1. Is hepatopancreatoduodenectomy an acceptable operation for biliary cancer?
Eung Chang Lee, Sung-Sik Han, Hyeong Min Park,
Seung Duk Lee, Seong Hoon Kim, Sang-Jae Park
Center for Liver Cancer
National Cancer Center, Korea

2. Introduction
HPD
- first introduced In 1980 for locally advanced GB cancer
After HPD was first introduced in 1980, recent studies have generally reported a mortality rate of (클릭) 0–20%
, and 5-year survival rate of approximately (클릭) 10–65% in BD cancer and (클릭) 0-25% in GB cancer.
J HEPATO-BIL-PAN SCI 2014

3. Introduction Safety? Survival benefit?
Nevertheless, questions still persist concerning the safety and survival benefit of HPD.

4. Purpose To investigate surgical outcomes of BD and GB cancer after HPD
So, the purpose of this study is to investigate the surgical outcomes of BD & GB cancer after HPD

5. Patients and Methods Jan 2004 – Dec 2013 22 patients Indication
- BD cancer 14
- GB cancer 8
Indication
BD cancer
(n = 14 )
GB cancer
(n = 8 )
Diffuse bile duct infiltration
11 (78.6%) -
Common bile duct cancer with r/o GB cancer
3 (21.4%)
LN#13 metastasis
6 (75.0%)
LN#12 metastasis with intrapancreatic CBD invasion
1 (12.5%)
Duodenal invasion
From January 2004 to December 2013, a total of 22 patients were included in this study. In BD cancer, mostly diffuse bile duct infiltration, and In GB cancer, LN metastasis and Duodenal invasion were indicated for HPD
The detailed indication of HPD are listed here, as you see.
In BD cancer, diffuse bile duct infiltration and CBD cancer with suspicious concurrent GB cancer
but the final pathologic report of these GB lesions were 2 xanthogranulomatous cholecystitis and 1 cystic duct cancer.
And In GB cancer, The detailed indication are listed here, as you see.
And In GB cancer, Retropancreas LN metastasis and, hepatoduodenal LN metastasis with intrapancreatic CBD invasion, Duodenal invasion were indicated for HPD

6. Patients and Methods Extent of surgery BD cancer (n = 14 ) GB cancer
Extent of hepatectomy
Major hepatectomy‡
Right hemiliver, S4b, S1
11 (78.6%)
2 (25.0%)
Right hemiliver, S4b -
Left hemiliver, S5
1†(12.5%)
Minor hepatectomy
Anatomic resection of S4b, S5
3*(21.4%)
Wedge resection of the GB bed
1 (12.5%)
Type of PD PD
2 (14.3%)
3 (37.5%)
PPPD
12 (85.7%)
5 (62.5%)
Portal vein resection and reconstruction
1 (7.1%)
In BD & GB cancer, Almost 70% underwent major hepatectomy and 2 PV R&A was conducted.
In BD cancer, 11 extended right hemihepatectomy and 3 minor hepatectomy with S4b,S5 for who were suspicious for concurrent CBD and GB cancer. Likewise, the Extent of HPD for GB caner are described here.
(including the right hemiliver, S4b and S1) was performed in 11 (78.6%) patients, whereas in 3 (21.4%) patients who were suspicious for concurrent BD and GB cancer , only S4b, S5 were resected. Two PD, and 12 PPPD was done and one PV resection and reconstruction was performed
Likewise, the Extent of HPD for GB caner are listed here. And, (가리키며) This patient who underwent Lt. Hemihepatectomy received neoadjuvant chemotherapy before HPD, and the final pathological report was Stage 0.
*Bile duct cancer with R/O GB cancer 1

7. Results Mortality 4.5% (1/22) Morbidity 68.2% (15/22)
Clavien-Dindo grade ≥ % (8/22)
wound 4, sepsis 1, bleeding 1, pleural effusion 1, C-J leak 1
- No liver failure
Pancreatic fistula 50.0% (11/22)
Grade A 40.9% (n=9), B 9.1% (n=2)
BD cancer (n = 14 )
GB cancer (n = 8 )
Number
5-year (%)
Median (mo) P
Overall complication
0.556
0.448
Absent
5 (35.7)
20.1
2 (25.0)
50.0
16.4
Present
(total/C-D grade≥3)
9/5
(64.3/35.7)
22.2/NA
11.0/10.9
6/3
(75.0/37.5)
16.7/0
8.2/17.9
Pancreatic fistula
7 (50.0)
28.6
11.3
4 (50.0)
25.0
8.2 A
20.0
11.0 B
2 (14.3) NA
0 (0.0)
Bile leakage
1 (7.1)
10.9
Intra-abdominal abscess
10.2
Intra-abdominal bleeding
Pneumonia
3 (21.4)
1 (12.5)
Wound infection
Sepsis
1† (7.1)
0.2
The overall mortality rate was 4.5% (n=1), and the morbidity rate was 68.2% (n=15). And, the patients with Clavien-Dindo more than grade 3 was 36.4% (n=8). No patient had liver failure, while overall pancreatic fistula occurred in 50.0% (11): but, only 9.1% (2) of them was grade B.
(클릭클릭!!) In BD cancer, one (7.1%) patient died on postoperative day 5 due to multi-organ failure secondary to sepsis, and morbidity occurred in 64%(9). In GB cancer, there was not mortality but morbidity in 75.0% (6)

8. Results Stage (0/I/II/III/IV) Preop. biliary drainage 63.6% (14/22)
- BD cancer (0/3/6/3/2)
GB cancer (1/0/0/7/0)
Preop. biliary drainage 63.6% (14/22)
BD cancer 92.9% (n=13), GB cancer 12.5% (n=1)
Neoadjuvant Chemotherapy
GB cancer 25% (n=2)
R0 86.4% (19/22)
- BD cancer 78.6% (n=11), GB cancer 100% (n=8)
The stage of BD and GB cancer are described here. Which shows GB cancer patients had more advanced disease.
Preoperative biliary drainage was performed in about 60%.
Two (25.0%) GB cancer patients received neoadjuvant chemotherapy
R0 resection was acheved in total 86.% (19/22) 2

9. Overall Survival 5-yr OS -GB cancer 25.0% -BD cancer 17.9%
The 5-year overall survival rate was about 18% in BD cancer , and 25.0% in GB cancer and there is no meaningful differences.
The median survival length was 13.0 months in BD cancer and 16.4 months in GB cancer (P = 0.768)

10. Analysis of Risk Factors
BD cancer (n = 14 )
GB cancer (n = 8 )
Number
5-year (%)
Median (mo) P
Age (years)
0.115
0.290
<65
9 (64.3)
27.8
32.2
6 (75.0)
33.3
17.9
≥65
5 (35.7)
13.0
2 (25.0)
8.2
Sex
0.520
0.353
Male
10 (71.4)
20.0
16.8
1 (12.5)
Female
4 (28.6) NA
10.9
7 (87.5)
28.6
CEA (ng/mL)
0.444
0.554
<5.0
26.7
3 (37.5)
23.5
≥5.0
11.3
5 (62.5)
16.4
CA19–9 (U/mL), [1]
0.315
0.841
<300
29.6
≥300
6.4
TB (mg/dL)
0.351
<4.0
25.0
8 (100.0)
≥4.0
0 (0.0)
Preoperative biliary drainage
0.706
0.822
Absent
1 (7.1)
Present
13 (92.9)
20.5
PVE
0.168
10.3
Neoadjuvant chemotherapy
0.338
14 (100.0)
12.9
16.7
50.0
Operation time (hours)
0.036
0.366
<10
7 (50.0)
38.1
32.8
7.5
≥10
Blood loss (mL)
0.589
0.654
<1000
≥1000, <2000
20.1
≥2000
6 (42.9)
11.0
In this Risk Factor analysis, we can see the survival difference of BD cancer according to (클릭) operation time.
Besides that, the other perioperative variables in this page including age, sex, CEA, CA19-9, TB, peoperative biliary drainage, PVE, and neoadjuvant chemotherapy, blood loss showed no significant difference in overall survival in either BD or GB cancer.

11. Analysis of Risk Factors
BD cancer (n = 14 )
GB cancer (n = 8 )
Number
5-year (%)
Median (mo) P
Tumor size (cm)
0.030
0.700
<4.0
8 (57.1)
31.3
32.2
5 (62.5)
40.0
16.4
≥4.0
6 (42.9)
10.9
3 (37.5)
17.9
Histological type
0.592
0.203 WD
3 (21.4)
16.8
0 (0.0) NA MD
5 (35.7)
20.0 PD
33.3
11.0
1 (12.5)
7.5 UD
8.2
Others
1† (12.5)
100
115.6
Microvascular invasion
0.693
0.221
Absent
9 (64.3)
4 (50.0)
50.0
Present
13.0
Lymphatic invasion
0.829
0.209
4 (28.6)
10 (71.4)
15.0
7 (87.5)
14.3
Perineural invasion
0.206
2 (14.3)
17.8
12 (85.7)
12.5
11.3
Portal vein invasion
0.022
0.822
13 (92.9)
19.2
28.6
1 (7.1)
6.4
23.5
In addition, (클릭) tumor size ,(클릭) PV invasion,

12. Analysis of Risk Factors
BD cancer (n = 14 )
GB cancer (n = 8 )
Number
5-year (%)
Median (mo) P
T stage
<0.001
0.343
Tis
0 (0.0) NA
1† (12.5)
100
115.6 1
1 (7.1) 2
5 (35.7)
30.0
32.2
2 (25.0)
0.50
5.0 3
6 (42.9)
11.3
5 (62.5)
16.4 4
2 (14.3)
0.2
N stage
0.248
0.209
7 (50.0)
28.6
20.1
7 (87.5)
14.3
Multiple LN metastasis‡
0.020
0 or 1
10 (71.4)
25.0 ≥2
4 (28.6)
10.2
AJCC 7th Stage
0.001 I
3 (21.4) II
16.7
13.0
III
11.0 IV
R0 resection
0.399
Yes
11 (78.6)
24.2
16.8
8 (100.0) No
(클릭) T stage .(클릭) multiple LN metastasis ,(클릭) cancer Stage.
But, In GB cancer, there were no variables affecting overall survival.

13. Analysis of Risk Factors
BD cancer (n = 14 )
GB cancer (n = 8 )
Number
5-year (%)
Median (mo) P
Adjuvant Chemotherapy
0.081
0.841
Absent
7 (50.0) NA
10.9
3 (37.5)
33.3
8.2
Present
19.0
32.2
5 (62.5)
20.0
17.9
Radiotherapy
0.506
0.187
6 (75.0)
14.3
20.1
2 (25.0)
7.5
Length of hospital stay (weeks)
0.526
0.353
< 4
6 (42.9)
16.7
7 (87.5)
28.6
≥ 4
8 (57.1)
11.0
1 (12.5)
Overall complication
0.556
0.448
5 (35.7)
50.0
16.4
(total/C-D grade≥3)
9/5
(64.3/35.7)
22.2/NA
11.0/10.9
6/3
(75.0/37.5)
16.7/0
8.2/17.9
Pancreatic fistula
11.3
4 (50.0)
25.0 A B
2 (14.3)
0 (0.0)
Bile leakage
1 (7.1)
Intra-abdominal abscess
10.2
Intra-abdominal bleeding
Pneumonia
3 (21.4)
Wound infection
Sepsis
1† (7.1)
0.2
And, Post-operative variables listed this page did not affect the overall survival of biliary cancer

14. Risk Factors for Survival of BD cancer
Tumor size
Portal vein invasion
Multiple LN mets
Operation time
So, In this study, we found that besides the TNM stage,
(클릭) tumor size, (클릭) PV invasion, (클릭) multiple LN metastasis, and (클릭) operative time significantly affected the overall survival of BD cancer.
Furthermore, (클릭) we can see here that overall survival was noticeably better when there is no risk factor in comparison to when there are more than one risk factors (P = 0.002).

15. Summary & Conclusions
Acceptable mortality 4.5%
High morbidity 68.2%
- but, Clavien-Dindo grade ≥ %
GB cancer
- comparable 5-yr OS(25.0%) against BD(17.9%) cancer after HPD
BD cancer
long-term survival when poor prognostic factors (-)
 HPD can be considered in some selected cases to expect long-term survival
In summary,
First, (클릭) HPD can be done with acceptable mortality.
Second, (클릭) HPD has high morbidity, about 70%. But considering complication rate with more than Clavien-Dindo grade 3 was about half of them, it can be considered acceptable.
Third, (클릭) although in our data, the stage of GB cancer was more advanced in comparison to BD cancer, the overall survival of GB cancer after HPD were comparable.
And, finally, (클릭) in BD cancer, a better overall survival can be predicted when there is no poor prognositic factor.
So, (클릭) our conclusion is that HPD can be considered in some selected cases to expect long-term survival.

16. Thank you for listening