Extrahepatic Bile Duct Adenocarcinoma Research Articles

Adjuvant Chemoradiation in Resected Biliary Adenocarcinoma: Evaluation of SWOG S0809 with a Large National Database

BackgroundThere is a paucity of evidence supporting the use of adjuvant radiation therapy in resected biliary cancer. Supporting evidence for use comes mainly from the small SWOG S0809 trial, which demonstrated an overall median survival of 35 months. We aimed to use a large national database to evaluate the use of adjuvant chemoradiation in resected extrahepatic bile duct and gallbladder cancer.MethodsUsing the National Cancer Database, we selected patients from 2004 to 2017 with pT2-4, pN0-1, M0 extrahepatic bile duct or gallbladder adenocarcinoma with either R0 or R1 resection margins, and examined factors associated with overall survival (OS). We examined OS in a cohort of patients mimicking the SWOG S0809 protocol as a large validation cohort. Lastly, we compared patients who received chemotherapy only with patients who received adjuvant chemotherapy and radiation using entropy balancing propensity score matching.ResultsOverall, 4997 patients with gallbladder or extrahepatic bile duct adenocarcinoma with available survival information meeting the SWOG S0809 criteria were selected, 469 of whom received both adjuvant chemotherapy and radiotherapy. Median OS in patients undergoing chemoradiation was 36.9 months, and was not different between primary sites (p = 0.841). In a propensity score matched cohort, receipt of adjuvant chemoradiation had a survival benefit compared with adjuvant chemotherapy only (hazard ratio 0.86, 95% confidence interval 0.77–0.95; p = 0.004).ConclusionUsing a large national database, we support the findings of SWOG S0809 with a similar median OS in patients receiving chemoradiation. These data further support the consideration of adjuvant multimodal therapy in resected biliary cancers.

Development and validation of a prognostic nomogram for extrahepatic bile duct adenocarcinoma.

The aim of this study is to establish a prognostic nomogram for patients with extrahepatic bile duct adenocarcinoma (EBDA). From the Surveillance, Epidemiology, and End Results database, we retrieved clinical data from 1,485 patients diagnosed with EBDA between 2004 and 2015. These patients were randomly assigned to either the training or validation group in a ratio of 2:1. Cox proportional risk regression models were used to analyze the association of each variable with overall survival (OS). Univariate and multifactorial Cox regression analyses were performed to identify prognostic factors, and prognostic nomograms were created on the basis of the results of Cox multifactorial regression analysis. Performance was assessed by calibration curves and ROC curves. Internal validation was performed using the validation cohort. The Kaplan-Meier method was used to perform log-rank constructions for different risk groups. The results indicated that age, race, N and M stages of tumor-lymph node metastases based on AJCC version 6, surgery, and chemotherapy were independent prognostic factors for OS in patients with EBDA. The constructed nomograms showed decent classification in predicting both 3- and 5-year survival rates. The calibration curves also show a high degree of agreement between the predicted and actual operating systems. The nomogram that we constructed provides a relatively accurate and applicable prediction of survival outcome in patients with EBDA, which helps to provide reference and guidance for patient treatment.

New approach to the treatment of cancer of large duodenal papilla and extrahepatic bile ducts with photodynamic therapy

The study is based on the treatment of 79 patients with adenocarcinoma of large duodenal papilla and extrahepatic bile ducts. 29 patients received palliative bile drainage operations with PDT. 50 patients in the group of chronological control only palliative bile drainage operations had been performed. Patients in research group received from 1 to 3 PDT courses in a year. In total 29 patients received 52 PDT courses. Outcomes were assessed by determining the median survival. The treatment was well-tolerated by the patients. The median survival time was 18 months (11–60 months). In patients who had only one PDT session during the year median survival was 12,5 months; in patients who had two or more PDT sessions median survival was 29 months (15–60 months). Results of PDT treatment for cancer of this localization are comparable with the results of radical surgeries and overcome palliative surgeries. Decrease of tumor growth rate and longer survival period in patients after PDT are determined by vascular mechanisms produced by PDT (vascular thrombosis and impaired tumor blood supply), these factors provide long-term process stabilization. Repeated PDT courses signifi cantly improve treatment results.

Robotic pancreaticoduodenectomy in a patient with situs inversus totalis and variant celiacomesenteric trunk

Situs inversus totalis (SIT) is a rare congenital anomaly characterized by right–left reversal of visceral organs and dextrocardia; the use of robotic pancreaticoduodenectomy (RPD) may be challenging in these patients. A male patient presented with jaundice; imaging studies revealed a bile duct tumor and SIT with variant celiacomesenteric trunk and multiple vascular anomalies. RPD was carried out cautiously and successfully. The trocar port design mirrored that of a normal patient. Pathological examination revealed extrahepatic bile duct adenocarcinoma, classified as pT3N1M0, stage IIB. The patient recovered uneventfully. Although difficult, RPD is technically feasible in an SIT patient with cholangiocarcinoma.

Photodynamic therapy of cancer of large duodenal papilla and extrahepatic bile ducts

The problem of treating patients with malignant neoplasms of the extrahepatic bile ducts and the large duodenal papilla remains relevant due to the growing incidence, high mortality, and a pronounced decrease in the quality of life of patients, despite the radical surgery. The purpose of this study was to evaluate the effectiveness of photodynamic therapy (PDT) in inoperable patients with malignant tumors of these localizations.The study is based on the treatment of 79 patients with adenocarcinoma of large duodenal papilla and extrahepatic bile ducts. 29 patients received palliative bile drainage operations with PDT. 50 patients in the control group only had palliative bile drainage operations. Patients in the study group received from 1 to 3 PDT courses in a year. In total, 29 patients received 52 PDT courses. The tolerance to the method and the life expectancy of patients were evaluated. The median survival of patients who underwent PDT was 18 months (11–60 months); in the control group – 11.5 months. PDT, in combination with bile drainage operation, is an effective method for the treatment of inoperable patients with malignant neoplasms of the extrahepatic bile ducts and the large duodenal papilla in the absence of severe complications and with easy tolerance to therapy by patients. For the treatment and prolongation of life of patients whose radical surgical treatment is associated with a high risk of death, PDT seems to be the best treatment option. Results of PDT treatment for cancer of this localization are comparable with the results of radical surgeries and exceed those for palliative surgeries.

Differentiation grade for extrahepatic bile duct adenocarcinoma: Assessed by diffusion-weighted imaging at 3.0-T MR

Purpose—To assess the pathological differentiation grade in the patients with extrahepatic bile duct adenocarcinoma (EBDA) using diffusion-weighted imaging (DWI) at 3.0-T MR. Methods—Sixty-eight patients who were clinically and histologically diagnosed with EBDA underwent abdominal DWI within 2 weeks before surgery. The lesion signal intensity, signal intensity ratio of the lesion and hepar (SIR-LH) value, and apparent diffusion coefficient (ADC) value in patients with EBDA were retrospectively analysed. Results—In the 68 patients, 22 well-differentiated, 36 moderately-differentiated, and 10 poorly-differentiated EBDAs were histopathological confirmed. These EBDAs exhibited hyper-intensity on DWI in 95.59% of patients. Hyper-intensity lesions were found in 90.91% of patients with good-differentiation, in 97.22% with moderate-differentiation and in 100% with poor-differentiation. There showed no statistical difference for the lesion signal intensity (P=0.426) and SIR-LH value (P=0.766) on DWI among three groups. The median ADC value of the well-differentiated, moderately-differentiated and poorly-differentiated EBDAs were 1.506×10−3mm2/s, 1.275×10−3mm2/s and 1.154×10−3mm2/s, respectively. As the pathological differentiation grade decreased, the lesion ADC value of EBDA gradually declined (x2=51.220, P=0.000). The ADC value <1.184×10−3mm2/s can predict the poorly-differentiated EBDA with a sensitivity of 100% and a specificity of 94.83%. The ADC value >1.316×10−3mm2/s can forecast the well-differentiated EBDA with a sensitivity of 100% and a specificity of 84.78%. Conclusions—The histopathological differentiation grade of EBDA can be detected non-invasively using DWI at 3.0-T MR.

神経内分泌細胞癌と腺癌を合併した胆管癌の1例

症例は80歳，女性．食思不振を主訴に近医を受診し黄疸を指摘され，精査目的に当院を受診した．腹部造影CT検査で下部胆管に全周性壁肥厚を認めた．リンパ節等への転移は認めなかった．内視鏡的逆行性胆道膵管造影で下部胆管に欠損像を認め，上流の総胆管ならびに肝内胆管の拡張を認めた．下部胆管癌の診断で亜全胃温存膵頭十二指腸切除術を施行した．標本では下部胆管の2箇所に腫瘍形成を認めた．末梢側の腫瘍は免疫染色でsynaptophysinならびにchromogranin A陽性であり，Ki-67指数50～60％であったため，WHO2010分類でNECと診断した．中枢側の腫瘍では高分化管状腺癌の増殖を認めた．両者の間に連続性は認められなかった．現在術後1年で無再発生存中である．これまで，胆管原発の神経内分泌細胞癌と腺癌を独立して合併した症例については報告がなく貴重と考えられたため，若干の文献的考察を加えて報告する．

The utility of villin and mammaglobin in the differential diagnosis between intrahepatic cholangiocarcinoma and breast cancer.

Liver metastasis is common for breast cancer. In breast cancer patients, differentiation between metastasis and intrahepatic cholangiocarcinoma (ICC) is crucial but not always possible, especially when estrogen receptor (ER) is negative. Villin and mammaglobin are gastrointestinal and breast markers, respectively, but were considered not useful in cholangiocarcinoma. The aim of this study was to reevaluate these 2 markers in the differential diagnosis between breast ductal carcinoma and ICC. Fifty-two cases of breast ductal carcinoma (including ER positive and negative, in situ, and invasive carcinomas), 27 cases of ICC, and 19 cases of extrahepatic bile duct adenocarcinoma were retrieved. Immunohistochemical staining for villin and mammaglobin was performed. The results showed that villin was negative in all breast cancers with a specificity of 100%, and positive in all ICCs with a sensitivity of 100%. Its sensitivity in extrahepatic bile duct adenocarcinoma was 63.2%. Mammaglobin was positive in a smaller percentage of breast cancers with no relationship to ER status. Discordant mammaglobin expression among matched invasive, in situ, and metastatic carcinomas of the same patient was common. Mammaglobin was negative in all ICCs with a specificity of 100%, when care was taken not to misinterpret patchy staining in adjacent normal hepatocytes as positive. In conclusion, the data showed that villin expression was highly accurate in the differential diagnosis between ICC and breast ductal carcinoma, which was particularly useful in ER-negative cases. Mammaglobin may be useful when it is positive.

Adequate Lymph Node Assessment for Extrahepatic Bile Duct Adenocarcinoma

To examine the importance of adequate lymph node sampling in staging of extrahepatic bile duct cancer (EHBDCA). The American Joint Committee on Cancer staging manual (sixth edition) states that histologic examination of at least 3 lymph nodes is required for adequate N stage determination for EHBDCA. This recommendation has not been validated; however, there has been no comparative assessment of the proximal versus distal bile duct cancer. A total of 257 patients (144 hilar cholangiocarcinoma [HCCA] and 113 distal bile duct adenocarcinoma [DBDCA]) who underwent curative intent resection (1987-2007) were analyzed; patients with gallbladder cancer were excluded. Final disease staging, including lymph node status and total number of nodes examined (total lymph node count), was obtained from the final pathology report. Differences in disease-specific survival, according to nodal status, were compared using the log-rank test. R1 resections (n = 51) were excluded from this analysis. Metastasis to regional lymph nodes was noted in 89 patients (34.6%) and was an independent prognostic factor of poor survival (median disease-specific survival N0 vs. N1: 53.5 vs. 19.3 months, P < 0.0001, hazard ratio = 2.1 [95% CI: 1.4-3.2]). The median total lymph node count was 6 (range: 0-42), and was significantly lower for HCCA compared with DBDCA (median = 3 [range: 0-16] vs. 12 [range: 1-42], P < 0.001, respectively). For the entire cohort, patients who underwent R0 resection and were classified as N0, based on total lymph node count <11, had a disease-specific survival that was significantly worse than that of patients classified as N0 based on total lymph node count >or=11 (52.6 +/- 9.8 months vs. not reached, P = 0.008). The estimated optimal total lymph node count for HCCA differed from that of DBDCA (n = 7 vs. n = 11, respectively). Adequate lymph nodes assessment of EHBDCA, based on the current AJCC recommendations, results in understaging of these tumors. With respect to the optimal total lymph node count, HCCA, and DBDCA should be considered separately.

Efficacy and Safety of S-1 Monotherapy in Patients with Advanced Biliary Tract Adenocarcinoma

Aim: We investigated the efficacy and safety of S-1 monotherapy for the treatment of advanced biliary tract adenocarcinoma (BTA) in a clinical practice setting. Methods: We reviewed clinical data from 217 patients with advanced BTA who were treated with S-1 monotherapy between August 2004 and September 2007. Results: 162 eligible patients were identified. The primary tumors were intrahepatic (n = 57), in the gall bladder (n = 50), in extrahepatic bile ducts (n = 41) and in the ampulla of Vater (n = 14). Sixteen of 120 assessable patients achieved partial responses, with a response rate of 13.3% (95% CI 7.2–19.4%). Another 51 patients had stable disease, with an overall tumor control rate of 55.8% (95% CI 46.9–64.7%). The median time to progression was 2.7 months and the median overall survival time was 6.9 months. Response rates and survival differed significantly according to the primary site of the tumor (p = 0.002 and p < 0.001, respectively), with extrahepatic bile duct adenocarcinoma having the best prognosis. The treatment regimen produced only mild toxicity in most cases (grade 1 or 2), even for patients with hyperbilirubinemia. Conclusion: S-1 has a favorable toxicity profile and can be safely administered to BTA patients with hyperbilirubinemia. The efficacy of S-1 against advanced BTA depends on the tumor site and is most effective in patients with extrahepatic BTA.

Expression of syndecan-1 and E-cadherin is inversely correlated with poor patient's prognosis and recurrent status of extrahepatic bile duct carcinoma

Extrahepatic bile duct carcinoma is one of the most extremely aggressive cancers with poor prognosis after curative resection. Syndecan-1 and E-cadherin are transmembrane glycoproteins, and have important roles in cell-cell adhesion and tumor progression. In this study, we examined 84 surgically resected cases of extrahepatic bile duct adenocarcinoma to clarify clinicopathological significance of syndecan-1/E-cadherin expression. Reduced expressions of syndecan-1 and Ecadherin were found in 69.0% (58/84) and 46.4% (39/84) of the bile duct carcinomas. Reduced syndecan-1 expression was correlated with lymphatic/venous/nervous invasion (P < 0.0001), and was associated with short overall survival (P = 0.0002). Reduced E-cadherin expression was correlated with lymphatic and nervous invasion (P = 0.008, P < 0.0001, respectively), and was associated with short overall survival (P = 0.0038). The results indicated that reduced syndecan-1/E-cadherin expression may be good indicators of recurrence and prognosis in extrahepatic bile duct carcinoma.

Extrahepatic bile duct adenocarcinoma: patients at high-risk for local recurrence treated with surgery and adjuvant chemoradiation have an equivalent overall survival to patients with standard-risk treated with surgery alone.

Patients with resected extrahepatic bile duct adenocarcinoma who have microscopically positive resection margins and/or pathologic locoregional nodal involvement (R1pN1) have a high-risk of locoregional recurrence, and therefore, we advocate the use of adjuvant chemoradiation. To evaluate the safety and effectiveness of this treatment, we compared survival and side effects outcomes between such patients and patients with negative resection margins and pathologically negative nodes (R0pN0) who did not receive adjuvant treatment. Between 1984 and 2005, 65 patients were treated with curative-intended resection for extrahepatic bile duct adenocarcinoma. Patients with tumors arising in the gallbladder and periampullary region were excluded. Pathology and diagnostic images were centrally reviewed. Overall survival and locoregional recurrence outcomes for patients with standard-risk R0pN0 (surgery alone, or S group, n = 23) were compared with those of patients with high locoregional recurrence risk, R1 and/or pN1 (R1pN1) status who received adjuvant chemoradiation (S-CRT group, n = 42). The median follow-up for the entire group was 31 months. Patients in the S-CRT and S groups had a similar 5-year overall survival (36% vs. 42%, P = .6) and locoregional recurrence (5-year rate: 38% vs. 37%, P = .13). In the S-CRT group, three patients (7%) experienced an acute (grade 3 or more) side effect. Our finding of a lack of a survival difference between the S and S-CRT groups suggests that for patients with extrahepatic bile duct adenocarcinoma at high risk for locoregional recurrence (i.e., R1 resection or pN1 disease), adjuvant chemoradiation provides an equivalent overall survival despite of these worse prognostic features.

Radiochemotherapy Followed by Gemcitabine and Capecitabine in Extrahepatic Bile Duct Cancer

Both radiotherapy and chemotherapy with gemcitabine and capecitabine have efficacy in biliary cancer. Our aim was to determine the toxicity and efficacy of a postoperative regimen combining both treatment modalities in extrahepatic bile duct cancer. Patients were eligible after surgery for extrahepatic bile duct adenocarcinoma. Surgery included resection of lymph node positive cancer, incomplete resections and diagnostic laparotomy in unresectable tumors. Patients received a fractionated radiotherapy of 49.6 Gy accompanied by gemcitabine once a week. After a 2-week rest, patients were treated with gemcitabine and capecitabine on a 3-week cycle. The treatment continued for 6 cycles in nonmeasurable disease or until disease progression or intolerable toxicity. There were 18 patients (resection/laparotomy 7/11) enrolled between August 2003 and April 2005. Radiotherapy was completed in all patients and a total of 66 cycles of chemotherapy was applied. Fatigue and nausea were the most common mild adverse events. Grade 3 and 4 toxicity was rare after resection but frequent in unresectable disease and consisted of fatigue, nausea, duodenal ulcer, cachexia, and cholangitis in 1, 2, 2, 4, and 4 patients, respectively. We observed a 50% disease stabilization rate in patients with measurable disease. Median overall survival was 7.9 months in patients with unresectable tumors. Median overall survival in patients after resection has not been reached at a median follow-up of 19.5 months. Radiochemotherapy using gemcitabine followed by gemcitabine and capecitabine is an active regimen with manageable toxicity after resection of extrahepatic bile duct cancer but has significant toxicity in unresectable disease.

P.1.044 WAY-181187: neurochemical profile of a novel and selective 5-HT6 receptor agonist

To assess the pathological differentiation grade in the patients with extrahepatic bile duct adenocarcinoma (EBDA) using diffusion-weighted imaging (DWI) at 3.0-T MR.Sixty-eight patients who were clinically and histologically diagnosed with EBDA underwent abdominal DWI within 2 weeks before surgery. The lesion signal intensity, signal intensity ratio of the lesion and hepar (SIR-LH) value, and apparent diffusion coefficient (ADC) value in patients with EBDA were retrospectively analysed.—In the 68 patients, 22 well-differentiated, 36 moderately-differentiated, and 10 poorly-differentiated EBDAs were histopathological confirmed. These EBDAs exhibited hyper-intensity on DWI in 95.59% of patients. Hyper-intensity lesions were found in 90.91% of patients with good-differentiation, in 97.22% with moderate-differentiation and in 100% with poor-differentiation. There showed no statistical difference for the lesion signal intensity (P = 0.426) and SIR-LH value (P = 0.766) on DWI among three groups. The median ADC value of the well-differentiated, moderately-differentiated and poorly-differentiated EBDAs were 1.506 × 10−3 mm2/s, 1.275 × 10−3 mm2/s and 1.154 × 10−3 mm2/s, respectively. As the pathological differentiation grade decreased, the lesion ADC value of EBDA gradually declined (x2 = 51.220, P = 0.000). The ADC value <1.184 × 10−3 mm2/s can predict the poorly-differentiated EBDA with a sensitivity of 100% and a specificity of 94.83%. The ADC value >1.316 × 10−3 mm2/ s can forecast the well-differentiated EBDA with a sensitivity of 100% and a specificity of 84.78%.The histopathological differentiation grade of EBDA can be detected non-invasively using DWI at 3.0-T MR.

A fatal overdose of the ergot derivative cabergoline

A 79-year-old woman, with Parkinson’s disease treated with cabergoline, was admitted to a hospital due to jaundice and weakness. She was found confused, absent minded, and died after 2 weeks. Autopsy showed an extrahepatic bile duct adenocarcinoma with spread to the gall bladder, the liver, and regional lymphnodes. While cleaning the hospital bed after her death, the nurses found several tablets hidden in the bed. Biological samples obtained at the autopsy were screened for common drugs and narcotics. Several drugs such as buprenorphine, codeine, paracetamol, and propranolol were detected in the blood at therapeutic levels. A method to determine cabergoline in whole blood and other forensic matrices was developed, and further investigations determined cabergoline concentrations in whole blood and liver tissue of 94 and 3100 μg/kg, respectively. The blood concentration was 100 times above the therapeutic level reported on cabergoline in plasma and in combination with her symptoms, suggest she took a fatal overdose of cabergoline.

A fatal overdose of the ergot derivative cabergoline

A 79-year-old woman, with Parkinson’s disease treated with cabergoline, was admitted to a hospital due to jaundice and weakness. She was found confused, absent minded, and died after 2 weeks. Autopsy showed an extrahepatic bile duct adenocarcinoma with spread to the gall bladder, the liver, and regional lymphnodes. While cleaning the hospital bed after her death, the nurses found several tablets hidden in the bed. Biological samples obtained at the autopsy were screened for common drugs and narcotics. Several drugs such as buprenorphine, codeine, paracetamol, and propranolol were detected in the blood at therapeutic levels. A method to determine cabergoline in whole blood and other forensic matrices was developed, and further investigations determined cabergoline concentrations in whole blood and liver tissue of 94 and 3100 μg/kg, respectively. The blood concentration was 100 times above the therapeutic level reported on cabergoline in plasma and in combination with her symptoms, suggest she took a fatal overdose of cabergoline.

Sialyl Lex and Sialyl Lea Expression in Human Extrahepatic Bile Duct Adenocarcinoma

Sialyl Le x (FH6) and sialyl Le a (CA19-9) antigens, members of a family of high molecular weight glycoproteins, are ligands for E-selectin and may play important roles in tumor metastasis. However, expression patterns ofsialyl Le x and sialyl Le a have not been established in human extrahepatic bile duct cancer. In this study, we examined sialyl Le x and Le a expression in human extrahepatic bile duct adenocarcinoma and their clinicopathological significance. Sialyl Le x immunoreactivity was detected not only in cancer cells (cytoplasmic type; 57.7%, 30/52), but also in cancer stroma (stromal type; 19.2%, 10/52). Sialyl Le a immunoreactivity was found in cancer cells (cytoplasmic type; 84.6%, 44/52) and in cancer stroma (stromal type; 63.5%, 33/52). Stromal sialyl Le a expression was more frequent than stromal sialyl Le x expression (p<0.001). According to TNM classification, cytoplasmic sialyl Le x and sialyl Le a expression was detected in 62.5% (30/48) and 85.4% (41/48) of the T2-3 cancers (T2-3 vs T1, sialyl Le x , p=0.015; and sialyl Le a , p = 0.310). Cytoplasmic sialyl Le a positive cancers frequently showed lymph node metastasis (p = 0.029). These observations suggested that sialyl Le a expression plays more important roles than sialyl Le x in metastasis of human extrahepatic bile duct adenocarcinoma.

Image analysis of Transwell assays in the assessment of invasion by malignant cell lines

This study aims to determine if layering of extracellular matrix (ECM) can achieve a physiological basement membrane thickness of 8 μm and to assess the use of paraffin wax-embedded Transwell plates coupled with digital image analysis as a means of determining invasion by malignant cell lines. Layers of Matrigel, a sarcomaderived ECM was built to a concentration of 7.4 μg/mm2 in the upper chamber of a Transwell plate invasion assay. Two cell lines from extrahepatic bile duct adenocarcinoma were tested in serum-free growth medium. Conditioned medium was added to the lower chamber to act as a chemoattractant. Following attachment, cells were incubated for 48 h and the Matrigel-coated insert cut from its holder and fixed in 10% unbuffered formalin saline. Each insert was bisected and processed to paraffin wax. Serial levels were stained by haematoxylin and eosin. A Kontron image analysis system was used to measure the mean thickness of Matrigel for each cell line and the degree of invasion was assessed by measuring the depth to which cells had degraded the Matrigel. A mean thickness of 8 μm was achieved using 5.0 μg/mm2 for the OCUCh-LM1 cell line and 7.4 μg/mm2 for the SKChA-l cell line. No significant difference was seen in the ability of either cell line to degrade Matrigel. Immunocytochemistry for laminin and cytokeratin helped to identify ECM components and cells, respectively. In conclusion, digital image analysis of paraffin wax-embedded inserts can be used to determine the invasive capacity of various cell lines; immunocytochemistry may help to identify ECM components and cells; and the assay used to assess different cell lines and their ability to degrade Matrigel.

SYNCHRONOUS DOUBLE CANCER OF THE EXTRAHEPATIC BILE DUCT AND LUNG -REPORT OF A RESECTED CASE ON A TWO-STEP APPROACH-

Recently double cancer has been increasingly reported with an increase in the aged population, an advance of diagnostic instruments and a technical improvement of cancer therapy.It is exceedingly rare that synchrous double cancer of the bile duct and lung has been successfully resected. This paper describes a resected case of synchronous cancer of extrahepatic bile duct (adenocarcinoma) and lung (squamous cell carcinoma).A 68-year-old man was admitted to the hospital for close examination because of bloody phlegm, a tumorous lesion on a X-ray film, and jaundice. By TBLB, a tumor of the left lower lobe was diangosed as squamous cell carcinoma. By PTCS biopsy, a stenosis of the distal bile duct was diagnosed as moderately differentiated adenocarcinoma. A preoperative diagnosis of synchronous double cancer of the bile duct and lung was made.It was judged impossible to resect the both carcinomas on an one-step approach in terms of surgical invasion. Intra-arterial infusion therapy with CDDP via the left bronchial artery was performed for the lung carcinoma, followed by left lower lobectomy with combined resection of the chest wall and ribs 42 days after pancreato-duodenectomy.It is generally accepted that we must give a surgical priority to the more advanced cancer responsible for the prognosis of the patient carrying synchronous double cancer.Multidisciplinary treatment and aggresive surgical intervention may bring the patient a long-term survival and favorable prognosis.