1. The prognosis of patients with intrahepatic cholangiocarcinoma after liver resection
Hsiao-Tien Liu, Chia-Yu Lai, Yi-Ju Chen, Shao-Bin Cheng, Cheng-Chung Wu
Division of general surgery, Department of surgery, Taichung Veterans General Hospital

2. Introduction
Intrahepatic cholangiocarcinoma is the most common biliary cancer and the second most common primary liver cancer in the word. (Everhart et. al., 2009, Gastoenterology 136: ; Primary liver cancer in Japan, 1990, Ann Surg 211: )
The prognostic factors vareis in articles, including tumor size, tumor number, vessles invasion, peri-ductal infiltrating, surgical margin, level of serum carcinoembryonic antigen (CEA) or serum carbohdrate antigen 19-9 (CA19-9). (Uenishi et. al., 2014, J Hepatobiliary Pancreat Sci 21: ; Cho et. al., 2010, Ann Surg Oncol 17: ; Hirohashi et. al., Hepatogastroenterology 49: ; Spolverato et. al., 2015, Cancer 121: ; Chang et. al., 2017, J Chin Med Assoc: Epub)
We conducted a retrospective study to evaluate the prognostic factors in patients with intrahepatic cholangiocarcinoma after curative liver resection.

3. Method and material
Retrospective data collection between Feb and Dec
Patients with distant metastases and combined hepatocellular/cholangiocellular carcinoma were excluded.
Perioperative fectors: age, gender, bilirubin (Bil), alanine aminotransferase (ALT), alkaline phosphatase (Alk-P), CEA, CA19-9, Creatitine (Cr), albumin (Alb), indocyanin green retention rate 15 minutes (ICGR15), hepatitis B surface antigen (HBsAg), anti-hepatitis C virus antibody (AntiHCV), alpha-feto protein (AFP), CEA, CA19-9, blood loss, blood transfusion.
Pathologic factors: tumor size, tumor number, vessel invasion, perineural invasion, peri-ductal infiltration, surgical margin.
Post-operative lomg-term result: overall survives.
Statistics: continuous variables showed as mean±standard deviation(SD). Survives revealed by Kaplan-Meier method. Univariate/multivariate comparison performed by log-rank and Cox regession methods. P < 0.05 as significant.

4. Result - demography Total N = 65 Age (year-old) 62.7±9.6 38 – 81
Gender (female/male)
30/35
46%/54%
HBsAg 17
26.1 %
Anti-HCV 10
15.3 %
ICGR15 (%)
10.4±4.9
3.6 – 24.3
CA19-9 (unit/ml)
1368.5±4358.6
0.0 –
CEA (ng/ml)
9.0±25.2
0.0 – 112.0
AFP (ng/ml)
128.4±593.5
1.2 –
ALT (U/L)
33.2±22.3
9.0 – 107.0
Alk-P (U/L)
157.2±95.2
50.0 – 527.0
Bil (mg/dl)
0.7±0.4
0.1 – 2.8
Alb (g/dl)
4.0±0.4
2.8 – 5.0
Cr (mg/dl)
0.9±0.4
0.4 – 3.0

5. Result – surgicopathological features
Total N = 65
Blood loss (ml)
658.0±535.5
Red bood cell transfusion 22
33.8%
Tumor size (cm)
5.9±3.4
1.4 – 21.0
Periductal infiltration 19
29.2%
Solitary tumor 52
83.8%
Vascular inasion 21
32.3%
Perineual invasion 17
26.1%
R1 resection (positive margin ) 18
27.6%
Lymph node metastasis 9
13.8%
Cirrhosis 6
9.2 %
Poorly differentiation 37
56.9%

6. Result – complications and long-term survives
Dindo-Clavien I II
III IV V n 8 5 3
Bile leakage (5)
DVT (1)
Delirium (1)
HBV flare-up (1)
Abscess
Biloma
Liver failure (2)
Sepsis (1)
Mortality (90d)
4.6%
Morbidity
24.6%
1-yr: 73.2%
3-yr: 44.4%
5-yr: 41.9%

7. Result – univariant analysis
Ovrall 5-year survival rate
P value
Gernder (Male;Female)
34.2%;49.6%
0.195
Age (≧65 year;＜65year)
48.0%;35.1%
0.779
CA19-9 (≧200U/ml; ＜200U/ml)
0%;45.5%
0.000
CEA (≧5ng/ml; ＜5ng/ml)
16.7%;45.0%
0.072
Red blood transfusion (Yes;No)
34.9%;44.6%
0.101
R1 resection (Yes;No)
24.5%;46.7%
0.124
Tumor size (＞5cm; ≦5cm)
26.5%;54.4%
0.004
Tumor number (Multiple;Solitary)
0%;51.7%
Periductal invasion (Yes;No)
0%;55.7%
Vascular invasion (Yes;No)
25.6%;50.0%
0.043
Perineual invasion (Yes;No)
0%;52.5%
0.002
Lymph node mets (Yes;No)
0%;49.1%
Cirrhosis (Yes;No)
66.7%;39.0%
0.986
Poorly differentiation (Yes;No)
30.3%;67.2%
0.119

8. Result – multivariant analysis
Hazard ratio
P value
CA19-9 (≧200U/ml; ＜200U/ml)
3.904
0.104
CEA (≧5ng/ml; ＜5ng/ml)
0.848
0.822
Tumor size (＞5cm; ≦5cm)
3.354
0.004
Tumor number (Multiple;Solitary)
2.725
0.058
Periductal invasion (Yes;No)
3.559
0.019
Vascular invasion (Yes;No)
1.520
0.338
Perineual invasion (Yes;No)
0.876
0.809
Lymph node mets (Yes;No)
1.799
0.264
Poorly differentiation (Yes;No)
1.236
0.625

9. Discussion
Tumor size and number are the well documented prognostic factors and also are included in staging of American Joint Committee on Cancer 8th edition.
Periductal infiltration is controversial in certain articles especially while associated with major biliary invasion, lymph node invasion, and limited resection margin. (Sakamoto et. al., 2016, Cancer 122:61-70; Hirohashi et. al., 2002, Hepatogastroenterology 49: )
The cut-off value of serum CA19-9 and CEA varies in articles and still directly influences prognosis. (Yeh et. al., 2016, Anticancer Res 36: ; Chang et. al., 2017, J Chin Med Assoc: Epub; Cho et. al., 2010, Ann Surg Oncol 17: Wang et. al., 2013, J Clin Oncol 31: ; Ohtsuka et. al., 2002, BJS 89: )

10. Discussion
Although there is no statistic significance of surgical margin for prognosis in our study, attempting to R0 surgery is still important. (Hirohashi et. al., 2002, Hepatogastroenterology 49: ; Yeh et. al., 2016, Anticancer Res 36: ; Cho et. al., 2010, Ann Surg Oncol 17: ; Ohtsuka et. al., 2002, BJS 89: )
Limitation: only patients with liver resection were included, lymph node status depended on range of lymphadenectomy, no routine post-operative adjuvant chemotherapy.

11. Conclusion
Primary tumor behaviors (size, number, periductal infiltration) are the most important prognostic factor in patients with intrahepatic cholangiocarcinoma.
Overall 5-year survival rate is below 50% in all articles, adjuvant chemotherapy might be considered in patients with poor prognostic features in the future.

12. Thank You for Your Attention