Open access peer-reviewed chapter

Novel Techniques in the Surgical Management of Hepatocellular Carcinoma

Written By

Vasileia Ntomi, Anna Paspala and Dimitrios Schizas

Submitted: April 5th, 2018 Reviewed: July 5th, 2018 Published: November 21st, 2018

DOI: 10.5772/intechopen.79982

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Hepatocellular carcinoma (HCC) is the most common primary liver malignancy with cirrhosis preceding its development in most cases. Surgical resection remains the primary therapeutic option despite the recent emergence of locoregional therapies. Novel surgical techniques are being proposed to overcome the limitations of traditional anatomical open liver resection. Laparoscopic resection is a safe and effective alternative to open liver resection, especially for left lateral or peripheral segment tumors. It is associated with less postoperative morbidity, intraoperative blood loss, and medial hospital stay with no difference in oncological outcomes. Robotic-assisted liver resection overcomes the technically difficult resection of tumors located at the posterosuperior segments with similar outcomes to laparoscopic resection. Associated liver partition and portal vein ligation for staged hepatectomy (ALPPS) procedure allows resection in patients with HCC, and associated major vascular resection or small future liver remnant (FLR) with long-term results yet to be announced. For patients with small solitary tumors or poor liver function, nonanatomical liver resection is a feasible therapeutic option due to minimal postoperative morbidity and similar oncological results of anatomical resection.


  • hepatocellular carcinoma
  • laparoscopic
  • robotic
  • novel

1. Introduction

Hepatocellular carcinoma (HCC) is the fifth most common malignancy and the third leading cause of cancer-related deaths worldwide [1]. Cirrhotic patients have the highest risk of developing HCC [2]. Numerous factors contribute to cirrhosis which precedes HCC development, including viral hepatitis, heavy drinking, and aflatoxin exposure. Hepatitis C epidemic in the Western world and Hepatitis B epidemic in China have attributed to the incidence of 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 after surgery [2].

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

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 for HCC.

The aim of this chapter is to analyze the aforementioned novel surgical techniques in the management of HCC and present the results from the relevant studies.


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, single-segment 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, 17, 18, 19, 20, 21, 22, 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:

  1. Operative outcomes, such as operative time, operative blood loss, and number of patients that needed transfusion.

  2. Postoperative outcomes, such as morbidity, mortality, and hospital stay.

  3. 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.

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, 37, 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.


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].

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.

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.


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.

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].

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, 70, 71, 72, 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.


5. Anatomical vs. nonanatomical resection for HCC

The incidence of HCC continues to increase due to the dissemination of hepatitis B and C virus infection. Hepatic resection is the gold standard treatment for HCC [74]. Nevertheless, postoperative recurrence of HCC, 3 and 5 years after hepatectomy is 50–60% and 70–90%, respectively [75, 76].

It is known that HCC invades mainly the intrahepatic vascular system and spreads along the portal and hepatic vein branches, producing intrahepatic metastases [77, 78].

Since Makuuchi et al. introduced the concept of anatomical resection (AR), the advantages of anatomic resection for HCC have been suggested in many studies [79]. On the other hand, limited nonanatomic resection (NR) with a minimal safety margin may be preferred for patients with impaired liver function [80]. Tanaka et al. showed that microscopic vascular invasion was more important than tumor size as a predictive factor for local recurrence [81].

Anatomical liver resection is a plausible option for patients with HCC, as HCC tends to cause intrahepatic metastasis through vascular invasion, and its advantages in improved OS or DFS for HCC patients have widely been reported [82].

In a systematic review of Cucchetti et al., AR seemed to yield improved 5-year OS and DFS compared to NR [83]. Zhou et al. [84] and Bigonzi et al. [85] presented significantly improved 5-year OS with AR.

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 the long-term prognosis [87, 89].

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 AR group [82].

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

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 liver function [93, 94].

In conclusion, there is a need for more, large, prospective, multicenter studies to confirm the data about any possible superiority of nonanatomic resection for HCC.


6. Conclusion

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 techniques.

Laparoscopic resection
  • Early ambulation

  • Decreased respiratory complications

  • Minimal abdominal trauma

  • Less postoperative pain

  • Decrease in PHLF

  • Reduced blood loss

  • Shorter length of hospital stay

  • Increase of R0 resection

  • Technical difficulties

  • Vascular control

  • Difficult access to posterosuperior segments

  • Massive bleeding

  • No manual palpation

  • Longer operative time

[13, 14, 15, 16, 17, 23, 26, 27]
Robotic resection
  • Precision of movement

  • 3-dimensional vision

  • 7 degrees of movement

  • Precise endosuturing

  • Dissection of the hilum

  • Biliary reconstruction

  • Shorter length of stay

  • High cost

  • Longer operative time

  • Specialized surgeons

[42, 43, 44, 46, 54]
  • Increase in FLR

  • Application to cirrhotic patients

  • Marginally resectable tumors

  • Locally advances tumors

  • Severe portal hypertension

  • High risk patients

  • High rates of post-operative morbidity and mortality

  • Bile leakage

  • Sepsis

[64, 65, 66, 67]
Nonanatomical resection
  • Repeat resection

  • Impaired liver function

  • No difference in recurrence rates

  • Less intra-operative blood loss

  • Cirrhotic patients

  • Worse 5-year OS and DFS

  • Width of resection margin

  • Microscopic vascular invasion

[80, 81, 83, 84, 85, 90, 91, 93, 94]

Table 1.

Advantages and limitations of novel surgical techniques for hepatocellular carcinoma management.


  1. 1. Torre L, Bray F, Siegel RL, et al. Global cancer statistics, 2012. CA: A Cancer Journal for Clinicians. 2015 Mar;65(2):87-108. DOI: 10.3322/caac.21262
  2. 2. Llovet JM, Burroughs A, Bruix J. Hepatocellular carcinoma. Lancet. 2003 Dec;362(9399):1907-1917. DOI: 10.1016/S0140-6736(03)14964-1
  3. 3. El-Serag HB. Hepatocellular carcinoma. The New England Journal of Medicine. 2011 Sep;365(12):1118-1127. DOI: 10.1056/NEJMra1001683
  4. 4. Shen JY, Li C, Wen TF, et al. Liver transplantation versus surgical resection for HCC meeting the Milan criteria: A propensity score analysis. Medicine (Baltimore). 2016 Dec;95(52):e5756
  5. 5. Crocetti L, Bargellini I, Cioni R. Loco-regional treatment of HCC: Current status. Clinical Radiology. 2017 Aug;72(8):626-635. DOI: 10.1016/j.crad.2017.01.013
  6. 6. Gagner M, Rheault M, Dubuc J. Laparoscopic partial hepatectomy for liver tumor. Surgical Endoscopy. 1992;6:97-98
  7. 7. Hashizume M, Takenaka K, Yanaga K, et al. Laparoscopic hepatic resection for hepatocellular carcinoma. Surgical Endoscopy. 1995;9(12):1289-1291
  8. 8. Beard RE, Tsung A. Minimally invasive approaches for surgical management of primary liver cancers. Cancer Control. 2017 Jul–Sep;24(3):1073274817729234. DOI: 10.1177/1073274817729234
  9. 9. Nguyen KT, Gamblin TC, Geller DA. World review of laparoscopic liver resection-2, 804 patients. Annals of Surgery. 2009 Nov;250(5):831-841. DOI: 10.1097/SLA.0b013e3181b0c4df
  10. 10. Nguyen KT, Laurent A, Dagher I, et al. Minimally invasive liver resection for metastatic colorectal cancer: A multi-institutional, international report of safety, feasibility, and early outcomes. Annals of Surgery. 2009 Nov;250(5):842-848
  11. 11. Buell JF, Cherqui D, Geller DA, et al. The international position on laparoscopic liver surgery: The Louisville statement, 2008. Annals of Surgery. 2009 Nov;250(5):825-830
  12. 12. Wakabayashi G, Cherqui D, Geller DA, et al. Recommendations for laparoscopic liver resection: A report from the second international consensus conference held in Morioka. Annals of Surgery. 2015 Apr;261(4):619-629. DOI: 10.1097/SLA.0000000000001184
  13. 13. Buell JF, Thomas MT, Rudich S, et al. Experience with more than 500 minimally invasive hepatic procedures. Annals of Surgery. 2008 Sep;248(3):475-486. DOI: 10.1097/SLA.0b013e318185e647
  14. 14. Vibert E, Perniceni T, Levard H, et al. Laparoscopic liver resection. The British Journal of Surgery. 2006 Jan;93(1):67-72. DOI: 10.1002/bjs.5150
  15. 15. Chen K, Pan Y, Zhang B, et al. Laparoscopic versus open surgery for hepatocellular carcinoma: A meta-analysis of high-quality case-matched studies. Canadian Journal of Gastroenterology and Hepatology. 2018 Mar;2018:1746895. DOI: 10.1155/2018/1746895
  16. 16. Jiang B, Yan XF, Zhang JH. Meta-analysis of laparoscopic versus open liver resection for hepatocellular carcinoma. Hepatology Research. 2018 Jul;48(8):635-663. DOI: 10.1111/hepr.13061
  17. 17. Sotiropoulos GC, Prodromidou A, Kostakis ID, et al. Meta-analysis of liver resection for hepatocellular carcinoma. Updates in Surgery. 2017 Sep;69(3):291-311. DOI: 10.1007/s13304-017-0421-4
  18. 18. Yin Z, Fan X, Ye H, et al. Short- and long-term outcomes after laparoscopic and open hepatectomy for hepatocellular carcinoma: A global systematic review and meta analysis. Annals of Surgical Oncology. 2013 Apr;20(4):1203-1215. DOI: 10.1245/s10434-012-2705-8
  19. 19. Xiong JJ, Altaf K, Javed MA, et al. Meta-analysis of laparoscopicvsopen liver resection for hepatocellular carcinoma. World Journal of Gastroenterology. 2012 Dec;18(45):6657-6668. DOI: 10.3748/wjg.v18.i45.6657
  20. 20. Li N, Wu YR, Wu B, et al. Surgical and oncologic outcomes following laparoscopic versus open liver resection for hepatocellular carcinoma: A meta-analysis. Hepatology Research. 2012;42(1):51-59. DOI: 10.1111/j.1872-034X.2011.00890.x
  21. 21. Fancellu A, Rosman AS, Sanna V, et al. Meta-analysis of trials comparing minimally invasive and open liver resections for hepatocellular carcinoma. The Journal of Surgical Research. 2011 Nov;171(1):e33-e45. DOI: 10.1016/j.jss.2011.07.008
  22. 22. Zhou YM, Shao WY, Zhao YF, et al. Meta-analysis of laparoscopic versus open resection for hepatocellular carcinoma. Digestive Diseases and Sciences. 2011 Jul;56(7):1937-1943. DOI: 10.1007/s10620-011-1572-7
  23. 23. Masutani S, Sasaki Y, Imaoka S, et al. The prognostic significance of surgical margin in liver resection of patients with hepatocellular carcinoma. Archives of Surgery. 1994 Oct;129(10):1025-1030
  24. 24. Silberhumer GR, Steininger R, Laengle F, et al. Intraoperative ultrasonography in patients who undergo liver resection or transplantation for hepatocellular carcinoma. Surgical Technology International. 2004;12:145-151
  25. 25. Arii S, Tanaka S, Mitsunori Y, et al. Surgical strategies for hepatocellular carcinoma with special reference to anatomical hepatic resection and intraoperative contrast-enhanced ultrasonography. Oncology. 2010 Jul;78(Suppl 1):125-130. DOI: 10.1159/000315240
  26. 26. Ishida H, Murata N, Yamada H, et al. Influence of trocar placement and CO(2) pneumoperitoneum on port site metastasis following laparoscopic tumor surgery. Surgical Endoscopy. 2000 Feb;14(2):193-197
  27. 27. Bouvy ND, Marquet RL, Jeekel H, et al. Impact of gas(less) laparoscopy and laparotomy on peritoneal tumor growth and abdominal wall metastases. Annals of Surgery. 1996 Dec;224(6):694-700
  28. 28. Bruix J, Castells A, Bosch J, et al. Surgical resection of hepatocellular carcinoma in cirrhotic patients: Prognostic value of preoperative portal pressure. Gastroenterology. 1996 Oct;111(4):1018-1022
  29. 29. Powell-Jackson P, Greenway B, Williams R. Adverse effects of exploratory laparotomy in patients with unsuspected liver disease. The British Journal of Surgery. 1982 Aug;69(8):449-451
  30. 30. Tranchart H, Di Giuro G, Lainas P, et al. Laparoscopic resection for hepatocellular carcinoma: A matched-pair comparative study. Surgical Endoscopy. 2010 May;24(5):1170-1176. DOI: 10.1007/s00464-009-0745-3
  31. 31. Yamashita Y, Ikeda T, Kurihara T, et al. Long-term favorable surgical results of laparoscopic hepatic resection for Hepatocellular carcinoma in patients with cirrhosis: A single-center experience over a 10-year period. Journal of the American College of Surgeons. 2014 Dec;219(6):1117-1123. DOI: 10.1016/j.jamcollsurg.2014.09.003
  32. 32. Twaij A, Pucher PH, Sodergren MH, et al. Laparoscopic vs open approach to resection of Hepatocellular carcinoma in patients with known cirrhosis: Systematic review and meta-analysis. World Journal of Gastroenterology. 2014 Jul;20(25):8274-8281. DOI: 10.3748/wjg.v20.i25.8274
  33. 33. Sotiropoulos GC, Prodromidou A, Machairas N. Meta-analysis of laparoscopic vs. open liver resection for hepatocellular carcinoma: The European experience. JBUON. 2017 Sep–Oct;22(5):1160-1171
  34. 34. Llovet JM, Schwartz M, Mazzaferro V. Resection and liver transplantation for hepatocellular carcinoma. Seminars in Liver Disease. 2005;25(2):181-200
  35. 35. Zhou Y, Sui C, Li B, et al. Repeat hepatectomy for recurrent hepatocellular carcinoma: A local experience and a systematic review. World Journal of Surgical Oncology. 2010 Jul;8:55. DOI: 10.1186/1477-7819-8-55
  36. 36. Ahn KS, Han HS, Yoon YS, et al. Laparoscopic liver resection in patients with a history of upper abdominal surgery. World Journal of Surgery. 2011 Jun;35(6):1333-1339. DOI: 10.1007/s00268-011-1073-z
  37. 37. Shelat VG, Serin K, Samim M, et al. Outcomes of repeat laparoscopic liver resection compared to the primary resection. World Journal of Surgery. 2014 Dec;38(2):3175-3180. DOI: 10.1007/s00268-014-2728-3
  38. 38. Zhang J, Zhou ZG, Huang ZX, et al. Prospective, single-center cohort study analyzing the efficacy of complete laparoscopic resection on recurrent hepatocellular carcinoma. Chinese Journal of Cancer. 2016 Mar;35:25. DOI: 10.1186/s40880-016-0088-0
  39. 39. Machairas N, Papaconstantinou D, Stamopoulos P, et al. The emerging role of laparoscopic liver resection in the treatment of recurrent hepatocellular carcinoma: A systematic review. Anticancer Research. 2018 May;38(5):3181-3186. DOI: 10.21873/anticanres.12582
  40. 40. Vigano L, Tayar C, Laurent A, et al. Laparoscopic liver resection: A systematic review. Journal of Hepato-Biliary-Pancreatic Surgery. 2009;16(4):410-421. DOI: 10.1007/s00534-009-0120-8
  41. 41. Giulianotti PC, Coratti A, Angelini M. Robotics in general surgery: Personal experience in a large community hospital. Archives of Surgery. 2003 Jul;138(7):777-784. DOI: 10.1001/archsurg.138.7.777
  42. 42. Giulianotti PC, Coratti A, Sbrana F, et al. Robotic liver surgery: Results for 70 resections. Surgery. 2011 Jan;149(1):29-39. DOI: 10.1016/j.surg.2010.04.002
  43. 43. Giulianotti PC, Sbrana F, Bianco FM, et al. Robot-assisted laparoscopic extended right hepatectomy with biliary reconstruction. Journal of Laparoendoscopic & Advanced Surgical Techniques. Part A. 2010 Mar;20(2):159-163. DOI: 10.1089/lap.2009.0383
  44. 44. Turchetti G, Palla I, Pierotti F, et al. Economic evaluation of da Vinci-assisted robotic surgery: A systematic review. Surgical Endoscopy. 2012 Mar;26(3):598-606. DOI: 10.1007/s00464-011-1936-2
  45. 45. Tsung A, Geller DA, Sukato DC, et al. Robotic versus laparoscopic hepatectomy: A matched comparison. Annals of Surgery. 2014 Mar;259(3):549-555. DOI: 10.1097/SLA.0000000000000250
  46. 46. Chen PD, Wu CY, Hu RH, et al. Robotic versus open hepatectomy for hepatocellular carcinoma: A matched comparison. Annals of Surgical Oncology. 2017 Apr;24(4):1021-1028. DOI: 10.1245/s10434-016-5638-9
  47. 47. Lai EC, Tang CN. Long-term survival analysis of robotic versus conventional laparoscopic hepatectomy for hepatocellular carcinoma: A comparative study. Surgical Laparoscopy, Endoscopy & Percutaneous Techniques. 2016 Apr;26(2):162-166. DOI: 10.1097/SLE.0000000000000254
  48. 48. Salloum C, Lim C, Malek A, et al. Robot-assisted laparoscopic liver resection: A review. Journal of Visceral Surgery. 2016 Dec;153(6):447-456. DOI: 10.1016/j.jviscsurg.2016.08.005
  49. 49. Tsilimigras DI, Moris D, Vagios S, et al. Safety and oncologic outcomes of robotic liver resections: A systematic review. Journal of Surgical Oncology. 2018 Jun;117(7):1517-1530. DOI: 10.1002/ jso.25018
  50. 50. Dindo D, Demartines N, Clavien PA. Classification of surgical complications: A new proposal with evaluation in a cohort of 6336 patients and results of a survey. Annals of Surgery. 2004 Aug;240(2):205-213
  51. 51. Buchs NC, Oldani G, Orci LA, et al. Current status of robotic liver resection: A systematic review. Expert Review of Anticancer Therapy. 2014 Feb;14(2):237-246. DOI: 10.1586/14737140.2014.863155
  52. 52. Ocuin LM, Tsung A. Robotic liver resection for malignancy: Current status, oncologic outcomes, comparison to laparoscopy, and future applications. Journal of Surgical Oncology. 2015 Sep;112(3):295-301. DOI: 10.1002/jso.23901
  53. 53. Ji WB, Wang HG, Zhao ZM, et al. Robotic-assisted laparoscopic anatomic hepatectomy in China: Initial experience. Annals of Surgery. 2011 Feb;253(2):342-348. DOI: 10.1097/SLA.0b013e3181ff4601
  54. 54. Milone L, Daskalaki D, Fernandes E, et al. State of the art in robotic hepatobiliary surgery. World Journal of Surgery. 2013 Dec;37(12):2747-2755. DOI: 10.1007/s00268-013-2276-2
  55. 55. Kishi Y, Abdalla EK, Chun YS, et al. Three hundred and one consecutive extended right hepatectomies: Evaluation of outcome based on systematic liver volumetry. Annals of Surgery. 2009 Oct;250(4):540-554. DOI: 10.1097/SLA.0b013e3181b674df
  56. 56. Zhang GQ, Zhang ZW, Lau WY, et al. Associating liver partition and portal vein ligation for staged hepatectomy (ALPPS): A new strategy to increase resectability in liver surgery. International Journal of Surgery. 2014;12(5):437-441. DOI: 10.1016/j.ijsu.2014.03.009
  57. 57. Makuuchi M, Thai BL, Takayasu K, et al. Preoperative portal embolization to increase safety of major hepatectomy for hilar bile duct carcinoma: A preliminary report. Surgery. 1990 May;107(5):521-527
  58. 58. Pandanaboyana S, Bell R, Hidalgo E, et al. A systematic review and meta-analysis of portal vein ligation versus portal vein embolization for elective liver resection. Surgery. 2015 Apr;157(4):690-698. DOI: 10.1016/j.surg.2014.12.009
  59. 59. Adam R, Laurent A, Azoulay D, et al. Two-stage hepatectomy: A planned strategy to treat unresectable liver tumors. Annals of Surgery. 2000 Dec;232(6):777-785
  60. 60. Schnitzbauer AA, Lang SA, Goessmann H, et al. Right portal vein ligation combined with in situ splitting induces rapid left lateral liver lobe hypertrophy enabling 2-staged extended right hepatic resection in small-for-size settings. Annals of Surgery. 2012 Mar;255(3):405-414. DOI: 10.1097/SLA.0b013e31824856f5
  61. 61. de Santibañes E, Clavien PA. Playing play-doh to prevent postoperative liver failure: The “ALPPS” approach. Annals of Surgery. 2012 Mar;255(3):415-417. DOI: 10.1097/SLA.0b013e318248577d
  62. 62. Donati M, Basile F, Oldhafer KJ. Present status and future perspectives of ALPPS (associating liver partition and portal vein ligation for staged hepatectomy). Future Oncology. 2015;11(16):2255-2258. DOI: 10.2217/fon.15.145
  63. 63. Cai X, Tong Y, Yu H, et al. The ALPPS in the treatment of hepatitis B-related hepatocellular carcinoma with cirrhosis: A single-center study and literature review. Surgical Innovation. 2017 Aug;24(4):358-364. DOI: 10.1177/1553350617697187
  64. 64. Alvarez FA, Ardiles V, Sanchez Claria R, et al. Associating liver partition and portal vein ligation for staged hepatectomy (ALPPS): Tips and tricks. Journal of Gastrointestinal Surgery. 2013 Apr;17(4):814-821. DOI: 10.1007/s11605-012-2092-2
  65. 65. Vennarecci G, Laurenzi A, Levi Sandri GB, et al. The ALPPS procedure for hepatocellular carcinoma. European Journal of Surgical Oncology. 2014 Aug;40(8):982-988. DOI: 10.1016/j.ejso.2014.04.002
  66. 66. Zhou Z, Xu M, Lin N, et al. Associating liver partition and portal vein ligation for staged hepatectomy versus conventional two-stage hepatectomy: A systematic review and meta-analysis. World Journal of Surgical Oncology. 2017 Dec 19;15(1):227. DOI: 10.1186/s12957-017-1295-0
  67. 67. Schadde E, Schnitzbauer AA, Tschuor C, et al. Systematic review and meta-analysis of feasibility, safety, and efficacy of a novel procedure: Associating liver partition and portal vein ligation for staged hepatectomy. Annals of Surgical Oncology. 2015 Sep;22(9):3109-3120. DOI: 10.1245/s10434-014-4213-5
  68. 68. Bertens KA, Hawel J, Lung K, et al. ALPPS: Challenging the concept of unresectability—A systematic review. International Journal of Surgery. 2015 Jan;13:280-287. DOI: 10.1016/j.ijsu.2014.12.008
  69. 69. Tanaka K. Modified ALPPS procedures: More safety through less invasive surgery. Langenbeck's Archives of Surgery. 2017 Jun;402(4):563-574. DOI: 10.1007/s00423-017-1588-3
  70. 70. Dokmak S, Belghiti J. Which limits to the ALPPS approach? Annals of Surgery. 2012 Sep;256:e6; author reply e16-7. DOI: 10.1097/SLA.0b013e318265fd64
  71. 71. Ardiles V, Schadde E, Santibanes E, et al. Commentary on happy marriage or dangerous liaison: ALPPS and the anterior approach. Annals of Surgery. 2014 Aug;260(2):e4. DOI: 10.1097/SLA.0000000000000735
  72. 72. Alvarez FA, Ardiles V, de Santibañes M, et al. Associating liver partition and portal vein ligation for staged hepatectomy offers high oncological feasibility with adequate patient safety: A prospective study at a single center. Annals of Surgery. 2015 Apr;261(4):723-732. DOI: 10.1097/SLA.0000000000001046
  73. 73. Hernandez-Alejandro R, Bertens KA, Pineda-Solis K, et al. Can we improve the morbidity and mortality associated with the associating liver partition with portal vein ligation for staged hepatectomy (ALPPS) procedure in the management of colorectal liver metastases? Surgery. 2015 Feb;157(2):194-201. DOI: 10.1016/j.surg.2014.08.041
  74. 74. Kudo M, Matsui O, Izumi N, et al. JSH consensus-based clinical practice guidelines for the management of hepatocellular carcinoma: 2014 update by the liver cancer study group of Japan. Liver Cancer. 2014 Oct;3(3-4):458-468. DOI: 10.1159/000343875
  75. 75. Colecchia A, Schiumerini R, Cucchetti A, et al. Prognostic factors for hepatocellular carcinoma recurrence. World Journal of Gastroenterology. 2014 May;20(20):5935-5950. DOI: 10.3748/wjg.v20.i20.5935
  76. 76. Shim JH, Jun MJ, Han S, et al. Prognostic nomograms for prediction of recurrence and survival after curative liver resection for hepatocellular carcinoma. Annals of Surgery. 2015 May;261(5):939-946. DOI: 10.1097/SLA.0000000000000747
  77. 77. Cucchetti A, Zanello M, Cescon M, et al. Improved diagnostic imaging and interventional therapies prolong survival after resection for hepatocellular carcinoma in cirrhosis: The university of bologna experience over 10 years. Annals of Surgical Oncology. 2011 Jun;18(6):1630-1637. DOI: 10.1245/s10434-010-1463-8
  78. 78. Tanaka S, Mogushi K, Yasen M, et al. Surgical contribution to recurrence-free survival in patients with macrovascular-invasion-negative hepatocellular carcinoma. Journal of the American College of Surgeons. 2009 Mar;208(3):368-374. DOI: 10.1016/j.jamcollsurg.2008.10.031
  79. 79. Makuuchi M, Hasegawa H, Yamazaki S. Ultrasonically guided subsegmentectomy. Surgery, Gynecology & Obstetrics. 1985 Oct;161(4):346-350
  80. 80. Yamashita Y, Taketomi A, Itoh S, et al. Longterm favorable results of limited hepatic resections for patients with hepatocellular carcinoma: 20 years of experience. Journal of the American College of Surgeons. 2007 Jul;205(1):19-26. DOI: 10.1016/j.jamcollsurg.2007.01.069
  81. 81. Vauthey JN, Lauwers GY, Esnaola NF, et al. Simplified staging for hepatocellular carcinoma. Journal of Clinical Oncology. 2002 Mar;20(6):1527-1536. DOI: 10.1200/JCO.2002.20.6.1527
  82. 82. Yamamoto T, Yagi S, Uryuhara K, et al. Clinical factors that affect the outcomes after anatomical versus non-anatomical resection for hepatocellular carcinoma. Surgery Today. 2017 Feb;47(2):193-201. DOI: 10.1007/s00595-016-1397-2
  83. 83. Cucchetti A, Cescon M, Ercolani G, et al. A comprehensive meta-regression analysis on outcome of anatomic resection versus nonanatomic resection for hepatocellular carcinoma. Annals of Surgical Oncology. 2012 Nov;19(12):3697-3705. DOI: 10.1245/s10434-012-2450-z
  84. 84. Zhou Y, Xu D, Wu L, et al. Meta-analysis of anatomic resection versus non anatomic resection for hepatocellular carcinoma. Langenbeck's Archives of Surgery. 2011 Oct;396(7):1109-1117. DOI: 10.1007/s00423-011-0784-9
  85. 85. Bigonzi E, Cucchetti A, Pinna AD. Meta-analysis of anatomic resection versus non-anatomic resection for hepatocellular carcinoma: Are they comparing apples with oranges? Langenbeck's Archives of Surgery. 2012 Jan;397(1):141-142. DOI: 10.1007/s00423-011-0816-5
  86. 86. Yune Y, Kim S, Song I, et al. Comparative analysis of intraoperative radiofrequency ablation versus non-anatomical hepatic resection for small hepatocellular carcinoma: Short-term result. Korean Journal of Hepato-Biliary-Pancreatic Surgery. 2015 Nov;19(4):173-180. DOI: 10.14701/kjhbps.2015.19.4.173
  87. 87. Huang X, Lu S. A meta-analysis comparing the effect of anatomical resection vs. non-anatomical resection on the long-term outcomes for patients undergoing hepatic resection for hepatocellular carcinoma. HPB: The Official Journal of the International Hepato Pancreato Biliary Association. 2017 Oct;19(10):843-849. DOI: 10.1016/j.hpb.2017.06.003
  88. 88. Zhang YM, Wang J. Progress of clinical application of anatomic resection and nonanatomic resection. Zhonghua Wai Ke Za Zhi. 2016 Dec;54(12):947-950. DOI: 10.3760/cma.j.issn.0529-5815.2016.12.016
  89. 89. Cucchetti A, Cescon M, Trevisani F, et al. Current concepts in hepatic resection for hepatocellular carcinoma in cirrhotic patients. World Journal of Gastroenterology. 2012 Nov;18(44):6398-6408. DOI: 10.3748/wjg.v18.i44.6398
  90. 90. Marubashi S, Gotoh K, Akita H, et al. Anatomical versus non-anatomical resection for hepatocellular carcinoma. The British Journal of Surgery. 2015 Jun;102(7):776-784. DOI: 10.1002/bjs.9815
  91. 91. Tanaka K, Shimada H, Matsumoto C, et al. Anatomic versus limited nonanatomic resection for solitary hepatocellular carcinoma. Surgery. 2008 May;143(5):607-615. DOI: 10.1016/j.surg.2008.01.006
  92. 92. Chen J, Huang K, Wu J, et al. Survival after anatomic resection versus nonanatomic resection for hepatocellular carcinoma: A meta-analysis. Digestive Diseases and Sciences. 2011 Jun;56(6):1626-1633. DOI: 10.1007/s10620-010-1482-0
  93. 93. Nagasue N, Yamanoi A, el-Assal ON, et al. Major compared with limited hepatic resection for hepatocellular carcinoma without underlying cirrhosis: A retrospective analysis. The European Journal of Surgery. 1999 Jul;165(7):638-646. DOI: 10.1080/11024159950189681
  94. 94. Minagawa M, Makuuchi M, Takayama T, et al. Selection criteria for repeat hepatectomy in patients with recurrent hepatocellular carcinoma. Annals of Surgery. 2003 Nov;238(5):703-710. DOI: 10.1097/01.sla.0000094549.11754.e6

Written By

Vasileia Ntomi, Anna Paspala and Dimitrios Schizas

Submitted: April 5th, 2018 Reviewed: July 5th, 2018 Published: November 21st, 2018