Differentiation of malignant and benign proximal bile duct strictures: The diagnostic dilemma

Table 1 Demographic features, presenting symptoms and laboratory findings in patients resected for presumed HCCA

	Malignant (n = 58)	Benign (n = 10)	P
Demographics
Gender male/female	35/23	3/7	0.09
Mean age (range)	62 (30-80)	61 (40-71)	0.62
Prior history of cholecystectomy	6 (10%)	3 (30%)	0.12
Presenting symptoms
Jaundice	46 (79%)	6 (60%)	0.23
Abdominal pain	27 (47%)	6 (60%)	0.51
Weight loss	34 (59%)	4 (40%)	0.32
Fever	2 (3%)	2 (20%)	0.10
Preoperative laboratory findings
Bilirubin (μmol/L)	144 (± 15)	107 (± 35)	0.36
AP (U/L)	430 (± 61)	371 (± 64)	0.73
AST (U/L)	119 (± 12)	58 (± 15)	0.02
ALT (U/L)	190 (± 21)	88 (± 22)	0.03
GGT (U/L)	675 (± 89)	405 (± 114)	0.32
LDH (U/L)	313 (± 20)	277 (± 30)	0.42
PT (Prolonged-Normal)	3-33 (8%)	1-6 (14%)	0.62

HCCA: Hilar cholangiocarcinoma; AST: Aspartate aminotransferase; ALT: Alanine aminotransferase; GGT: Gamma glutamyl transpeptidase; LDH: Lactate dehydrogenase; PT: Prothrombin time; AP: Alkaline phosphatase.

Table 2 Imaging studies and interventions in patients resected for presumed HCCA

	Malignant (n = 58)	Benign (n = 10)	P
No. of imaging studies
ERCP	51 (88%)	9 (90%)
PTC	13 (22%)	3 (30%)
US + colour Doppler	52 (90%)	8 (80%)
CT	56 (97%)	9 (90%)
MRC	17 (29%)	4 (40%)
Mean No. of procedures per patient	3.3	3.3
Stent placement procedure
ERCP	40	7
PTC	12	3
ERCP and PTC	4	1
Biliary brushing
No. of brushings performed	30/58 (52%)	6/10 (60%)	0.74
Highly suspicious	15/30 (50%)	0/6 (0%)	0.03
No malignant cells	9/30 (30%)	4/6 (67%)	0.16
Atypical cells, inconclusive	6/30 (20%)	2/6 (33%)	0.60
Diagnostic laparoscopy
No. of laparoscopies performed	53 (91%)	8 (80%)
Intra-operative US performed	15	1

Table 3 Results of imaging studies and intra-operative findings in patients resected for presumed HCCA

	Malignant (n = 58)	Benign (n = 10)	P
Findings on preoperative imaging
Presence of mass	56 (97%)	8 (80%)	0.10
Mean size (range, cm)	2.5 (0.7-7.0)	2.6 (1.0-3.7)	0.62
Bismuth classification
Type I, II	14	3	0.70
Type IIIa/b, IV	39	6
Intrahepatic	5	1
Vascular involvement1	21 (36%)	0 (0%)	0.03
Portal vein	19	0
Hepatic artery	6	0
Lobar atrophy	10 (17%)	1 (10%)	1.00
Lymph nodes (> 1 cm)	12 (21%)	1 (10%)	0.67
Intra-operative findings
FS performed2	57/58 (99%)	10/10 (100%)
FS positive for malignancy	20/57 (35%)	0/10 (0%)	0.03
Suspicious3-Not suspicious	51-7	5-5
Type of resection
Local bile duct resection	17 (29%)	3 (30%)
Concomitant partial hepatectomy	41 (71%)	7 (70%)

FS: Frozen section.

¹Non cumulative, patients with simultaneously portal v. and hepatic a. involvement;

²FS from suspicious lesions, lymph nodes and/or resection margins;

³A positive FS and/or palpable mass.

Table 4 Patients with benign proximal bile duct strictures: Preoperative, intra-operative and histological findings

Number of patient	Age/Gender	Medical history	Bismuth classification	Brush cytology	Intra-operative findings	Treatment	Final histological diagnosis
1	40/F	LC	Intrahepatic	Atypical cells	Suspicious	Hemihepatectomy le	Fibrosing cholangitis
2	54/F	-	Type IIIa	No malignancy	Suspicious	Hemihepatectomy ri1	Sclerosing cholangitis
3	56/M	IBD	Type IIIb	-	Not suspicious	Hemihepatectomy le12	Sclerosing cholangitis
4	60/F	-	Type II	No malignancy	Not suspicious	Local resection	Fibrosing cholangitis
5	63/F	LC	Type II	Atypical cells	Suspicious	Local resection	Erosive inflammation
6	65/F	-	Type IIIa	-	Not suspicious	Hemihepatectomy ri	Autoimmune-like cholangitis
7	68/F	LC	Type IIIa	-	Suspicious	Hemihepatectomy ri	Fibrosing cholangitis
8	69/F	-	Type IIIb	-	Not suspicious	Hemihepatectomy le	Sclerosing cholangitis
9	70/M	-	Type II	No malignancy	Not suspicious	Local resection	Erosive inflammation
10	71/M	CP	Type IIIa	No malignancy	Suspicious	Hemihepatectomy ri1	Autoimmune-like cholangitis

CP: Chronic pancreatitis; LC: Laparoscopic cholecystectomy; IBD: Inflammatory bowel disease.

¹Partial liver resection + local resection;

²Partial liver resection was performed because of atrophic liver lobes.

Table 5 Incidence of benign lesions in patients resected for presumed HCCA: Review of literature

Source, yr1	Period of inclusion	Number of patients2	Number of benign lesions (%)
Hadjis et al 1985[34]	1979-1983	1043	8 (8)
Wetter et al 1991[35]	1985-1990	594	8 (14)
Verbeek et al 1992[36]	1984-1990	82	11 (13)
Nakayama et al 1999[10]	1990-1997	99	14 (15)
Gerhards et al 2001[16]	1983-1997	132	20 (15)
Knoefel et al 2003[12]	1996-1999	33	6 (18)
Khalili et al 2003[13]	2000-2001	20	4 (20)
Koea et al 2004[37]	1998-2002	49	12 (24)
Corvera et al 2005[38]	1992-2003	2753	22 ( 8)
Are et al 2006[15]	1997-2001	59	9 (15)
Uhlmann et al 2006[39]	1998-2004	49	7 (14)
Present study	1998-2006	68	10 (15)

¹Listed chronologically;

²Indicates only patients undergoing resection;

³Patients evaluated of suspected hilar cholangiocarcinoma (not all resected);

⁴Patients resected for papillary tumours were excluded (n = 5).