Background: Prognosis of perihilar cholangiocarcinoma (PHCC) is poor, and curative-intent resection is the most effective treatment associated with long-term survival. Surgery is technically demanding since it involves a major hepatectomy with en bloc resection of the caudate lobe and extrahepatic bile duct. Furthermore, to achieve negative margins, it may be necessary to perform concomitant vascular resection or pancreatoduodenectomy. Despite this aggressive approach, recurrence is often observed, considering 5-year recurrence-free survival below 15% and 5-year overall survival that barely exceeds 40%. Summary: The literature reports that survival rates are better in patients with negative margins, and surprisingly, R0 resections range between 19% and 95%. This variability is probably due to different surgical strategies and the pathologist’s expertise with specimens. In fact, a proper pathological examination of residual disease should take into consideration both the ductal and the radial margin (RM) status. Currently, detailed pathological reports are lacking, and there is a likelihood of misinterpreting residual disease status due to the missing of RM description and the utilization of various definitions for surgical margins. Key Messages: The aim of PHCC surgery is to achieve negative margins including RM. More clarity in reporting on RM is needed to define true radical resection and consistent design of oncological studies for adjuvant treatments.

1.
Jarnagin
WR
,
Fong
Y
,
DeMatteo
RP
,
Gonen
M
,
Burke
EC
,
Bodniewicz Bs
J
, et al
.
Staging, resectability, and outcome in 225 patients with hilar cholangiocarcinoma
.
Ann Surg
.
2001
;
234
(
4
):
507
19
. doi: .
2.
Seyama
Y
,
Kubota
K
,
Sano
K
,
Noie
T
,
Takayama
T
,
Kosuge
T
, et al
.
Long-term outcome of extended hemihepatectomy for hilar bile duct cancer with No mortality and high survival rate
.
Ann Surg
.
2003
;
238
(
1
):
73
83
. doi: .
3.
Nishio
H
,
Nagino
M
,
Nimura
Y
.
Surgical management of hilar cholangiocarcinoma: the Nagoya experience
.
HPB
.
2005
;
7
(
4
):
259
62
. doi: .
4.
Iacono
C
,
De Bellis
M
,
Ruzzenente
A
,
Campagnaro
T
,
Conci
S
,
Guglielmi
A
.
Hepatopancreatoduodenectomy for multifocal cholangiocarcinoma in the setting of biliary papillomatosis
.
Ann Surg Oncol
.
2020
;
27
(
9
):
3356
7
. doi: .
5.
Tang
Z
,
Yang
Y
,
Zhao
Z
,
Wei
K
,
Meng
W
,
Li
X
.
The clinicopathological factors associated with prognosis of patients with resectable perihilar cholangiocarcinoma: a systematic review and meta-analysis
.
Medicine
.
2018
;
97
(
34
):
e11999
. doi: .
6.
Cillo
U
,
Fondevila
C
,
Donadon
M
,
Gringeri
E
,
Mocchegiani
F
,
Schlitt
HJ
, et al
.
Surgery for cholangiocarcinoma
.
Liver Int
.
2019
;
39 Suppl 1
(
Suppl Suppl 1
):
143
55
. doi: .
7.
Komaya
K
,
Ebata
T
,
Yokoyama
Y
,
Igami
T
,
Sugawara
G
,
Mizuno
T
, et al
.
Recurrence after curative-intent resection of perihilar cholangiocarcinoma: analysis of a large cohort with a close postoperative follow-up approach
.
Surgery
.
2018
;
163
(
4
):
732
8
. doi: .
8.
Esposito
I
,
Schirmacher
P
.
Pathological aspects of cholangiocarcinoma
.
HPB J
.
2008
;
10
(
2
):
83
6
. doi: .
9.
Castellano-Megías
VM
,
Ibarrola-de Andrés
C
,
Colina-Ruizdelgado
F
.
Pathological aspects of so called “hilar cholangiocarcinoma”
.
World J Gastrointest Oncol
.
2013
;
5
(
7
):
159
70
. doi: .
10.
Sakamoto
E
,
Nimura
Y
,
Hayakawa
N
,
Kamiya
J
,
Kondo
S
,
Nagino
M
, et al
.
The pattern of infiltration at the proximal border of hilar bile duct carcinoma: a histologic analysis of 62 resected cases
.
Ann Surg
.
1998
;
227
(
3
):
405
11
. doi: .
11.
Ogura
Y
,
Takahashi
K
,
Tabata
M
,
Mizumoto
R
.
Clinicopathological study on carcinoma of the extrahepatic bile duct with special focus on cancer invasion on the surgical margins
.
World J Surg
.
1994
;
18
(
5
):
778
84
. doi: .
12.
Washington
MK
,
Berlin
J
,
Branton
PA
,
Burgart
LJ
,
Carter
DK
,
Compton
CC
, et al
.
Protocol for the examination of specimens from patients with carcinoma of the perihilar bile ducts
.
Arch Pathol Lab Med
.
2010
;
134
(
4
):
e19
24
. doi: .
13.
Verbeke
CS
.
Resection margins in pancreatic cancer
.
Surg Clin North Am
.
2013
;
93
(
3
):
647
62
. doi: .
14.
Burt
A
,
Alves
V
,
Bedossa
P
,
Clouston
A
,
Guido
M
,
Hübscher
S
, et al
.
Data set for the reporting of intrahepatic cholangiocarcinoma, perihilar cholangiocarcinoma and hepatocellular carcinoma: recommendations from the International Collaboration on Cancer Reporting (ICCR)
.
Histopathology
.
2018
;
73
(
3
):
369
85
. doi: .
15.
Wyatt
J
,
Hübscher
S
,
Goldin
R
.
Standards and datasets for reporting cancers Dataset for histopathology reporting of liver resection specimens (including gall bladder) and liver biopsies for primary and metastatic carcinoma
. 2nd ed.
2012
; p.
1
51
.
16.
Bosma
A
.
Surgical pathology of cholangiocarcinoma of the liver hilus (Klatskin tumor)
.
Semin Liver Dis
.
1990
;
10
(
2
):
85
90
. doi: .
17.
Yamaguchi
K
,
Chijiiwa
K
,
Saiki
S
,
Shimizu
S
,
Takashima
M
,
Tanaka
M
.
Carcinoma of the extrahepatic bile duct: mode of spread and its prognostic implications
.
Hepatogastroenterology
.
1997
;
44
(
17
):
1256
61
.
18.
Kayahara
M
,
Nagakawa
T
,
Ohta
T
,
Kitagawa
H
,
Tajima
H
,
Miwa
K
.
Role of nodal involvement and the periductal soft-tissue margin in middle and distal bile duct cancer
.
Ann Surg
.
1999
;
229
(
1
):
76
83
. doi: .
19.
Sakamoto
Y
,
Kosuge
T
,
Shimada
K
,
Sano
T
,
Ojima
H
,
Yamamoto
J
, et al
.
Prognostic factors of surgical resection in middle and distal bile duct cancer : an analysis of 55 patients concerning the significance of ductal and radial margins
.
Surgery
.
2005
;
137
(
4
):
396
402
. doi: .
20.
Sakamoto
Y
,
Shimada
K
,
Nara
S
,
Esaki
M
,
Ojima
H
,
Sano
T
, et al
.
Surgical management of infrahilar /suprapancreatic cholangiocarcinoma : an analysis of the surgical procedures, surgical margins, and survivals of 77 patients
.
J Gastrointest Surg
.
2010
;
14
(
2
):
335
43
. doi: .
21.
Stremitzer
S
,
Stift
J
,
Laengle
J
,
Schwarz
C
,
Kaczirek
K
,
Jones
RP
, et al
.
Prognosis and circumferential margin in patients with resected hilar cholangiocarcinoma
.
Ann Surg Oncol
.
2021
;
28
(
3
):
1493
8
. doi: .
22.
D’amico
FE
,
Mescoli
C
,
Caregari
S
,
Pasquale
A
,
Billato
I
,
Alessandris
R
, et al
.
Impact of positive radial margin on recurrence and survival in perihilar cholangiocarcinoma
.
Cancers
.
2022
;
14
(
7
):
1680
13
. doi: .
23.
De Bellis
M
,
Mastrosimini
MG
,
Conci
S
,
Pecori
S
,
Campagnaro
T
,
Castelli
C
, et al
.
The prognostic role of true radical resection in perihilar cholangiocarcinoma after improved evaluation of radial margin status
.
Cancers
.
2022
;
14
(
24
):
6126
. doi: .
24.
Shinohara
K
,
Ebata
T
,
Shimoyama
Y
,
Mizuno
T
,
Yokoyama
Y
,
Yamaguchi
J
, et al
.
A study on radial margin status in resected perihilar cholangiocarcinoma
.
Ann Surg
.
2021
;
273
(
3
):
572
8
. doi: .
25.
Noji
T
,
Tanaka
K
,
Matsui
A
,
Nakanishi
Y
,
Asano
T
,
Nakamura
T
, et al
.
Transhepatic direct approach to the “limit of the division of the hepatic ducts” leads to a high R0 resection rate in perihilar cholangiocarcinoma
.
J Gastrointest Surg
.
2021
;
25
(
9
):
2358
67
. doi: .
26.
Gerhards
MF
,
Van Gulik
TM
,
Bosma
A
,
Ten Hoopen-Neumann
H
,
Verbeek
PCM
,
Gonzalez Gonzalez
D
, et al
.
Long-term survival after resection of proximal bile duct carcinoma (Klatskin tumors)
.
World J Surg
.
1999
;
23
(
1
):
91
6
. doi: .
27.
Kawasaki
S
,
Imamura
H
,
Kobayashi
A
,
Noike
T
,
Miwa
S
,
Miyagawa
S
.
Results of surgical resection for patients with hilar bile duct cancer: application of extended hepatectomy after biliary drainage and hemihepatic portal vein embolization
.
Ann Surg
.
2003
;
238
(
1
):
84
92
. doi: .
28.
Ratti
F
,
Cipriani
F
,
Piozzi
G
,
Catena
M
,
Paganelli
M
,
Aldrighetti
L
.
Comparative analysis of left- versus right-sided resection in Klatskin tumor surgery: can lesion side be considered a prognostic factor
.
J Gastrointest Surg
.
2015
;
19
(
7
):
1324
33
. doi: .
29.
Neuhaus
P
,
Jonas
S
,
Bechstein
WO
,
Lohmann
R
,
Radke
C
,
Kling
N
, et al
.
Extended resections for hilar cholangiocarcinoma
.
Ann Surg
.
1999
;
230
(
6
):
808
19
. doi: .
30.
Roos
E
,
Franken
LC
,
Soer
EC
,
van Hooft
JE
,
Takkenberg
RB
,
Klümpen
HJ
, et al
.
Lost in translation : confusion on resection and dissection planes hampers the interpretation of pathology reports for perihilar cholangiocarcinoma
.
Virchows Arch
.
2019
;
475
(
4
):
435
43
. doi: .
31.
Chatelain
D
,
Farges
O
,
Fuks
D
,
Trouillet
N
,
Pruvot
FR
,
Regimbeau
J
.
Assessment of pathology reports on hilar cholangiocarcinoma : the results of a nationwide, multicenter survey performed by the AFC-HC-2009 study group
.
J Hepatol
.
2012
;
56
(
5
):
1121
8
. doi: .
32.
Groot Koerkamp
B
,
Wiggers
JK
,
Allen
PJ
,
Besselink
MG
,
Blumgart
LH
,
Busch
ORC
, et al
.
Recurrence rate and pattern of perihilar cholangiocarcinoma after curative intent resection
.
Am Coll Surg
.
2015
;
221
(
6
):
1041
9
. doi: .
33.
Wang
G
,
Wang
Q
,
Fan
X
,
Ding
L
,
Dong
L
.
The significance of adjuvant therapy for extrahepatic cholangiocarcinoma after surgery
.
Cancer Manag Res
.
2019
;
11
:
10871
82
. doi: .
34.
Ben-Josef
E
,
Guthrie
KA
,
El-Khoueiry
AB
,
Corless
CL
,
Zalupski
MM
,
Lowy
AM
, et al
.
SWOG S0809: a phase II intergroup trial of adjuvant capecitabine and gemcitabine followed by radiotherapy and concurrent capecitabine in extrahepatic cholangiocarcinoma and gallbladder carcinoma
.
J Clin Oncol
.
2015
;
33
(
24
):
2617
22
. doi: .
35.
Horgan
AM
,
Amir
E
,
Walter
T
,
Knox
JJ
.
Adjuvant therapy in the treatment of biliary tract cancer: a systematic review and meta-analysis
.
J Clin Oncol
.
2012
;
30
(
16
):
1934
40
. doi: .
36.
Ebata
T
,
Hirano
S
,
Konishi
M
,
Uesaka
K
,
Tsuchiya
Y
,
Ohtsuka
M
, et al
.
Randomized clinical trial of adjuvant gemcitabine chemotherapy versus observation in resected bile duct cancer
.
Br J Surg
.
2018
;
105
(
3
):
192
202
. doi: .
37.
Primrose
JN
,
Fox
RP
,
Palmer
DH
,
Malik
HZ
,
Prasad
R
,
Mirza
D
, et al
.
Capecitabine compared with observation in resected biliary tract cancer (BILCAP): a randomised, controlled, multicentre, phase 3 study
.
Lancet Oncol
.
2019
;
20
(
5
):
663
73
. doi: .
38.
Stein
A
,
Arnold
D
,
Bridgewater
J
,
Goldstein
D
,
Jensen
LH
,
Klümpen
HJ
, et al
.
Adjuvant chemotherapy with gemcitabine and cisplatin compared to observation after curative intent resection of cholangiocarcinoma and muscle invasive gallbladder carcinoma (ACTICCA-1 trial) - a randomized, multidisciplinary, multinational phase III trial
.
BMC Cancer
.
2015
;
15
:
564
. doi: .
39.
Nassour
I
,
Mokdad
AA
,
Porembka
MR
,
Choti
MA
,
Polanco
PM
,
Mansour
JC
, et al
.
Adjuvant therapy is associated with improved survival in resected perihilar cholangiocarcinoma: a propensity matched study
.
Ann Surg Oncol
.
2018
;
25
(
5
):
1193
201
. doi: .
40.
Im
JH
,
Choi
GH
,
Lee
WJ
,
Han
DH
,
Park
SW
,
Bang
S
, et al
.
Adjuvant radiotherapy and chemotherapy offer a recurrence and survival benefit in patients with resected perihilar cholangiocarcinoma
.
J Cancer Res Clin Oncol
.
2021
;
147
(
8
):
2435
45
. doi: .
41.
Shroff
RT
,
Kennedy
EB
,
Bachini
M
,
Bekaii-Saab
T
,
Crane
C
,
Edeline
J
, et al
.
Adjuvant therapy for resected biliary tract cancer: ASCO clinical practice guideline
.
J Clin Oncol
.
2019
;
37
(
12
):
1015
27
. doi: .
42.
Mansour
JC
,
Aloia
TA
,
Crane
CH
,
Heimbach
JK
,
Nagino
M
,
Vauthey
JN
.
Hilar cholangiocarcinoma: expert consensus statement
.
HPB
.
2015
;
17
(
8
):
691
9
. doi: .
43.
Esposito
I
,
Kleeff
J
,
Bergmann
F
,
Reiser
C
,
Herpel
E
,
Friess
H
, et al
.
Most pancreatic cancer resections are R1 resections
.
Ann Surg Oncol
.
2008
;
15
(
6
):
1651
60
. doi: .
44.
Knight
WRC
,
Zylstra
J
,
Wulaningsih
W
,
Van Hemelrijck
M
,
Landau
D
,
Maisey
N
, et al
.
Impact of incremental circumferential resection margin distance on overall survival and recurrence in oesophageal adenocarcinoma
.
BJS Open
.
2018
;
2
(
4
):
229
37
. .
45.
Amri
R
,
Bordeianou
LG
,
Sylla
P
,
Berger
DL
.
Association of radial margin positivity with colon cancer
.
JAMA Surg
.
2015
;
150
(
9
):
890
8
. doi: .
You do not currently have access to this content.