Biliary Duct Carcinoma Research Articles

Lobar and Segmental Atrophy of the Liver: Differential Diagnoses and Treatments

Segmental or lobar liver atrophy is a common but not well-understood clinical condition. Hepatic atrophy can be classified into hepatic atrophy secondary to other pathologies and primary segmental hepatic atrophy, which is a benign intrahepatic lesion (pseudotumor) not associated with any other pathology. The pathophysiological mechanisms underlying atrophy can be divided into three main situations: obstruction of biliary outflow, obstruction of the systemic venous outflow, and obstruction of incoming portal venous flow. For what may concern secondary hepatic atrophy, there are many pathologies that could underlie this condition, ranging from benign to intrahepatic malignancies, with particular reference to particularly hepatocellular carcinoma and biliary duct carcinoma. An accurate and prompt differential diagnosis between the various forms and causes of atrophy is important for early identification and adequate treatment of underlying pathologies. A comprehensive review of the literature on the etiology and the radiological and histological characteristics of different types of hepatic atrophy is currently unavailable. Therefore, the aim of this review is to summarize the primary and secondary causes of segmental or lobar liver atrophy (excluding forms involving the entire liver parenchyma) and to provide practical tools for clinical and radiological differential diagnosis.

Particle Beam Therapy for Intrahepatic and Extrahepatic Biliary Duct Carcinoma: A Multi-Institutional Retrospective Data Analysis.

To examine the efficacy and toxicity of particle beam therapy (PT) for biliary duct carcinoma (BDC) and compare the outcomes between extrahepatic BDC (eBDC) and intrahepatic BDC (iBDC). We analyzed multi-institutional data from May 2009 to December 2019. The primary endpoint was overall survival (OS), and the secondary endpoints were local control (LC), progression-free survival (PFS) and toxicity. We included 150 patients with unresectable BDC treated with PT using a median prescribed dose of 70.2 GyRBE (range, 44-77 GyRBE) in 25 fractions (range, 10-38 fractions). With a median follow-up of 13.0 months, median survival time (MST) was 21 months, and 2-year OS was 44.8%. For eBDC and iBDC, the MSTs were 20 and 23 months, respectively. Two-year PFS and LC rates were 20.6% and 66.5%, respectively. Vascular invasion, prescribed dose and serum tumor marker level (carcinoembryonic antigen: CEA) were identified as poor prognostic factors for OS. A higher radiation dose EQD2 ≥ 67 Gy showed superior OS, with a hazard ratio of 0.341. The radiation dose of PT is an important predisposing factor for overall survival. The MST for patients with eBDC given a higher radiation dose was 25 months, compared to 15 months for those given the lower dose and 23 months for patients with iBDC (all iBDC given higher doses). iBDC and eBDC duct carcinomas showed equivalent outcomes with PT, especially when treated with a high radiation dose. In detailed analysis, baseline CEA level in iBDC, and radiation dose and GTV in eBDC were statistically significant predicators for OS. Acute and late toxicity grade ≥3 occurred in 2.2% and 2.7% of patients, respectively, including two late grade-5 toxicities. In conclusion, PT showed good efficacy for BDC, both eBDC and iBDC, with a low incidence of severe toxicity.

Metzolimos metronomic cyclophosphamide (CP) and methotrexate (MTX) combined with zoledronic acid (ZA) and sirolimus (SIR) in patients with advanced solid tumor with bone metastasis and advanced pretreated osteosarcoma (OSS): A phase Ib study.

11526 Background: Advanced pretreated OSS has a very poor prognosis. Metronomic CP and MTX have shown little activity in pediatric cancers, including OSS. Preclinical data suggest that ZA could have a synergic effect when combined with mTOR inhibition in OSS. Methods: This is a prospective phase Ib study investigating the combination of SIR with CP, MTX and ZA trough a dose-escalation phase (3 + 3 design) in patients ≥ 18 years with bone metastatic solid tumors (part I) and an expansion cohort dedicated to patients ≥ 13 years with advanced pretreated OSS (part II). SIR was given at two dose levels (4 mg and 6 mg) continuously, in combination with CP 50 mg x 2 per day, 1 week on / 1 week off, MTX at 2.5 mg x 2 per day, on day 1 and day 4 every week, and ZA 4mg IV every 4 weeks. Primary endpoints were dose limiting toxicities (DLT), maximum tolerated dose and recommended phase II dose (RP2D) of SIR combined with CP, MTX and ZA for Part I, and 6-month non-progression rate (NPR) according to RECIST v1.1 for part II. Secondary endpoints included safety, 6-month objective response rate (ORR), one-year progression-free (PFS) and overall survivals (OS), and pharmacodynamics biomarker analyses. At least one non-progression at 6 months after centralized review of imaging was needed among 14 patients to consider activity of the combination. Results: From February 2015 to March 2021, 23 patients were included in the three participating centers. In part I, nine patients with breast (56%), prostate (33%) or biliary duct carcinoma (11%) were included. Median number of cycles was 2 (1-6). Two DLT were reported at dose level 2: one grade 3 neutropenia and one grade 3 anemia, therefore dose level 1 was the RP2D for part II. In part II, 14 OSS patients were included. Median age was 27 years (14 - 80). Median number of previous lines in the advanced disease was 1 (1-3). At the time of analysis, 11 patients had died. Reason for study discontinuation was progressive disease for 10 patients (72%), toxicity for two (14%) (one grade 2 platelet count decrease and one grade 5 unrelated lung infection), and investigator decision for two (14%) , including one for cryotherapy of a residual lesion after an excellent partial response. Overall, 64 adverse events related to study drugs were reported, of which 14 (22%) grade 3, and 2 grade 4 (3%). They were mainly asthenia, nausea, mucositis oral, anemia, lymphocyte and platelet count decrease. Median follow up was 27.5 months [95% CI : 12.8-27.5]. Two non-progressions at 6 months (14%) were observed, including a partial response (7%). One-year PFS was 21.4% [95%CI 5.2-44.8] and median OS was 12.8 months [95% CI : 2.8-20.4]. Conclusions: The combination of SIR at 4 mg daily with CP, MTX and ZA has an acceptable toxicity profile and reached the initial targeted efficacy rate in advanced pretreated OSS patients. Clinical trial information: NCT02517918.

Radiotherapy as treatment option in biliary cancer patients: a national survey of AIRO (Italian Association of Radiation Oncology) Gastroenterology Group.

BackgroundThe aim is to find out how many radiation oncology centres treat biliary duct carcinoma (BDC), what treatments they offer and whether they would be interested in developing prospective trials.Materials and methodsA questionnaire was posted to all 220 Italian Radiation Oncology Centres. The survey consisted of 31 eligibility questions in a combination of multiple and forced choice formats addressing the following parameters: characteristics of the centre, numbers of BDC patients treated, treatment options, radiotherapy parameters (target definition, schedule, technique, dose constraints) and interest in developing future randomized trials.ResultsNo major differences emerged in BDC management, whatever the site, and whether it was resectable or not. Discrepancies in routine clinical practice were, however, observed with lack of agreement on expansion margins, dose constraints and treatment schedules for the stereotactic technique and palliative treatments.ConclusionsThe present survey attempted to fill the gaps in the role of radiotherapy in patients with BDC. Since lack of prospective randomized studies and disease rarity have mitigated against an evidence-based approach, patients with BDC should be enrolled in prospective studies. The above-mentioned results should also emphasize the need to combine analysis of treatment results from all Italian centres in order to create predictive models.

Analysis of somatic copy number alterations in biliary tract carcinoma using a single nucleotide polymorphism array.

Aim:Biliary tract carcinoma (BTC), including gall bladder carcinoma (GBC) and biliary duct carcinoma (BDC), has a poor prognosis. Comprehensive genomic profiling has important roles in evaluation of the carcinogenesis of BTC.Materials & methods:We examined somatic copy number alterations (SCNAs) using a single nucleotide polymorphism array system to analyze 36 BTC samples (11 GBCs and 25 BDCs).Results:In hierarchical cluster analysis, two clusters were identified (subgroup 1 with low SCNAs and subgroup 2 with high SCNAs). GBC was predominant in subgroup 1, whereas BDC was predominant in subgroup 2, suggesting that GBC and BDC had different genetic backgrounds in terms of SCNAs.Conclusion:These findings could be helpful for establishing the molecular carcinogenesis of BTCs.

Hospitalization outcomes between intrahepatic bile duct carcinoma versus extrahepatic biliary cholangiocarcinoma

Background: Cholangiocarcinoma is an uncommon cancer with a very bad prognosis despite advances made in treatment. The location of the tumor (intrahepatic versus extrahepatic) determines surgical options. In our study, we examine variations in outcomes between patients admitted to the hospital with intrahepatic versus extrahepatic disease. Methods: Data from the NIS, a database developed for the healthcare Cost and Utilization project (HCUP) was used for our analysis. We identified patients who were 18 years and older with intrahepatic or extrahepatic biliary duct carcinoma who underwent a procedure (biliary stent, resection, bypass, pancreatic resection, liver resection and transplantation) during a hospitalization. Our primary aim was to describe outcomes in terms of inpatient mortality, length of stay and hospitalization cost based on tumor location. We used multivariable logistic regression to calculate adjusted odd ratios and mean differences for each cohort. We controlled for patient level characteristics (age, race, sex, comorbidity burden), hospital level characteristics (hospital region, size and teaching status), insurance type and procedure received during hospitalization using multivariable analysis. Results: We identified a total of 18,840 admissions in 2014 with a discharge diagnosis of cholangiocarcinoma (intrahepatic or extrahepatic). Of these, 13,930 (73.1%) were intrahepatic while 4,930 (26.1%) were extrahepatic. Inpatient mortality amongst patents with extrahepatic bile duct carcinoma was 5.5% while that for intrahepatic bile duct carcinoma was 7.69%. After controlling for confounders, including treatment received during hospitalization, patients with extrahepatic disease were 30% less likely (Adjusted Odds Ratio 0.70, 95 % CI 0.512-0.966) to die during hospitalization compared to patients admitted for intrahepatic bile duct carcinoma. Length of stay was similar between the two groups (Adjusted Mean Difference -0.10, 95 % CI -0.64 -0.44) as was average cost of hospitalization (Adjusted Mean Difference. -4126, 95% CI -1.0986.5 - 2733.16). Conclusion: The location of biliary duct carcinoma predicts inpatient mortality, even after controlling for treatment received. Intrahepatic cholangiocarcinoma has a worse prognosis than extrahepatic tumors, although length of stay and average cost of hospitalization are similar across the two cohorts. The two carcinomas have different histology, molecular characteristics, and associated genetic abnormalities. Intrahepatic cholangiocarcinoma is more likely to be associated with cirrhosis due to underlying viral hepatitis or non alcoholic fatty liver disease. It is unclear if these pathological characteristics or underlying chronic inflammation influence outcomes. We recommend prospective studies to better understand reasons for variation in hospitalization mortality seen in patients with intrahepatic cholangiocarcinoma.

A case of biliary duct carcinoma accompanied by congenital complete visceral inversion

A case of biliary duct carcinoma accompanied by congenital complete visceral inversion

Anti-mitochondrial therapy in bile duct cancer.

e15661 Background: Biliary duct carcinoma is a rare but highly fatal malignancy. The five-year survival rate for advanced bile duct cancer is 2%, per SEER data. As such, new treatment options are desperately needed. CPI-613, a novel anticancer agent that selectively inhibits mitochondrial metabolism in cancer cells, was employed in this study. Methods: This phase 1 study utilized a two-stage dose-escalation schema to determine the maximum-tolerated dose (MTD) and safety of single agent CPI-613 in patients with locally advanced or metastatic bile duct cancers. The 1st cohort enrolled 4 patients at 2300 mg/m2, with no dose-limiting toxicities (DLT) observed. The 2nd cohort enrolled patients at 1200 mg/m2/day for pre-cycle (days 1-5) and 3000 mg/m2 on days 1 and 4 weekly for 3 weeks (28 day cycle). The 5th and 6th patient experienced a DLT. The 3rd cohort was initiated at 600 mg/m2 pre-cycle and 3000 mg/m2 weekly with no other DLTs observed. Results: To-date, 14 patients have been enrolled in the study. The MTD was determined at 600 mg/m2/day pre-cycle and 3000 mg/m2 as per schedule. Once the MTD was determined, the cohort was expanded and, 8 patients have been treated at the MTD with no DLTs observed. Two additional patients are planned to be enrolled at this dose prior to trial completion. Of these 8 patients, 3 are still alive with 1 having prolonged survival (15 months) and the other 2 still on treatment. The most commonly observed toxicities were mild, such as anemia, anorexia, dehydration, fatigue, nausea and thrombocytopenia. Conclusions: Treatment with CPI-613 was well tolerated by patients with heavy tumor burden and refractory disease. CPI-613 has recently been shown to be well tolerated in combination with FOLFIRINOX in pancreatic cancer patients. Due to the low toxicity of CPI-613 in this study, even among highly symptomatic patients, it is anticipated that combination with other active agents is feasible in patients with advanced bile duct cancer. CPI-613 represents a novel treatment that could prove to be an exciting therapeutic alternative for patients with previously limited options and poor survival. Clinical trial information: NCT01766219.

Multicystic biliary hamartoma mimicking intrahepatic bile duct cancer

Although multicystic biliary hamartoma of the liver is a rare entity, recently several case reports have been described. The criteria proposed by Zen et al. include the presence of honeycomb-like nodules located around the hepatic capsule that are close to the hepatic falciform ligament and characteristically protrude from the liver. In this report, we present a case of multicystic biliary hamartoma, which also features intrahepatic bile duct dilatation, and could therefore mimic a malignant neoplasm such as bile duct carcinoma. Our case highlights the potential difficulties in differentiating between multicystic biliary hamartoma and bile duct carcinomas under such circumstances.

Radiotherapy and Chemotherapy as Therapeutic Strategies in Extrahepatic Biliary Duct Carcinoma

this report aims to provide an overview on radiotherapy and chemotherapy in extrahepatic biliary duct carcinoma (BDC). a PubMed research identified clinical trials in BDC through April 1, 2010 including randomised controlled trials, SEER analyses and retrospective trials. Additionally, publications on the technical progress of radiotherapy in or close to the liver were analysed. most patients with cholangiocarcinoma present with unresectable disease (80-90%), and more than half of the resected patients relapse within 1 year. Adjuvant and palliative treatment options need to be chosen carefully since 50% of the patients are older than 70 years at diagnosis. Adjuvant radiotherapy or chemotherapy after complete resection (R0) has not convincingly shown a prolongation of survival but radiotherapy did after R1 resection. However, data suggest that liver transplantation could offer long-term survival in selected patients when combined with neoadjuvant chemoradiotherapy in patients with marginally resectable disease. For patients with unresectable biliary tract carcinoma (BTC), palliative stenting was previously the treatment of choice. But recent SEER analyses show that radiotherapy prolongs survival, relieves symptoms and contributes to biliary decompression and should be regarded as the new standard. Novel technical advances in radiotherapy may allow for dose-escalation and could significantly improve outcome for patients with cholangiocarcinoma. both the literature and recent technical progress corroborate the role of radiotherapy in BDC offering chances for novel clinical trials. Progress is less pronounced in chemotherapy.

Safety and efficacy of single-day GemOx regimen in patients with pancreatobiliary cancer: a single institution experience

Background: GemOx (gemcitabine 1000 mg/m2 > 100 min on day 1 and oxaliplatin 100 mg/m2 on day 2 every 2 weeks) achieved a response rate of 26.8%, improved progression-free survival (PFS) but failed to demonstrate a benefit in overall survival (OS) compared with gemcitabine in pancreatic cancer. This regimen has regained attention after recent pooled- and meta-analysis suggested a survival benefit of gemcitabine–platinum doublets over gemcitabine. However, GemOx is associated with inconvenience to patients, early cumulative dose developing neuropathy and thrombocytopenia. In addition, fixed dose rate of gemcitabine showed no benefit > 30 min infusion schedule in the ECOG6201 study. Pharmacokinetic profiles of both drugs did not show statistically significant difference regardless of the order of administration.Patients and methods: In order to create a more convenient and equally effective regimen, we conducted a retrospective study to evaluate the efficacy and safety of single-day modified GemOx (S-GemOx, gemcitabine 1000 mg/m2 > 30 min and oxaliplatin 85 mg/m2 > 2 h on day 1 every 2 weeks) in patients with pancreatic and biliary cancers.Results: In all, 34 patients (median age 60 years, male/female: 17/17) received S-GemOx including locally advanced or metastatic pancreatic cancer (26) and biliary duct carcinoma (8). Median treatment was six cycles with duration of 12 weeks (range (r): 2 – 56). Median cumulative dose of oxaliplatin was 517.5 mg/m2 (r: 85 – 2380). A total of 27 of 34 patients were evaluated for efficacy after initial staging: 1 (3.7%) complete response (CR), 4 (14.8%) partial response (PR), 18 (66.7%) stable disease and 4 (14.8%) progression of disease. Overall response rate (CR + PR) was 18.5%. Median PFS and OS were 7 and 11.6 months, respectively. All patients were assessed for toxicities. Grade 3/4 hematological toxicities include anemia (8%), neutropenia (11%), thrombocytopenia (5%), nausea/vomiting (3%), diarrhea (3%), hypersensitivity reaction (14%) and neuropathy (3%). No deaths occurred due to therapy.Conclusions: S-GemOx regimen provides convenient schedule, toxicities appear to be comparable with GemOx. The incidence of neuropathy (3 vs 19.1%) and thrombocytopenia (5 vs 14%) are substantially lower compared with GemOx. Prospective studies of S-GemOx in a large patient population are warranted.

Endoscopic transpapillary bile duct drainage in malignant obstructive jaundice

Endoscopic biliary duct drainage was performed in 54 patients with obstructive jaundice caused by papillary carcinoma (n = 4), periampullar carcinoma (n = 4), carcinoma of head of pancreas (n = 16), primary biliary duct carcinoma (n = 14), biliary bladder carcinoma (n = 14) and hilar lymph node metastases (n = 2) using a bilioduodenal endoprosthesis. Drainage was successful in 45 cases; serum bilirubin decreased rapidly, well-being improved, appetite and weight increased. The average survival time was 4.8 months. The initially high rate of complications, mainly due to cholangitis, with a mortality rate of 9.3% could be reduced drastically after use of a duodenoscope with a 3.7 mm bore instrumentation canal enabling insertion of well-draining wide-lumen endoprostheses. Drainage should only be used in non-resectable tumours, general inoperability or for preoperative relief of biliary ducts in jaundice and prospective curative surgical intervention. As results improve with mounting experience it may be expected that endoscopic biliary duct drainage will replace palliative surgery, especially in elderly patients at risk.

Vergleich bildgebender Verfahren in der Diagnostik von Gallenblasen- und Gallengangkarzinomen

Fourteen patients with carcinomas of the gallbladder and eight patients with biliary duct carcinomas were examined by CT, sonography, percutaneous transhepatic cholangiography (PTC), endoscopic retrograde cholangiography (ERC) and angiography. The results were compared retrospectively. Sonography proved suitable as a screening method. For accurate demonstration, this should be supplemented by CT. PTC and ERC demonstrate intraductal extension of biliary carcinomas and of gallbladder carcinomas infiltrating the bile ducts. The value of angiography consists merely in the preoperative demonstration of the vascular anatomy.

Anticancer effect of cation lipofectin-mediated CD/5-FC suicide gene system on liver, biliary duct and pancreas carcinoma cells in vitro

Anticancer effect of cation lipofectin-mediated CD/5-FC suicide gene system on liver, biliary duct and pancreas carcinoma cells <i>in vitro</i>

Oxaliplatin combined with leucovorin plus 5-FU (FOLFOX) in patients with advanced/metastatic biliary tract carcinoma

14093 Background: Biliary tract carcinoma is often diagnosed at advanced stage, with median survival rarely exceeding 6 months. There is currently no established palliative standard of care. A phase II trial was conducted to study a FOLFOX regimen as first- or second- line therapy in biliary tract carcinoma. Methods: Patients with unresectable or metastatic intrahepatic or extrahepatic biliary duct carcinoma and gallbladder carcinoma were enrolled. Eligible patients were between 18 and 75 years of age and had histologically confirmed, measurable adenocarcinoma. Patients were stratified according to prior chemotherapy(6) and no prior chemotherapy(15). Treatment consisted of intravenous oxaliplatin (100mg/m2) as a 2 hours infusion on day 1 followed by leucovorin 100mg/m2 on day1 and 5-FU 1000∼1200mg/m2 as a 24 hours infusion on day 1,2. Treatment was repeated every 3 weeks for up to 6 cycles. Tumor response, survival and safety were determined Results: A total of 21 patients were evaluable;12 men and 9 women with a median age of 57(range 37–71). Tumor sites were: intrahepatic (n=7) and extrahepatic biliary duct (n=9); gallbladder (n=4); and ampulla (n=1). Total 115 cycles were administered (median 5 cycles, range 2∼12). According to RECIST criteria, partial response 3(14.3%), stable disease 10(47.7%) and disease progression.8(38%). The overall response rate with and without prior chemotherapy were 0%(0/6) and 20%(3/15), respectively. In patients without prior chemotherapy (15), median progression-free-survival and overall survival were 6.6(range, 1.2∼12.8) and 8.7(range, 3.7∼19.3) months. Grade 1–2 neurotoxicity, fatigue, diarrhea, anorexia, nausea were common. Grade 3 neutropenia and thrombocytopenia occurred in 23% and 4.7% of the patients respectively. There was no treatment related death. Conclusions: FOLFOX should be considered an active and well tolerated first-line combination chemotherapy regimen for patients with advanced/metastatic biliary tract carcinoma. No significant financial relationships to disclose.

Capecitabine combined with gemcitabine (CapGem) as first‐line treatment in patients with advanced/metastatic biliary tract carcinoma

Biliary tract carcinoma is an aggressive cancer, with median survival rarely exceeding 6 months. There is currently no established palliative standard of care. A Phase II trial was conducted to study a combination of oral capecitabine and gemcitabine (CapGem) as first-line therapy in patients with advanced and/or metastatic biliary carcinoma. Patients with unresectable or metastatic intrahepatic or extrahepatic biliary duct carcinoma and gallbladder carcinoma were enrolled. Eligible patients had histologically or cytologically confirmed, measurable adenocarcinoma and had not received prior therapy with capecitabine or gemcitabine. Treatment consisted of intravenous (i.v.) gemcitabine (1000 mg/m(2) on Days 1 and 8) plus oral capecitabine (650 mg/m(2) twice daily on Days 1-14) every 3 weeks for up to 6 cycles. Tumor response, survival, and safety were determined. A total of 44 patients were evaluable. Primary tumor sites were: intrahepatic (n = 14) and extrahepatic biliary duct (n = 16); gallbladder (n = 7); and ampulla (n = 7). Fourteen (32%) patients had a partial response and 15 (34%) patients had stable disease. Median time to disease progression and overall survival were 6.0 (range, 3.8-8.1) and 14 (range, 11.4-16.6) months, respectively. The 1-year survival rate was 58%. No Grade 4 adverse events were seen. Transient Grade 3 neutropenia/thrombocytopenia and manageable (almost invariably Grade 2) nausea, diarrhea, and hand-foot syndrome were the most common adverse events. CapGem is an active and well tolerated first-line combination chemotherapy regimen for patients with advanced/metastatic biliary tract carcinoma that offers a convenient home-based therapy.

Genetic alterations and growth pattern in biliary duct carcinomas: loss of heterozygosity at chromosome 5q bears a close relation with polypoid growth

Biliary duct carcinomas (BDCs) are relatively rare and the carcinogenic mechanisms underlying their induction are poorly understood. There are two growth patterns, polypoid and non-polypoid infiltrative type, but little information...

Radiotherapy and multimodality management of cholangiocarcinoma

Purpose: To evaluate the results of radiotherapy in cholangiocarcinoma patients managed with various combinations of chemotherapy and surgical resection with selective liver transplantation. Methods and Materials: From January 1990 to December 1995, 61 patients with histologically confirmed biliary duct adenocarcinoma were seen in the Radiation Oncology Department of the University of Pittsburgh. Median follow-up was 22 months (1 to 91 months). The extent of surgery was complete resection in 23 patients (including 17 with orthotopic liver transplant), partial resection in 4, and biopsy in 34. All patients had radiotherapy; median dose was 49.5 Gy. Thirty patients received chemotherapy: 5-fluorouracil (5-FU)–leucovorin with interferon alpha (IFNα) in 27, and taxol in 3. Results: The median survival was 20 months (95% CI 15–25 months). The 5-year actuarial survival was 23.8 ± 6.8%. The only significant variable in multivariate analysis was achieving a complete resection with negative margins through conventional surgery or liver transplantation ( p = 0.001, hazard rate ratio [HRR] = 0.25, 95% CI 0.12–0.54). Patients with complete resections had a 5-year actuarial survival of 53.5 ± 10.9%. Conclusion: Combined modality therapy that includes complete surgical resection with or without transplantation can be curative in the majority of patients with biliary duct carcinoma. Further study is needed to better define the roles of chemotherapy and radiotherapy in cholangiocarcinoma.

Mutations of K-ras but not p53 genes in biliary duct and pancreatic duct carcinomas induced in hamsters by cholecystoduodenostomy with dissection of the common duct followed by N-nitrosobis(2-oxopropyl)amine

An experimental model for the induction of extrahepatic biliary duct carcinomas in hamsters given cholecystoduodenostomy with dissection of the extrahepatic duct at the distal end of the common duct (CDDB) followed by N-nitrosobis(2-oxopropyl) amine (BOP) has been reported [Tajima et al. (1994) Jpn. J. Cancer Res., 85, 780–788]. The CDDB procedure greatly accelerates cell turnover in the biliary epithelium. In the present experiment, mutations of K-ras and p53 genes in the induced lesions were investigated by the reverse transcriptase-polymerase chain reaction-single strand conformation polymorphism (RT-PCR-SSCP) method followed by direct sequencing. Mutations of K-ras, involving a G to A transition in second position of codon 12 of K-ras exon 1, were detected in six out of eight (75%) extrahepatic bile duct carcinomas and six out of eleven (54.5%) pancreatic duct carcinomas. However, no mutations of p53 were observed in either tumor type. The results indicate an association between anomalous pancreaticobiliary junction and development of biliary carcinomas that may be pertinent to the human situation, and indicate that conditions of the model predispose to mutations occurring in K-ras but not p53.

External beam radiation therapy as an agent in the aetiology of carcinoma of the bile duct: A report on two patients

Two cases of biliary duct carcinoma occurring in patients who had received prophylactic abdominal irradiation 17 years previously are described. Although external beam radiation has been implicated in the aetiology of many malignancies, there is only one previous report of it being associated with carcinoma of the bile duct. All patients receiving external beam irradiation for curable malignancies require long term follow-up so that treatment induced malignancies may be detected.