Is laparoscopic liver resection for hepatocellular carcinoma in patients with well-preserved liver cirrhosis superior to conventional open liver resection?
Editorial

Is laparoscopic liver resection for hepatocellular carcinoma in patients with well-preserved liver cirrhosis superior to conventional open liver resection?

Toru Beppu1,2, Hiromitsu Hayashi2, Tastunori Miyata2, Nobutaka Sato1,2, Yasushi Yoshida1,2

1Department of Surgery, Yamaga City Medical Center, Kumamoto, Japan; 2Department of Gastroenterological Surgery, Graduate School of Life Sciences, Kumamoto University, Kumamoto, Japan

Correspondence to: Toru Beppu, MD, PhD, FACS. Department of Surgery, Yamaga City Medical Center, Kumamoto, 511 Yamaga, Kumamoto 861-0593, Japan. Email: tbeppu@yamaga-mc.jp.

Provenance: This is an invited article commissioned by the Editor-in-Chief Giovanni Battista Levi Sandri (Division of General Surgery, Santa Scolatisca Hospital, Cassino, Lazio, Italy).

Comment on: Wu X, Huang Z, Lau WY, et al. Perioperative and long-term outcomes of laparoscopic versus open liver resection for hepatocellular carcinoma with well-preserved liver function and cirrhotic background: a propensity score matching study. Surg Endosc 2018. [Epub ahead of print].


Received: 13 November 2018; Accepted: 21 November 2018; Published: 27 November 2018.

doi: 10.21037/ls.2018.11.06


Laparoscopic liver resection (LLR) has become the standard treatment for various tumors of the liver including hepatocellular carcinoma (HCC) (1-3). LLR for liver tumors are considered to possess several perioperative advantages compared with conventional open liver resection (OLR). The Oslo-CoMet is the only randomized-controlled trial (RCT) to provide solid evidence that LLR is safer, less invasive, and cost-effective compared with OLR in patients with colorectal liver metastases (4). Unfortunately, there are no RCTs comparing LLR and OLR in patients with HCC. Numerous original studies, reviews, and meta-analyses comparing LLR with OLR for HCC harbor evident selection biases in the size, number, and location of the tumor, because LLR was performed in cases that tended to be less challenging, especially in the learning phase of this new approach. Importantly, several studies including HCC patients utilized propensity score matching (PSM) to minimalize such selection biases (5) and demonstrated that LLR was associated with slightly longer surgical times, reduced intraoperative blood loss and transfusion rates, shorter hospital stays, lower morbidity, and similar mortality compared with OLR (6-13). From an oncological viewpoint, LLR can provide long-term outcomes comparable with OLR with no specific recurrence patterns. Although several reports compared LLR and OLR specifically in patients with HCC and liver cirrhosis (14-17), the definition of liver cirrhosis varied among the studies.

We congratulate Dr. Wu and colleagues for their recently published study entitled “Perioperative and long-term outcomes of laparoscopic versus open liver resection for hepatocellular carcinoma with well-preserved liver function and cirrhotic background: a propensity score matching study” in Surgical Endoscopy (18). In this unique study, the authors compared LLR with OLR for patients with limited HCC and well-preserved liver cirrhosis and used one-to-one PSM to minimalize the confounding factors. The background variables were well investigated and well matched after PSM, including baseline characteristics, preoperative laboratory and intraoperative data, and pathological tumor characteristics in both groups. The authors compared surgical outcomes and long-term prognosis in patients who underwent LLR and OLR. The primary endpoint was to determine the risk factors for post-hepatectomy liver failure (PHLF) proposed by the International Study Group of Liver Surgery (ISGLS) (19). ISGLS grades B and C PHLF were reported to be an accurate predictor of postoperative mortality in a recent international multicenter study (20). In their study, Wu et al. indeed found that the frequency of grade B PHLF was significantly higher in the OLR group than the LLR group. Factors that might have contributed to this outcome can be categorized as patient-, surgery-, and background liver function-related (21). Among the surgery-related factors are small liver remnant, massive intraoperative bleeding, transfusion of red cell concentrates, and postoperative major complications. Conversely, the lower rate of morbidity was a major cause of the lower PHLF rate. The study included several resection approaches; however, minor resection was the most frequent method in both the LLR (73.3%) and the OLR (82.6%) groups.

We would like to ask Wu and colleagues to elucidate their finding of OLR as the only independent risk factor for PHLF (odds ratio, 2.539, 95% confidence interval: 1.127-7.851, P=0.014). The article was unclear on assignment of the study patients to undergo LLR or OLR. Certainly, the authors stated that the choice between LLR and OLR in all cases was determined by comprehensive assessment by surgeons with informed consent from the patients (18). PSM is quite difficult to achieve if the target patient selection to undergo LLR or OLR is completely separated. Although the background factors were well-matched between the two groups; efforts to match factors that determine surgical difficulty were not insufficient (22,23). Unresolved selection bias such as frailty and sarcopenia might exist which can influence the PHLF rate between the two groups (24,25).

Additionally, the definition of well-preserved liver function and cirrhotic background is critical. The inclusion criteria used in this study (18) were: (I) histopathological diagnosis of HCC and a background of cirrhosis; and (II) well-preserved liver function defined as Child-Pugh class A with less than 10% retention rate of indocyanine green (ICG) retention at 15 min and adequate future liver remnant (FLR) at >40% of total liver volume. Patients with pathological cirrhosis are well known to occasionally exhibit abnormal ICG retention rates at 15 min (26). In our experience, only 7 of 34 (20.6%) HCC patients with histologically confirmed liver cirrhosis who underwent LLR showed normal ICG retention rates at 15 min (8). This criterion should be considered as another limitation that could have contributed to the selection of patients with severe cirrhosis in the current study. We propose that patients considered for LLR should be selected carefully with adaptation on the laparoscopic technique.

The authors also found that the morbidity in the LLR group was significantly lower than that in the OLR group (7.0% vs. 19.8%, P=0.014) and was accompanied with a lower rate of ascites (0% vs. 7.0%, P=0.029). The median hospital stay was significantly shorter in the LLR group (8 vs. 13 days, P=0.018). These advantages can be explained by the hemostatic effect of pneumoperitoneum, better magnification, and application of newly developed devices for parenchymal transection. Conversely, the amount of blood loss and the rate of blood transfusion were comparable between the two groups. These results are different that those reported in previous comparative studies of cirrhotic HCC patients undergoing LLR or OLR (14-17), in which the conversion rate was relatively high at 9.3%. Albeit slightly higher in the LLR group compared to the OLR group, the survival curves were not significantly different between the two groups. Similar, comparable survival rates were reported previously (6-15,17). However, one pivotal study of cirrhotic patients demonstrated that LLR was associated with a significantly higher median overall survival (136 vs. 120 months for OLR) and greater 5-year overall survival (83.7% vs. 67.4% for OLR) (P<0.033) (16). This survival advantage was detected only in patients with stage II HCC (P=0.045). This difference was suggested to be due to less blood loss and less tissue manipulation, defined as “no-touch isolation”, in LLR compared to OLR.

In recent years, LLR has become an especially useful tool for patients with advanced liver cirrhosis. To minimize the incision wound can preserve portosystemic collaterals and lymphatic circulation. Additionally, refractory ascites can be controlled by avoiding liver mobilization. Conversely, high-pressure pneumoperitoneum can lead to a decrease in the portal vein flow in the cirrhotic liver. The study by Wu et al. included only HCC patients with well-preserved liver function and a cirrhotic background; therefore, their findings are less impactful compared to other studies investigating patients with more advanced cirrhosis (14-17). Therefore, further prospective studies are critical to investigate the utility of LLR and its potential superiority to OLR based on to the extent of liver cirrhosis.


Acknowledgements

None.


Footnote

Conflicts of Interest: The authors have no conflicts of interest to declare.


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. Fretland ÅA, Dagenborg VJ, Bjørnelv GMW, et al. Laparoscopic versus open resection for colorectal liver metastases: The OSLO-COMET randomized controlled trial. Ann Surg 2018;267:199-207. [Crossref] [PubMed]
  5. 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]
  6. 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]
  7. 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]
  8. 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]
  9. 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]
  10. 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]
  11. Yoon SY, Kim KH, Jung DH, et al. Oncological and surgical results of laparoscopic versus open liver resection for HCC less than 5 cm: case-matched analysis. Surg Endosc 2015;29:2628-34. Erratum in: Surg Endosc 2015;29:2635. [Crossref] [PubMed]
  12. 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]
  13. Han DH, Choi SH, Park EJ, et al. Surgical outcomes after laparoscopic or robotic liver resection in hepatocellular carcinoma: a propensity-score matched analysis with conventional open liver resection. Int J Med Robot 2016;12:735-42. [Crossref] [PubMed]
  14. Kanazawa A, Tsukamoto T, Shimizu S, et al. Impact of laparoscopic liver resection for hepatocellular carcinoma with F4-liver cirrhosis. Surg Endosc 2013;27:2592-7. [Crossref] [PubMed]
  15. Morise Z, Kawabe N, Kawase J, et al. Pure laparoscopic hepatectomy for hepatocellular carcinoma with chronic liver disease. World J Hepatol 2013;5:487-95. [Crossref] [PubMed]
  16. Cheung TT, Dai WC, Tsang SH, et al. Pure Laparoscopic Hepatectomy Versus Open Hepatectomy for Hepatocellular Carcinoma in 110 Patients With Liver Cirrhosis: A Propensity Analysis at a Single Center. Ann Surg 2016;264:612-20. [Crossref] [PubMed]
  17. 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]
  18. Wu X, Huang Z, Lau WY, et al. Perioperative and long-term outcomes of laparoscopic versus open liver resection for hepatocellular carcinoma with well-preserved liver function and cirrhotic background: a propensity score matching study. Surg Endosc 2018. [Epub ahead of print]. [Crossref] [PubMed]
  19. Rahbari NN, Garden OJ, Padbury R, et al. Posthepatectomy liver failure: a definition and grading by the International Study Group of Liver Surgery (ISGLS). Surgery 2011;149:713-24. [Crossref] [PubMed]
  20. Sultana A, Brooke-Smith M, Ullah S, et al. Prospective evaluation of the International Study Group for Liver Surgery definition of post hepatectomy liver failure after liver resection: an international multicentre study. HPB (Oxford) 2018;20:462-9. [Crossref] [PubMed]
  21. Rahnemai-Azar AA, Cloyd JM, Weber SM, et al. Update on Liver Failure Following Hepatic Resection: Strategies for Prediction and Avoidance of Post-operative Liver Insufficiency. J Clin Transl Hepatol 2018;6:97-104. [Crossref] [PubMed]
  22. 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]
  23. 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]
  24. Louwers L, Schnickel G, Rubinfeld I, et al. Use of a simplified frailty index to predict Clavien 4 complications and mortality after hepatectomy: analysis of the National Surgical Quality Improvement Project database. Am J Surg 2016;211:1071-6. [Crossref] [PubMed]
  25. Valero V 3rd, Amini N, Spolverato G, et al. Sarcopenia adversely impacts postoperative complications following resection or transplantation in patients with primary liver tumors. J Gastrointest Surg 2015;19:272-81. [Crossref] [PubMed]
  26. Lee SG, Hwang S. How I do it: assessment of hepatic functional reserve for indication of hepatic resection. J Hepatobiliary Pancreat Surg 2005;12:38-43. [Crossref] [PubMed]
doi: 10.21037/ls.2018.11.06
Cite this article as: Beppu T, Hayashi H, Miyata T, Sato N, Yoshida Y. 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.