Radiol Oncol 2023; 57(2): 270-278. doi: 10.2478/raon-2023-0026
270
research article
Two-stage hepatectomy in resection of 
colorectal liver metastases − a single-
institution experience with case-control 
matching and review of the literature
Spela Turk
1,2
,
 
Irena Plahuta
1,2
, Tomislav Magdalenic
1
, Tajda Spanring
1,2
, Kevin Laufer
1,2
,  
Zan Mavc
1
, Stojan Potrc
1,2
, Arpad Ivanecz
1,2
1 
Clinical Department of Abdominal and General Surgery, University Medical Centre Maribor, Maribor, Slovenia
2
 Department of Surgery, Faculty of Medicine, University of Maribor, Maribor, Slovenia
Radiol Oncol 2023; 57(2): 270-278.
Received 18 March 2023 
Accepted 15 May 2023
Correspondence to: Assist. Prof. Arpad Ivanecz, M.D., Ph.D., Clinical Department of Abdominal and General Surgery, University Medical 
Centre Maribor, Ljubljanska ulica 5, SI-2000 Maribor, Slovenia. E-mail: arpad.ivanecz@ukc-mb.si
Spela Turk and Irena Plahuta contributed equally to this work.
Disclosure: No potential conflicts of interest were disclosed. The abstract was accepted for presentation at the 15th Biennial Congress of the 
European Hepato-Pancreato-Biliary Association in June 2023 in Lyon, France.
This is an open-access article distributed under the terms of the CC-BY licence (https://creativecommons.org/licenses/by/4.0/).
Background. Two-stage hepatectomy (TSH) has been proposed for patients with bilateral liver tumours who have 
a high risk of posthepatectomy liver failure after one-stage hepatectomy (OSH). This study aimed to determine the 
outcomes of TSH for extensive bilateral colorectal liver metastases.
Patients and methods. A retrospective review of a prospectively maintained database of liver resections for 
colorectal liver metastases was conducted. The TSH group was compared to the OSH group in terms of perioperative 
outcomes and survival. Case-control matching was performed.
Results. A total of 632 consecutive liver resections for colorectal liver metastases were performed between 2000 
and 2020. The study group (TSH group) consisted of 15 patients who completed TSH. The control group included 151 
patients who underwent OSH. The case-control matching-OSH group consisted of 14 patients. The major morbidity 
and 90-day mortality rates were 40% and 13.3% in the TSH group, 20.5% and 4.6% in the OSH group and 28.6% and 
7.1% in the case-control matching-OSH group, respectively. The recurrence-free survival, median overall survival, and 
3- and 5-year survival rates were 5 months, 21 months, 33% and 13% in the TSH group; 11 months, 35 months, 49% and 
27% in the OSH group; and 8 months, 23 months, 36% and 21%, respectively, in the case-control matching-OSH group, 
respectively.
Conclusions. TSH used to be a favourable therapeutic choice in a select population of patients. Now, OSH should 
be preferred whenever feasible because it has lower morbidity and equivalent oncological outcomes to those of 
completed TSH.
Key words: colorectal cancer; liver metastases; hepatectomy; future liver remnant; posthepatectomy liver failure; 
survival analysis
Introduction
Colorectal cancer is the third most diagnosed 
cancer worldwide.
1
 At diagnosis, the disease has 
spread to the liver in 15% to 25% of patients, and 
another 25% develop colorectal liver metastases 
metachronously.
2
 Liver resection remains the on-
ly potentially curative treatment option for these 
patients.
2
 Despite the ability of the liver to regen-
erate after significant tissue loss, a future liver 

Radiol Oncol 2023; 57(2): 270-278.
Turk S et al. / Two-stage hepatectomy in resection of colorectal liver metastases 271
remnant, which contributes 25–30% of the total 
liver volume, has been the minimal requirement 
in patients with a noncirrhotic liver.
2
 Therefore, 
major hepatectomies are associated with a high 
risk of posthepatectomy liver failure.
3
 Innovative 
approaches have been developed to improve colo-
rectal liver metastases resectability, i.e., two-stage 
hepatectomy (TSH).
2,4
 Their initial phase can be 
portal vein embolization or intraoperative selec-
tive portal vein ligation. The novelist approach is 
the associating liver partition and portal vein liga-
tion for staged hepatectomy (ALPPS) procedure.
2
This study aimed to determine the feasibility 
and safety of TSH for patients with extensive bi-
lateral colorectal liver metastases by comparing 
perioperative and long-term outcomes between 
TSH and one-stage hepatectomy (OSH) groups.
Patients and methods
Study population
A retrospective review of a prospectively ob-
tained database of 632 consecutive liver proce-
dures for colorectal liver metastases at the Clinical 
Department of Abdominal and General Surgery of 
the University Medical Centre Maribor in Slovenia 
was performed. This department is a specialised 
referral centre for hepato-pancreato-biliary sur-
gery. The study period was from 1 January 2000 
until 31 December 2020.
Before the surgery, patients consented to 
their anonymous data being used for research. 
Therefore, their records were anonymised and dei-
dentified before analysis. Ethical approval for this 
study was obtained from the National Medical 
Ethics Committee of the Republic of Slovenia 
(0120-455/2020/3). All methods were performed 
following the relevant guidelines and regulations.
Inclusion and exclusion criteria
The inclusion criteria were patients with bilateral 
colorectal liver metastases who:
• completed TSH or
• underwent their first OSH for colorectal 
liver metastases,
• the TSH group was formed from patients 
who underwent portal vein embolization 
or portal vein ligation, as proposed by 
Regimbeau.
5
The exclusion criteria were as follows:
• explorative laparotomies without liver re-
sections,
• repeated liver resections,
• patients with unilateral colorectal liver me-
tastases,
• radiofrequency ablation (RFA) or its combi-
nations with liver resections.
Definitions
Routinely available clinical characteristics were 
analysed, including patient demographics, perfor-
mance status defined according to the American 
Society of Anaesthesiologists Classification (ASA 
classification)
6
, application of neoadjuvant chemo-
therapy, preoperative carcinoembryonic antigen 
(CEA) level, and presence of extrahepatic disease. 
Primary colorectal tumour variables included the 
tumour location and nodal invasion. Liver metasta-
sis variables included synchronous/metachronous 
metastases and the number and size of metastases.
Patients were presented at the multidisciplinary 
team meeting.
2
 Bilateral colorectal liver metastases 
were resected in a single procedure when both the 
volume and function of the future liver remnant 
were considered sufficient. The parenchyma-spar-
ing principle of liver surgery for colorectal liver me-
tastases was applied.
7
 The types of liver resections 
were classified according to the Brisbane terminol-
ogy.
8
 Major liver resections involved three or more 
adjacent liver segments, including conventional 
major resections (left/extended left hepatectomies, 
right/extended right hepatectomies, central hepa-
tectomies).
8
 The analysis of future liver remnant 
consisted of computed tomography (CT) volume-
try, laboratory liver tests (prothrombin time and al-
bumins), and the indocyanine green clearance test.
2
Specimens were analysed by a gastrointestinal 
histopathologist who assessed the resection mar-
gin. The histological surgical margins for malig-
nant lesions were defined as microscopically nega-
tive (R0) or positive (<1 mm, R1).
7
 In addition, the 
Clinical Risk Score devised by Fong et al. was ap-
plied.
9
Two-stage hepatectomy
Portal vein embolization, intraoperative selective 
portal vein ligation, or the ALPPS procedure were 
performed when the analysis suggested an insuf-
ficient future liver remnant.
2
 Portal vein emboli-
zation was followed by atrophy of the embolized 
hemiliver and hypertrophy of the other hemiliver.
2
 
TSH with portal vein ligation was performed when 
the intraoperative findings were unfavourable.
4
 In 
the first stage, the metastasectomy of one hemiliver 

Radiol Oncol 2023; 57(2): 270-278.
Turk S et al. / Two-stage hepatectomy in resection of colorectal liver metastases 272
was performed along with portal vein ligation for 
the other hemiliver.
4
 The effect was similar to that of 
preoperative portal vein embolization.
10
 The second 
stage followed a few weeks later and consisted of a 
major hepatectomy.
2,4
 ALPPS was performed with 
the same rationale; the difference was the addition 
of liver parenchyma transection in the first stage.
11
RFA has been applied where radical liver re-
section has been infeasible due to the proximity 
of large vessels.
2
 Therefore, RFA has been applied 
intraoperatively as an independent procedure or 
adjunct to liver resection.
2
 RFA has also been used 
as a percutaneous procedure. However, these pa-
tients were excluded from the analyses.
Follow-up
Patients were followed-up at the outpatient clinic 
at periodic intervals. The follow-up protocol con-
sisted of a CEA level, a chest radiograph or CT, an 
abdominal ultrasound, CT, or magnetic resonance 
imaging every three months for the first two years 
and every six months afterwards.
2
Study endpoints
Primary outcomes ‒ overall survival and 
recurrence-free survival
The primary outcome was overall survival (OS). 
It was defined as the interval between the date of 
liver resection (the second stage in the TSH group) 
of colorectal liver metastases and the date of death 
or the last follow-up in surviving patients.
The second primary outcome was recurrence-
free survival (RFS). It was calculated from the 
date of liver resection (the second stage in the TSH 
group) to the date of any detected recurrence or 
the last follow-up in patients without recurrence.
Secondary outcomes ‒ morbidity and mortality
Morbidity was reported according to the Clavien-
Dindo (CD) classification.
12
 Major morbidity was 
defined as CD ≥ 3a. Mortality rates were reported 
as the number of patients who died within 90 post-
operative days.
Posthepatectomy haemorrhage, bile leak-
age, and liver failure were graded according to 
the International Study Group of Liver Surgery 
(ISGLS).
13-15
Statistical analysis
IBM SPSS for Windows Version 28.0 (IBM Corp., 
Armonk, NY, USA) was used for the statistical 
analysis. Percentages are reported to one decimal 
place. A P value ≤ 0.05 was considered statistically 
significant.
Categorical variables are displayed as numbers 
with percentages. The differences between cat-
egorical variables were tested using the chi-square 
or Fisher-Freeman Halton test when more than 
two categories were present. Continuous vari-
ables were expressed as medians (minimum-max-
imum, interquartile range) and analysed with the 
Mann-Whitney test since the distribution analysis 
showed the non-normal distribution of data.
Survival data for median OS and RFS are pre-
sented as Kaplan-Meier curves, and groups were 
compared by a log-rank test. The results are ex-
pressed in months as the median (95% confidence 
interval (95% CI)). Survival tables were used for 3- 
and 5-year OS and RFS, given in percentages.
Case–control matching 
CCM-OSH group 
n=14 
Liver procedures for CLMs 
n=632 
Liver resection 
n=469 
Liver resection 
and RFA 
n=29 
Open RFA 
n=42 
Percutaneous RFA 
n=22 
Exploration only 
n=30 
One-stage procedures 
n=592 
OSH group 
Bilateral liver metastases 
n=151 
Two-stage 
hepatectomy 
Only the first stage 
performed due to 
disease progression 
n=6 
 
TSH group 
n=15 
Both stages 
completed 
First stage 
n=23 
Right PVE: n=6 
Right PVL: n=13 
ALPPS: n=4 
Excluded: 
Unilateral CLMs 
or repeated liver resection 
n=318 
 
Excluded: 
Unilateral CLMs 
n=2 
FIGURE 1. The study flowchart. The study period covers 1 January 2000 to  
31 December 2020. 
ALPPS = associating liver partition and portal vein ligation for staged hepatectomy; CCM-OSH 
= case-control matching one-stage hepatectomy; CLMs = colorectal liver metastases; OSH 
= one-stage hepatectomy; PVE = portal vein embolization; PVL = portal vein ligation; RFA = 
radiofrequency ablation; TSH = two-stage hepatectomy

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Turk S et al. / Two-stage hepatectomy in resection of colorectal liver metastases 273
TABLE 1. Clinical characteristics and perioperative outcomes of the 166 patients
Clinical characteristics OSH (n=151) TSH (n=15) P value
Male sex 
a
109 (72.2%) 13 (86.7%) 0.365
Age (years) 
b
62 (34–84; 14) 64 (45–75; 12) 0.819
ASA score ≥ 3 
a
32 (21.2%) 2 (13.3%) 0.701
Primary tumour location 
c
    Right colon 27 (17.9%) 1 (6.7%)
0.166
    Left colon 61 (40.4%) 6 (40.0%)
    Rectum 61 (40.4%) 7 (46.7%)
    > 1 primary tumour 2 (1.3%) 1 (6.7%)
Primary tumour nodal invasion 
a
99 (66.0%) 10 (66.7%) 1.000
Synchronous liver metastases 
a
81 (53.6%) 11 (73.3%) 0.179
Number of liver metastases 
b
 3 (1–19; 3) 5 (2–12; 6) 0.001
Size of liver metastases (cm) 
b
 4 (0.6–20; 3) 5 (1.5–11; 5.5) 0.183
Neoadjuvant chemotherapy
 a
79 (52.3%) 13 (86.7%) 0.013
Preoperative CEA level (ng/mL) 
b
14 (1–1359; 47.5) 12 (2–1312; 60) 0.464
Extrahepatic disease 
a
27 (17.9%) 3 (20.0%) 1.000
Clinical risk score 3–5 
a
92 (60.9%) 10 (66.7%) 0.875
Major liver resection 
a
58 (38.4%) 15 (100%) <0.001
    Atypical resection 29 (19.2%) 0 (0.0%) /
    Segmentectomy/segmentectomy &
    atypical resection
3 (2.0%)/14 (9.3%) 0 (0.0%) /
    Bisegmentectomy/bisegmentectomy &
    atypical resection
10 (6.6%)/37 (24.5%) 0 (0.0%) /
    Right/extended right hepatectomy 28 (18.5%)/6 (4.0%) 13 (86.7%)/2 (13.3%) /
    Left/extended left hepatectomy 6 (4.0%)/3 (2.0%) 0 (0.0%) /
    Trisegmentectomy 6 (4.0%) 0 (0.0%) /
    Trisegmentectomy & atypical resection 5 (3.3%) 0 (0.0%) /
    Central resection 4 (2.6%) 0 (0.0%) /
R0 resection 
a
118 (78.1%) 10 (66.7%) 0.492
CD ≥ 3a 
a
31 (20.5%) 6 (40.0%) 0.161
90-day mortality 
a
 7 (4.6%) 2 (13.3%) 0.189
ISGLS haemorrhage grade C
 a
2 (1.3%) 0 (0.0%) 1.000
ISGLS bile leakage grade C 
a
5 (3.3%) 1 (6.7%) 1.000
ISGLS liver failure – any grade 
a
40 (26.5%) 12 (80.0%) <0.001
    Grade A 
a
16 (10.6%) 5 (33.3%) 0.034
    Grade B 
a
19 (12.6%) 6 (40.0%) 0.014
    Grade C 
a
5 (3.3%) 1 (6.7%) 1.000
Hospital stay (days)
 b
10 (5–63; 7) 14 (8–158; 11) 0.028
a
 Categorical variable reported as n (%), chi-square test; 
b
 continuous variable, non-normal distribution, reported as median (minimum-maximum, 
interquartile range), Mann-Whitney test; 
c 
categorical variable with more than two groups, reported as n (%), Fisher-Freeman-Halton test; 
ASA = American Society of Anaesthesiologists; CEA = carcinoembryonic antigen; CD = Clavien-Dindo classification; ISGLS = International Study 
Group of Liver Surgery; OSH = one-stage hepatectomy; TSH = two-stage hepatectomy
Case-control matching was performed for 15 
patients from the TSH group.
16
 Patients from the 
OSH group (controls) were selected based on the 
variables that were statistically significant in a 
bivariate analysis. The sampling was performed 
without replacement and with maximising execu-

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Turk S et al. / Two-stage hepatectomy in resection of colorectal liver metastases 274
TABLE 2. Clinical characteristics of the matched groups
Clinical characteristics CCM-OSH (n = 14) TSH (n = 15) P value
Male sex 
a
11(78.6%) 13(86.7%) 1.000
Age (years) 
b
60 (53–78; 13) 64 (45–75; 12) 0.463
ASA score ≥ 3 
a
2 (14.3%) 2 (13.3%) 1.000
Primary tumour in right colon 
a
2 (14.3%) 1 (6.7%) 1.000
Primary tumour in left colon 
a
10 (71.4%) 6 (40%) 0.125
Primary tumour in rectum 
a
2 (14.3%) 7 (46.7%) 0.063
> 1 primary tumour 
a
0 (0.0%) 1 (6.7%) 1.000
Primary tumour nodal invasion 
a
10 (71.4%) 10 (66.7%) 1.000
Synchronous liver metastases 
a
11(78.6%) 11(73.3%) 1.000
Number of liver metastases 
b
 5 (2–12; 6) 5 (2–12; 6) 0.317
Size of liver metastases (cm) 
b
 4.6 (1–20; 7) 5 (1.5–11; 5.5) 0.463
Neoadjuvant chemotherapy
 a
13 (92.9%) 13 (86.7%) 1.000
Preoperative CEA level (ng/mL) 
b
9 (1–261; 76) 12 (2–1312; 60) 0.975
Extrahepatic disease 
a
1 (7.1%) 3 (20.0%) 1.000
Clinical risk score 3–5 
a
13 (92.9%) 10 (66.7%) 0.250
Major hepatectomy 
a
14(100%) 15 (100%) 1.000
    Right/extended right hepatectomy 8 (57.1%)/2 (14.3%) 13 (86.7%)/2 (13%) /
    Left hemihepatectomy 1 (7.1%) 0 (0.0%) /
    Trisegmentectomy & atypical resection 3 (21.4%) 0 (0.0%) /
R0 resection 
a
8 (57.1%) 10 (66.7%) 1.000
CD ≥ 3a 
a
4 (28.6%) 6 (40.0%) 0.688
90-day mortality 
a
 1 (7.1%) 2 (13.3%) 1.000
ISGLS haemorrhage grade C
 a
0 (0.0%) 0 (0.0%) 1.000
ISGLS bile leakage grade C 
a
1 (7.1%) 1 (6.7%) 1.000
ISGLS liver failure – any grade 
a
10 (71.4%) 12 (80%) 1.000
    Grade A 
a
4 (28.6%) 5 (33.3%) 1.000
    Grade B 
a
5 (35,7%) 6 (40.0%) 1.000
    Grade C 
a
1 (7.1%) 1 (6.7%) 1.000
Hospital stay (days)
 b
16 (6–63; 13) 14 (8–158; 11) 0.406
a
 Categorical variable reported as n (%), McNemar test; 
b
 continuous variable, nonnormal distribution, reported as the median (minimum-
maximum, interquartile range), Wilcoxon signed ranks test
ASA = American Society of Anaesthesiologists; CCM-OSH = case-control matching one-stage hepatectomy; CEA = carcinoembryonic antigen; 
CD = Clavien-Dindo classification; ISGLS = International Study Group of Liver Surgery; TSH = two-stage hepatectomy
tion performance modality. Matched patients were 
assigned to the case-control matching-OSH group. 
The statistical analysis of continuous variables 
was performed with the Wilcoxon signed ranks 
test. The analysis of categorical variables was per-
formed with the McNemar test.
16
 Survival was es-
timated as described previously.
Results
The study population was stratified into two 
groups. The study group TSH consisted of 15 pa-
tients who completed TSH. The control group 
OSH included 151 patients. The study flowchart is 
shown in Figure 1.

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Turk S et al. / Two-stage hepatectomy in resection of colorectal liver metastases 275
Clinical characteristics of patients
This study included 166 patients: 151 in the OSH 
group and 15 in the TSH group. Their clinical char-
acteristics and perioperative outcomes are sum-
marised in Table 1.
Case-control matching
To reduce the bias and equilibrate the number 
of group members, case-control matching was 
conducted. Patients from the OSH group (con-
trols) were selected based on the predictors that 
were statistically significant in bivariate analysis 
(Table 1): number of liver metastases, neoadjuvant 
chemotherapy, and extent of liver resection.
Case-control matching returned 14 controls 
among the OSH group, annotated as case-control 
matching-OSH. All three variables were statisti-
cally significant in the case-control matching mod-
el (P < 0.001). The Wilcoxon signed ranks test for 
the median of differences between before and after 
matching was insignificant (P = 0.317).
Analyses after case-control matching
After case-control matching, the TSH and OSH 
groups were compared (Table 2).
Morbidity and mortality
Perioperative morbidity and 90-day mortality rates 
are provided in Table 1 and Table 2.
In the OSH group, seven (4.6%) patients died 
postoperatively. The causes of death were sepsis 
TABLE 3. Survival analysis
Overall OSH (n = 151) TSH (n = 15) P value
Median OS (months) [95% CI] 35 [30–40] 35 [31–39] 21 [17–25] 0.063
3-year OS 48% 49% 33% 0.107
5-year OS 26% 27% 13% 0.107
RFS (months) [95% CI] 11 [8 –14] 11 [9–13] 5 [2–8] 0.138
3-year RFS 14% 15% 13% 0.070
5-year RFS 10% 10% 7% 0.070
After case-control matching
Overall CCM-OSH (N=14) TSH (N=15) P value
Median OS
(months) [95% CI]
23 [19–27] 23 [5–41] 21 [17.0–25.0] 0.575
3-year OS 34% 36% 33% 0.743
5-year OS 17% 21% 13% 0.743
RFS (months) [95% CI] 7 [4–10] 8 [1–15] 5 [2–8] 0.888
3-year RFS 14% 14% 13% 0.498
5-year RFS 3% 0% 7% 0.498
CI = confidence interval; CCM = case-control matching; OS = overall survival; OSH = one-stage hepatectomy; RFS = recurrence-free survival; TSH 
= two-stage hepatectomy
FIGURE 2. Overall survival after case-control matching (TSH 
vs. case-control matching-OSH groups), P = 0.575. 
CCM-OSH = case-control matching one-stage hepatectomy; TSH = 
two-stage hepatectomy

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Turk S et al. / Two-stage hepatectomy in resection of colorectal liver metastases 276
(n = 1), cardiorespiratory failure (n = 1), multiorgan 
failure (n = 3), and posthepatectomy liver failure (n 
= 2). In the TSH group, two (13.3%) patients died 
postoperatively. One patient suffered from colonic 
perforation, was reoperated on several times, and 
died of multiorgan failure. The second patient died 
of cardiorespiratory failure after acute myocardi-
al infarction. In the case-control matching-OSH 
group, the patient (7.1%) died of posthepatectomy 
liver failure.
Survival analysis
Patients were followed until their death or until 
31 December 2022. The median follow-up was 174 
(95% CI 113–235) months. A summary of the sur-
vival analysis is provided in Table 3 and Figure 2.
The RFS, median OS, and 3- and 5-year survival 
rates were 5 months, 21 months, 33% and 13% in 
the TSH group; 11 months, 35 months, 49% and 
27% in the OSH group; and 8 months, 23 months, 
36% and 21% in the case-control matching-OSH 
group, respectively.
Discussion
The main finding of our research is that the TSH 
group had a similar survival to that of the case-
control matching-OSH group (median OS: 21 vs. 23 
months), while the major morbidity rate was lower 
in the case-control matching-OSH group (40% vs. 
28.6%).
The first TSH was performed on the proposition 
that a liver resection where some tumour tissue 
remains in place could be justified if it could be 
removed by second liver resection.
4
 The time dur-
ing surgeries was intended for liver hypertrophy, 
which was enhanced by portal vein embolization 
or portal vein ligation.
4,17
Our first TSH was performed in 2005, and 23 pa-
tients with the most difficult patterns of colorectal 
liver metastases were allocated for this demand-
ing treatment (Figure 1).
18-20
 Only 15 patients who 
finished both stages were eligible for this study. 
This figure is among the lowest, especially com-
pared to the most recent multicentre studies, but 
close to those in earlier studies.
2
 Regimbeau et al. 
TABLE 4. Literature review of surgical outcomes and survival after two-stage hepatectomy for colorectal liver metastases
Authors Year
Study 
period
N of 
patients
Major liver 
resection 
(%)
R0
resection 
(%)
Morbidity
(%)
Mortality
(%)
Median
follow-up 
(months)
Median 
RFS 
(months)
3-y RFS
(%)
5-y RFS
(%)
Median 
OS 
(months)
3-y OS 
(%)
5-y OS 
(%)
Adam et al., 
France
4
2000 1992–1999 13 62 NR 45 15 22 NR 31 31 44 35 NR
Tanaka et al.,
 
Japan
17
2007 1992–2004 22 67 87 23 0 NR NR 6 NR NR 33 NR
Wicherts et al., 
France
24
2008 1992–2007 41 76 NR 59 7 24 NR 26 13 39 60 42
Narita et al., 
France
25
2011 1996–2009 61 95 NR 54 0 30 NR 15 8 40 59 32
Turrini et al., 
France
26
2012 2000–2010 34 91 100 20 6 41 NR 24 14 44 59 35
Omichi et al., 
Japan
27
2022 2013–2019 32 NR 78 22 0 17 6 NR NR 41 61 NR
The present 
study, Slovenia
2023 2000–2020 15 100 67 40 13 174 7 13 7 21 33 13
Multicentre studies
Tsai et al., USA 
and Portugal
28
2010 1994–2008 35 80 NR 26 5 NR NR NR NR 16 58 NR
Regimbeau 
et al. 
LiverMetSurvey 
registry
5
2017 2000–2014 625 NR 58 25 9 84
a
41
a
43 23 40a 45 23
Petrowsky 
et al. ALPPS 
registry
29
2020 2009–2019 510 100 73 21 5 38 11 19 12 37 52 27
Chavez et al. 
Five centres in 
the USA
22
2021 2000–2016 196 76 92 23 5 28 NR 19 18 50 64 44
a
 = mean
ALPPS = associating liver partition and portal vein ligation for staged hepatectomy; N = number; NR = not reported; OS = overall survival; RFS = recurrence-free survival; 
USA = United States of America

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Turk S et al. / Two-stage hepatectomy in resection of colorectal liver metastases 277
and Chavez et al. published large multicentre stud-
ies.
5,22 
Their study periods overlap with previous 
analyses from included centres, as shown in some 
reviews (Table 4).
21,23
The diversity of first-step procedures challeng-
es further analysis.
30
 Nevertheless, this research 
adheres to the criteria by Regimbeau et al.
5
 except 
for one case of completed ALPPS.
The clinical characteristics of patients in the 
OSH and TSH groups differed only in the medi-
an number of colorectal liver metastases (3 vs. 5) 
and the rate of chemotherapy treatment (52.3% vs. 
86.7%). Both characteristics denote an extensive tu-
mour burden in the TSH group.
27 
The concept of parenchyma-sparing liver sur-
gery for colorectal liver metastases was estab-
lished approximately 30 years ago.
7
 This explains 
the large group of one-stage hepatectomies (n = 
151), even in the case of bilateral colorectal liver 
metastases, and the lower rate of major hepatecto-
mies in this group (38.4%) (Tables 1 and 2). In the 
TSH group, the rate of major hepatectomies was 
100%, and the difference from the OSH group was 
statistically significant. The reported rates of major 
liver resections are given in Table 4.
There was a significant difference in posth-
epatectomy liver failure when comparing the TSH 
(80%) and OSH groups (26.5%) (P < 0.001) (Table 1). 
However, this difference disappeared after case-
control matching because the matched group was 
selected based on neoadjuvant chemotherapy, the 
extent of liver resection and the number of liver 
metastases. In the case-control matching-OSH 
group, 71% of patients had any grade of posthepa-
tectomy liver failure (Table 2), and one patient died 
of it. However, the reported rates of posthepatec-
tomy liver failure are from 2.6 to 16%.
5,25,27-28
 This 
wide range may also be due to several definitions 
of it.
31
 The most commonly used definitions were 
the following: peak bilirubin > 7 mg/dL
32
, the “50-
50” criteria (50% of normal for the prothrombin in-
dex and 50 µmol/L for bilirubin on postoperative 
day 5)
33
,
 
and the definition by the ISGLS used in 
this study.
14
The high rate of major morbidity (40% in the 
TSH group) reflects the burden of demanding two-
stage procedures. On the other hand, 4 (28.6%) pa-
tients suffered from major morbidity in the case-
control matching-OSH group, and the difference 
between these two groups was statistically insig-
nificant (P = 0.688). The 90-day mortality in our 
TSH group (13%) did not exceed the reported 15% 
(Table 4).
TSH aims to improve the survival of patients by 
resecting all tumoral tissue and enabling sufficient 
future liver remnant. Our last TSH was performed 
in 2016, a year before Torzilli et al. published re-
sults of enhanced OSH as a safe alternative to TSH 
for multiple bilateral deep-located colorectal liver 
metastases.
34
The prognosis was thought to depend on the 
size and number of colorectal liver metastases.
2
 
Whether the resection of colorectal liver metasta-
ses could achieve R0, survival was the same re-
gardless of the number of lesions.
2
 However, Fong 
et al. showed that the prognosis depends on the 
combination of survival factors, i.e., Clinical Risk 
Score.
9
There was no significant difference (P = 0.063) 
in the median OS between the OSH (35 months) 
and TSH groups (21 months). The rate of R0 re-
sections and the high Clinical Risk Score did not 
differ. After case-control matching, the OS in the 
case-control matching-OSH group was 23 months. 
However, the median OS in recent reports is long-
er (37–50 months) (Table 4).
Our study showed an insignificant difference 
in the 3-year RFS between the TSH group (13%) 
and the case-control matching-OSH group (14%). 
The 3-year RFS in our study was similar to that re-
ported by Narita et al. and Chavez et al., but much 
shorter than the 43% reported by Regimbeau et al. 
(Table 4).
5,22,25
Limitations of our study could explain these dif-
ferences in survival. First, this was a single-institu-
tion, retrospective study covering a wide period. 
We had a small group of patients who underwent 
TSH. Furthermore, the operative technique and 
use of portal vein embolization have changed over 
time; thus, it is difficult to apply this study to other 
modern scenarios. In addition, the interpretation 
of data and their comparison to other reports was 
difficult because the TSH group consisted of vari-
ous first-stage procedures.
To conclude, parenchyma-sparing surgery is a 
principle of liver surgery for colorectal liver me-
tastases. TSH used to be a safe and favourable 
therapeutic choice in a select population of pa-
tients because it could prevent posthepatectomy 
liver failure and enable good oncological results. 
Now, OSH should be preferred whenever feasible 
because it has lower morbidity and equivalent on-
cological outcomes as completed TSH.

Radiol Oncol 2023; 57(2): 270-278.
Turk S et al. / Two-stage hepatectomy in resection of colorectal liver metastases 278
Acknowledgements
The University Medical Centre Maribor funded 
this study but had no role in its design, practice, 
or analysis.
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