Systemic therapy and local therapy for biliary tract cancer: Current status and advances / 临床肝胆病杂志

Biliary tract cancer (BTC) is a digestive system malignancy with extremely poor prognosis, and the survival time of patients with BTC has been prolonged with the development of various treatment methods in recent years. This article reviews the current status and advances in surgery, systemic therapy, radiotherapy, and interventional therapy for BTC, so as to provide a reference for the treatment of BTC in clinical practice.

Rendimiento diagnóstico de las punciones de lesiones biliopancreáticas guiadas por ultrasonido endoscópico con patólogo en sala / Diagnostic performance of endoscopic ultrasound-guided fine needle aspiration of pancreatobiliary lesions with rapid on-site evaluation

Resumen Introducción y objetivos: El ultrasonido endoscópico con punción-aspiración con aguja fina (USE-PAAF) en lesiones neoplásicas biliopancreáticas suele tener un rendimiento alto, que depende de características de la lesión; aspectos técnicos de la USE-PAAF y la experiencia del endoscopista. De los factores menos estudiados es la presencia de patólogo en sala. Se plantea la realización de USE-PAAF con patólogo en sala para disminuir el número de pases, la tasa de muestras inadecuadas y la necesidad de repetir el procedimiento. Material y métodos: Estudio observacional, retrospectivo, con recolección prospectiva de enero de 2018 a junio de 2019, en pacientes adultos sometidos a USE-PAAF. Las muestras obtenidas fueron extendidas y evaluadas en salas de endoscopia por médico patólogo con coloración Diff-Quick y cuando se obtenía una muestra suficiente se enviaba en frasco con formol para bloque celular o biopsias. Resultados: Se realizaron 48 USE-PAAF biliopancreáticas en individuos con una edad mediana de 64 años. Las indicaciones más frecuentes fueron punciones por masa o pseudomasa pancreática (71 % de casos); Se diagnosticaron 35 malignidades (77 % correspondientes a adenocarcinoma, y 14 % a tumores neuroendocrinos). La mediana de tamaño de lesiones fue de 28 mm; el número de pases promedio fue de 3. Se obtuvieron resultados diagnósticos en 89 % frente a 11 % de falsos negativos. Se presentó 1 complicación menor (2,1 %), que fue dolor abdominal. Conclusiones: La USE-PAAF con patólogo en sala tiene alto rendimiento diagnóstico, con escasos resultados falsos negativos. Se requiere una mediana de pases menor, que podría minimizar los riesgos del procedimiento y la necesidad de repetir la prueba.

Abstract Introduction: Endoscopic ultrasound with fine-needle aspiration (EUS-FNA) of pancreatobiliary neoplastic lesions usually has a high performance that depends on the characteristics of the lesion, technical aspects, and expertise of the endoscopist. One of the least studied factors is rapid on-site evaluation with a pathologist in the room. Objective: To perform EUS-FNA with a pathologist in the endoscopy room to reduce the number of passes, the rate of inadequate samples and the need to repeat the procedure. Material and methods: Observational retrospective study with a prospective data collection approach from January 2018 to June 2019 of adult patients undergoing EUS-FNA. The samples obtained were spread and evaluated in endoscopy rooms by a pathologist with Diff-Quick stain, and when a sufficient sample was obtained, it was sent in a vial with formalin for cell block and/or biopsy. Results: 48 pancreatobiliary EUS-FNA were performed in individuals with a median age of 64 years. The most frequent indication was aspiration due to pancreatic mass (71%); 35 malignancies were diagnosed (77% were adenocarcinomas and 14% were neuroendocrine tumors). The median size of the lesions was 28mm, and the average number of passes was 3. Diagnostic results were obtained in 89% vs. 11% of false negatives. There was 1 minor complication (2.1%), which was abdominal pain. Conclusions: EUS-FNA with an in-room pathologist has a high diagnostic performance, with few false negative results. Also, a lower median number of passes is required, minimizing the risks of the procedure and the need for repeating it.

Prediction model for survival in patients with biliary tract cancer: a development and validation study / 中华流行病学杂志

Objective@#The aim of the present study was to investigate the survival rate and its prognostic factors for patients with biliary tract cancer, and then a prognostic risk prediction model was constructed to predict the survival probability of patients.@*Methods@#A total of 14 005 patients with biliary tract cancer (including gallbladder cancer, extrahepatic bile duct cancer, and ampulla of Vater cancer), who were diagnosed between 2010 and 2015 in the US National Cancer Institute Surveillance, Epidemiology, and End Results Program (SEER) were included in the development cohort. The prognostic risk factors of biliary tract cancer were investigated using multivariate Cox regression models. The predictive nomograms were then constructed to predict the overall survival probability of 1, 3, and 5 years, and the predictive discrimination and calibration ability of the nomograms were further evaluated. Meanwhile, 11 953 patients who were diagnosed during 2004 to 2009 from SEER Program were then selected to validate the external predictive accuracy of the prediction models.@*Results@#The 1, 3 and 5-year cumulative survival rates of patients with biliary tract cancer were 41.9%, 20.4% and 15.3%, respectively, in the development cohort. Age greater than 50 years, African Americans and Native Americans and Alaska Natives, higher T, N and M stage and poor histological differentiation grade were risk factors for death, while married status, Asia-Pacific Islanders, insured status and surgery on primary site were protective factors. Gender was not significantly associated with the overall survival. The C statistic of the prediction model was 0.73 (95%CI: 0.72-0.74), and the calibration curve showed that the interaction curves of predictive and actual survival rates of 1, 3 and 5 years were close to the 45 degree diagonal. Results in the validation cohort were similar with those in the construction cohort, with a C statistic of 0.70 (95%CI: 0.69-0.72), indicating high external applicability of the prediction model. Findings from gallbladder cancer, extrahepatic bile duct cancer, and ampulla of Vater cancer are in consistent with the overall biliary tract cancer.@*Conclusions@#The survival rate of patients with biliary tract cancer is relatively poor, and the survival prediction model based on prognostic factors has high prediction accuracy. In the future, this prognostic prediction model could be applied to clinical practice to guide individualized treatment for patients with biliary tract cancer.

Thromboembolic Events as Prognostic Clinical Markers in Advanced Pancreatic and Biliary Tract Cancer / 대한내과학회지

BACKGROUND/AIMS: Venous thromboembolic events (VTEs) are common events in patients with advanced cancer. We analyzed the clinical characteristics of VTEs in advanced pancreatic and biliary tract cancer to determine the clinical significance, especially in palliative settings. METHODS: Seventy-nine patients with advanced pancreatic cancer or biliary tract cancer who had thromboembolic events were retrospectively reviewed. We investigated the correlation between clinical course and thromboembolic events, and the laboratory risk factors, such as complete blood count profile. RESULTS: The 79 patients consisted of 40 men (50.6%) and 39 women (49.4%) with a median age of 65 years old (range: 41–80). Forty-three patients (54.4%), had thromboembolic events without any symptoms. Pulmonary thromboembolism occurred in only 31 cases (39.2%), and combined thrombosis at more than two sites occurred in 17 cases (21.5%). Of the 51 patients with active chemotherapy, 45 showed progressive disease. The median survival times were 11.9 weeks in all patients, 15.3 weeks in the treatment group, and 3.4 weeks in the palliative group. There was no difference in survival time between patients treated with dalteparin only and those treated with dalteparin combined with thrombolytic intervention. CONCLUSIONS: VTE can be poor prognostic indicator in pancreatic and biliary tract cacner patients, suggestive of progressive disease and a sign of short life expectancy, requiring hospice and terminal care.

Efficacy and Safety of Chemotherapy with or without Targeted Therapy in Biliary Tract Cancer: A Meta-analysis of 7 Randomized Controlled Trials / 华中科技大学学报（医学）（英德文版）

The systematic treatment based on gemcitabine plus cisplatin is recommended as the current standard chemotherapy for unresectable or metastatic biliary tract cancers.However,the exact benefits from the recognized regime are still dismal.We thus elicit this study in an attempt to analyze whether targeted therapy coupled with various chemotherapy could produce improvement of survival benefits.The clinical trials were searched electronically from databases till July 2016 published in English and Chinese.Nine hundred and sixty-four patients from 7 trials were identified in our analysis.The overall analysis achieved a significantly higher overall response rate (ORR) among the patients treated with targeted drugs plus chemotherapy than chemotherapy alone (OR=1.87;95％ CI:1.37-2.57;P=0.000),but failed in the overall progression-free survival (PFS) [mean difference (MD)=0.63;95％ CI:-0.45-1.72;P=0.26] and overall survival (OS) (MD=-0.67;95％ CI:-2.54-1.20;P=0.49).In the sub analysis,better ORR was obtained with the addition of EGFR (OR=1.75;95％ CI:1.20-2.56;P=0.004) and VEGFR (OR=2.5;95％ CI:1.28-4.87;P=0.007) targeted therapy.Furthermore,the sub analysis of EGFR target showed an significant improvement on PFS (MD=l.36;95％ CI:0.29-2.43;P=0.01).No significant differences were observed in the incidences ofneutropenia (OR=1.37;95％ CI:0.89-2.12),thrombocytopenia (OR=l.40;95％ CI:0.83-2.39),anemia (OR=l.21;95％ CI:0.62-2.38),peripheral neuropathy (OR=1.52;95％ CI:0.81-2.88),increased AST/ALT (OR=l.40;95％ CI:0.82-2.39) as well as fatigue (OR=1.65;95％ CI:0.96-2.84) in either of the treatment groups.In conclusion,better ORR associated with chemotherapy combined with targeted therapy (both targeting EGFR and VEGF) is found in the present mcta-analysis without the cost of increased unacceptable toxicities,but regretfully not for the OS.The sub-analysis of targeting EGFR instead of VEGF obtains a superior PFS.Otherwise,there is no statistically significant difference in the overall PFS between the combination regime and chemotherapy alone.Given the paucity of favorable data,we need further studies to characterize optimal targeted agents to confirm the potential value to biliary tract cancer.

Comparison of Outcomes between 7-French and 10-French Plastic Stents for Patients with Biliary Tract Cancer / 대한췌담도학회지

BACKGROUND/AIM: There is little data on whether plastic stents with a larger diameter are patent for longer than small stents in patients with bile duct cancer. The aim of this study was to compare the stent survival between 7-French (Fr) and 10-Fr plastic stents and evaluate the factors affecting stent survival. METHODS: Patients with biliary obstruction due to biliary tract cancer were enrolled at Yonsei University Wonju College of Medicine from January 2010 to October 2014. RESULTS: A total of 215 patients (7-Fr:10-Fr = 89:126 patients) were retrospectively enrolled. The primary tumor sites were common bile duct (n = 111), hilar (n = 45), and ampulla of Vater (n = 59). Rates of stent migration and stent obstruction were not different between the two groups. The median duration of stent survival was 3.3 months in the 7-Fr group and 5.9 months in the 10-Fr group (p = 0.543). The diameter of the stent did not have an effect on stent survival (hazard ratio 1.11, 95% confidence interval 0.71-1.73, p = 0.649). CONCLUSIONS: 7-Fr and 10-Fr stents have similar rates of stent migration and stent obstruction. The stent survival of 7-Fr was not inferior to 10-Fr stents in the management of biliary tract cancer.

Expression and clinicopathological significance of antiapoptotis protein survivin in gallbladder cancer.

Background: Clinical significance of survivin (antiapoptosis protein) in gallbladder cancer is not yet established. Aims: This study was performed to assess the expression pattern of survivin in benign and malignant gallbladder lesions using immunohistochemistry (IHC), and to assess its clinicopathological significance. Settings and Design: Prospective study from July 2012 to July 2014 was performed as a part of intramural research project. Materials and Methods: Tissue samples from resected gallbladder for cholelithiasis (n = 27) and carcinoma gallbladder (n = 24) were evaluated for survivin expression by IHC using a scoring system. Their expression was correlated with different clinicopathological parameters. Statistical Analysis: Fisher’s exact test, Student’s t‑test, and Chi‑square test were used as appropriate for data analysis. Kaplan–Meier methods were used to calculate overall and disease‑free survival rates among different groups. Two‑sided P < 0.05 was considered as significant. Results: Benign group (19 females, age [mean ± standard deviation [SD]] 45 ± 14 years) and malignant group (20 females, age [mean ± SD] 48.9 ± 13.4 years) were comparable with respect to menopausal status, presence, size and types of stones. However, survivin expression was significantly higher (66.7%, 95% confidence interval [CI] 24–75) in gallbladder cancer than in cholelithiasis group (33%, CI 46–83), P = 0.025). Its expression did not correlate with gender, age, menopausal status, presence of gallstones or their size, number and type, tumor differentiation, and tumor stage. Conclusions: Significantly higher expression of survivin protein in gallbladder cancer as compared to cholelithiasis group suggests its role in gallbladder carcinogenesis though it may not have prognostic value.

Frecuencia de cáncer hepatobiliopancreático y su relación con diabetes mellitus en pacientes del Hospital Universitario de Maracaibo / Hepatobiliopancreatic cancer frequency and its relationship to diabetes mellitus in patients of the hospital universitario de Maracaibo

La diabetes mellitus se ha asociado con la presencia de algunos tipos de cáncer del tracto digestivo, sobre todo en los últimos años se ha relacionado con el cáncer de hígado, el páncreas y las vías biliares. Es por ello que se realizó el presente estudio retrospectivo con el objetivo de determinar la frecuencia del cáncer hepatobiliopancreático y su asociación con la presencia de diabetes en pacientes del Hospital Universitario de Maracaibo durante el periodo 2006-2012. Noventa y siete casos fueron registrados; con diagnóstico de neoplasias hepáticas malignas primarias (hepatocarcinoma-colangiocarcinoma intrahepático) 26,8%, Colangiocarcinomas extrahepáticos distales 21,6%, tumor de Klatskin 16,5%, cáncer de páncreas 10,3%, tumor periampular 5,2% y tumor de vesícula biliar 5,2%. En los pacientes diabéticos los tumores más frecuentes fueron el cáncer de páncreas y neoplasias hepáticas malignas primarias (94,8%, p<0,01). No se observó en el resto de los pacientes estudiados asociación significativa entre el diagnóstico de cáncer con la presencia de diabetes. Se necesitan estudios prospectivos con el fin de establecer los factores que pudieran influir en la génesis del cáncer en los pacientes diabéticos, tales como el tipo de tratamiento, alteraciones metabólicas y otros factores inflamatorios que pudiesen estar involucrados.

Diabetes mellitus has been associated with the presence of some types of cancer of the digestive tract, especially in recent years has been linked to cancer of the liver, pancreas and bile ducts. That is why we undertook the present retrospective study in order to determine the frequency of hepatobiliopancreatic cancer and its association with the presence of diabetes in patients at Maracaibo University Hospital during the period 2006-2012. 97 cases were reported, with a diagnosis of primary hepatic malignancies (hepatocellular carcinoma, intrahepatic cholangiocarcinoma) 26.8% 21.6% distal extrahepatic cholangiocarcinoma, Klatskin tumor 16.5% 10.3% pancreatic cancer, tumor periampullar 5,2% and gallbladder tumor 5.2%. In diabetic patients, the most common tumors were pancreatic cancer and primary hepatic malignancies (94.8%, p<0,01). It was not observed in the rest of the patients significant association between cancer diagnosis and the presence of diabetes. Prospective studies are needed in order to establish the factors that may influence the genesis of cancer in diabetic patients, such as the type of treatment, metabolic and inflammatory factors that may be involved.

<b>A Case of Advanced Biliary Tract Cancer Successfully Treated </b><b>with Single-agent Gemcitabine Chemotherapy </b><b>in Combination with Juzentaihoto </b> / 日本東洋医学雑誌

We report the case of an 84-year-old woman with advanced biliary tract cancer and accompanying colonic invasion and hepatic metastasis, who was successfully treated with single-agent gemcitabine chemotherapy in combination with juzentaihoto (a traditional Japanese herbal medicine). Response to this combination chemo therapy was extremely good, and the patient's tumors disappeared. There have been no reports like our case until today. These findings suggest that combined treatment with juzentaihoto and gemcitabine is effective not only for reducing tumor size, decreasing the side effects of chemotherapy, and maintaining general condition but also for mediating immune antitumor activity.

Clinical Characteristics of Biliary Tract Cancer Associated with Choledochal Cyst

PURPOSE: Choledochal cysts are rare congenital or acquired cystic dilatations of the intra- or extra-hepatic bile ducts. The mechanism of carcinogenesis in choledochal cyst has not been clearly elucidated, although stasis of bile and reflux of pancreatic juice appear to be important factors. The aim of this study was to identify the clinical risk factors predicting development of biliary tract cancers in patients with choledochal cyst. METHODS: The study subjects included 170 consecutive patients who underwent surgery for choledochal cysts at Seoul National University Hospital between December 1980 and May 2008. We analyzed the demographic characteristics, clinical symptoms, laboratory findings, type of choledochal cysts, pathologic characteristics, and long-term outcomes of the patients with associated biliary tract cancers. RESULTS: Out Of 170 patients with choledochal cysts, combined biliary tract cancers ware identified in 29 patients, which included extrahepatic bile duct (n=15; 51.7%), gallbladder (n=12; 41.4%), and ampulla of Vater cancers (n=2; 6.9%). There were no significant differences in gender, clinical symptoms (abdominal pain, jaundice, and abdominal masses), laboratory findings (leukocytosis, hyperbilirubinemia, and increased alkaline phosphatase), and Todani classification of choledochal cysts between the two groups with or without combined biliary tract cancer. Multivariate analysis revealed that age > or =41 years and pancreatico-choledochal type APBDU were associated with the development of biliary tract cancers in patients with choledochal cysts. CONCLUSION: Age > or =41 years and pancreatico-choledochal type APBDU were associated with the development of biliary tract cancers in patients with choledochal cysts. Therefore, the possibility of associated biliary tract cancers should be considered when planning surgical management for patients with these risk factors.

Clinical Characteristics of Biliary Tract Cancer Associated with Choledochal Cyst

PURPOSE: Choledochal cysts are rare congenital or acquired cystic dilatations of the intra- or extra-hepatic bile ducts. The mechanism of carcinogenesis in choledochal cyst has not been clearly elucidated, although stasis of bile and reflux of pancreatic juice appear to be important factors. The aim of this study was to identify the clinical risk factors predicting development of biliary tract cancers in patients with choledochal cyst. METHODS: The study subjects included 170 consecutive patients who underwent surgery for choledochal cysts at Seoul National University Hospital between December 1980 and May 2008. We analyzed the demographic characteristics, clinical symptoms, laboratory findings, type of choledochal cysts, pathologic characteristics, and long-term outcomes of the patients with associated biliary tract cancers. RESULTS: Out Of 170 patients with choledochal cysts, combined biliary tract cancers ware identified in 29 patients, which included extrahepatic bile duct (n=15; 51.7%), gallbladder (n=12; 41.4%), and ampulla of Vater cancers (n=2; 6.9%). There were no significant differences in gender, clinical symptoms (abdominal pain, jaundice, and abdominal masses), laboratory findings (leukocytosis, hyperbilirubinemia, and increased alkaline phosphatase), and Todani classification of choledochal cysts between the two groups with or without combined biliary tract cancer. Multivariate analysis revealed that age > or =41 years and pancreatico-choledochal type APBDU were associated with the development of biliary tract cancers in patients with choledochal cysts. CONCLUSION: Age > or =41 years and pancreatico-choledochal type APBDU were associated with the development of biliary tract cancers in patients with choledochal cysts. Therefore, the possibility of associated biliary tract cancers should be considered when planning surgical management for patients with these risk factors.

Bile Acid Analysis in Biliary Tract Canacer

The etiology of biliary tract cancer is obscure, but there are evidences that bile acid plays a role in carcinogenesis. To find the association between biliary tract cancer and bile acid, this study compared the bile acid concentration and composition among patients with biliary cancer, biliary tract stones, and no biliary disease. Bile was compared among patients with biliary tract cancer (n = 26), biliary tract stones (n = 29), and disease free controls (n = 9). Samples were obtained by percutaneous transhepatic biliary drainage, endoscopic nasobiliary drainage, or gallbladder puncture, and analyzed for cholic, deoxycholic, chenodeoxycholic, lithocholic, and ursodeoxycholic acid composition. Total bile acid concentration was lower in the cancer group than the biliary stone and control groups; the proportions of deoxycholic (2.2% vs. 10.2% and 23.6%, p < 0.001 and p < 0.001, respectively) and lithocholic acid (0.3% vs. 0.6% and 1.0%, p = 0.065 and p < 0.001, respectively) were also lower. This result was similar when disease site was limited to bile duct or gallbladder. Analysis of cases with bilirubin < or = 2.0 mg/dL also showed lower total bile acid concentration and deoxycholic acid composition in the cancer group compared to controls (5.7% vs. 23.6%, p = 0.003). Although the presence of bile duct obstruction explains some of the difference in total concentration and composition of bile acid, there are other contributing mechanisms. We suspect the alteration of bile acid transport might decrease bile acid excretion and cause the accumulation of carcinogenic bile acid in bile duct epithelium.

Bile Acid Analysis in Biliary Tract Canacer

The etiology of biliary tract cancer is obscure, but there are evidences that bile acid plays a role in carcinogenesis. To find the association between biliary tract cancer and bile acid, this study compared the bile acid concentration and composition among patients with biliary cancer, biliary tract stones, and no biliary disease. Bile was compared among patients with biliary tract cancer (n = 26), biliary tract stones (n = 29), and disease free controls (n = 9). Samples were obtained by percutaneous transhepatic biliary drainage, endoscopic nasobiliary drainage, or gallbladder puncture, and analyzed for cholic, deoxycholic, chenodeoxycholic, lithocholic, and ursodeoxycholic acid composition. Total bile acid concentration was lower in the cancer group than the biliary stone and control groups; the proportions of deoxycholic (2.2% vs. 10.2% and 23.6%, p < 0.001 and p < 0.001, respectively) and lithocholic acid (0.3% vs. 0.6% and 1.0%, p = 0.065 and p < 0.001, respectively) were also lower. This result was similar when disease site was limited to bile duct or gallbladder. Analysis of cases with bilirubin < or = 2.0 mg/dL also showed lower total bile acid concentration and deoxycholic acid composition in the cancer group compared to controls (5.7% vs. 23.6%, p = 0.003). Although the presence of bile duct obstruction explains some of the difference in total concentration and composition of bile acid, there are other contributing mechanisms. We suspect the alteration of bile acid transport might decrease bile acid excretion and cause the accumulation of carcinogenic bile acid in bile duct epithelium.

Epidermal Growth Factor Receptor and c-erbB-2 Expressions in Biliary Tract Cancers

PURPOSE: The expressions of epidermal growth factor receptor (EGFR) and c-erbB-2 have been considered to be implicated in the genesis and progression of cholangiocarcinomas. However, their clinical roles and pathological characteristics remain uninvestigated. The purpose of this study was to assess the expressions of EGFR and c-erbB-2, and to identify their clinical and pathological significances in biliary tract cancers. METHODS: One hundred and fourteen samples were obtained from surgically resected biliary tract cancers (72 extrahepatic bile duct cancers, 33 gallbladder cancers, and 9 intrahepatic bile duct cancers). Expressions of EGFR and c-erbB-2 were examined by immunohistochemical staining. Expression rates were analyzed according to the location of the tumor, histologic differentiation, depth of invasion, lymph node metastasis, lymphovascular invasion, recurrence, and survival rate. RESULTS: The expression rate of EGFR was 10.7% in biliary tract cancers. EGFR expression was more often observed in moderately- or poorly-differentiated carcinomas than in well-differentiated carcinomas (p=0.0252). No correlations were observed with age, gender, location of tumor, depth of invasion, lymph node metastasis, lymphovascular invasion, recurrence rate, or survival rate. c-erbB-2 was expressed in 4.5% of biliary tract cancers. c-erbB-2 expression had no significant relationships with clinical and pathological prognostic factors. CONCLUSION: EGFR expression can be used restrictively as a prognostic indicator of biliary tract cancers. c-erbB-2 expression in biliary tract cancers is very low, and does not show any prognostic significance.

Nursing about percutaneous biliary tract stent implantation to cure malignant obstructive jaundice / 中国实用护理杂志

Objective To study the nursing method about percutaneous biliary tract stent implantation to cure malignant obstructive jaundice.Methods Careful perioperative nursing cares and finished post-hospital direction were applied among 21 patients with malignant obstructive jaundice when by percutaneous biliary tract stent implantation.Results There were 20 patients obtained successful operation,the successful rate was 95%.The postoperative of glutamic pyruvic transaminase were(96.60?89.36) U/L,the total bilirubin was(137.96?103.95) ?mmol/L,the directed bilirubin was((85.67)?62.95) ?mmol/L and the indirected bilirubin was(56.76?37.37) ?mmol/L.All the indexes which have mentioned above were significant lower than those of before operative,P

Epidemiological studies on the distribution and determinants of biliary tract cancer

With the help of my colleagues, I have been conducting epidemiological studies on biliary tract cancer (BTC), including gallbladder cancer (GBC) and extrahepatic bile duct cancer (BDC), in Japan and Chile for about 19 years. Clustered areas with high mortality rates, especially for female GBC were found to correspond with places or prefectures in Japan that were famous for rice production. The roles of known risk factors, such as gallstones and cholecystitis, were examined, but no single factor was implicated in the high mortality rates for GBC in these areas. A working hypothesis, called the "rice production hypothesis" was formulated; this initial hypothesis was replaced by a new multifactorial causation hypothesis: GBC is more likely to occur in individuals with a genetic susceptibility and a past history of gallstones or cholecystitis who are exposed to geographically specific environmental factors, such as agricultural chemicals. On the basis of various analytical studies, it is concluded that a certain agricultural chemical was responsible for the occurrence of GBC. At the time of writing, no evidence has been obtained to disprove our hypothesis. We have also conducted international collaborative studies in Chile, which has the highest mortality rate for GBC in the world. Bile from Chileans was found to have a higher mutagenic activity than that from Japanese subjects; Chileans with a history of constipation or a habit of consuming red chilli pepper had a high risk of developing GBC, if they also had gallstone(s). The presence of a regional difference in p53 mutagenesis was also observed.

Epidemiological Studies on the Distribution and Determinants of Biliary Tract Cancer

With the help of my colleagues, I have been conducting epidemiological studies on biliary tract cancer (BTC), including gallbladder cancer (GBC) and extrahepatic bile duct cancer (BDC), in Japan and Chile for about 19 years. Clustered areas with high mortality rates, especially for female GBC were found to correspond with places or prefectures in Japan that were famous for rice production. The roles of known risk factors, such as gallstones and cholecystitis, were examined, but no single factor was implicated in the high mortality rates for GBC in these areas. A working hypothesis, called the “rice production hypothesis” was formulated; this initial hypothesis was replaced by a new multifactorial causation hypothesis: GBC is more likely to occur in individuals with a genetic susceptibility and a past history of gallstones or cholecystitis who are exposed to geographically specific environmental factors, such as agricultural chemicals. On the basis of various analytical studies, it is concluded that a certain agricultural chemical was responsible for the occurrence of GBC. At the time of writing, no evidence has been obtained to disprove our hypothesis. We have also conducted international collaborative studies in Chile, which has the highest mortality rate for GBC in the world. Bile from Chileans was found to have a higher mutagenic activity than that from Japanese subjects; Chileans with a history of constipation or a habit of consuming red chilli pepper had a high risk of developing GBC, if they also had gallstone(s). The presence of a regional difference in p53 mutagenesis was also observed.

Klaskin tumor – diagnosis and surgical treatment

A study on 3 patients with Klaskin tumor (male: 2, female: 1) in strasbourg, France during 1996-1997 has shown that the diagnosis involved in the clinical examination, biochemical and functional test, tumor markers, hepatobiliary ultrasound, hepatic angiography; the surgical treatment included the local tumor resection, combination of local tumor resection and PTI resection, local tumor resection + PTI resection + liver resection and anastomosis.

Surgical Treatment and Prognosis for 268 Patients with Biliary Tract Cancers

PURPOSE: Carcinomas of the biliary tract are considerably rare conditions. In spite of recent progress in diagnosis and treatment, resectability remains low, and the prognosis is still discouraging. This review summarizes our 12-year experience with biliary tract cancers, with particular focus on the survival rates after operation and the prognostic factors that affected the survival of patients. METHODS: Between 1987 and 1998, 268 patients with biliary tract cancers were operated on at our institution. The clinical and the pathologic data were collected, and a survival analysis was performed. RESULTS: The tumor was located in the gallbladder in 90 patients, in the proximal bile duct in 74 patients, in the distal bile duct in 54 patients, and in the ampulla of Vater in 50 patients. One hundred ninety-seven patients underwent a radical resection (resection rate: 73.5%). A curative resection was achieved in 140 patients (curative resection rate: 71.1%). The overall operative mortality after resection was 3.0%. The cumulative survival rates at five years after resection were 61.1% for carcinomas of the gallbladder, 25.8% for proximal bile duct cancers, 28.9% for distal bile duct cancers, and 48.7% for ampulla of Vater cancers. The one-year survival rates for the non-resection group were 18.2% and 26.6% for gallbladder cancers and proximal bile duct cancers, respectively. The mean survival periods for unresectable distal bile duct cancers and ampullary cancers were 4.7 months and 8.3 months, respectively. Positive lymph-node metastasis was a statistically significant, poor prognostic factor. CONCLUSION: Long-term survivals can be expected by a radical surgery for patients with biliary tract cancers. Increasing the resection rate by performing an extended procedure is essential for the improvement of treatment outcomes.