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

Table 1 Summary of the terms used singly or in combination for evidence acquisition

Primary MeSH terms	Secondary MeSH terms (Epidemiology, diagnosis)	Secondary MeSH terms (treatment, palliation)
Cholangiocarcinoma(s)	Epidemiology	Hepatectomy
Adenocarcinoma(s)	Classification	Resection
Carcinoma(s)	Diagnosis	Therapeutic(s)
Bile duct neoplasm(s)	Differential diagnosis	Treatment outcome(s)
Biliary tract neoplasm(s)	Early diagnosis	Surgery
Common bile duct neoplasm(s)	Risk factor(s)	Transplantation
Liver neoplasm(s)	Diagnostic imaging	Biliary tract
Bile duct(s)	Magnetic resonance imaging	Surgical procedures
Common bile duct	Endosonography	Liver transplantation
Intrahepatic bile duct(s)	Ultrasonography	Organ transplantation
Extrahepatic bile duct(s)	Emission computed tomography	Clinical trial
Biliary tract disease(s)	Radionuclide imaging	Controlled clinical trial(s)
Bile duct disease(s)	Positron emission tomography	Randomized controlled trial(s)
	X-ray	Clinical trial (phase I)
	Computed tomography	Clinical trial (phase II)
	Biopsy (needle)	Clinical trial (phase III)
	Biopsy (fine needle)	Clinical trial (phase IV)
	Cytology	Drug therapy
	Cytodiagnosis	Chemotherapy
	Tumor markers (biological) antigen(s)	Adjuvant
	Carcinoembryonic antigen	Antineoplastic agent(s)
	Ca 19-9 antigen	Combined modality therapy
	Ca 125 antigen	Antineoplastic
	Endoscopic retrograde cholangiopancreatography	Combined chemotherapy protocols
	Cholangiography	Neoadjuvant therapy
	In situ hybridization	Radiotherapy
	Fluorescence in situ hybridization	Adjuvant embolization
	Nucleic acid hybridization	Portal vein embolization
	Computed assisted image processing	Drainage
		Cholestasis
		Obstructive jaundice

Table 2 Known risk factors for cholangiocarcinomas

General risk factors

Old age (older than 65 years)

Smoking

Obesity

Diabetes

Post surgical

Biliary-enteric anastomosis

Chronic inflammatory diseases

Primary sclerosing cholangitis (PSC)

Hepatolithiasis (Oriental Cholangiohepatitis)

Hepatitis C

Hepatitis B

Human Immunodeficiency Virus (HIV)

Liver cirrhosis

Parasitic infections

Opisthorchis viverrini

Clonorchis sinensis

Congenital

Choledochal cysts

Caroli’s disease

Congenital hepatic fibrosis

Chemical agents

Thorotrast

Dioxin

Nitrosamines

Asbestos

Medications

Oral Contraceptive Pills

Isoniazid

Table 3 Presenting symptoms of patients affected by cholangiocarcinomas

Symptoms	Percentage (%)
Jaundice	84
Weight loss	35
Abdominal pain	30
Nausea and vomiting	20
Fever	10

Table 4 AJCC staging of ICC

Stage	Tumor	Node	Metastasis
I	T1	N0	M0
II	T2	N0	M0
IIIA	T3	N0	M0
IIIB	T4	N0	M0
IIIC	Any T	N1	M0
IV	Any T	Any N	M1

T1: Solitary tumor without vascular invasion; T2: Solitary tumor with vascular invasion or multiple tumors none > 5 cm; T3: Multiple tumors > 5 cm or tumor involving a major branch of the portal or hepatic vein(s); T4: Tumor(s) with direct invasion of adjacent organs other than the gallbladder or with perforation of visceral peritoneum; N0: No regional lymph node metastasis; N1: Regional lymph node metastasis; M0: No distant metastasis; M1: Distant metastasis. AJCC: American Joint Committee on Cancer; ICC: Intrahepatic cholangiocarcinoma.

Table 5 AJCC staging of ECC

Stage	Tumor	Node	Metastasis
0	Tis	N0	M0
IA	T1	N0	M0
IB	T2	N0	M0
IIA	T3	N0	M0
IIB	T1-T3	N1	M0
III	T4	Any N	M0
IV	Any T	Any N	M1

Tis: Carcinoma in situ; T1: Tumor confined to the bile duct histologically; T2: Tumor invades beyond the wall of the bile duct; T3: Tumor invades the liver, gallbladder, pancreas, and/or unilateral branches of the portal vein (right or left) or hepatic artery (right or left); T4: Tumor invades any of the following: main portal vein or its branches bilaterally, common hepatic artery, or other adjacent structures, such as the colon, stomach, duodenum, or abdominal wall; N0: No regional lymph node metastasis; N1: Regional lymph node metastasis; M0: No distant metastasis; M1: Distant metastasis.

Table 6 Proposed T-Stage criteria for hilar cholangiocarcinomas (MSKCC)

Stage	Criteria
T1	Tumor involving biliary confluence with or without unilateral extension to second-order biliary radicles
T2	Tumor involving biliary confluence with or without unilateral extension to second-order biliary radicles and ipsilateral portal vein involvement with or without ipsilateral hepatic lobar atrophy
T3	Tumor involving biliary confluence with bilateral extension to second-order biliary radicles; or unilateral extension to second-order biliary radicles with contralateral portal vein involvement; or unilateral extension to second-order biliary radicles with contralateral hepatic lobar atrophy; or main or bilateral portal vein involvement

Table 7 Criteria for unresectability of HCC

Local tumor invasion

Bilateral hepatic duct involvement up to secondary biliary radicles

Encasement or occlusion of the main portal vein

Unilateral tumor extension to secondary biliary radicles with contralateral portal vein or hepatic artery encasement or occlusion

Hepatic lobar atrophy with contralateral portal vein or hepatic artery encasement or occlusion

Hepatic lobar atrophy with contralateral tumor extension to secondary biliary radicles

Metastatic disease

Lymph node metastases beyond the hepatoduodenal ligament (N2 lymph nodes)1

Distant metastasis (e.g. lung, liver, peritoneal)

¹Peripancreatic, periduodenal, periportal, celiac, or superior mesenteric lymph nodes.

Table 8 Survival rates after resection of ICC

Author (yr)	Resections (n)	Overall 5-year survival (%)	R0 5-year survival (%)
DeOliveira et al[67], 2007	34	40	63
Miwa et al[195], 2006	41	29	36
Jan et al[196], 2005	81	15	NR
Ohtsuka et al[197], 2003	50	23	NR
Uenishi et al[198], 2001	28	27	67
Inoue et al[199], 2000	52	36	55
Yamamoto et al[200], 1999	83	23	53
Madariaga et al[201], 1998	34	35	41

NR: Not reported.

Table 9 Survival rates after resection of HCC

Author (yr)	Resections (n)	Liver resection (%)	R0 resection (%)	Overall 5-year survival (%)	R0 5-year survival (%)
Hasegawa et al[213], 2007	49	92	78	40	50
DeOliveira et al[67], 2007	173	20	19	10	30
Dinant et al[214], 2006	99	38	31	27	33
Hemming et al[205], 2005	53	98	80	35	45
Rea et al[208], 2004	46	100	80	26	30
Kawasaki et al[182], 20031	79	96	68	NR	40
Kawarada[215], 2002	87	75	64	26	NR
Jarnagin et al[166], 2001	80	78	78	37	NR
Tabata et al[216], 2000	75	71	60	23	40
Kosuge et al[217], 1999	65	88	52	35	52
Miyazaki et al[218], 1998	76	86	71	26	40

¹Five-year survival for patients with R1 resection is 6%; NR: Not reported.

Table 10 Survival rates after resection of distal ECC

Author (yr)	Resections (n)	Overall 5-year survival (%)	R0 5-year survival (%)
DeOliveira et al[67], 2007	229	23	27
Cheng et al[219], 2007	112	25	26
Murakami et al[224], 2007	36	50	62
Yoshida et al[225], 2002	26	37	44
Fong et al[222], 1996	45	27	541

¹Patients had node negative tumors as well.