Minimally invasive liver resection—more evidence of oncologic advantage

Minimally invasive liver resection—more evidence of oncologic advantage

Rajesh Ramanathan, David A. Geller

Division of Hepatobiliary Surgery, Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA, USA

Correspondence to: David A. Geller, MD. Division of Hepatobiliary Surgery, Department of Surgery, University of Pittsburgh Medical Center, 3459 Fifth Ave., Pittsburgh, PA 15213-2582, USA. Email:

Provenance: This is an invited article commissioned by the Editor-in-Chief Minhua Zheng (Department of General Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Minimal Invasive Surgery Center, Shanghai, China).

Comment on: Kawai T, Goumard C, Jeune F, et al. Laparoscopic liver resection for colorectal liver metastasis patients allows patients to start adjuvant chemotherapy without delay: a propensity score analysis. Surg Endosc 2018. [Epub ahead of print].

Received: 17 April 2018; Accepted: 25 April 2018; Published: 10 May 2018.

doi: 10.21037/ales.2018.04.11

Liver resection for colorectal cancer liver metastases (CRCLM) improves survival in patients with metachronous and synchronous metastases, and adjuvant systemic chemotherapy (AC) is often utilized (1,2). Furthermore, the timing of AC seems to be important, with studies reporting a survival benefit to initiation within 8 weeks of resection (3,4).

Utilization of minimally invasive laparoscopic liver resection (LLR) is increasing in CRCLM, with robust evidence that LLR is safe and offers clinical advantages over open liver resection (OLR) (5-9). To further elucidate the oncologic advantages of LLR, Kawai et al. report results of a retrospective, propensity-matched analysis of LLR vs. OLR in patients with CRCLM (10). They examine time to AC as the primary endpoint. Over a 2-year period, they report on 30 LLR and 87 OLR, with a propensity-matched comparison of 22 LLR and 44 OLR. The two groups were propensity-matched according to baseline and comorbidity variables, preoperative receipt of chemotherapy, pathologic tumor factors, and extent of resection. On overall analysis, the LLR cohort was older, and had a greater proportion of solitary metastasis. There was no difference in postoperative complications or length of stay (LOS). LLR, however, had a shorter time to AC initiation (45 vs. 53 days), and a higher proportion of those initiating AC within 8 weeks (100% vs. 70%) compared to OLR. Propensity-matched analysis reinforced these findings with continued 12-day delay to AC initiation in OLR, and a 34% rate of failure to initiate AC within 8 weeks.

The findings by Kawai et al. are consistent with other reports on the oncologic benefits of LLR over OLR with regards to time to AC initiation. Our group has previously reported that LLR was associated with a shorter time to AC (42 vs. 63 days), and higher recurrence-free survival compared to OLR (11). In addition, we found that LLR was associated with less blood loss, shorter LOS (4 vs. 5 days), and less 30-day overall, complications (26% vs. 28%). After adjusting for blood loss, LOS, and complications, LLR remained an independent contributor to earlier AC initiation with a two-fold higher likelihood as compared to OLR. This same topic was analyzed by Mbah et al. in a series of major liver resections alone for CRCLM (12). They compared 44 LLR to 76 OLR matched by extent of resection, and found that time to AC was significantly shorter after LLR (24 vs. 39 days). In addition, they also identified less blood loss, shorter LOS (5 vs. 9 days), and less complications (14% vs. 36%) with LLR as compared to OLR. This echoes the large body of literature whereby OLR has been reported to have increased incidence of postoperative complications and LOS as compared to LLR (13-17). In the present study by Kawai et al., however, there was no statistically significant difference in complications or LOS between LLR and OLR. Interpreted in the context of a longer than expected LOS of 8 days in both groups, it does raise concerns for postoperative complications or other confounders not captured in the analysis.

Taken together, these studies indicate that LLR for CRCLM is associated with earlier time to initiation of AC. The specific mechanism of this benefit remains unclear. Although LLR is usually associated with fewer complications than OLR, decreased postoperative complications and shorter LOS do not seem to explain the entire benefit. In the series by Tohme et al., LLR remained an independent predictor of earlier AC initiation after adjusting for postoperative complications and LOS (11), and Kawai et al. also identified a shorter time to AC after LLR that cannot be attributed to a difference in complications, blood loss, extent of resection, pathologic tumor factors or LOS.

There is emerging evidence that minimally invasive approaches may be associated with different levels of circulating cytokines as compared to open surgery, affecting overall recovery as well as oncologic outcomes (18). Yamashita et al. recently reported lower postoperative serum C-reactive protein (CRP) levels following minimally invasive esophagectomy (19). Those patients with lower CRP levels demonstrated improved disease-free survival and improved overall survival. Furthermore, in the Oslo-CoMet randomized clinical trial of LLR vs. OLR of CRCLM, five inflammatory cytokines including CRP were present at significantly higher levels after OLR, reaffirming the association between operative approach and the inflammatory state postoperatively (18). Given the known association between surgical inflammation and cancer proliferation, modulation of the circulating inflammatory milieu could explain why LLR is associated with earlier initiation of AC and survival (20). Further mechanistic studies detailing the impact of minimally invasive surgery on the surrounding inflammatory milieu may thus serve to improve our understanding of the molecular basis for the improved oncologic outcomes. Other hypotheses worth considering for the independent effect of LLR on earlier AC initiation include improved patient perceptions and referring medical oncologist perceptions of health after minimally invasive surgery. Given that one of the main criterion to initiate AC is the subjective medical ‘readiness’ of a patient, smaller incisions and smaller scars psychologically may make patients and medical oncologists ‘feel’ that a patient is ready to initiate AC earlier than after OLR.

In conclusion, Kawai et al. contribute to the growing body of literature supporting LLR over OLR for improved cancer-related quality benchmarks and outcomes (21). Additional investigations are certainly warranted to provide more mechanistic explanations for this advantage.




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


  1. Choti MA, Sitzmann JV, Tiburi MF, et al. Trends in long-term survival following liver resection for hepatic colorectal metastases. Ann Surg 2002;235:759-66. [Crossref] [PubMed]
  2. Nordlinger B, Sorbye H, Glimelius B, et al. Perioperative FOLFOX4 chemotherapy and surgery versus surgery alone for resectable liver metastases from colorectal cancer (EORTC 40983): long-term results of a randomised, controlled, phase 3 trial. Lancet Oncol 2013;14:1208-15. [Crossref] [PubMed]
  3. Biagi JJ, Raphael MJ, Mackillop WJ, et al. Association between time to initiation of adjuvant chemotherapy and survival in colorectal cancer: a systematic review and meta-analysis. JAMA 2011;305:2335-42. [Crossref] [PubMed]
  4. Day AR, Middleton G, Smith RV, et al. Time to adjuvant chemotherapy following colorectal cancer resection is associated with an improved survival. Colorectal Dis 2014;16:368-72. [Crossref] [PubMed]
  5. Nguyen KT, Geller DA. Outcomes of laparoscopic hepatic resection for colorectal cancer metastases. J Surg Oncol 2010;102:975-7. [Crossref] [PubMed]
  6. 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. Ann Surg 2009;250:842-8. [Crossref] [PubMed]
  7. Schiffman SC, Kim KH, Tsung A, et al. Laparoscopic versus open liver resection for metastatic colorectal cancer: a metaanalysis of 610 patients. Surgery 2015;157:211-22. [Crossref] [PubMed]
  8. Nguyen KT, Gamblin TC, Geller DA. World review of laparoscopic liver resection-2,804 patients. Ann Surg 2009;250:831-41. [Crossref] [PubMed]
  9. Fretland ÅA, Dagenborg VJ, Bjørnelv GM, et al. Laparoscopic Versus Open Resection for Colorectal Liver Metastases: The OSLO-COMET Randomized Controlled Trial. Ann Surg 2018;267:199-207. [Crossref] [PubMed]
  10. Kawai T, Goumard C, Jeune F, et al. Laparoscopic liver resection for colorectal liver metastasis patients allows patients to start adjuvant chemotherapy without delay: a propensity score analysis. Surg Endosc 2018. [Epub ahead of print]. [Crossref] [PubMed]
  11. Tohme S, Goswami J, Han K, et al. Minimally Invasive Resection of Colorectal Cancer Liver Metastases Leads to an Earlier Initiation of Chemotherapy Compared to Open Surgery. J Gastrointest Surg 2015;19:2199-206. [Crossref] [PubMed]
  12. Mbah N, Agle SC, Philips P, et al. Laparoscopic hepatectomy significantly shortens the time to postoperative chemotherapy in patients undergoing major hepatectomies. Am J Surg 2017;213:1060-4. [Crossref] [PubMed]
  13. Geller DA, Tsung A. Long-term outcomes and safety of laparoscopic liver resection surgery for hepatocellular carcinoma and metastatic colorectal cancer. J Hepatobiliary Pancreat Sci 2015;22:728-30. [Crossref] [PubMed]
  14. Cannon RM, Scoggins CR, Callender GG, et al. Laparoscopic versus open resection of hepatic colorectal metastases. Surgery 2012;152:567-73. [Crossref] [PubMed]
  15. Simillis C, Constantinides VA, Tekkis PP, et al. Laparoscopic versus open hepatic resections for benign and malignant neoplasms--a meta-analysis. Surgery 2007;141:203-11. [Crossref] [PubMed]
  16. Mala T, Edwin B, Gladhaug I, et al. A comparative study of the short-term outcome following open and laparoscopic liver resection of colorectal metastases. Surg Endosc 2002;16:1059-63. [Crossref] [PubMed]
  17. Nguyen KT, Marsh JW, Tsung A, et al. Comparative benefits of laparoscopic vs open hepatic resection: a critical appraisal. Arch Surg 2011;146:348-56. [Crossref] [PubMed]
  18. Fretland AA, Sokolov A, Postriganova N, et al. Inflammatory Response After Laparoscopic Versus Open Resection of Colorectal Liver Metastases: Data From the Oslo-CoMet Trial. Medicine (Baltimore) 2015;94:e1786. [Crossref] [PubMed]
  19. Yamashita K, Watanabe M, Mine S, et al. Minimally invasive esophagectomy attenuates the postoperative inflammatory response and improves survival compared with open esophagectomy in patients with esophageal cancer: a propensity score matched analysis. Surg Endosc 2018. [Epub ahead of print]. [Crossref] [PubMed]
  20. Tohme S, Simmons RL, Tsung A. Surgery for Cancer: A Trigger for Metastases. Cancer Res 2017;77:1548-52. [Crossref] [PubMed]
  21. Aloia TA, Zimmitti G, Conrad C, et al. Return to intended oncologic treatment (RIOT): a novel metric for evaluating the quality of oncosurgical therapy for malignancy. J Surg Oncol 2014;110:107-14. [Crossref] [PubMed]
doi: 10.21037/ales.2018.04.11
Cite this article as: Ramanathan R, Geller DA. Minimally invasive liver resection—more evidence of oncologic advantage. Ann Laparosc Endosc Surg 2018;3:43.