Perihilar cholangiocarcinoma: Current therapy

Table 1 Memorial sloan-kettering cancer center classification

Stage	Criteria
T1	Tumor involving biliary confluence ± unilateral extension to second-order biliary radicles.
T2	Tumor involving biliary confluence ± unilateral extension to second-order biliary radicles and ipsilateral portal vein involvement ± ipsilateral hepatic lobar atrophy
T3	Tumor involving biliary confluence + 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 venous involvement

Table 2 Criteria for unresectability[15]

Patient factors

Medically unfit or otherwise unable to tolerate a major operation

Hepatic cirrhosis

Local tumor-related factors

Tumor extension to secondary biliary radicles bilaterally

Encasement or occlusion of the main portal vein proximal to its bifurcation

Atrophy of one hepatic lobe with contralateral portal vein branch encasement or occlusion

Atrophy of one hepatic lobe with contralateral tumor extension to secondary biliary radicles

Unilateral tumor extension to secondary biliary radicles with contralateral portal vein branch

encasement or occlusion

Metastatic disease

Histologically proven metastases to N2 lymph nodes1

Lung, liver, or peritoneal metastases

¹Metastatic disease to peripancreatic, periduodenal, celiac, superior mesenteric, or posterior pancreaticoduodenal lymph nodes was considered to represent disease not amenable to a potentially curative resection. By contrast, metastatic disease to cystic duct, pericholedochal, hilar, or portal lymph nodes (i.e., within the hepatoduodenal ligament) did not necessarily constitute unresectability.

Table 3 Results of surgical resection for perihilar cholangiocarcinoma

Ref.	Published year	Resections	Resectablity(%)	Negative margin(%)	Liver resection(%)	Morbidity	Mortality	5-yr survival rate(%)
Hadjis et al[18]	1990	27	NA	56	60	NA	7	22
Nakeeb et al[2]	1996	109	56	26	14	47	4	11
Su et al[19]	1996	49	28	49	57	47	10	15
Klempnauer et al[20]	1997	151	45	77	77	NA	10	28
Miyazaki et al[21]	1998	76	NA	71	86	34	13	26
Neuhaus et al[22]	1999	80	NA	61	85	55	8	22
Kosuge et al[8]	1999	65	73	52	80	37	9	33
Gerhards et al[23]	2000	112	NA	14	29	65	18	NA
Nimura et al[24]	2000	142	80	61	90	49	9	26
Todoroki et al[25]	2000	101	89	14	58	14	4	28
Jarnagin et al[15]	2001	80	50	78	78	64	10	26
Kawarada et al[27]	2002	65	89	64	75	28	2.3	26
Capussotti et al[26]	2002	36	NA	89	83	47	3	27
Kawasaki et al[28]	2003	79	75	68	87	14	1.3	22
Seyama et al[29]	2003	87	94	64	67	43	0	40
Rea et al[32]	2004	46	NA	80	100	52	9	26
Kondo et al[31]	2004	40	95	95	65	48	0	NA
I.Jitsma et al[30]	2004	42	NA	65	100	76	12	19
Hemming et al[33]	2005	53	50	80	98	40	9	35
Jarnagin et al[34]	2005	106	70	77	82	62	8	NA
Dinant et al[35]	2006	99	NA	31	38	66	15	27
DeOliveira et al[3]	2007	173	62	19	20	61	5	10
Ito et al[36]	2008	38	55	63	53	32	0	33
Konstadoulakis et al[37]	2008	59	81	68.6	86.4	25.5	6.8	34.9
Igami et al[41]	2010	298	70	74	98	43	2	42
Hirano et al[40]	2010	146	NA	87	87	44	3.4	35.5
Lee et al[42]	2010	302	86	70.9	89	43	1.7	32.5
Unno et al[44]	2010	125	NA	63.2	100	48.7	8	34.7
Ercolani et al[38]	2010	51	49.6	72.5	98	51	10	34.1
Shimizu et al[43]	2010	224	NA	69.1	78	47.6	10.7	30.3
Giuliante et al[39]	2010	43	29	77	93	52.5	6.9	36.1
Regimbeau et al[45]	2011	56	NA	76.9	100	72	8	NA
Young et al[48]	2012	83	92	42.2	93	62.7	7	20
Saxena et al[47]	2012	54	64	64.3	42	45.2	2.4	24
Ribero et al[46]	2012	82	NA	81.7	91.5	64.6	9.7	28
De Jong et al[50]	2012	305	NA	64.2	73	NA	10.6	20.2
Matsuo et al[17]	2012	157	78	76	90	59.2	7.6	37.5
Cheng et al[49]	2012	176	34	78.4	97	26.3	2.9	13.5
Nagino et al[51]	2013	574	76.1	76.5	96.7	57.3	4.7	32.5

NA: Not applicable.

Table 4 Surgery performed according to the time period[51] n (%)

		Time period
	Total	Earlier period		Later period		P
		1997-1990	1991-2000	2001-2005	2006-2010
Number of patients resected	574	72	116	168	218
Resectability	574/754 (76.1)	72/93 (77.4)	116/148 (78.4)	168/216 (77.8)	218/297 (73.4)	0.406
Type of hepatectomy1						< 0.001
S1,4,5,6,7,8	43 (7.5)	5 (6.9)	11 (9.5)	4 (2.4)	23 (10.6)
S1,5,6,7,8	177 (30.8)	17 (23.6)	40 (34.5)	53 (31.5)	67 (30.7)
S1,2,3,4,5,8,	110 (19.2)	4 (5.6)	12 (10.3)	29 (17.3)	65 (29.8)
S1,2,3,4	187 (32.6)	27 (37.5)	35 (30.2)	68 (40.5)	57 (26.1)
S1,4,5,8/S1,5,8/S1,4/S1	38 (6.6)	13 (18.1)	10 (8.6)	11 (6.5)	4 (1.8)
Without hepatectomy	19 (3.3)	6 (8.3)	8 (6.9)	3 (1.8)	2 (0.9)
Combined resection
Pancreatoduodenectomy	74 (12.9)	9 (12.5)	13 (11.2)	20 (11.9)	32 (14.7)	0.553
Portal vein resection	206 (35.9)	23 (31.9)	36 (31.0)	58 (34.5)	89 (40.8)	0.116
Wedge resection	36	15	6	10	5
Segmental resection	170	8	30	48	84
Hepatic artery resection	76 (13.2)	0	5 (4.3)	25 (14.9)	46 (21.1)	< 0.001
Operative time, min2	668 ± 134	664 ± 162	787 ± 170	675 ± 145	605 ± 134	< 0.001
Blood loss, mL2	2491 ± 2156	4414 ± 2791	3773 ± 3024	1898 ± 1268	1768 ± 1130	< 0.001
Homologous blood transfusion	271 (47.2)	68 (94.4)	93 (80.2)	46 (27.4)	64 (29.4)	< 0.001

Homologous blood includes packed red blood cell and fresh-frozen plasma. Note that P indicates the statistical difference between the earlier period (1977-2000) and the later period (2001-2010).

¹Expressed as Couinaud’s hepatic segments resected;

²Excluding 19 patients who did not undergo hepatectomy.

Table 5 Criteria for neoadjuvant therapy and liver transplantation[82]

Diagnosis of cholangiocarcinoma

Transcatheter biopsy or brush cytology

CA-19.9 > 100 mg/mL and/or a mass on cross-sectional imaging with a malignant appearing stricture on cholangiography

Biliary ploidy by FISH with a malignant appearing stricture on cholangiography

Unresectable tumor above cystic duct

Pancreatoduodenectomy for microscopic involvement of the common bile duct

Resectable cholangiocarcinoma arising in PSC

Radial tumor diameter ≤ 3 cm

Absence of intra- and extrahepatic metastases

Candidate for liver transplantation

PSC: Primary sclerosing cholangitis.