Ex-situ hepatectomy: Indications, Techniques
and Results
Danilo Coco MD1 and Silvana Leanza MD2
1Department of General Surgery, Ospedali Riuniti Marche Nord, Pesaro (Italy)
ISSN: 0000-0000
https://orcid.org/0000-0002-5839-1767 Danilo Coco Author
Published 00 11 0000
2Department of General Surgery, Carlo Urbani Hospital, Jesi (Ancona) (Italy)
https://orcid.org/0000-0001-8672-7486 Silvana Leanza Co-Author
O R I G I NA L
Abstract
Background: Ex-situ hepatectomy is a novel approach, used in treating complicated liver tu-
mours, which are otherwise unresectable via conventional methods including organ perfusion,
liver transplant, hemodynamic management, vascular reconstruction or even extended hepatic
resection.
Aim of the study: We conducted a literature review of studies reporting Ex vivo liver resection
and autotransplantation (EVLRAT) to investigate the outcomes of this method.
Methods: We have retrospectively evaluated PUBMED databases. Studies were evaluated from
2000 to 2020. Only very few studies analyzed an “Ex vivo liver resection”.
Results: Studies demonstrated Ex vivo liver resection and autotransplantation ( EVLRAT )is a
feasible but very complex technique. It can apply to a few patients with unresectable hepatic
tumours fit for surgery. Conclusion: At present, the future use of Ex situ hepatectomy is a
technique used in patients with conventionally unresectable liver tumours to achieve a radical
(R0) resection in difficult cases.
Keywords : Ex-situ hepatectomy, Liver Resection, Liver Transplantation, Ex vivo liver resection
and autotransplantation (EVLRAT)
Introduction
Patients who suffer from liver malignancies such as liver and intrahepatic bile duct cancers as well
as hepatic metastases, often have a median survival time of less than a year without receiving
the appropriate medical attention. The main approaches which have been used in addressing
the commonly occurring tumours are Liver resection, liver transplantation as well as the use of
chemotherapy (1) .
The vast majority of such disorders can be treated with resection, which ensures long-term
survival. Regrettably, not all patients are candidates for resection using traditional methods such
as parenchyma sparing or right/left hepatectomy or Two-Stage Hepatectomy(TSH) or associating
OPEN ACCESS
liver partition and portal vein ligation for staged hepatectomy (ALPPS procedure). Nonetheless,
Edited by
some tumours prove difficult to treat through conventional tumour treatment techniques. The
A.Hussain
traditional techniques limit liver tumour treatment due to wanting intraoperative, limitation of the
Submitted 27 Oct 2021
various indication standards as well as other complicated aspects. Selected cases of conventionally
Accepted 16 Nov 2021
unresectable liver tumours might be treated with alternative innovative options in hepatobiliary
and transplantation surgery performed in recent decades. Ex Situ hepatectomy was developed in
Citation
Danilo Coco , Silvana Leanza
light of the above challenges, to increase the success of the operation of otherwise difficult liver
. Ex-situ hepatectomy:
tumour surgeries. The core indicators for undertaking Ex-situ hepatectomy are liver tumours that
Indications, Techniques and
are unresectable or are not amenable to resection through conventional surgical techniques, which
Results
would otherwise pose a danger given the proximity of venous confluence or the interference of
.BJOSS.2021(1):1;20-26
the hepatic veins. Ex vivo liver resection and autotransplantation (EVLRAT) is a procedure that
involves a total hepatectomy, extracorporeal liver resection, and autologous transplantation of
the remnant hepatic parenchyma (2). Nonetheless, the high morbidity as well as the mortality
rates limit the application of the above technique, despite numerous efforts, forwarded towards
improving the above approach. As such, several surgeons have advanced significant skills, required
for the technique, such as venovenous bypass, reimplantation as well as revascularization (3). The
above procedures are regarded as some of the most complicated and high-risk approaches to
surgeries conducted on humans. We conducted a literature review of studies reporting EVLRAT
to investigate the outcomes of this method.
Methods
We searched (last updated on October 2021) PubMed, Embase, Scopus, and Web of Science
databases for eligible studies. Peer-reviewed each query, dates of searches, their results, and
other relevant details are reported. Studies were evaluated from 2000 to 2020. Only very few
studies analyzed an “Ex vivo liver resection”. Two independent research DC and SL performed
the review. The search terms were identified with the medical subject heading (MeSH).
2.1 Inclusion criteria
Research inclusion criteria were ”Ex vivo liver resection ”,” Ex situ liver resection”, “extracorpo-
real liver resection”, “liver autotransplantation”. The outcomes were complete were indications,
operative time, blood loss, morbidity, and mortality.
2.2 Exclusion criteria
Unpublished data, book chapters, or conference abstracts and non-English manuscripts were
excluded. No dates of coverage restrictions were applied After rejecting review articles and
repetitive reports, the relevant literature included 9 manuscripts.
Results
(4) analyzed fifty-three studies with a total of 244 patients through a Meta-analysis. The study
revealed R0 resection rate was achieved in 93% of cases with major surgical complications of
25%, 30-day mortality of 10%, the 90-day mortality rate was 12% for malignant tumours versus
8% in benign tumours and 1-year survival of 79%.In particular postoperative 1-year survival was
65% for malignant tumours and 90% for benign tumours. (5) describe EVLRAT in 43 patients
suffering from Hepato Carcinoma and Cholangiocarcinoma (HCC/CCC). They demonstrated some
notes: duration operative time 8 hours, blood loss about 1500 cc, anhepatic time high of 250
minutes, the mortality rate of 20% 9/43 patients.
(6)analyzed 69 cases of EVLRAT for echinococcosis demonstrated similar operative time and blood
loss but a better 30 day and 90-day mortality respectively of 7% and 11% and 1-year survival rate
of 87% of patients, showing a better prognosis and utility of this technique for non-malignant liver
tumours. Applying EVLRAT for alveolar Echinococcosis, (7) noted that the survival rate in the group
of autotransplantation was greater than those who underwent allotransplantation. (8) applied the
ex-situ technique repair in a patient with severe liver trauma in such an emergency. (9; 10; 11)used
a temporary portacaval shunt avoiding an extracorporeal veno-venous bypass. (12) described the
resection of a huge HCC of 18 cm involved IVC and RHC in a young patient. (13) described 22 cases
of EVLRAT 22 colorectal metastases (n = 9), leiomyosarcoma (n = 3), hepatocellular carcinoma (n
= 2), cholangiocellular carcinoma (n = 2), Klatskin tumors (n = 4), focal nodular hyperplasia (n =
2) with in-mortality rate of 6/22. (14) EVLRAT for 4 cases of colorectal metastases with1/4 in
mortality while (15; 16) demonstrated no mortality after EVLRAT after hilar cholangiocarcinoma
resections. (17) published a case of resection of hemangiomas with no mortality.
(18) in their literature review of 388 cases, demonstrated Ex vivo liver resection and autotrans-
plantation ( EVLRAT )is a feasible but very complex technique. It can apply in a few patients with
unresectable hepatic tumour fit for surgery, benign tumour or malignant low-grade tumour with
21/26
long term survival with R0 resection about 60%-90% but outcomes are less satisfactory due to
high complications rate of about 25% and low survival in 3 years. EVLRAT may offer a last resort
when a conventional technique is not applicable.
Discussion
Ex-situ hepatectomy is a novel approach, used in treating complicated liver tumours, which are
otherwise unresectable via conventional methods including organ perfusion, liver transplant,
hemodynamic management, vascular reconstruction or even extended hepatic resection The
Ex-situ hepatectomy technique denotes the entire removal of the liver, which is then perfused in
a cold preservation solution, which allows the surgeon to remove tumours, which were otherwise
unreachable when the liver is situated in the body. In so doing, the tumour is restricted ex-situ on
the surgeon stable, while the remaining liver is implanted orthotopically. Notably, the works on
Ex-situ hepatectomy techniques are credited to (19) , who proposed the surgical approach in the
treatment of bilateral liver leiomyosarcoma.
The technique has been described in many patients with various types of liver tumours including
hepatocellular carcinoma [HCC], cholangiocarcinoma [CCC], and colorectal cancer metastases
[CRM]) as well as nonmalignant lesions including hepatic alveolar echinococcosis, focal nodular
hyperplasia (FNH), and hemangioma. More to that, there are only a handful of successful Ex-situ
hepatectomy cases which have been recorded on a global scale, given the complexity of the
operation. Currently, there is no established report on the utilization of Ex situ hepatectomy as an
alternative approach. The Ex-situ hepatectomy approach bears several advantages in comparison
to the orthodox approaches, such as liver transplants. Some of the advantages include: reduced
blood loss, optimal access to all sites of the liver, but some disadvantages include: a prolonged
period for dissection as well as vascular reconstruction (20).
More to that, it reduces the redundancy associated with the shortage of liver donors, in the
case of a transplant. On the other hand, (19) warns that the patients selected for the process
have to meet a specified minimum criterion, given that the procedure cannot accommodate
persons suffering from particular conditions. The selection of the patients, therefore, comes
about as one of the most vital measures to achieving the success of the surgery. In developing the
Ex-situ hepatectomy technique, various scholars such as (21) , have refined the technical details
associated with the procedures and further developed the ante situm technique, regarding liver
resection in a bid to increase the safety standards of the operation. Markedly, the ante situm
technique is similar to the ex-situ procedures, but involves the training of the vital structure of
the liver hilum and the division of three hepatic veins or a section of the IVC, before the liver
is perfused with a cold preservative solution, via the portal vein. The ante situm approach is
better than the Ex-situ hepatectomy in that it does not call for biliary as well as hepatic arterial
anastomoses. The result is that it reduces the ischemia timeframe, as well as potential anastomotic
complications which arise from the same (8). However, the approach does not provide the proper
liver exposure as associated with the Ex-situ hepatectomy technique. In a longitudinal study
conducted by (14) , the median survival time for six patients who underwent ex-situ resection
was twenty-one months.
The study also indicated that one of the patients, who underwent an Ex-situ hepatectomy for HCC,
lived disease-free for a period of seven years, following the date of the surgery. Additional studies,
such as by (17)and (22), have found that Ex-situ hepatectomy operations have been curative
to some patients, who were diagnosed with unresectable tumours. The technical experience
required for Ex-situ hepatectomy is often gained from liver transplantation. However, some of the
technical challenges associated with the procedure will be addressed in future developments of
Ex situ hepatectomy. Furthermore, unlike other surgeries involving the liver, Ex-situ hepatectomy
is delicate and requires a sufficient investigation of technical details as well as potential indicators,
which may be used in guiding the surgeon, in terms of increasing the safety of the use of the
model.
22/26
4.0.1 Technical aspects of Ex situ hepatectomy
The Ex-situ hepatectomy technique, hordes its distinct set of technicalities, which are brought
about by the complexity of the procedure. For instance, the long period spent in the operation of
the procedure dictates the necessity to be able to maintain the stability of blood dynamics, as well
as avoid venous congestion which may occur due to the longer time spent at the operation table.
The use of bypass from the portal, left femoral veins, to the left axillary of the jugular vein, through
the use of heparin-coated shunts as well as the roller pump, is the most common technique to
provide the stability of blood and to prevent venous congestions (23) . Additional techniques to
avoid the adjuvant incision as well as other challenges associated with the conventional veno-
venous bypass, the IVC was replaced with artificial blood vessel, as well as temporary veno-venous
bypass, could be performed through liver removal via anatomization of the portal vein, as well as
the supra-and intrahepatic vena cava. Nonetheless, some situations did not require the application
of the veno-venous bypass, especially without the involvement of IVC (13; 24; 25; 26).
Table 1. Included Studies And The Outcomes
Authors Studies Type
Major
30-
1-year
R0
Anhep- Oper-
Hospit-
of
sur-
day
sur-
resec-
atic
ative
al stay
study
gical
mor-
vival
tion
phase
time
com-
tality
(min)
plica-
tions
Zawis- Fifty-
Meta-
50.0% 11.3% 65.0% 98.6% 314
16.0
34 [7-
towski three
analysis (ma-
(malig- (malig-
[102-
[6.4-
128]
et al. stud-
lignant) nant)
nant)
879]
31.0]
day
2020
ies
21.0% 6.3%
89.7%
min-
hours
(not-
(not
(not
utes
malig-
malig-
malig-
nat)
nat)
nat)
Cheng 43 pa- Retros- 6%-
9/43
NR
NR
250±45 8h
26.1±
F
et tients
pective 23%
min-
10.3
al.2018
utes
days
Aji et 69 pa- Retros- 10/69 7.24% 11.5% NR
360
15.9
34.5
al.2018 tients
pective pa-
(5/69)
(8/69)
(104–
(8–24)h (12–
tients
879)min
128)
days
Oldhafer 22 pa- Retros- 4/22
9/22
6/15
NR
5.6 +/- 17-
36.5
KJ. Et tients
pective pa-
pa-
pa-
1.1 h
19h
+/- 16
al.2000
tients
tients
tients
days
had
liver
failure
Coco
388
Review 25%
12%-
65%
60%-
250
8h
NR
et
pa-
20%
for
90%
min-
Leanza, tients
malig-
malig-
utes
2021
nant
nant
7%-
tu-
11%
mors
be-
and
nign
87%-
90%
for be-
nign
tu-
mors
23/26
4.0.2 Risk of bias and limitations
The field of research on EVLRAT lacks evidence-based data or studies of reliable statistical
significance of randomized controlled trials. Some limitations may result from the included studies’
low level of evidence due to a lack of high-quality research in this field. It is the last resort therapy
reserved for a small and selected group of patients who, after resection, maintain a preserved one
liver function and normal Future Liver Remanent (FLR). The results for patients with malignant
diseases appear to be lower than for benign diseases based on the results of studies showing a
higher relapse rate and prevalence of mortality at 30 days, 90 days and in hospital.
Conclusion
Liver resection has become a safe operation, and its mortality rate is now almost zero. During the
classic technique of right or left hepatectomy, studies demonstrated fewer complications rates
compared to EVLRAT: Post-Hepatectomy Liver Failure (PHLF) is the most serious complication
after liver resection. Renal failure is closely associated with PHLF. Studies stated that complications
such as ascites, surgical site infections, coagulation disorders have a percentage inferior to ERAT.
The incidence of BL is reported to be 4.0% to 17% and the overall morbidity rate of open liver
surgery has been reported to range from 4.1% to 47.7%. In conclusion, EVLRAT is a complex
procedure, applicable only in patients selected with unresectable liver tumours with normal
conventional techniques. It can reveal itself as a potentially curative radical treatment.
It is, however, the last resort therapy reserved for a small and selected group of patients who, after
resection, maintain a preserved one liver function and normal Future Liver Remnant (FLR). ERAT
allows the complete reduction of heat ischemia and allows resection of the tumour (s) in a bloodless
and total field without the pressure of time. Ex vivo liver resection and autotransplantation for
end stage hepatic alveolar echinococcosis seem to demonstrate an overall mortality rate of 12%
after a mean follow-up of 22 months. Although experience with the procedure evolves, some
controversies are still present. The studies show the proven fact of excellent efficacy in patients
suffering from echinococcosis. The results for patients with malignant diseases appear to be
lower than for benign diseases based on the results of studies showing a higher relapse rate and
prevalence of mortality at 30 days, 90 days and in hospital.
Conflicts Of Interest
All the aforementioned authors declare no competing commercial, personal, political, intellectual,
or religious conflicts of interest in relation to the present work. No grant or other financial support
has been received for the drawing up of the present paper.
Ethical Approval
All procedures were in accordance with the ethical standards of the Institutional and National
Research Committee and with the Helsinki Declaration and its later amendments or comparable
ethical standards.
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