**3. Robotic liver resection for HCC**

Robotic liver resection (RLR) has been incorporated into clinical practice with increasing frequency since 2003 when the first report of a robotic liver resection was published by Giulianotti et al. [41].

Robotic technology was developed to overcome the technical difficulties of laparoscopic surgery; precision of movement, three-dimensional vision, magnification of the operative field, motion scaling, tremor filtering, and seven degrees of movement mimicking the human hand provide steady and careful dissection as well as prompt and precise endosuturing in case of intraoperative bleeding. A major advantage of the robotic technology in liver surgery is the dissection of the hilum and the hepatocaval dissection in right hepatectomy [42] as well as the possibility of biliary reconstruction due to the microsuturing capacity of the robotic system [43].

factor for the development of postoperative decompensation [28, 29]. The benefits of LLR can be attributed to the preservation of the abdominal wall collateral circulation and the preservation of the round ligament which may contain significant collateral veins [18]. In a study by Tranchart et al., LLR had lower rates of liver decompensation, with the occurrence of postoperative liver failure and ascites ranging from 7 to 8% in LLR vs. 26–36% in OLR [30]. One study from Japan showed lower rates of morbidity, ascites formation, and shorter hospital stay following LLR with no difference in survival [31]. A recent meta-analysis presented intraoperative and postoperative outcomes of patients with known cirrhosis undergoing resection for HCC, comparing results for OLR and LLR [32]. This meta-analysis showed wider resection margins, reduced intraoperative blood loss and transfusion need, as well as reduced morbidity rates and shorter lengths of stay with the laparoscopic approach. Another study by Sotiropoulos et al. [33] mentioned the difference in results concerning cirrhotic patients that undergo LLR vs. OLR. The operative time was longer as anticipated, but the blood loss and morbidity had no statistical difference from the noncirrhotic group. The mortality rate was significantly lower in the cirrhotic subgroup when LLR was performed. Although patients with preserved liver function are the best candidates for LLR, cirrhotic patients benefit from LLR in terms of shorter hospital stay, complication rate, and long-term oncologic outcomes. Tumor recurrence after primary HCC has been shown to be 30–70% at 5 years, limiting the overall survival of these patients [34, 35]. Numerous studies have been published reporting the results of repeat laparoscopic liver resection (RLLR) in patients with recurrent HCC [36–38]. A recent systematic review by Machairas et al. demonstrates RLLR as a safe and promising approach for the treatment of recurrent HCC, with significant benefits in terms of

short-term outcomes with the oncologic adequacy not compromised [39].

about the survival probability of the LLR vs. the OLR groups.

**3. Robotic liver resection for HCC**

ary to difficult exposure.

80 Liver Cancer

Giulianotti et al. [41].

The conversion rate has decreased from 5–15% [9, 40] to 4%, indicative of the surgeons' growing experience, with the most common causes being bleeding and failure to progress second-

Overall, LLR can facilitate a safe and feasible approach to the surgical management of HCC. Major laparoscopic hepatectomy still remains a technically demanding procedure and should only be performed by highly experienced hepatobiliary surgeons with training in laparoscopic surgery. Longer follow-up periods are needed for more definite conclusions

Robotic liver resection (RLR) has been incorporated into clinical practice with increasing frequency since 2003 when the first report of a robotic liver resection was published by

Robotic technology was developed to overcome the technical difficulties of laparoscopic surgery; precision of movement, three-dimensional vision, magnification of the operative field, motion scaling, tremor filtering, and seven degrees of movement mimicking the human hand provide steady and careful dissection as well as prompt and precise endosuturing in case of All published liver resections were performed using the da Vinci Surgical System (Intuitive Surgical Inc., Sunnyvale, CA USA). The major disadvantage of robotic surgery is the high cost due to the longer operating time and the instruments required, in spite of the similar hospitalization costs [44]. The purchase and maintenance costs are significant, and that is the reason for the limited incorporation of the robotic system in many facilities.

A large series by Tsung et al. [45] compared RLR to LLR and with the exception of operative time, and they found no significant differences comparing operative and postoperative results of RLR and LLR. The R0 status did not change, and the oncologic margin was not compromised. It must be highlighted that using a minimally invasive technique, a greater percentage of minor and major hepatectomies was completed; 93% of RLRs were accomplished in a purely minimally invasive manner compared with 49.1% performed laparoscopically.

Chen et al. [46] compared RLR with OLR for HCC providing superior short-term outcomes for RLR (shorter length of stay and decreased need for patient-controlled analgesia) and similar long-term outcomes (DFS and OS) despite longer operative times for RLR. A substantial proportion of patients suffered from cirrhosis and half of patients underwent major hepatectomy. They reported a DFS in 1 year of 91.5% with the RLR, whereas DFS was 79.2%. Overall survival in 1 and 3 years did not differ between the two groups. The authors reported that the patients treated with RLR had significantly wider surgical margins compared with OLR. This matched comparison offers support for further RLR in patients with HCC, performed by experienced surgeons.

Another study by Lai et al. [47] presented the results of RLR vs. LLR for HCC. Robotic group had longer mean operating time (207.4 vs. 134.2 min). Both groups had similar blood loss (334.6 vs. 336 ml) and no difference in morbidity. Mortality rate was 0% in both groups. They reported a comparable 5-year DFS and 5-year OS between RLR and LLR (42 vs. 38% and 65 vs. 48%, respectively) in patients with HCC.

Salloum et al. [48] included 14 studies in their systematic review, with HCC comprising the majority of the malignant cases. Mortality was 0%, and overall morbidity ranged from 0 to 43.3%, results comparable to laparoscopy. The mean duration of LOS was similar in both techniques. There was no statistically significant difference between RLR and LLR concerning the surgical margins or R1 resections. No clear advantages of RLR over LLR were noted; therefore, it is difficult to establish the true indications for RLR. Nevertheless, RLR has the same advantages as LLR in terms of shorter LOS and postoperative return to normal activities. Also, it seems that the learning curve for RLR is shorter than that of LLR.

The most recent systematic review from Tsilimigras et al. [49] included 31 studies with HCC being the leading indication among malignancies, comparing RLR to LLR or OLR. Median operative time was 295.5 min, EBL was 224.5 ml, conversion rate was 5.9%, and complication rate was 17.6% in the RLR group. The complications were graded according to the Clavien-Dindo classification [50], with the most common complication being bile leak (2.9%). In minor resections, the complication rate was 14.8% compared with the major resections, where the complication rate was 17%. Most of the studies show no benefit of RLR over LLR concerning safety and feasibility and multicenter, and randomized, prospective trials are needed to validate the exact indications and benefits of RLR.

FLR, morbidity, mortality, and tumor progression [58]. This meta-analysis revealed that the difference in the mean percentile increase in the FLR between those two techniques was not statistically significant, with similar results in morbidity, mortality, and disease

Novel Techniques in the Surgical Management of Hepatocellular Carcinoma

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In 2000s, Adam et al. first described the two-staged hepatectomy for liver malignancies in which a single surgical procedure was not possible [59]. The primary reason for the failure of TSH is tumor progression between two stages or an insufficient hypertrophy in FLR after the

An innovative, accelerated two-staged technique utilizing PVL and in situ split (ISS) of hepatic parenchyma was first described in 2012 by Schnitzbauer et al. [60]. In the same year, De Santibanes et al. named this procedure as ALPPS procedure (associating liver partition and portal vein ligation for staged hepatectomy) [61]. In 2007, ALPPS was first performed by chance by German surgeon Dr. Schlitt [62, 63]. In an attempt to perform an extended right hepatectomy for a perihilar cholangiocarcinoma, he intraoperatively realized that FLR was inadequate. He resected the liver adjacent to the falciform ligament after performing a left hepaticojejunostomy. The right portal vein was also ligated for the purpose of left lobe hypertrophy. Out of curiosity, on postoperative day 8, he performed a computed tomography (CT) scan. To his surprise, the left lateral section had extensively grown in size. He successfully

ALPPS indications are an FLR < 30% in patients with a normal liver or an FLR < 40% in patients with a cholestatic, steatotic or fibrotic liver [64]. Therefore, ALPPS can be performed for marginally resectable or locally advanced tumors with an inadequate FLR. This technique constitutes a surgical strategy for colorectal liver metastases, hilar cholangiocarcinoma, and hepatocellular carcinoma [64]. On the other hand, contradictions for ALPPS procedure include unresectable liver metastases in the FLR, unresectable extrahepatic metastases, severe portal hypertension, high anesthetic risks, and a poor condition of the patient prior to this major operation [64]. Patients with cirrhotic liver are less capable for hypertrophy of FLR after portal vein obstruction (PVL or PVE) than patients with healthy liver parenchyma. Vennarecci et al. reported that ALPPS for HCC is safe even when performing a major hepatectomy in a cirrhotic liver. They also mentioned that ALPPS induces a significant increase in FLR between the first and the second stage of the procedure and after hepatectomy, either in healthy or

It has been reported that postoperative morbidity and mortality after ALPPS are 16–64 and 12–23%, respectively, with the main cause of morbidity being bile leakage and sepsis and the main cause of mortality being PHLF [66, 67]. In the latest systematic review and meta-analysis by Zhou et al., 719 patients were included, and the aim was to compare the regeneration efficiency, safety, and complication rates of ALPPS and TSH. The degree of FLR regeneration in ALPPS was significantly higher than that in TSH, and the interval of the two stages in ALPPS was obviously shorter than that in TSH. Bile fistulas were much more common after ALPPS with the reason being the liver splitting that is mandatory during this procedure.

progression.

first stage of the procedure (portal vein occlusion).

removed the diseased liver in a second operation.

cirrhotic patients [65].

Buchs et al. [51], in a systematic review of eight studies, compared RLR to LLR with the majority of the malignant cases being HCC (50.3%). There were minor and major hepatectomy procedures, and tumor size ranged from 8 to 120 mm. In the RLR group, there was no mortality, and the overall complication rate was 23.3% which fell to 19% when only postoperative complications were considered. A reduction of the conversion rate during major hepatectomy was reported as well. Overall, there was no clear outcome difference between RLR and LLR.

Ocuin et al. [52] included 14 major series in their review with the most common indication for resection being HCC. The estimated blood loss (EBL) ranged from 50 to 413 ml and transfusion rates from 0 to 44%. An overall conversion rate of 7% and an overall complication rate of 21% were reported. No perioperative mortality was associated with RLR. Length of stay (LOS) varied from 4 to 12 days. One study by Ji et al. showed a shorter LOS following RLR than OLR (10 vs. 7 days) [53]. Most series reported a high R0 resection rate with no port site recurrences. Recurrence rates following RLR were similar to those reported for LLR [9].

In conclusion, robotic liver resection is an acceptable alternative to open surgery with the robotic approach allowing an increased proportion of major hepatectomies to be performed in a minimally invasive manner [54]. These encouraging results should prompt the expansion of the robotic approach by highly specialized surgeons in experience centers worldwide.
