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Klinična študija / Clinical study
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2022; 15 (1): 41–53
Članek prispel / Received
4. 3. 2021
Članek sprejet / Accepted
18. 5. 2022
Abstract
Purpose: Colorectal cancer repre-
sents the third most frequently occur-
ring malignant disease worldwide that 
most often disseminates into the liver. 
The present report describes the treat-
ment possibilities and results of a sur-
gical approach to treat colorectal liver 
metastases (CLM). 
Methods: A retrospective review of a 
prospectively maintained database of 
patients who underwent surgical tre-
atment for CLM at the Clinical De-
partment of Abdominal and General 
Surgery of University Medical Centre 
Maribor in Slovenia was performed. 
The study was based on the intention-
-to-treat principle. All procedures, redo 
procedures, morbidity, and survival 
were analyzed.
Results: The study covered the 
period between January 2000 and 
Izvleček
Namen: Rak debelega črevesa in 
danke (RDČD) je v svetovnem merilu 
tretja najpogostejša maligna bolezen 
in najpogosteje zaseva v jetra. Namen 
raziskave je predstaviti možnosti ki-
rurškega zdravljenja jetrnih zasevkov 
in rezultate zdravljenja.
Metode: Opravili smo retrospektivni 
pregled prospektivno vodene datoteke 
resekcij jetrnih zasevkov RDČD na 
Kliničnem oddelku za abdominalno 
in splošno kirurgijo Univerzitetnega 
kliničnega centra Maribor. Raziskava 
temelji na principu pristopa k zdra-
vljenju z namenom ozdravitve. Ana-
lizirali smo število posegov, ponovne 
posege, zaplete in preživetje.
Rezultati: Od januarja 2000 do 
decembra 2020 je bilo izvedenih 631 
kirurških posegov zaradi jetrnih zasev-
kov RDČD. 352 (74,4 %) bolnikov je 
Ključne besede: 
rak debelega črevesa in danke, jetrni 
zasevki, hepatektomija, preživetje 
Key words: 
colorectal cancer, liver metastases, 
hepatectomy, survival
Dosežki kirurškega zdravljenja 
bolnikov z jetrnimi zasevki raka 
debelega črevesa in danke od 2000 do 2020
Achievements in surgical treatment for 
colorectal liver metastases from 2000 until 2020
Avtor / Author Irena Plahuta1, Tomislav Magdalenić1, Špela Turk1, Stojan Potrč1,2, 
Arpad Ivanecz1,2
Ustanova / Institute 1Univerzitetni klinični center Maribor, Klinika za kirurgijo, Klinični oddelek za abdominalno 
in splošno kirurgijo, Ljubljanska ulica 5, 2000 Maribor, Slovenija; 2Univerza v Mariboru, 
Medicinska fakulteta, Katedra za kirurgijo, Taborska ulica 8, Maribor, Slovenija;
1University Medical Centre Maribor, Division of Surgery, Clinical Department of Abdominal 
and General Surgery, Ljubljanska ulica 5, Maribor, Slovenia; 2University of Maribor, Faculty 
of Medicine, Department of Surgery, Taborska ulica 8, 2000 Maribor, Slovenia;
https://doi.org/10.18690/actabiomed.231, CC BY 4.0
© 2022 University of Maribor, University Press
42
INTRODUCTION
Colorectal cancer (CRC) currently represents the 
third most frequently occurring malignant disease 
affecting 1,800,000 people worldwide (1, 2). At the 
time of diagnosis, the disease is already metastasized 
in 15%–25% of patients (2). In addition, 25% of 
patients develop metachronous colorectal liver 
metastases. Liver is the most frequent site of distant 
dissemination (2). 
In recent decades, a significant improvement in the 
survival of patients with colorectal liver metastases 
(CLM) has been achieved. In the 1990s, the reported 
two-year overall survival (OS) was just 21% (2). Then, 
advancements in systemic chemotherapy with better 
efficacy, improvements in surgical techniques, and 
enhancement in perioperative care have increased 
the number of patients treated for CLM and 
significantly contributed to better outcomes (2). 
Different risk scores have been developed for 
forecasting recurrence and survival (3, 4). The 5-year 
OS after CLM resection is 35%–40%, but can reach 
up to 60% in patients with favorable prognostic 
factors (2). Unfortunately, the disease recurs in 
40%–75% of patients, and in half of them it recurs 
in the liver (2).
The present report describes the evolution of 
treatment possibilities for CLM at a single tertiary 
referral center. It also presents treatment results for 
a surgical approach to CLM.
imelo en poseg in 121 (25,6 %) bolni-
kov več kot enega. Resekcij jeter je bilo 
541 (85,7 %), in sicer 389 manjših 
in 152 velikih resekcij. Radiofrekvenč-
no ablacijo smo opravili v 61 (9,7 %) 
in eksploracijo v 29 (4,6 %) primerih. 
Ponovnih posegov je bilo 138 (21,9 
%). Hudi zapleti (stopnja ≥ 3a po kla-
sifikaciji Clavien-Dindo) so se pojavili 
po 84 (13,3 %) posegih. 90-dnevna 
pooperativna smrtnost je znašala 3,8 
%. Mediano preživetje pri seštevku 0 
v Clinical Risk Score je 69 mesecev; 
5- in 10-letni preživetji sta 57-% ozi-
roma 38-%.
Zaklju~ek: Kirurška odstranitev 
jetrnih zasevkov v celoti in ugodni 
prognostični dejavniki omogočajo 
dolgoročno preživetje bolnikov z jetrni-
mi zasevki RDČD.
December 2020, during which 631 
surgical liver procedures were perfor-
med. A total of 352 (74.4%) patients 
underwent a single procedure, and 
121 (25.6%) patients had more than 
one procedure. The largest portion of 
surgeries consisted of 541 (85.7%) 
liver resections (389 minor and 152 
major). Radiofrequency ablation was 
performed in 61 (9.7%) cases and 
exploration in 29 (4.6%) cases. There 
were 138 (21.9%) redo procedures. A 
major morbidity (Clavien-Dindo grade 
≥ 3a) was present in 84 (13.3%) ca-
ses. The 90-day mortality was 3.8%. 
In cases with a clinical risk score of 
0, the median survival time was 69 
months and 5- and 10-year overall sur-
vival was 57% and 38%, respectively. 
Conclusion: The complete surgical 
removal of metastases accompanied 
by favorable prognostic factors offers 
long-term survival in CLM patients.
Naslov za dopisovanje /  
Correspondence
Arpad Ivanecz, Univerzitetni klinični 
center Maribor, Klinika za kirurgijo, 
Klinični oddelek za abdominalno in 
splošno kirurgijo, Ljubljanska ulica 5, 
2000 Maribor, Slovenija.
Telefon: +386 41 962 402
E-pošta: arpad.ivanecz@ukc-mb.si
Klinična študija / Clinical study
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2022; 15 (1): 41–53
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PATIENTS AND METHODS
Patients
A retrospective review of a prospectively obtained 
database of patients who underwent surgical treatment 
for CLM at the Clinical Department of Abdominal 
and General Surgery of the University Medical Centre 
Maribor in Slovenia was performed. This department 
is a specialized referral center for hepato-pancreato-
biliary surgeries.
The study covered the period between January 1, 2000 
and December 31, 2020. The study was based on the 
intention-to-treat principle. At the time of their surgery, 
the patients consented that their anonymized data 
could be used for research purposes. 
The patient records were anonymized and de-identified 
before the analysis. The ethical approval for the study 
was obtained from the institutional review board.
Diagnostic and therapeutic workup and follow-up protocol 
Available characteristics were obtained from the database 
and analyzed after the patients underwent a routine 
diagnostic workup, which included a colonoscopy, 
blood work, thoracic computed tomography (CT), 
and abdominal CT with contrast enhancement. If 
any uncertainties were present, liver-specific contrast 
magnetic resonance imaging was performed to identify 
liver lesions. A positron emission tomography (PET) 
scan was performed when dissemination of the disease 
was suspected (5). 
The patients were presented at a multidisciplinary team 
meeting (2). Those with metastases confined to the 
liver were considered for liver resection, radiofrequency 
ablation (RFA), or a combination of both. 
The most frequently utilized chemotherapy 
schemes were fluorouracil, leucovorin, and 
oxaliplatin; fluorouracil, leucovorin, and irinotecan; 
capecitabine plus oxaliplatin; and capecitabine plus 
irinotecan. These treatment regimens have recently 
been supplemented with biological agents, such 
as bevacizumab. The Rat sarcoma virus gene and 
B-Rapidly accelerated fibrosarcoma gene status was 
crucial in deciding whether cetuximab therapy would 
be useful (2). Neoadjuvant chemotherapy was used 
as a downsizing strategy to transform unresectable 
CLM into resectable cancer (2).
The follow-up protocol consisted of a carcinoembryonic 
antigen (CEA) evaluation, chest radiograph or CT, 
abdominal ultrasound, or magnetic resonance imaging 
every three months for the first two years and every six 
months afterwards.
Perioperative considerations and definitions
The preoperative liver function was assessed according 
to the Child-Pugh classification (6). In addition, the 
future liver remnant (FLR) was considered when 
establishing the indications for liver resection. At least 
25%–40% of metastasis-free liver parenchyma had to be 
preserved (5). The CT volumetric analysis was routinely 
utilized when major liver surgery was planned (2).
When the analysis suggested an insufficient FLR, 
portal vein embolization (PVE), intraoperative 
selective portal vein ligation, or the associating liver 
partition and portal vein ligation (ALPPS) procedure 
was performed (2, 5). A PVE was followed by atrophy 
of the embolized hemiliver and hypertrophy of the 
other hemiliver (5). The two-stage hepatectomy (TSH) 
was conducted when intraoperative findings were 
unfavorable (7). In the first stage, the metastasectomy 
of one hemiliver was performed along with the 
portal vein ligation for the other hemiliver (7). The 
effect was similar to that of the preoperative PVE 
(8). The second stage followed a few weeks later and 
usually consisted of a major hepatectomy (2, 7). The 
ALPPS was performed with the same rationale; the 
difference was the liver parenchyma's transection in 
the first stage (9, 10).
Local ablation methods were applied when the radical 
liver resection was not feasible due to the proximity of 
large vessels (2). RFA was utilized in two ways: the first was 
percutaneous, which has been used as an independent 
procedure, and the second was an intraoperative RFA, 
which was an open and independent procedure or an 
adjunct to liver resection (2). 
The previously established liver anatomy and resection 
terminology were used (11). Hepatectomies were 
classified as major when at least three adjacent liver 
segments were removed. Otherwise, they were defined 
as minor (11). A histopathological examination 
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confirmed the final diagnosis. The R0 resection was 
defined by clear microscopic margins in the case of liver 
resection (2). Liver resections where a histopathologic 
examination revealed a tumoral infiltration of surgical 
margins were defined as R1 (2).
Outcome
The 90-day postoperative morbidity and mortality 
were graded according to the Clavien-Dindo 
classification (12). 
The 5- and 10-year OS was calculated from the first 
diagnosis of CLM until death or until the last follow-
up visit. Recurrence-free survival (RFS) was calculated 
from the date of first therapy for CLM until the 
first radiologic proof of disease recurrence. Hepatic 
recurrence-free survival (HRFS) was calculated from 
the date of the first therapy for CLM until the first 
radiologic proof of disease recurrence in the liver.
The clinical risk score (CRS) by Fong et al. (13) 
was utilized for prognostication. Its parameters 
(infiltrated lymph nodes in CRC, number of CLMs 
> 1, CLM size ≥ 5 cm, CLM appearance in less than 
one year, and CEA) were calculated for every case. 
The lowest score was 0, and the highest was 5 (13).
Statistical analysis
The IBM SPSS for Windows Version 26.0 (IBM 
Corp., Armonk, NY, USA) was used for the statistical 
analysis. Descriptive statistical methods were used. 
Categorical variables were expressed as frequencies 
(percentages). Continuous variables were expressed 
as medians (minimum-maximum, interquartile 
range (IQR)). The survival tables with the Wilcoxon 
test were utilized for the survival analysis.
RESULTS  
A total of 631 liver procedures were performed in 473 
patients. Of these, 315 (66.6%) were men and 158 
(33.4%) were women. At the first CLM diagnosis, 
the patients’ median age was 65.5 years (27–85, IQR 
15). At the end of the study, 358 (75.7%) patients 
were dead, of which 311 (65.8%) died of the disease, 
115 (24.3%) patients were alive, 83 (17.5%) patients 
had no evidence of the disease, and 32 (6.7%) 
patients were alive with disease. The median follow-
up duration was 34 months (0–230, IQR 44). 
Characteristics of primary CRC
The primary CRC tumor developed in the right 
colon in 85 (17.9%) patients. A total of 187 (39.5%) 
patients had CRC in the left colon. Rectal cancer 
developed in 188 (39.7%) patients. Thirteen (2.7%) 
patients had multiple primary CRCs. Regional 
lymph node metastases were present in 303 (64.1%) 
patients. According to the tumor-node-metastasis 
classification, 14 (3.0%), 93 (19.7%), 143 (30.2%), 
and 223 (47.1%) patients were classified as stage I, 
II, III, and IV, respectively (14).
Characteristics of colorectal liver metastases
Among 631 liver procedures, unilateral CLM was 
present in 344 (54.5%) patients and bilateral CLM in 
287 (45.5%) patients. The median CLM number was 
2 (1–20, IQR 3). The median diameter of the largest 
CLM was 3.6 cm (0.2–25.0, IQR 2.5). The median 
CEA value was 12.7 mcg/L (0.30–4237.0, IQR 44.28).
Synchronous CLM was present in 223 (47.1%) 
patients. Three therapeutic strategies were utilized 
for these cases: the liver-first strategy in 13 (5.9%) 
patients, simultaneous resection of CRC and CLM 
in 97 (43.5%) patients, and colorectal-first strategy in 
113 (50.6%) patients (15, 16).
A total of 250 (52.9%) patients had metachronous 
CLM, and the median time from the operation of 
primary CRC until the detection of CLM was 18 
months (6–160, IQR 16). Extrahepatic malignant 
disease was present in 124 (19.7%) cases.
Surgical treatment and postoperative course
Of the 473 patients, 352 (74.4%) underwent a 
single procedure, and 121 (25.6%) had more than 
one procedure. Overall, 95 (20.0%), 19 (4%), five 
(1.1%), one (0.2%), and one (0.2%) patient had two, 
three, four, five, and six procedures, respectively. 
Neoadjuvant chemotherapy was administered in 
304 (48.2%) and adjuvant chemotherapy in 432 
(68.4%) CLM cases. The diversity of 631 surgical 
procedures for CLM is shown in Table 1. There were 
138 (21.9%) redo procedures. PVE was performed 
in 23 (3.6%) cases. Ligation of the right portal 
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Table 1. Summary of 631 surgical procedures for colorectal liver metastasis
Surgical procedure N of procedures % Surgical procedure N of procedures %
One-stage liver procedures–
first procedure 454 71.9
One-stage liver 
procedures–redo 
procedure
138 21.9
First hepatectomy 383 60.7 Second hepatectomy 75 11.9
Open RFA 27 4.3 Open RFA 17 2.7
Hepatectomy and RFA 21 3.3 Percutaneous RFA 17 2.7
Exploration 18 2.9 Exploration 11 1.7
Percutaneous RFA 5 0.8 Third hepatectomy 8 1.3
TSH 39 6.2 Hepatectomy and RFA 8 1.3
First stage 22 3.6
Fourth hepatectomy 2 0.3
Second stage 17 2.6
RFA – radiofrequency ablation, TSH – two-stage hepatectomy
vein was necessary in 19 (3.0%) cases, and ALPPS 
was attempted in three patients. Five patients did 
not proceed to the second stage due to the disease 
progression.
When evaluating surgical procedures, explorations 
accounted for 4.6% (29 cases) and RFA for 9.7% 
(61 cases) of all surgeries. The largest portion of the 
procedures consisted of 541 (85.7%) liver resections 
(Table 2). An R0 resection was performed in 430 
(79.4%) cases. There were a total of 93 (17.1%) 
re-resections. Since 2017, 74 patients underwent 
a liver resection for CLM, which were performed 
laparoscopically in 35 (47.3%) patients (17-19).
The morbidity and mortality rates are shown 
in Table 3. The cause of death was multi-organ 
failure in ten (1.6%), sepsis in six (1.0%), cardio-
respiratory failure in three (0.5%), pulmonary 
embolism in three (0.5%), and liver failure in two 
(0.3%) patients. The median hospital stay was nine 
(1–162, IQR 6) days. 
Survival analysis
The 5- and 10-year OS in patients treated with a 
different surgical method is shown in Table 4. The 
difference between groups was statistically significant 
(Wilcoxon test, P < 0.001). The 5- and 10-year OS 
based on the CRS is represented in Table 5. The 5- 
and 10-year RFS and HRFS in patients based on the 
CRS are shown in Table 6. Finally, an overview of 
morbidity, mortality, and survival from other centers 
is demonstrated in Table 7.
DISCUSSION 
Thirty years ago, the primary objective of stage IV 
CRC treatment was palliative care, and the patients' 
OS was poor. Understanding tumor biology, the 
arrival of effective systemic chemotherapy treatment, 
and extension of the frontiers of surgical indications 
have transformed CLM management and improved 
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Table 2. Minor and major liver resections, their frequency, and percentages in 631 procedures
Minor resections N=389 61.6% Major resections N=152 23.0%
ALPPS – first stage 3 0.5 Trisegmentectomy 14 2.2
Metastasectomy 136 21.6
Trisegmentectomy and 
metastasectomy
6 1.0
79 12.5Right hemihepatectomy
Segmentectomy 75 11.9 Extended right hepatectomy 8 1.3
Segmentectomy and 
metastasectomy 22 3.5 Left hemihepatectomy 29 4.6
Bisegmentectomy 73 11.6 Extended left hepatectomy 4 0.6
Bisegmentectomy and 
metastasectomy 46 7.3 Central resection 6 1.0
Minor resection and RFA 34 5.4 Major resection and RFA 6 1.1
ALPPS – associating liver partition and portal vein ligation; RFA – radiofrequency ablation 
the OS since then (2). Nevertheless, improvements in 
diagnostics highly impacted the patients’ selection. 
The PET scanner has been available in Slovenia 
since 2002 in Splošna bolnišnica Maribor (20). Four 
years later, the Institute of Oncology Ljubljana was 
supplied with a PET-CT machine, which started 
operating in September 2007 (21). Since 2017, a 
PET-CT apparatus has also been available in the 
University Medical Centre Maribor (20).
Metastases develop after dissociation of the tumoral 
cells from the primary CRC tumor and their entrance 
into lymph vessels and portal circulation (2). CRCs 
arising in the middle or lower rectal third have 
venous outflow into the inferior vena cava, which 
promotes systemic spreading (22). In the present 
cohort, 17.9% of patients had the primary CRC in 
the right colon and 39.5% in the left colon. Rectal 
cancer developed in 39.7% of patients. In the study 
by McCracken et al., 37% of primary CRCs were 
in the right colon, 36% in the left colon, and 27% 
in the rectum (23). The prognosis of the right-sided 
CRC was worse (23, 24).
Furthermore, the target tissue microenvironment 
and the circulating tumor cell organotropism also 
define the metastatic site (25, 26). Micro-RNAs 
are short RNA molecules compatible with parts 
of mRNA. Micro-RNAs specifically bind to these 
mRNA portions and diminish the transcription 
into proteins. This alters the metabolism in the 
target organ. For example, CLM patients have a 
low expression of miR-31-5p, whereas it is high in 
peritoneal carcinomatosis of CRC (25). This can 
explain why CRC metastases in certain patients 
develop only in the liver. Therefore, re-resections or/
and RFA were performed in 20.2% of our patients. 
The reported rates of liver re-resections are 38% by 
Engstrand et al. (27) and 36.6% by Vigano et al. (28), 
whereas the present study rate is 17.1%.
When performing a liver resection for CLM, the 
principle is to be “radical but conservative”, that 
is, radical in oncological terms and conservative in 
preserving non-tumoral liver parenchyma (29). This 
principle is reflected in the present results because 
61.1% of all procedures were minor liver resections. 
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Similarly, Gasser et al. (24) have reported 69% as a 
rate of minor resections.
A two-stage procedure was carried out when an 
extended hepatectomy was indicated, and the 
volumetric analysis suggested an insufficient FLR 
(2). Enhancement of liver hypertrophy via portal 
vein ligation were first described by Cantlie et al. in 
1897 and Rous et al. in 1920, and then developed by 
Honjo et al. in 1975 (2, 30, 31). PVE was introduced 
in the late 1980s by Kinoshita et al. (32) and Makuuci 
et al. (2, 33). In 2002, Broering et al. have compared 
both methods (8) and found that PVE results in a 
significantly more efficient increase in liver volume 
and shorter hospital stay. Adam et al. (7) have 
proposed a two-stage hepatectomy in 2000. Our first 
two-stage hepatectomy for CLM was performed in 
2006. ALPPS was introduced in 2012 (9), and our 
first procedure for CLM was carried out in 2016. 
The first guidelines for laparoscopic liver resection 
(LLR) were published in 2008 (34), which was also 
when the University Medical Centre Maribor in 
Slovenia first began performing the procedure. The 
first LLR for CLM was carried out in 2012 (15). The 
first treatment results for 12 patients were presented 
in 2017 (15). Our first propensity score matching 
study of simultaneous resection of CLM and primary 
tumors in 20 patients was published in 2018 (16) 
and was internationally acknowledged (35-37). Since 
2017, 74 patients underwent liver resection for 
CLM, which was performed laparoscopically in 35 
(47.3%) patients (17-19).
Severe morbidity in liver surgery occurs due to 
bleeding, bile leakage, or liver insufficiency (24). 
Anastomotic dehiscence was the major cause of severe 
morbidity when a simultaneous colorectal resection 
was performed (24). The severe morbidity and 
mortality rates were 13.3% and 3.8%, respectively, 
which are comparable to rates at other high-volume 
centers (Table 7).
Finally, the advancements in systemic therapy, surgical 
technique, and perioperative care contributed to the 
5-year OS reaching 35%–40% (2). The 5- and 10-year 
OS values for different surgical treatment modalities 
are represented in Table 4. Furthermore, survival rates 
were up to 60% (2, 13, 38) when the most favorable 
prognostic factors were considered (CRS 0), which 
Table 3. Morbidity and mortality after 631 surgical proce-
dures for colorectal liver metastases
Morbidity grades N %
Without morbidity 375 59.4
CD 1 – any deviation from normal 
postoperative course 4 0.6
CD 2 – mild deviations requiring 
antibiotics, blood transfusion, or 
parenteral nutrition
144 22.8
Major morbidity 84 13.3
CD 3a – intervention without general 
anesthesia 43 6.8
CD 3b – intervention under general 
anesthesia 27 4.3
CD 4a – single-organ dysfunction 4 0.6
CD 4b – multi-organ dysfunction 10 1.6
CD 5 – mortality 24 3.8
Grading according to the Clavien-Dindo classification (12)
Table 4. Five- and 10-year overall survival in patients with 
colorectal liver metastases treated with different surgical methods
N of 
patients
Median 
survival 
time 
(months)
5-year OS
(%)
10-year 
OS
(%)
Liver resection 
R0 334 41 33 10
Percutaneous 
RFA 5 30 20 NR
Open RFA 20 24 15 15
Liver resection 
R1 49 27 10 NR
Liver resection 
and RFA 20 21 5 NR
Liver resection 
R2 3 21 NR NR
Exploration 
only – no liver 
resection
19 17 NR NR
RFA – radiofrequency ablation; NR – not reached; OS – 
overall survival.
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Table 5. Five- and 10-year overall survival and clinical risk score (13)
Surgical procedure N of patients CRS Median survival (months)
5-year OS 
(%)
10-year OS 
(%)
Liver resection R0
21 0 69 57 38
67 1 56 46 19
107 2 43 31 7
80 3 35 28 5
23 4 33 22 9
2 5 24 NR NR
Liver resection R1
1 0 42 NR NR
2 1 96 50 NR
12 2 30 NR NR
17 3 35 24 NR
6 4 20 NR NR
2 5 18 NR NR
Open RFA
8 2 36 38 38
2 3 36 NR NR
4 4 24 NR NR
Percutaneous RFA
1 0 66 100 NR
2 2 24 NR NR
Liver resection and RFA
3 2 27 NR NR
7 3 22 NR NR
4 4 20 NR NR
1 5 18 NR NR
CRS – clinical risk score; RFA – radiofrequency ablation; NR – not reached; OS – overall survival
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Table 6. Five-year and 10-year recurrence-free and hepatic recurrence-free survival and CRS (13)
Surgical procedure N of patients CRS
Median
recurrence-free 
interval (months)
5-year
RFS
10-year
RFS
Median hepatic
recurrence-
free interval 
(months)
5-year
HRFS
10-year
HRFS
Liver resection R0
21 0 54 43 38 57 48 38
67 1 34 31 13 41 34 13
107 2 23 18 7 29 20 7
80 3 21 13 3 21 14 3
23 4 16 17 9 18 17 9
2 5 12 NR NR 12 NR NR
Liver resection R1
1 0 42 NR NR 42 NR NR
12 2 17 NR NR 19 NR NR
17 3 16 NR NR 17 NR NR
6 4 16 NR NR 16 NR NR
Open RFA
8 2 24 25 25 24 38 38
2 3 12 NR NR 12 NR NR
Liver resection and RFA
3 2 15 NR NR 15 NR NR
7 3 11 NR NR 11 NR NR
4 4 20 NR NR 20 NR NR
1 5 18 NR NR 18 NR NR
CRS – clinical risk score; HRFS – hepatic recurrence-free survival; RFA – radiofrequency ablation; NR – not reached; RFS 
– recurrence-free survival.
was reflected in the present results (Tables 5, 6). For 
patients whose CRS was 0, the median survival time 
was 69 months or 5.75 years, while the 5- and 10-year 
OS was 57% and 38%, respectively. Median survival 
time was 3.9 years for the delayed resection group 
and 5.9 years for the simultaneous resection group in 
the study by the METASYNC study group in France 
(39). The median survival time was 4.9 years at the 
Memorial Sloan Kettering Cancer Center in New 
York (40). The 5-year OS in the OSLO-COMET trial 
in Norway was 54% in the laparoscopic group and 
55% in the open resection group (41). The 10-year 
OS in the Memorial Sloan Kettering Cancer Center 
was 24% (40). More data on OS, RFS, and survival 
intervals from these centers are presented in Table 7.
In conclusion, redo procedures are important for the 
treatment of CLM. Morbidity and mortality rates are 
comparable among high-volume centers specialized 
in liver surgery worldwide. The R0 resection 
accompanied by favorable prognostic factors offers 
long-term survival in patients with CLM.
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Table 7. Overview of reported morbidity, mortality, and survival analysis in selected centers
Authors, year Study period, N of patients Subgroups Morbidity Mortality Survival analysis
MEMORIAL SLOAN KETTERING CANCER CENTER, NEW YORK, USA
Kingham et al. (42), 2015 1993–2012
1993–1999 53% 5%
Not researched2000–2006 34% 2.3%
2007– 2012 20% 1.6%
Creasy et al. (40), 2018 1992–20041211 Not researched.
10-year OS: 24%
Med. survival: 4.9 y
10-year RFS: 20%
METASYNC STUDY GROUP, FRANCE
Boudjema et al. (39), 2021 2006–2015
simultaneous 
resection
Overall 49%,
Colorectal 28%,
liver 15%.
7.4% Med. OS: 5.9 yMed. DFS 1.3 y
delayed resection
Overall 46%,
colorectal 13%, 
liver 17%.
3.2% Med. OS: 3.9 yMed. DFS: 1.0 y
OSLO-COMET TRIAL, NORWAY
Fretland et al. (43), 2018; 
Aghayan et al. (41), 2021 2012–2016
laparoscopic group 19% 0% 5-y OS: 54%5-y RFS: 30%
open group 31% 0.7% 5-y OS: 55%5-y RFS: 36%
THE UNIVERSITY OF TEXAS MD ANDERSON CANCER CENTRE, HOUSTON, TEXAS, USA
Lillemoe et al. (44), 2018 2003–2016137 23%, at either stage of TSH Not reported.
Med. RFS after 
TSH was 12 
months.
Med. OS in 
recurrence:
resection: 143 
months,
no resection: 49 
months.
DSF – disease-free survival; Med. – median; OS – overall survival; OSLO-COMET – Oslo Randomized Laparoscopic Versus 
Open Liver Resection for Colorectal Metastases Trial; RFS – recurrence-free survival; TSH – two-stage hepatectomy; UK – 
United Kingdom; USA – United States of America; y – year
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