What prognostic factors are important for resected intrahepatic cholangiocarcinoma?

Paik KY, Jung JC, Heo JS, Choi SH, Choi DW, Kim YI (2008) What prognostic factors are important for resected intrahepatic cholangiocarcinoma? J Gastroenterol Hepatol, 23(5):766-770

Introduction

Intrahepatic cholangiocarcinoma (ICC) are tumors that arise from either the second order branches of the intrahepatic bile duct or the more peripheral bile duct branches.

Methods

The cumulative and disease-free survival rates were calculated using the Kaplan–Meier method. The univariate correlation between the clinicopathological factors and survival were examined by the log-rank test. Factors independently associated with the survival were identified by the proportional hazard regression analysis. A P-value of less than 0.05 was considered to be statistically significant.

Intrahepatic cholangiocarcinoma: rising frequency, improved survival, and determinants of outcome after resection

Endo I, Gonen M, Yopp AC, et al. (2008) Intrahepatic cholangiocarcinoma: rising frequency, improved survival, and determinants of outcome after resection. Ann Surg, 248(1):84-96


Abstract
BACKGROUND: Despite data suggesting a rising worldwide incidence, intrahepatic cholangiocarcinoma (IHC) remains an uncommon disease. This study analyzes changes in IHC frequency, demographics, and treatment outcome in a consecutive and single institutional cohort. METHODS: Consecutive patients with confirmed IHC seen and treated over a 16-year period were included. The trend in IHC frequency over the study period was compared with that of hilar cholangiocarcinoma patients (HCCA) seen during the same time. Demographics and patient disposition, histopathologic, treatment, recurrence, and survival data were analyzed; changes in these variables over time were assessed.

Trends in Survival after Surgery for Cholangiocarcinoma: A 30-Year Population-Based SEER Database Analysis

Nathan H, Pawlik TM, Wolfgang CL, Choti MA, Cameron JL, Schulick RD (2007) Trends in survival after surgery for cholangiocarcinoma: a 30-year population-based SEER database analysis. J Gastrointest Surg, 11(11):1488-1496; discussion 1496-1487

Introduction
Data on long-term survival of patients after surgical resection are limited to single-institution case series. Reported 5-year survival rates in recent surgical series (irrespective of margin status) vary widely, from 17 to 40% for ICC6–14 and from 9 to 41% for ECC.

Aggressive surgical treatment of intrahepatic cholangiocarcinoma: predictors of outcomes

Roayaie S, Guarrera JV, Ye MQ, et al. (1998) Aggressive surgical treatment of intrahepatic cholangiocarcinoma: predictors of outcomes. J Am Coll Surg, 187(4):365-372
CODE: ICCSR98

Abstract: Median actuarial survivals were 42.9 6 8.9 months for resectable and 6.7 6 3.6 months for unresectable patients (p 5 0.005). Noncurative resection offers a survival advantage over no resection.

Introduction: Lack of etiologic factors such as intrahepatic lithiasis and liver flukes make this tumor 10 times less prevalent in Western countries.3,4

Liver Resection for Hilar and Peripheral Cholangiocarcinomas: A Study of 62 Cases

Madariaga JR, Iwatsuki S, Todo S, Lee RG, Irish W, Starzl TE (1998) Liver resection for hilar and peripheral cholangiocarcinomas: a study of 62 cases. Ann Surg, 227(1):70-79
CODE: ICCJRM98

Abstract: The survival rates for HCCA and PCCA were 79% (+8%) and 67% (+8%) at 1 year; 39% (+10%) and 40% (+9%) at 3 years; and 8% (+7%) and 35% (+10%) at 5 years, respectively.The median survival was 24 (±4) months for HCCA and 19 (+8) months for PCCA.

Surgical management of intrahepatic cholangiocarcinoma: a 31-year experience

Lieser MJ, Barry MK, Rowland C, Ilstrup DM, Nagorney DM (1998) Surgical management of intrahepatic cholangiocarcinoma: a 31-year experience. J Hepatobiliary Pancreat Surg, 5(1):41-47

Abstract: Intrahepatic cholangiocarcinoma (ICC) is the second most common malignant primary tumor of the liver. It is, though, a rare tumor and little is known regarding its natural history, clinicopathologic characteristics, or the outcomes of surgical therapy.

Hepatic Resection and Transplantation for Peripheral Cholangiocarcinoma

Casavilla FA, Marsh JW, Iwatsuki S, et al. (1997) Hepatic resection and transplantation for peripheral cholangiocarcinoma. J Am Coll Surg, 185(5):429-436

Abstract: Recent publications have questioned the role of orthotopic liver transplantation (OLT) in treating advanced or unresectable peripheral cholangiocarcinoma (Ch-Ca). We reviewed our experience with Ch-Ca to determine survival rates, recurrence patterns, and risk factors. Table 3

Cholangiocarcinoma: A compact review of the literature

Ustundag Y, Bayraktar Y (2008) Cholangiocarcinoma: a compact review of the literature. World J Gastroenterol, 14(42):6458-6466
CODE: ICCYU08

Abstract: These tumors progress insidiously, and liver failure, biliary sepsis, malnutrition and cancer cachexia are general modes of death associated with this disease. CC is resectable for cure in only a small percentage of patients.

The Epidemiology of Cholangiocarcinoma

Shaib Y, El-Serag HB (2004) The epidemiology of cholangiocarcinoma. Semin Liver Dis, 24(2):115-125

Introduction
Because ICC originates in small biliary ducts or ductules, it usually presents as an intrahepatic mass and is therefore grouped in some studies with hepatocellular carcinoma (HCC) as a primary liver tumor. However, Klatskin tumors, which occur at the bifurcation of the right and left hepatic ducts, have traditionally been classified as extrahepatic.10,11

Diagnosis and management of cholangiocarcinoma

Sandhu DS, Roberts LR (2008) Diagnosis and management of cholangiocarcinoma. Curr Gastroenterol Rep, 10(1):43-52

Cholangiocarcinoma (CC) is a rare yet frequently fatal tumor that causes significant morbidity and mortality due to late presentation. Radiology is the mainstay of CC diagnosis; however, advances in understanding the pathogenesis of CC, including the role of oncogenes, inflammation-mediated genomic instability, and interleukin-6/STAT-3 signaling pathways, may allow development of new diagnostic and prognostic markers and targets for CC therapy.

Natural History and Prognostic Factors of Advanced Cholangiocarcinoma without Surgery, Chemotherapy, or Radiotherapy: A Large-Scale Observational Study

Park J, Kim MH, Kim KP, et al. (2009) Natural History and Prognostic Factors of Advanced Cholangiocarcinoma without Surgery, Chemotherapy, or Radiotherapy: A Large-Scale Observational Study. Gut Liver, 3(4):298-305

Abstract
Result: The overall survival time of the entire cohort (n=330) was median 3.9 months (range; 0.2 to 67.1). The survival time was significantly shorter in the intrahepatic cholangiocarcinoma group (3.0±5.3 months) than in the hilar cholangiocarcinoma group (5.9±10.1 months; Kaplan-Meier survival analysis).

A new staging system for mass-forming intrahepatic cholangiocarcinoma: analysis of preoperative and postoperative variables

Okabayashi T, Yamamoto J, Kosuge T, et al. (2001) A new staging system for mass-forming intrahepatic cholangiocarcinoma: analysis of preoperative and postoperative variables. Cancer, 92(9):2374-2383


Abstract
RESULTS: The rate of operative mortality in this patient cohort was 5%, and the overall 1-year, 3-year, and 5-year survival rates were 68%, 35%, and 29%, respectively, with a median survival of 19.6 months. A multivariate analysis revealed that independent negative prognostic factors were 1) hepatic regional lymph node metastasis, 2) multiple tumor presentation, 3) symptomatic tumor, and 4) the presence of vascular invasion.

Cholangiocarcinoma A Spectrum of Intrahepatic, Perihilar, and Distal Tumors

Nakeeb A, Pitt HA, Sohn TA, et al. (1996) Cholangiocarcinoma. A spectrum of intrahepatic, perihilar, and distal tumors. Ann Surg, 224(4):463-473; discussion 473-465

Statistical Analysis

All data are presented as percentage of patients or mean ± standard error of the mean. Percentages were compared by chi square analysis, and means were analyzed by analysis of variance. Survival curves were constructed by the Kaplan-Meier technique and were compared by the log-rank test. Cox's proportional hazard survival analysis was used to determine which parameters affected survival. A p value < 0.05 was considered significant.

Cholangiocarcinoma: Modern Advances in Understanding a Deadly Old Disease

Malhi H, Gores GJ (2006) Cholangiocarcinoma: modern advances in understanding a deadly old disease. J Hepatol, 45(6):856-867

Introduction

Most cholangiocarcinomas arise in the absence of any known predisposition (5)

Classification

Cholangiocarcinomas can be classified into 3 distinct categories by anatomic location. These are intrahepatic cholangiocarcinoma, hilar cholangiocarcinoma and distal extrahepatic bile duct cancers (Fig. 1 v Imp).

Cholangiocarcinoma: Morphologic Classification According to Growth Pattern and Imaging Findings

Lim JH (2003) Cholangiocarcinoma: morphologic classification according to growth pattern and imaging findings. AJR Am J Roentgenol, 181(3):819-827


IntroductionThe prognosis for mass-forming and periductal-infiltrating cholangiocarcinomas is generally unfavorable, whereas the prognosis for intraductal-growing cholangiocarcinoma is much better (or excellent) after surgical resection  [11–14].

Guidelines for the diagnosis and treatment of cholangiocarcinoma: consensus document

Khan SA, Davidson BR, Goldin R, et al. (2002) Guidelines for the diagnosis and treatment of cholangiocarcinoma: consensus document. Gut, 51 Suppl 6:VI1-9

DIAGNOSIS
Clinical Features: Cholangiocarcinoma usually presents after the disease is advanced. This is particularly true with more proximal intrahepatic and perihilar tumours obstructing one duct, which often present with systemic manifestations of malignancy, such as malaise, fatigue, and weight loss. Some cases are detected incidentally as a result of deranged liver function tests, or ultrasound scans performed for other indications.

New insights on cholangiocarcinoma

Gatto M, Alvaro D (2010) New insights on cholangiocarcinoma. World J Gastrointest Oncol, 2(3):136-145

Introduction

CCA is characterized by a bad prognosis, with a median survival of less than 24 mo[2-4] and a scarce response to chemotherapy[5-9] The only curative therapy is surgical resection or liver transplantation but, unfortunately, the majority of patients are diagnosed at advanced stage, when surgical therapies are excluded. This should stimulate research on the identification of effective surveillance strategies that would permit detection of early CCA or, better yet, premalignant lesions in patients at increased risk, particularly patients with primary sclerosing cholangitis (PSC). Serum and bile tumor markers, non invasive and endoscopic-based imaging modalities, and histology and cytology have been attempted with varying success[11].

Cholangiocarcinoma – current treatment options

Friman S (2011) Cholangiocarcinoma--current treatment options. Scand J Surg, 100(1):30-34

Summary

In intrahepatic CCA, HR remains the treatment of choice whereas with concomitant liver disease such as cirrhosis or primary sclerosing cholangitis (PSC), LT is the only option.

Cholangiocarcinoma (CCA) is a malignant disease of the epithelial cells in the intra- and extrahepatic bile ducts. While still a rare malignant disease, CCA is the second most common primary malignancy of the liver. The incidence is increasing; especially the incidence of intrahepatic CCA (1).

Cholangiocarcinoma: Advances in Pathogenesis, Diagnosis, and Treatment

Blechacz B, Gores GJ (2008) Cholangiocarcinoma: advances in pathogenesis, diagnosis, and treatment. Hepatology, 48(1):308-321

Introduction

Cholangiocarcinoma (CCA) is an epithelial cancer originating from the bile ducts with features of cholangiocyte differentiation.1 CCA is the second most common primary hepatic malignancy, and epidemiologic studies suggest its incidence is increasing in Western countries. 2 Advanced CCA has a devastating prognosis, with a median survival of <24 months.3 Three different growth patterns of extrahepatic CCA can be observed: (1) periductal infiltrating, (2) papillary or intraductal, and (3) mass forming.4 Intrahepatic CCA typically presents as an intrahepatic mass. An additional goal is to stimulate further interest in this disease with the hope of improving outcomes for this still highly lethal malignancy.

Etiologic and Clinical Characteristics of Peripheral and Hilar Cholangiocarcinoma

Altaee MY, Johnson PJ, Farrant JM, Williams R (1991) Etiologic and clinical characteristics of peripheral and hilar cholangiocarcinoma. Cancer, 68(9):2051-2055

Abstract: Prolonged high alcohol consumption was a prominent feature in both categories (45% and 37%, respectively). Among the women, 35% of those with the peripheral tumor had used oral contraceptive preparations.

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