**4. Associating liver partition and portal vein ligation for liver surgery (ALPPS) for HCC**

Surgical resection is the only potential curative treatment for hepatocellular carcinoma (HCC). In many cases, a major hepatectomy is required to achieve tumor-free surgical margins. However, the volume and functional reserve of the future liver remnant (FLR) are essential to avoid post-hepatectomy liver failure (PHLF), which is a crucial and important cause of morbidity and mortality after extensive liver resection [55]. In recent decades, some new strategies, such as portal vein embolization (PVE), portal vein ligation (PVL), and two-staged hepatectomy (TSH) have been developed to induce regeneration of FLR, minimizing the risk of PHLF and finally expanding the resectability criteria in HCC and generally in liver tumors [56]. Makuuchi et al. first introduced portal vein embolization into clinical practice in 1980s [57]. In 2015, a systematic review and meta-analysis from Pandanaboyana et al. compared PVL and PVE to assess the percentile increase of the 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 progression.

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

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

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

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

Surgical resection is the only potential curative treatment for hepatocellular carcinoma (HCC). In many cases, a major hepatectomy is required to achieve tumor-free surgical margins. However, the volume and functional reserve of the future liver remnant (FLR) are essential to avoid post-hepatectomy liver failure (PHLF), which is a crucial and important cause of morbidity and mortality after extensive liver resection [55]. In recent decades, some new strategies, such as portal vein embolization (PVE), portal vein ligation (PVL), and two-staged hepatectomy (TSH) have been developed to induce regeneration of FLR, minimizing the risk of PHLF and finally expanding the resectability criteria in HCC and generally in liver tumors [56]. Makuuchi et al. first introduced portal vein embolization into clinical practice in 1980s [57]. In 2015, a systematic review and meta-analysis from Pandanaboyana et al. compared PVL and PVE to assess the percentile increase of the

**4. Associating liver partition and portal vein ligation for liver** 

validate the exact indications and benefits of RLR.

RLR and LLR.

82 Liver Cancer

reported for LLR [9].

**surgery (ALPPS) for HCC**

worldwide.

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 first stage of the procedure (portal vein occlusion).

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 removed the diseased liver in a second operation.

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 cirrhotic patients [65].

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. Although ALPPS had lower 1-year DFS rate, no significant difference in the 90-day mortality rate was discovered comparing the two techniques [66]. ALPPS was associated with a higher completion rate, a lower probability of tumor progression during the stage interval, and a lower insufficient regeneration rate; these findings are similar to those of previous studies [56, 67, 68].

Nonanatomic resection is recommended for patients with impaired liver function [86, 87]. The plausible reason is that NR can preserve as much functional liver as possible, with surgical curability and hepatic function equally important [87, 88]. The preservation of hepatic functional reserve allows effective treatment options in HCC recurrence, which may also improve

Novel Techniques in the Surgical Management of Hepatocellular Carcinoma

http://dx.doi.org/10.5772/intechopen.79982

85

The superiority of anatomical resection (AR) over nonanatomic resection (NR) for hepatocellular carcinoma (HCC) remains controversial. Marubashi et al. reported no significant differences in OS, DFS or recurrence within 2 years after hepatectomy between the AR and NR groups [90]. Likewise, Tanaka et al. reported no outstanding difference in the recurrence rates and OS between AR and NR patient groups; it was also stated that survival rates after recurrence and median survival time after recurrence were higher in the NR group compared to the AR group for patients with a solitary HCC confined to 1 or 2 liver segments [91]. Chen et al. reported in their meta-analysis that AR contributed to better DFS, but did not improve OS [92]. Thus, the superiority of AR over NR is still controversial. Furthermore, Yamamoto et al. reported that AR is associated with more perioperative risks. The same study revealed significantly greater intraoperative blood loss and longer postoperative hospital stay for the

In 2010, Yamashita et al. [80] published a retrospective study of 321 patients with HCC. About 120 patients underwent limited nonanatomic resection (NR) for a single HCC < 5 cm. In noncirrhotic patients (n = 215), both 5-year OS and DFS rates in the AR group were considerably better than those in the NR group (87 vs. 76% and 63 vs. 35%, respectively). In cirrhotic patients (n = 106), both 5-year OS and DFS in the AR group were worse than those in the NR

According to their results, the width of the resection margin did not influence postoperative recurrence, and major hepatic resections did not improve patients' survival. The main disadvantage of AR in comparison with NR is the limitation of a repeat resection, which would be the most effective treatment for recurrence, because of its disadvantageous effects on remnant

In conclusion, there is a need for more, large, prospective, multicenter studies to confirm the

Hepatocellular carcinoma is a malignancy with an increasing incidence and a dismal prognosis. Patients are often referred to specialists in an advanced stage of the disease. Surgery is the primary treatment and novel surgical techniques are developed offering better perioperative and oncological results (**Table 1**). Nevertheless, prospective, randomized controlled studies have to be designed for the confirmation of such possible advantages of those new surgical

data about any possible superiority of nonanatomic resection for HCC.

the long-term prognosis [87, 89].

group (48 vs. 72% and 28 vs. 43%, respectively).

AR group [82].

liver function [93, 94].

**6. Conclusion**

techniques.

Many variations of the ALPPS technique have been recently mentioned in the literature with the aim of improving safety and extending indications of hepatectomy. Modifications, such as avoiding liver mobilization and hepatoduodenal skeletonization, seem to prevent tumor spreading, adhesions, overall invasiveness, and parenchymal ischemia [69–73]. In addition, anterior approaches, portal vein embolization (PVE) as an alternative to ligation, partial liver splitting, tourniquet application or ablation procedures replacing parenchymal transection, and laparoscopic approaches represent fundamental modifications to the original ALPPS procedure that aim to improve safety [15]. The result of these modifications is the reduction of morbidity and mortality in this innovative surgical procedure. Furthermore, prospective controlled studies are needed to confirm which of these modifications should be considered as a reliable and safe alternative strategy to classical ALPPS.
