Clinical Characteristics of Intrahepatic Cholangiocarcinoma and Prognostic Factors in Patients Who Received Non-surgical Treatment

Jong Ryul Eun; Byung Ik Jang; Jun Young Lee; Kyung Ok Kim; Si Hyung Lee; Tae Nyeun Kim; Heon Ju Lee

doi:10.4166/kjg.2009.54.4.227

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Eun, Jang, Lee, Kim, Lee, Kim, and Lee: Clinical Characteristics of Intrahepatic Cholangiocarcinoma and Prognostic Factors in Patients Who Received Non-surgical Treatment

Original Article

Korean J Gastroenterol 2009;54(4):227-234.

Published online: 21 February 2009

DOI: https://doi.org/10.4166/kjg.2009.54.4.227

Clinical Characteristics of Intrahepatic Cholangiocarcinoma and Prognostic Factors in Patients Who Received Non-surgical Treatment

Jong Ryul Eun, M.D., Byung Ik Jang, M.D., Jun Young Lee, M.D., Kyung Ok Kim, M.D., Si Hyung Lee, M.D., Tae Nyeun Kim, M.D., Heon Ju Lee, M.D.

Department of Internal Medicine, Yeungnam University College of Medicine, Daegu, Korea

Correspondence to: Byung Ik Jang, M.D. Department of Internal Medicine, Yeungnam University College of Medicine, 317-1, Daemyeong 5-dong, Nam-gu, Daegu 705-717, Korea Tel: +82-53-620-3830, Fax: +82-53-654-8386 E-mail: jbi@med.yu.ac.kr

Received 15 July 2009 Accepted 28 July 2009

Abstract

Background/Aims

This study was conducted to analyze the prognostic factors in patients with intrahepatic cholangiocarcinoma (ICC) who did not receive surgery.

Methods

Between August 1997 and November 2007, the medical records of 175 patients (mean age; 66 years, male/female 126/49), who were diagnosed as ICC, were reviewed retrospectively.

Results

Clonorchiasis and hepatolithiasis was found in 14.9%, and 6.3% of all patients, and no risk factors were identified in 77.8% of them. Surgical resection was performed in 29.1% (51 patients), chemotherapy ＋/− radiotherapy in 12.6% (22 patients), and palliative therapy in 58.3% (102 patients). The proportion of patients with stage I was 23.4% (41 patients). The prognostic factors in patients who did not receive surgery were alkaline phosphatase (ALP) and bilirubin levels by univariate and multivariate analysis. The median survival of patients with normal ALP and bilirubin levels was six months, whereas only one month in patients with elevated ALP and bilirubin levels (p＜0.001). Tumor characteristics of patients with elevated bilirubin and ALP levels were infiltrative tumor, bile duct involvement, and very huge tumor.

Conclusions

The prognostic factors of ICC in patients who did not receive surgery were ALP and bilirubin levels, but not lymph node metastasis.

Keywords: Intrahepatic cholangiocarcinoma, Prognostic factor, Survival, Bilirubin, Alkaline phosphatase

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Fig. 1.

Comparison of survival rate according to clinical variables; lymph node metastasis (A), tumor size (B), stages (C), bilirubin level (D), ALP level (E), and bilirubin plus ALP levels (F).

Table 1.

Baseline Clinical Characteristics

Clinical factors	Surgical treatment (n=51)	Non-surgical treatment (n=124)	p-value
Gender, male, n (%)	31 (60.8)	95 (76.6)	0.034
Age, years
≤39, n (%)	1 (2.0)	0
40-49, n (%)	0	9 (7.3)
50-59, n (%)	9 (17.6)	21 (16.9)	0.083
60-69, n (%)	24 (47.1)	45 (36.3)
70-79, n (%)	16 (31.4)	38 (30.6)
≥80, n (%)	1 (2.0)	11 (8.9)
Age, years (range)	64.5±7.9 (37-83)	66.5±10.0 (44-86)	0.024^∗
Risk factors, n (%)
Clonorchiasis	11 (21.6)	15 (12.1)
IHD stone	5 (9.8)	6 (4.8)
HCV	0	3 (2.4)	NS
Smoking	6 (11.8)	17 (13.7)
Papillomatosis	2 (3.9)	0
Symptoms, n (%)
Abdominal pain	22 (43.1)	69 (55.6)
Jaundice	2 (3.9)	16 (1.3)
Palpable mass	1 (1.7)	5 (4.0)	NS
Weight loss	1 (1.7)	7 (5.6)	NS
Dyspepsia or nausea	4 (7.8)	18 (1.5)
Asymptomatic	22 (43.1)	22 (1.8)
Laboratory findings
Total bilirubin, mg/dL	1.2±1.9	2.4±4.5	NS^∗
≥2.0, n (%)	4 (7.8)	20 (15.6)	NS
ALP, U/L	340.6±193.6	567.0±450.2	0.001^∗
≥300, n (%)	21 (41.2)	81 (65.3)	0.005
CA 19-9, u/mL	1,314.0±3,052.1	3,879.4±15,282.7	NS^∗
≥37, n (%)	26 (51.0)	74 (59.7)
＜37	18 (35.3)	24 (19.4)	NS
NA	7 (13.7)	26 (21.0)
Diagnostic modalities, n (%)
CT	51 (100)	124 (100)	NS
MRI	5 (9.8)	9 (7.3)	NS
Angiography	6 (11.8)	11 (8.9)	NS
Biopsy	17 (33.3)	82 (66.1)	0.001
Median duration of F/U, mo (range)	9.0 (0-122)	3.5 (0-31)	＜0.001^∗

ALP, alkaline phosphatase; CT, computed tomography; F/U, follow-up; HCV, hepatitis C virus; IHD, intrahepatic duct; MRI, magnetic resonance image; NA, not available; NS, non-specific. The values were expressed mean±standard deviation. These are analyzed by chi-square test and

^∗ Student's t-test.

Table 2.

Tumor Characteristics

Characteristics	Surgical treatment (n=51)	Non-surgical treatment (n=124)	p-value
Location, n (%)
Right	23 (45.1)	76 (61.3)
Left	25 (49.0)	29 (23.4)	0.003
Both	3 (5.9)	19 (15.3)
Number
One	47 (92.2)	98 (79.0)
Two Three	2 (3.9) 1 (2.0)	5 (4.0) 16 (12.9)	0.076
Uncountable	1 (2.0)	5 (4.0)
Size, cm, n (%)
≤2.0	6 (11.8)	3 (2.4)
2.1-5.0	20 (39.2)	32 (25.8)
5.1-10.0	22 (43.1)	69 (55.6)	0.006
≥10.1	2 (3.9)	17 (13.7)
Unmeasurable	1 (2.0)	3 (2.4)
(infiltrating tumor)
Size, cm (range)	5.4±2.7	7.4±3.3	＜0.001^∗
Stage, n (%)
I	20 (39.2)	21 (16.9)
II	10 (19.6)	3 (2.4)
III_A III_B	0 16 (31.4)	3 (2.4) 55 (44.4)	＜0.001
IV	5 (9.8)	42 (33.9)
LN metastasis, n (%)	17 (33.3)	86 (69.4)	＜0.001
Distant metastasis, n (%)	5 (9.8)	42 (33.9)	0.001
Lung	1	14
Bone	0	11
Peritoneal cavity	1	11
Adrenal	3	5
Brain	0	2
Others	1	4

LN, lymph node. The values were expressed mean±standard deviation. These are analyzed by chi-square test and

^∗ Student's t-test.

Table 3.

Prognostic Factors in Patients Who Received Nonsurgical Treatment by Univariate Analysis

Clinical factors	Survival (months)	p-value
Gender
Male (n=95)	4.2±3.9	0.309
Female (n=29)	5.2±6.0	0.309
Age, years
<60 (n=30)	3.9±3.4
≥60 (n=94)	4.6±4.8	0.434
Stage
I (n=21)	6.0±7.5
II (n=3)	7.7±3.2
III_A (n=3)	2.7±1.2	0.272^∗
III_B (n=55)	4.0±3.9
IV (n=42)	4.1±3.1
Size
＜5 cm (n=25)	5.8±7.2	0.109
≥5 cm (n=96)	4.1±3.5	0.109
LN metastasis
Yes (n=87)	4.0±3.7	0.114
No (n=37)	5.4±5.9	0.114
CA 19-9, U/mL
＜37 (n=24)	5.5±6.3	0.127
≥37 (n=74)	4.0±3.4	0.127
Total bilirubin, mg/dL
＜2.0 (n=99)	4.7±4.6	0.034
≥2.0 (n=20)	2.4±3.0	0.034
ALP, U/L
＜300 (n=38)	6.7±5.9	＜0.001
≥300 (n=81)	3.2±3.0	＜0.001

ALP, alkaline phosphatase; LN, lymph node. The values were expressed mean±standard deviation. These are analyzed by Student's t-test and

^∗ one-way ANOVA.

Table 4.

Prognostic Factors in Patients Who Received Nonsurgical Treatment by Multivariate Analysis

	Odd ratio	95% CI	p-value
ALP, U/L
＜300	1	1.344-3.378	0.001
≥300	2.131	1.344-3.378	0.001
Total bilirubin, mg/dL
＜2.0	1	1.006-3.268	0.048
≥2.0	1.813	1.006-3.268	0.048
Stage
I	1	0.390-2.042	0.788
II, III, IV	0.892	0.390-2.042	0.788
Tumor size, cm
＜5	1	0.390-2.042	0.599
≥5	1.160	0.390-2.042	0.599
CA 19-9, U/mL
＜37	1	0.417-1.149	0.155
≥37	0.692	0.417-1.149	0.155
LN metastasis
No	1	0.698-2.541	0.384
Yes	1.265	0.698-2.541	0.384

ALP, alkaline phosphatase; LN, lymph node. These are analyzed by Cox regression hazard model.

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