**2. Laparoscopic liver resection for HCC**

Laparoscopic surgery has become widely accepted as a feasible alternative to traditional open surgery for many surgical indications. The first laparoscopic hepatectomy was performed in 1992, for a benign tumor by Gagner et al. [6], and the first laparoscopic resection for HCC was reported in 1995 [7].

The liver presents many and significant technical challenges for minimally invasive techniques. Its mobilization is difficult, the space is limited, its vascular and biliary anatomy is complex and the parenchyma is fragile, friable and often fibrotic or cirrhotic [8]. Nevertheless, numerous studies have already shown the feasibility and safety of wedge resections, singlesegment resections, and left lateral sectionectomies [9, 10].

The first international consensus conference on laparoscopic liver resection (LLR) was held in Louisville in 2008. It was suggested that the best indications for laparoscopic excision were solitary lesions less than 5 cm, located in the anterior segments. Also, the resection should be far from the hepatic hilum and the vena cava [11]. The second international consensus was held in Morioka, Japan in 2014, stating that anatomical resection for HCC is standard of care procedure, but the laparoscopic version needs to be standardized to increase propagation [12].

There are many reasons why laparoscopic major hepatectomy has not been widely accepted and performed yet. There are technical difficulties related to liver mobilization, vascular control, inability for manual palpation, access to posterosuperior liver segments, and intraoperative hazards such as gas embolism, massive bleeding, and bile duct injury [13, 14].

The benefits of laparoscopic surgery, though, have long been proven. Early postoperative ambulation, decreased respiratory complications, minimization of blood loss, minimal abdominal trauma, and less postoperative pain are some of the accepted benefits of laparoscopic surgery. For cirrhotic patients with HCC, the minimization of the surgical incision and the subsequent preservation of the abdominal wall circulation and lymphatic flow explains the decrease in postoperative liver failure and ascites formation [15].

The last decade, several meta-analyses of laparoscopic vs. open resection for HCC have been published [16–23]. These meta-analyses have analyzed and compared the results of many nonrandomized control trials and case-matched studies. Three categories of outcomes were used to compare the two operative techniques:


HCC [3]. However, HCC has a dismal prognosis, mainly due to the early recurrence; about 40% of patients that have undergone hepatectomy develop recurrence within the first year

Although liver transplantation is considered as the ideal treatment, hepatic resection remains the only curative method of therapy for HCC. Other methods of potentially curative therapy are radiofrequency ablation (RFA), microwave ablation (MWA), high power focused ultra-

Novel surgical techniques are being proposed to overcome the limitations of traditional anatomical open liver resection. Laparoscopic and robotic resection as well as nonanatomical resection and ALPPS procedure have emerged as new and effective ways of surgical therapy

The aim of this chapter is to analyze the aforementioned novel surgical techniques in the

Laparoscopic surgery has become widely accepted as a feasible alternative to traditional open surgery for many surgical indications. The first laparoscopic hepatectomy was performed in 1992, for a benign tumor by Gagner et al. [6], and the first laparoscopic resection for HCC was

The liver presents many and significant technical challenges for minimally invasive techniques. Its mobilization is difficult, the space is limited, its vascular and biliary anatomy is complex and the parenchyma is fragile, friable and often fibrotic or cirrhotic [8]. Nevertheless, numerous studies have already shown the feasibility and safety of wedge resections, single-

The first international consensus conference on laparoscopic liver resection (LLR) was held in Louisville in 2008. It was suggested that the best indications for laparoscopic excision were solitary lesions less than 5 cm, located in the anterior segments. Also, the resection should be far from the hepatic hilum and the vena cava [11]. The second international consensus was held in Morioka, Japan in 2014, stating that anatomical resection for HCC is standard of care procedure, but the laparoscopic version needs to be standardized to

There are many reasons why laparoscopic major hepatectomy has not been widely accepted and performed yet. There are technical difficulties related to liver mobilization, vascular control, inability for manual palpation, access to posterosuperior liver segments, and intraopera-

The benefits of laparoscopic surgery, though, have long been proven. Early postoperative ambulation, decreased respiratory complications, minimization of blood loss, minimal abdominal trauma, and less postoperative pain are some of the accepted benefits of laparoscopic

tive hazards such as gas embolism, massive bleeding, and bile duct injury [13, 14].

sound ablation (HIFU), and transarterial chemoembolization (TACE) [4, 5].

management of HCC and present the results from the relevant studies.

**2. Laparoscopic liver resection for HCC**

segment resections, and left lateral sectionectomies [9, 10].

after surgery [2].

78 Liver Cancer

for HCC.

reported in 1995 [7].

increase propagation [12].

**c.** Oncologic results, such as pathologic resection margins, incidence of port-site recurrence, disease-free survival (DFS), and overall survival (OS).

Jiang et al. [16] reported the superiority of laparoscopic liver resection (LLR) concerning the reduced intraoperative blood loss and blood transfusion, the expansion of the pathologic resection margins, the increase of R0 resection, and the shorter length of hospital stay. Laparoscopic resection has similar OS, DFS, and recurrence rate as open liver resection (OLR).

Sotiropoulos et al. [17], in a recent meta-analysis of 44 studies, showed that laparoscopic resection is superior to open resection in terms of resection margin and R0 resection. It is possible that this difference in resection margin and R0 excision is due to the smaller size of tumors resected in the laparoscopic group. It was confirmed that the laparoscopic technique is strongly associated with less blood loss, fewer blood transfusions, less postoperative pain, faster recovery, and shorter hospital stay. Operative time and tumor recurrence were not statistically different between LLR and OLR as well as the long-term oncological results such as OS and DFS. These results confirm those of previous authors [15, 18, 21, 22]. Hand-assisted laparoscopic or laparoscopy-assisted resections (hybrid group) gain statistical advantage over the OLR group concerning the negative resection margin width and influence the results in favor of LLR. They, however, showed no difference as to the OS and 30-day mortality compared to the OLR group.

The main concerns about LLR are the inadequate tumor resection margins and the potential risk of port-site recurrence. Tumor recurrence is the main cause of death in patients with HCC. The adequate tumor-free margin is a prognostic indicator of HCC [23]. Due to the lack of tactile sensation in laparoscopic surgery, the tumor location is sometimes difficult to determine. Intraoperative ultrasonography is a useful tool for precise identification of lesions and its borders [24, 25]. Another concerning factor is the risk of tumor peritoneal dissemination and port-site metastases [26, 27]. Interestingly, there has not been any evidence so far of tumor peritoneal dissemination or port-site metastases [20, 22]. The use of a plastic bag to remove the specimen can help to prevent this complication.

Concern has also been raised about the safety of laparoscopic techniques in cirrhotic patients. A plethora of patients with HCC also suffer from cirrhosis. Portal hypertension is a major risk 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.

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].

Novel Techniques in the Surgical Management of Hepatocellular Carcinoma

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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

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

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

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

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 activi-

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

ties. Also, it seems that the learning curve for RLR is shorter than that of LLR.

purely minimally invasive manner compared with 49.1% performed laparoscopically.

reason for the limited incorporation of the robotic system in many facilities.

experienced surgeons.

vs. 48%, respectively) in patients with HCC.

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].

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 secondary to difficult exposure.

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