Can laparoscopic liver resection for colorectal liver metastases provide early initiation of adjuvant chemotherapy?

Can laparoscopic liver resection for colorectal liver metastases provide early initiation of adjuvant chemotherapy?

Toru Beppu1,2, Katsunori Imai2, Koichi Kinoshita1,2, Yasushi Yoshida1,2, Hideo Baba2

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, 511 Yamaga, Kumamoto 861-0593, Japan. Email:

Provenance: This is an invited Editorial 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: 03 April 2018; Accepted: 10 April 2018; Published: 23 April 2018.

doi: 10.21037/ales.2018.04.06

The long-term outcome of patients with colorectal liver metastases (CRLM) has improved because of advances in surgical technique and perioperative chemotherapy (1-3). Liver resection followed by adjuvant chemotherapy (AC) provides better recurrence-free survival in patients with CRLM than surgery alone (4,5).

Laparoscopic liver resection (LLR) has become a standard procedure worldwide for CRLM (6,7). LLR for CRLM has some advantages compared with conventional open liver resection (OLR). Several studies using propensity score matching (PSM) and one meta-analysis of PSM studies have demonstrated comparable results in patients having LLR compared with patients having OLR, including longer or similar operative times, reduced intraoperative blood loss, less need for transfusion, similar surgical margins, shorter hospital stays, lower or equal morbidity, and equivalent mortality (8-11). From an oncological perspective, LLR can result in a similar long-term outcome without any specialized recurrence pattern. Furthermore, the results of the OSLO-COMET randomized controlled trial (RCT) have provided solid evidence that LLR for patients with CRLM is safer, less invasive, and cost effective (12,13).

We congratulate Dr. Kawai and colleagues for publishing “Laparoscopic liver resection for colorectal liver metastasis patients allows patients to start adjuvant chemotherapy without delay: a propensity score analysis” in Surgical Endoscopy (14). Several studies have demonstrated that AC is beneficial for stage III colorectal cancer (15,16), and it should be started within 8 weeks postoperatively to prevent tumor relapse and metastasis (17,18).

Two papers have focused on the impact of LLR on the timing of postoperative AC in patients with CRLM (19,20); however, these studies could not rule out the influence of confounding background factors between LLR and OLR patients. Furthermore, both studies have shown higher complication rates in LLR than in OLR, which strongly influenced the timing of postoperative AC. Another study demonstrated that a delay in AC initiation could be associated with worse overall and recurrence-free survival (21).

In the current paper, the authors performed a one to two PSM analysis to decrease the influence of cofounding factors in LLR and OLR groups (14). After PSM, all clinicopathological findings were well balanced between 22 LLR patients and 44 OLR patients. Finally, after LLR, all patients were administered postoperative AC within 8 weeks. In contrast, 34% of OLR patients had delayed postoperative AC initiation. This study showed a significantly shorter interval between LLR and AC initiation than OLR (43±11 vs. 53±18 days, P=0.011), despite comparable postoperative complications and hospital stays. The authors asserted that the diminished surgical trauma in LLR could shorten postoperative recovery, allowing patients to begin with postoperative AC within the optimal timeframe.

It is difficult to determine why LLR can shorten the interval between surgery and AC initiation. The complication rates were similar in both Clavien-Dindo grades I–II and III–IV (22), and reoperation was never encountered. Postoperative stay was 1 day shorter in LLR, but the difference was not significant. Simultaneous resection of primary colorectal cancer could delay AC initiation; however, this was not addressed in the report. In addition, the preference of the surgeon in determining AC initiation is important, and similarities between surgeons performing LLR and OLR should be clarified.

One previous paper showed better health-related quality of life (HRQOL) assessed with the 36-item Medical Outcomes Study Short Form (SF-36) test in LLR compared to OLR within a year after surgery (23). In a recent RCT, HRQOL was similarly determined using SF-36 test 1 month after surgery (12). Mean values were significantly different: 0.713 and 0.665 in LLR and OLR, respectively. The frequency of postoperative scar discomfort or stiffness was significantly lower in the assisted LLR group than in the OLR group (2.6% vs. 31.2%; P<0.001) (24). Better HRQOL and less subjective symptoms immediately after LLR could influence a timing of AC initiation.

Very recently, a meta-analysis of PSM studies demonstrated a better 3-year overall survival of patients with CRLM who underwent LLR than those who underwent OLR (11). To keep the duration of liver resection and the AC start within 8 weeks might be essential to achieve excellent long-term prognosis. Further prospective large-size studies will be required.




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


  1. Nordlinger B, Sorbye H, Glimelius B, et al. Perioperative chemotherapy with FOLFOX4 and surgery versus surgery alone for resectable liver metastases from colorectal cancer (EORTC Intergroup trial 40983): a randomised controlled trial. Lancet 2008;371:1007-16. [Crossref] [PubMed]
  2. Adam R, De Gramont A, Figueras J, et al. The oncosurgery approach to managing liver metastases from colorectal cancer: a multidisciplinary international consensus. Oncologist 2012;17:1225-39. [Crossref] [PubMed]
  3. Beppu T, Sakamoto Y, Hasegawa K, et al. A Nomogram Predicting Disease-free Survival in Patients with Colorectal Liver Metastases Treated with Hepatic Resection: Multicenter Data Collection as a Project Study for Hepatic Surgery of the Japanese Society of Hepato-Biliary-Pancreatic Surgery. J Hepatobiliary Pancreat Sci 2012;19:72-84. [Crossref] [PubMed]
  4. Mitry E, Fields AL, Bleiberg H, et al. Adjuvant chemotherapy after potentially curative resection of metastases from colorectal cancer: a pooled analysis of two randomized trials. J Clin Oncol 2008;26:4906-11. [Crossref] [PubMed]
  5. Hasegawa K, Saiura A, Takayama T, et al. Adjuvant Oral Uracil-Tegafur with Leucovorin for Colorectal Cancer Liver Metastases: A Randomized Controlled Trial. PLoS One 2016;11:e0162400. [Crossref] [PubMed]
  6. 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]
  7. Wakabayashi G, Cherqui D, Geller DA, et al. Recommendations for laparoscopic liver resection: a report from the second International Consensus Conference held in Iwate. Ann Surg 2015;261:619-29. [PubMed]
  8. Beppu T, Wakabayashi G, Hasegawa K, et al. Long-term and perioperative outcomes of laparoscopic versus open liver resection for colorectal liver metastases with propensity score matching: a multi-institutional Japanese study. J Hepatobiliary Pancreat Sci 2015;22:711-20. [Crossref] [PubMed]
  9. Allard MA, Cunha AS, Gayet B, et al. Colorectal Liver Metastases-French Study Group. Early and long-term oncological outcomes after laparoscopic resection for colorectal liver metastases: A propensity score-based analysis. Ann Surg 2015;262:794-802. [Crossref] [PubMed]
  10. Cipriani F, Rawashdeh M, Stanton L, et al. Propensity score-based analysis of outcomes of laparoscopic versus open liver resection for colorectal metastases. Br J Surg 2016;103:1504-12. [Crossref] [PubMed]
  11. Zhang XL, Liu RF, Zhang D, et al. Laparoscopic versus open liver resection for colorectal liver metastases: A systematic review and meta-analysis of studies with propensity score-based analysis. Int J Surg 2017;44:191-203. [Crossref] [PubMed]
  12. 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]
  13. 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]
  14. 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]
  15. André T, Boni C, Navarro M, et al. Improved overall survival with oxaliplatin, fluorouracil, and leucovorin as adjuvant treatment in stage II or III colon cancer in the MOSAIC trial. J Clin Oncol 2009;27:3109-16. [Crossref] [PubMed]
  16. André T, de Gramont A, Vernerey D, et al. Adjuvant Fluorouracil, Leucovorin, and Oxaliplatin in Stage II to III Colon Cancer: Updated 10-Year Survival and Outcomes According to BRAF Mutation and Mismatch Repair Status of the MOSAIC Study. J Clin Oncol 2015;33:4176-87. [Crossref] [PubMed]
  17. Hershman D, Hall MJ, Wang X, et al. Timing of adjuvant chemotherapy initiation after surgery for stage III colon cancer. Cancer 2006;107:2581-8. [Crossref] [PubMed]
  18. Bos AC, van Erning FN, van Gestel YR, et al. Timing of adjuvant chemotherapy and its relation to survival among patients with stage III colon cancer. Eur J Cancer 2015;51:2553-61. [Crossref] [PubMed]
  19. 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]
  20. 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]
  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]
  22. 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. Ann Surg 2004;240:205-13. [Crossref] [PubMed]
  23. Giuliani A, Migliaccio C, Ceriello A, et al. Laparoscopic vs. open surgery for treating benign liver lesions: assessing quality of life in the first year after surgery. Updates Surg 2014;66:127-33. [Crossref] [PubMed]
  24. Kitajima T, Kaido T, Iida T, et al. Short-term outcomes of laparoscopy-assisted hybrid living donor hepatectomy: a comparison with the conventional open procedure. Surg Endosc 2017;31:5101-10. [Crossref] [PubMed]
doi: 10.21037/ales.2018.04.06
Cite this article as: Beppu T, Imai K, Kinoshita K, Yoshida Y, Baba H. Can laparoscopic liver resection for colorectal liver metastases provide early initiation of adjuvant chemotherapy? Ann Laparosc Endosc Surg 2018;3:35.