Advances in diagnosis, treatment and palliation of cholangiocarcinoma: 1990-2009

Aljiffry M, Walsh MJ, Molinari M (2009) Advances in diagnosis, treatment and palliation of cholangiocarcinoma: 1990-2009. World J Gastroenterol, 15(34):4240-4262


Abstract: While the incidence of intra-hepatic CC is increasing, the incidence of extra-hepatic CC is trending down.

Introduction
Cholangiocarcinomas (CC) are malignant tumors originating from epithelial cells lining the biliary tree and gallbladder[1].

Treatment Options for Hepatobiliary and Pancreatic Cancer

Alberts SR, Gores GJ, Kim GP, et al. (2007) Treatment options for hepatobiliary and pancreatic cancer. Mayo Clin Proc, 82(5):628-637


Symptoms, if present, include abdominal discomfort, night sweats, low-grade fever, weight loss, and anorexia. Results of liver serum biochemical tests are nonspecific and can even be normal. Serum tumor markers such as CA 19-9 and carcinoembryonic antigen may be elevated. Compared with HCCs, intrahepatic cholangiocarcinomas on cross-sectional abdominal imaging by CT or  magnetic resonance imaging do not demonstrate the same degree of contrast enhancement during arterialphase studies. However, delayed peripheral venous–phase enhancement is common.

A phase II trial of gemcitabine and capecitabine in patients with unresectable or metastatic gallbladder cancer or cholangiocarcinoma: Southwest Oncology Group study S0202

Iqbal S, Rankin C, Lenz HJ, et al. (2011) A phase II trial of gemcitabine and capecitabine in patients with unresectable or metastatic gallbladder cancer or cholangiocarcinoma: Southwest Oncology Group study S0202. Cancer Chemother Pharmacol

Introduction

An estimated 9,760 new cases of gallbladder and other biliary cancers are diagnosed each year in the United States [1]. The highest prevalence of gallbladder tumors and cholangiocarcinomas in the United States is in Native Americans, for reasons that are unclear. Other countries with high rates of gallbladder cancer are Chile, Bolivia, and Mexico [2]

Two cases of curatively resected intrahepatic cholangiocellular carcinomas through effective response to neoadjuvant chemotherapy

Kamo N, Mori A, Nitta T, et al. (2011) [Two cases of curatively resected intrahepatic cholangiocellular carcinomas through effective response to neoadjuvant chemotherapy]. Gan To Kagaku Ryoho, 38(2):305-308
CODE: ICCNK11

A 61-year-old man was diagnosed as cholangiocellular carcinoma with para-aortic lymph node metastasis (T4N1M0, cStage IV B). After 9 courses of chemotherapy using gemcitabine(GEM), CT scan showed that primary lesion and metastatic lymph nodes were reduced in size, and FDG-PET showed no FDG accumulation in the lymph nodes. The patient decided to continue additional chemotherapy with GEM and hyperthermia. Despite the chemo-hyperthermia, the primary tumor re-grew. He then underwent right trisegmentectomy, lymph node dissection, and reconstruction of the biliary tract. The final stage was T3N0M0, fStage III . Case 2: A 65-year-old man was diagnosed as cholangiocellular carcinoma with massive arterial invasion(T3N1M0, cStage IV B). After 3 courses of chemotherapy for GEM plus S-1, a CT scan revealed that the main tumor and metastatic lymph nodes were reduced in size, and he underwent extended left lobectomy of liver, lymph node dissection, and reconstruction of the biliary tract. The final stage was T1N0M0, fStage I . These cases indicated that neoadjuvant chemotherapy by gemcitabine was indeed promising for some cases of biliary tract cancer.

Radiofrequency ablation for the treatment of primary intrahepatic cholangiocarcinoma

Kim JH, Won HJ, Shin YM, Kim KA, Kim PN (2011) Radiofrequency ablation for the treatment of primary intrahepatic cholangiocarcinoma. AJR Am J Roentgenol, 196(2):W205-209

Abstract: Intrahepatic cholangiocarcinoma was unresectable because of poor hepatic reserve due to liver cirrhosis in nine patients, extrahepatic extension in two, atrophy of the left hepatic lobe in one, and underlying comorbidities in one. Median local progression-free survival and overall survival periods were 32.2 and 38.5 months, respectively. The 1-, 3-, and 5-year survival rates were 85%, 51%, and 15%, respectively. CONCLUSION: RFA may provide successful local tumor control in patients with primary intrahepatic cholangiocarcinomas of intermediate (3-5 cm) or small (< 3 cm) diameter. RFA for unresectable primary intrahepatic cholangiocarcinoma resulted in a median overall survival period of 38.5 months.

Effectiveness of percutaneous metal stent placement in cholangiocarcinoma patients with midterm follow-up: Single center experience

Kose F, Oguzkurt L, Besen A, et al. (2011) Effectiveness of percutaneous metal stent placement in cholangiocarcinoma patients with midterm follow-up: Single center experience. Eur J Radiol

Abstract: Bilirubin level was normalized in 10 days. Median time to stent occlusion was 10 weeks. 

Transarterial chemoembolization versus supportive therapy in the palliative treatment of unresectable intrahepatic cholangiocarcinoma

Park SY, Kim JH, Yoon HJ, Lee IS, Yoon HK, Kim KP (2011) Transarterial chemoembolization versus supportive therapy in the palliative treatment of unresectable intrahepatic cholangiocarcinoma. Clin Radiol, 66(4):322-328

Abstract: The Kaplan-Meier survival analysis showed that the survival period was significantly longer in the TACE group (median 12.2 months) than in the symptomatic treatment (median 3.3 months) group (p <0.001).

Introduction

Intrahepatic cholangiocarcinoma (ICC) is the second most common primary liver malignancy after hepatocellular carcinoma (10 versus 90%, respectively), and has an increasing global incidence and mortality.1-4 Due to a late diagnosis, untreated ICC results in rapid death.7

Outcomes in unresectable and locally advanced resected cholangiocarcinoma

Payne SJ, Stebbing J, Wilson P, Slater S (2011) Outcomes in unresectable and locally advanced resected cholangiocarcinoma. Expert Rev Anticancer Ther, 11(5):705-709

Table 1


The overall survival of patients with unresectable or locally advanced resected biliary tract cancer (Gall bladder cancer, cholangiocarcinoma, ampullar cancer) who received Gemcitabine as a single agent (primary chemotherapy or relapse disease) is 2.9 months.

Biliary Tract Cancers

de Groen PC, Gores GJ, LaRusso NF, Gunderson LL, Nagorney DM (1999) Biliary tract cancers. N Engl J Med, 341(18):1368-1378

Introduction

In the United States, an estimated 20,000 new cases of liver and biliary tract cancer are diagnosed annually. 1 Biliary tract cancer is the second most common primary hepatobiliary cancer, after hepatocellular cancer. Approximately 7500 new cases of biliary tract cancer are diagnosed per year; about 5000 of these are gallbladder cancer, and between 2000 and 3000 are bile-duct cancers. 1 Biliary tract cancers have traditionally been divided into cancers of the gallbladder, the extrahepatic bile ducts, and the ampulla of Vater, whereas intrahepatic bileduct cancers have been classified as primary liver cancers. 2 The term “cholangiocarcinoma” was originally intended to refer only to primary tumors of the intrahepatic bile ducts and was not used for tumors of the extrahepatic bile ducts. 3Most cholangiocarcinomas involve the perihilar and distal extrahepatic bile ducts.

Cholangiocarcinoma: principles and current trends

Zografos GN, Farfaras A, Zagouri F, Chrysikos D, Karaliotas K (2011) Cholangiocarcinoma: principles and current trends. Hepatobiliary Pancreat Dis Int, 10(1):10-20


Abstract: Surgical treatment involves major resections of the liver, pancreas and bile duct, with considerable mortality and morbidity

Introduction

CCA is relatively uncommon with an annual incidence of 1-2 cases per 100 000 in the Western countries. However, rates have been rising worldwide over the past decades, partly due to advances in diagnostic techniques.[2, 3]

Yttrium-90 Radiotherapy for Unresectable Intrahepatic Cholangiocarcinoma: A Preliminary Assessment of This Novel Treatment Option

Saxena A, Bester L, Chua TC, Chu FC, Morris DL (2009) Yttrium-90 radiotherapy for unresectable intrahepatic cholangiocarcinoma: a preliminary assessment of this novel treatment option. Ann Surg Oncol, 17(2):484-491

Abstract: Patients were assessed at 1 month and then at 3-month intervals after treatment. Clinical and biochemical toxicities were prospectively recorded. No patient was lost to follow-up.

Introduction
Recent epidemiologic studies have shown that although ICC remains rare in developed countries, its age adjusted incidence has increased rapidly from .32 per 100,000 in 1975–1979 to .85 per 100,000 in 1995–1999.1–3. These patients with unresectable disease have a poor prognosis, with a median survival of 6 to 12 months from the time of diagnosis.3

Transarterial Hepatic Yttrium-90 Radioembolization in Patients with Unresectable Intrahepatic Cholangiocarcinoma: Factors Associated with Prolonged Survival

Hoffmann RT, Paprottka PM, Schon A, et al. (2011) Transarterial Hepatic Yttrium-90 Radioembolization in Patients with Unresectable Intrahepatic Cholangiocarcinoma: Factors Associated with Prolonged Survival. Cardiovasc Intervent Radiol

Abstract: Radioembolization (RE) using yttrium-90 (90Y) microspheres is an accepted therapy for patients with hepatocellular-carcinoma or metastatic liver tumors. However, there are limited data on the value of RE in  patients with ICC and few data on factors influencing prognosis.

Introduction

Intrahepatic cholangiocarcinoma (ICC) is a rare disease with approximately 3,000 cases diagnosed every year in the United States; increasing incidence and mortality rates have been reported [16, 24].In contrast to other gastrointestinal and liver malignancies, the molecular pathogenesis remains poorly understood [10]. There is no recognized standard palliative treatment for advanced or metastatic cholangiocarcinoma. Several chemotherapeutic regimens have been tested in mostly small studies in biliary tract cancers with limited success [6]. Recently, the first randomized phase III clinical study comparing gemcitabine versus gemcitabine plus cisplatin has been published [32]. In this study, combination treatment resulted in a median overall survival of 11.7 months compared with 8.1 months in the gemcitabine group. Locoregional therapies, such as radiofrequency ablation [31, 35] and transarterial chemoembolization [3, 9], have been proposed, but, in contrast to their role in hepatocellular cancer (HCC) [2], they are currently not regarded as a standard of care in locally advanced intrahepatic cholangiocarcinomas.

Comparison of yttrium-90 radioembolization and transcatheter arterial chemoembolization for the treatment of unresectable hepatocellular carcinoma

Kooby DA, Egnatashvili V, Srinivasan S, et al. (2009) Comparison of yttrium-90 radioembolization and transcatheter arterial chemoembolization for the treatment of unresectable hepatocellular carcinoma. J Vasc Interv Radiol, 21(2):224-230

Introduction

Radioembolization is a form of brachytherapy that allows for concentrated beta-radiation administration to tumor tissue while minimizing damage to surrounding liver parenchyma (13,14). It appears to be somewhat tumor-selective based on natural disruptions to the micro-vasculature surrounding liver tumors (15,16) and can be delivered selectively with segmental, lobar, or whole-liver approaches (17). Radioembolization appears to rely less on static arterial embolization than chemoembolization and, as such, may induce less hepatocyte damage in patients with impaired baseline liver function and therefore be preferable in patients with portal vein tumor thrombus.

Treatment of unresectable cholangiocarcinoma using yttrium-90 microspheres: results from a pilot study

Ibrahim SM, Mulcahy MF, Lewandowski RJ, et al. (2008) Treatment of unresectable cholangiocarcinoma using yttrium-90 microspheres: results from a pilot study. Cancer, 113(8):2119-2128

Introduction
Traditional systemic chemotherapies have been relatively unsuccessful in treating patients with advanced disease.5,6. The results of recent phase 2 studies using gemcitabine as a single agent only rarely improved survival in advanced biliary tract cancers.6