BACKGROUND/AIMS: Despite the development in diagnostic tools, gallbladder carcinoma is often diagnosed at an advanced stage. Therefore, early diagnosis and radical resection are most important factors for the prognosis of gallbladder carcinoma. However, prognostic factors after radical resection of gallbladder carcinoma have not been well identified. The aim of this study was to evaluate the prognostic factors of gallbladder carcinoma after curative resection. METHODS: We reviewed the records of the 115 patients with gallbladder carcinoma who underwent curative surgery between 1989 and 2004 at Yonsei University Medical Center (YUMC). The relationship between survival and clinicopathological variables was assessed. RESULTS: In 311 patients presenting with gallbladder carcinoma, 195 patients (62.5%) were radically resected. Among 195 patients, 80 patients were excluded because of incomplete clinicopathologic data and unsatisfactory follow-up. The 5 year overall survival rate was 36.0%, and disease free 5 year survival rate was 3.9%. Univariate analysis showed that survival was closely related to gross morphology, depth of tumor invasion, lymph node metastasis and preoperative serum CA19-9 level. Three significant factors identified by multivariate analysis were depth of tumor invasion, gross morphology, and preoperative serum CA19-9 level. CONLUSIONS: Depth of tumor invasion, gross morphology, and preoperative serum CA19-9 level are independent significant prognostic factors of resectable gallbladder carcinoma.

Mutación del gen K-ras en tumores pancreático-biliares / Frequency of K-ras mutation in biliary and pancreatic tumors

Background: The ras gene family (H-ras, N-ras and K-ras) are oncogenes that mutate frequently in human cancer, specially in tumors of the biliary tract and pancreas. Aim: To determine the frequency of K-ras gene codon 12 mutation in pancreatic and biliary tumors. Material and Methods: Samples of 35 gallbladder, 15 ampulla of Vater, 10 biliary tract and 9 pancreatic tumors, were analyzed. The tumor tissue was microdissected from paraffin embedded biopsies. The mutation was detected by a combination of polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP). Results: Overall, 46% of samples had K-ras gene mutations. Mutation frequency was 80, 56, 50 and 29% for ampulla of Vater, pancreatic, biliary tract and gallbladder tumors, respectively. When compared with the rest, gallbladder tumors had a significantly lower frequency of the mutation. Median survival for biliary tract tumors was 6 months, compared with 65 months for gallbladder tumors (p <0.05). Conclusions: Gallbladder carcinoma had the lower frequency of K-ras mutation, when compared with pancreatic, biliary tract and ampulla of Vater tumors.