Is laparoscopic mesohepatectomy superior to the open approach for patients with centrally located hepatocellular carcinoma?

Laparoscopic liver resection (LLR) has become a standard procedure for hepatocellular carcinoma (HCC) as well as liver metastases and other benign and malignant liver tumors (1-3). Numerous cohort studies and their reviews or meta-analyses comparing LLR with open liver resection (OLR) for HCC frequently have serious selection biases in terms of the differences in the size, number, tumor location, and malignancy degree (4-6).

To our knowledge, no randomized controlled trials (RCTs) have compared LLR and OLR for HCC. In most cohort studies, LLR was selected for easier and newly diagnosed cases; therefore, number of studies has been increasing using propensity score matching (PSM) to minimalize selection biases (7). PSM studies that have used entire patients’ cohort have clearly demonstrated that LLR involves less intraoperative blood loss and transfusion rates, lower morbidity, shorter hospital stays, and similar mortality compared as that achieved with OLR (8-13). In addition, the long-term survival was comparable in both the groups. A recent Japanese multi-center study for limited elderly HCC patients (age ≥75 years) confirmed similar results that showed the superiority of short-term outcomes with LLR (14). A recent meta-analysis of PSM studies has showed that LLR can be performed with 50% lower rates of blood transfusion and postoperative complications, can shorten the hospital stay by an average of 4 days, and achieve lower 30-day mortality compared to OLR (5).

Mesohepatectomy is usually applied for centrally located HCC (CL-HCC). Mesohepatectomy has two large cutting live surfaces; therefore, it must be one of complexed liver resections even if being performed with open approach. Further, mesohepatectomy is performed to preserve the liver parenchyma to lower the risk of postoperative liver dysfunction or liver failure (15). In LLR, owing to the technical complexities, wedge resection or left-sided hepatectomy is commonly selected over mesohepatectomy (1,2). With advances in laparoscopic instruments and procedures, pure laparoscopic mesohepatectomy (LM) is being increasingly used (15-18).

We congratulate Dr. Wei Li and colleagues for their recently published article entitled “Laparoscopic versus open mesohepatectomy for patients with centrally located hepatocellular carcinoma: a propensity score matched analysis” in Surgical Endoscopy (19). In this exceptional paper, the authors have compared LM and open mesohepatectomy (OM) for patients with CL-HCC. The authors stated that the selection of the surgical procedures (LM or OM) was based on the tumor number, tumor size, tumor location, residual liver volume, and underlying liver function. In both the procedures, harmonic scalpel (Ethicon Endo-Surgery, USA), cavitron ultrasonic aspiration (CUSA, ValleyLab, Inc., USA), and/or LigaSure (ValleyLab, Inc., USA) were used for transection of the liver parenchyma. However, information about the number of surgeons and their previous experience of LM or OM was unavailable.

CL-HCC was divided into 4 groups, mainly based on the tumor location (20,21). Total 78.0% of the patients in LM group were classified as type III, and no patient was classified as type IV. In OM group, 24.1% and 18.6% of the patients were classified as Type III and Type IV, respectively. Type III was defined by a tumor located between the segments IVa and VIII and segments V and IVb, not adjacent to the large Glissonean capsules; therefore, liver resection was relatively easier than other types of resection. Type IV was characterized by the presence of the tumor in the most challenging location and was defined as the presence of a tumor that occupied a large proportion of the parenchyma between the first and second Glissonean pedicle. As per the authors’ recommendation, type II and type IV patients with direct vascular invasion are contraindicated for LM in the present technical condition. It is important to use LM and OM appropriately.

In the overall cohort, the LM group had a smaller tumor size and earlier tumor stage compared to the OM group; however, background factors were well balanced in the two groups after 1 to 3 PSM. It is unclear why intraoperative and postoperative parameters were not investigated in the PSM cohort rather than in the overall cohort. In the overall cohort, despite early tumor stage, vascular occlusion time was significantly longer in the LM group; however, the postoperative peak level of liver transaminase in the LM group was lower than that in the OM group. Intraoperative blood loss was relatively small in both the groups (395.8±361.9 mL for OM and 328.2±328.0 mL for LM). It was reported that the average intraoperative blood loss during OM ranged from 380–2,450 mL (22). We think that the operative procedure in this study was stable. The postoperative complications were discussed in detail; however, no specific complications associated with the LM procedure were observed. The survival data were assessed using a PSM cohort. The median follow-up period of 20 months was too short to evaluate the long-term survival. The 3-year survival was 68.4% and 90.5% in the LM and OM groups, respectively. Only 2 patients (9.4%) in the LM group and 30 patients (31.3%) in the OM group were actually alive at 30 months. Based on these results, survival equivalence was unclear in this study. The authors reported in the previous paper that mesohepatectomy can provide better overall survival for CL-HCC than open extended hepatectomy based on a PSM cohort (23). Mesohepatectomy may have a survival benefit because of preservation of liver parenchyma.

Several recent studies have compared the benefits of LLR and OLR for HCC patients undergoing limited difficult procedures (24-27). A systematic review and meta-analysis for major hepatectomy was conducted using individual patient data of those who underwent LLR (n=427) and OLR (n=490) (25). This study included liver tumors other than HCC. The total morbidity was lower, and the hospital stay was significantly shorter in the LLR group. The incidence of major complications was not significantly different. The operative time was longer in the LLR group; however, intraoperative blood loss and blood transfusion were similar in the two groups. The overall survival in the HCC patients of the two groups was not significantly different. With respect to mesohepatectomy, in the recent PSM study that compared LM (n=18) and OM (n=36), the operation time was longer in the LM group; however, blood loss was lower, diet was resumed faster, and hospital stay was shorter for the LM group (26). All the patients were classified as Child’s class A cirrhosis. The long-term prognosis was comparable in the two groups.

Some scoring systems have been developed to assess the complexity of LLR. Ban’s difficulty scale (28) considers the following 5 factors: extent of liver resection, tumor location, tumor size, liver, function, and tumor proximity to major vessels. For centrally located tumors, 5 points for S8-located tumor is larger than 3 points for S4, S5-located tumor. Segmentectomy and sectionectomy or larger assigned 3 points and for 4 points, respectively. Hasegawa’s difficulty prediction model (29) was created to predict the surgical duration and considers the extent of resection (scored 0, 2, or 3), tumor location (scored 0, 1, or 2), presence of obesity (scored 0 or 1), and platelet count (scored 0 or 1). Anatomical segmentectomy had 2 points; however, central bisectionectomy was performed for only two patients. However, in the above two studies, those who underwent CM were not allocated to a separate group. As per Kawaguchi’s difficulty classification (30), those who underwent LM were allocated to Group III (most difficult group) that included posterosuperior segmentectomy, right posterior sectionectomy, right hepatectomy, and extended left/right hepatectomy. Even in this recent study, LM was actually performed for only 11 (2.4%) patients.

LM can become safer and easier with the use of an intrahepatic Glissonean approach, and anatomical resection is essential (17). Fluorescence imaging using indocyanine green (ICG) is now being used to identify the boundaries of hepatic segments for complete anatomical resection of the liver (31). In the present scenario, positive and negative staining techniques are used via portal injection of ICG solution and intravenous injection of ICG after closure or division of the target portal pedicle, respectively. This method is believed to be important for mesohepatectomy, and the latter is convenient to use in LM patients.

Finally, LM for CL-HCC is a technically challenging procedure with a steeper learning curve. The learning curve of major hepatectomy including central hepatectomy included the following three phases: phase 1 (45 initial patients), phase 2 (30 intermediate patients), and phase 3 (the subsequent 98 patients) (32). We believe that LM for CL-HCC should be performed by limited skilled LLR team who has sufficient experience of OM. It is important to note that the future of complicated LLR, including LM strongly depends on education initiatives that need to be carefully planned and regularly implemented (33).

Acknowledgments

Funding: None.

Footnote

Provenance and Peer Review: This article was commissioned by the editorial office, Laparoscopic Surgery. The article did not undergo external peer review.

Conflicts of Interest: The authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/ls.2019.09.06). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

References

1. Buell JF, Cherqui D, Geller DA, et al. The international position on laparoscopic liver surgery: the Louisville statement, 2008. Ann Surg 2009;250:825-30. [Crossref] [PubMed]
2. Wakabayashi G, Cherqui D, Geller DA, et al. Recommendations for laparoscopic liver resection: a report from the second international consensus conference held in Morioka. Ann Surg 2015;261:619-29. [PubMed]
3. Abu Hilal M, Aldrighetti L, Dagher I, et al. The Southampton consensus guidelines for laparoscopic liver surgery: from indication to implementation. Ann Surg 2018;268:11-8. [Crossref] [PubMed]
4. Beppu T, Hayashi H, Miyata T, et al. Is laparoscopic liver resection for hepatocellular carcinoma in patients with well-preserved liver cirrhosis superior to conventional open liver resection? Laparosc Surg 2018;2:64. [Crossref]
5. Xiangfei M, Yinzhe X, Yingwei P, et al. Open versus laparoscopic hepatic resection for hepatocellular carcinoma: a systematic review and meta-analysis. Surg Endosc 2019;33:2396-418. [Crossref] [PubMed]
6. Ciria R, Gomez-Luque I, Ocaña S, et al. A Systematic Review and Meta-Analysis Comparing the Short- and Long-Term Outcomes for Laparoscopic and Open Liver Resections for Hepatocellular Carcinoma: Updated Results from the European Guidelines Meeting on Laparoscopic Liver Surgery, Southampton, UK, 2017. Ann Surg Oncol 2019;26:252-63. [Crossref] [PubMed]
7. Lonjon G, Boutron I, Trinquart L, et al. Comparison of treatment effect estimates from prospective nonrandomized studies with propensity score analysis and randomized controlled trials of surgical procedures. Ann Surg 2014;259:18-25. [Crossref] [PubMed]
8. Kim H, Suh KS, Lee KW, et al. Long-term outcome of laparoscopic versus open liver resection for hepatocellular carcinoma: a case-controlled study with propensity score matching. Surg Endosc 2014;28:950-60. [Crossref] [PubMed]
9. Takahara T, Wakabayashi G, Beppu T, et al. Long-term and perioperative outcomes of laparoscopic versus open liver resection for hepatocellular carcinoma with propensity score matching: a multi-institutional Japanese study. J Hepatobiliary Pancreat Sci 2015;22:721-7. [Crossref] [PubMed]
10. Beppu T, Hayashi H, Okabe H, et al. Hybrid-including endoscopic versus open hepatic resection for patients with hepatocellular carcinoma meeting the Milan criteria: a propensity case-matched analysis. Anticancer Res 2015;35:1583-90. [PubMed]
11. Meguro M, Mizuguchi T, Kawamoto M, et al. Clinical comparison of laparoscopic and open liver resection after propensity matching selection. Surgery 2015;158:573-87. [Crossref] [PubMed]
12. Han HS, Shehta A, Ahn S, et al. Laparoscopic versus open liver resection for hepatocellular carcinoma: Case-matched study with propensity score matching. J Hepatol 2015;63:643-50. [Crossref] [PubMed]
13. Sposito C, Battiston C, Facciorusso A, et al. Propensity score analysis of outcomes following laparoscopic or open liver resection for hepatocellular carcinoma. Br J Surg 2016;103:871-80. [Crossref] [PubMed]
14. Nomi T, Hirokawa F, Kaibori M, et al. Laparoscopic versus open liver resection for hepatocellular carcinoma in elderly patients: a multi-centre propensity score-based analysis. Surg Endosc 2019; [Epub ahead of print]. [Crossref] [PubMed]
15. Chen X, Li B, He W, et al. Mesohepatectomy versus extended hemihepatectomy for centrally located hepatocellular carcinoma. Hepatobiliary Pancreat Dis Int 2014;13:264-70. [Crossref] [PubMed]
16. Yoon YS, Han HS, Cho JY, et al. Totally laparoscopic central bisectionectomy for hepatocellular carcinoma. J Laparoendosc Adv Surg Tech A 2009;19:653-6. [Crossref] [PubMed]
17. Machado MA, Kalil AN. Glissonian approach for laparoscopic mesohepatectomy. Surg Endosc 2011;25:2020-2. [Crossref] [PubMed]
18. Conrad C, Ogiso S, Inoue Y, et al. Laparoscopic parenchymal-sparing liver resection of lesions in the central segments: feasible, safe, and effective. Surg Endosc 2015;29:2410-7. [Crossref] [PubMed]
19. Li W, Han J, Xie G, et al. Laparoscopic versus open mesohepatectomy for patients with centrally located hepatocellular carcinoma: a propensity score matched analysis. Surg Endosc 2019;33:2916-26. [Crossref] [PubMed]
20. Qiu J, Wu H, Bai Y, et al. Mesohepatectomy for centrally located liver tumours. Br J Surg 2013;100:1620-6. [Crossref] [PubMed]
21. Qiu J, Chen S, Wu H, et al. The prognostic value of a classification system for centrally located liver tumors in the setting of hepatocellular carcinoma after mesohepatectomy. Surg Oncol 2016;25:441-7. [Crossref] [PubMed]
22. Lee SY. Central hepatectomy for centrally located malignant liver tumors: A systematic review. World J Hepatol 2014;6:347-57. [Crossref] [PubMed]
23. Li W, Li L, Minigalin D, et al. Anatomic mesohepatectomy versus extended hepatectomy for patients with centrally located hepatocellular carcinoma. HPB (Oxford) 2018;20:530-7. [Crossref] [PubMed]
24. Yoon YI, Kim KH, Kang SH, et al. Pure Laparoscopic Versus Open Right Hepatectomy for Hepatocellular Carcinoma in Patients With Cirrhosis: A Propensity Score Matched Analysis. Ann Surg 2017;265:856-63. [Crossref] [PubMed]
25. Kasai M, Cipriani F, Gayet B, et al. Laparoscopic versus open major hepatectomy: a systematic review and meta-analysis of individual patient data. Surgery 2018;163:985-95. [Crossref] [PubMed]
26. Kim WJ, Kim KH, Kim SH, et al. Laparoscopic versus open liver resection for centrally located hepatocellular carcinoma in patients with cirrhosis: A Propensity Score-matching Analysis. Surg Laparosc Endosc Percutan Tech 2018;28:394-400. [Crossref] [PubMed]
27. Zheng H, Huang SG, Qin SM, et al. Comparison of laparoscopic versus open liver resection for lesions located in posterosuperior segments: a meta-analysis of short-term and oncological outcomes. Surg Endosc 2019; [Epub ahead of print]. [Crossref] [PubMed]
28. Ban D, Tanabe M, Ito H, et al. A novel difficulty scoring system for laparoscopic liver resection. J Hepatobiliary Pancreat Sci 2014;21:745-53. [Crossref] [PubMed]
29. Hasegawa Y, Wakabayashi G, Nitta H, et al. A novel model for prediction of pure laparoscopic liver resection surgical difficulty. Surg Endosc 2017;31:5356-63. [Crossref] [PubMed]
30. Kawaguchi Y, Fuks D, Kokudo N, et al. Difficulty of Laparoscopic Liver Resection: Proposal for a New Classification. Ann Surg 2018;267:13-7. [Crossref] [PubMed]
31. Nakaseko Y, Ishizawa T, Saiura A. Fluorescence-guided surgery for liver tumors. J Surg Oncol 2018;118:324-31. [Crossref] [PubMed]
32. Nomi T, Fuks D, Kawaguchi Y, et al. Learning curve for laparoscopic major hepatectomy. Br J Surg 2015;102:796-804. [Crossref] [PubMed]
33. Beppu T, Yamamoto M. Laparoscopic versus open liver resection for colorectal liver metastases-Which is a more suitable standard practice? Ann Surg 2018;267:208-9. [Crossref] [PubMed]