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Pasini et al. Hepatoma Res 2020;6:26 I http://dx.doi.org/10.20517/2394-5079.2019.47 Page 3 of 9

this topic, showing that repeat hepatectomy (RH) can be performed safely with complication rates
[24]
comparable to the first resection . Another issue is the risk of further recurrence, which is dependent on
the presence of multinodular cirrhosis in the remnant liver [25,26] .

Most case series of rHCC treated with RH are from Eastern Asia. Since none were randomized trials
and patients were selected for resection according to different clinical criteria and hospital policies,
[27]
comparison is difficult. Nagasue et al. first reported a small series of RH carried out in 9 of 31 patients
who experienced tumor recurrence after initial resection of primary HCC. They reported that the survival
rate of resected patients was significantly better than that of patients treated with palliative methods.
[28]
Hu et al. described a retrospective analysis of 59 patients who were treated with RH. 43 had a second
recurrence (median follow up 19 months) and survival at three years was 44%. Another paper from the
[29]
same institution compared RH to TACE for rHCC and advocated for aggressive surgical treatment after
recurrence in selected patients.

Larger series have since been published in the last 20 years, again mainly from Eastern institutions, with
[34]
5-year overall survival (OS) ranging from 30% to 60% [30-33] . In 2011, Roayaie et al. presented the first and
largest Western series of RH (n = 35), showing an overall 5-year survival rate of 67%. Only patients with a
single recurrent tumor on imaging, Child’s A liver disease and a platelet count > 100,000/ll underwent RH.

Several studies have been published in recent years and have established RH as safe in referral centers
[35]
[Table 1]. The largest Eastern series by Zou et al. reported 635 consecutive patients who received a second
resection for rHCC. The median OS was 54.8 months and the 1-, 3-, and 5-year OS rates were 96.9%,
74.8%, and 47.8%, respectively. Post-recurrence survival (i.e., calculated from the date of reoperation)
rates were 75.8%, 45.7% and 37.6%, respectively. In this large, single institution series, a perioperative
complication rate of 22.8% was reported with a median blood loss of 303 mL (range 100-5300). With regard
to postoperative complications, a systematic review by Chan et al. reported a median mortality rate of
[36]
0% (ranging from 0% to 6%) and a postoperative bleeding rate (with need for transfusions) of 1%. Other
postoperative complications (ascites, bile leak, liver failure) were in line with those reported in the literature
for patients without preoperative liver surgery.

ROLE OF MINIMALLY-INVASIVE SURGERY
The adoption of laparoscopic liver resection (LLR) has increased over the past decade. Laparoscopy for
HCC has been shown in studies to produce superior short-term and equivalent long-term outcomes
compared to the open approach. However, due to the formation of intra-abdominal adhesions, LLR for
rHCC after previous hepatic resection may represent a challenge. For this reason, there are only a few
studies reporting a laparoscopic approach to treat liver recurrence. However, this number is believed to
rise in the next few years since liver resection will increasingly be approached laparoscopically. A recent
meta-analysis showed that LLR for rHCC offered a benefit in terms of lower in-hospital complication rates,
blood loss and a shorter hospital stay compared to open resection, although similar 90-day mortality was
[45]
observed between the two groups . This could be partially explained by the fact that, unlike conventional
laparotomy, the laparoscopic approach does not require a wide surgical field, thus minimizing the freeing
of adhesions and consequently, bleeding as well as other intraoperative complications. Even the scoring
[46]
system for predicting complications in LLR proposed by Halls et al. showed that a previous open liver
resection was the strongest among all independent risk factors (β coefficient = 1.401) of having high blood
loss or conversion to an open approach during surgery. This finding should prompt us to at least consider
more patients for minimally-invasive surgery at the time of primary resection so as to increase the number
of eligible patients who may benefit from a RH in the event of of rHCC. LLR has been also demonstrated
to facilitate liver transplantation (LT) in terms of decreasing blood loss and transfusion requirements.