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Anterior Approach vs Conventional Hepatectomy for Resection of Colorectal Liver MetastasisA Randomized Clinical Trial

Educational Objective
To identify whether an anterior approach hepatectomy vs a conventional hepatectomy for resection of colorectal liver metastasis results in a difference in tumor cell dissemination.
1 Credit CME
Key Points

Question  Does anterior approach hepatectomy reduce tumor cell dissemination during resection of colorectal liver metastasis compared with conventional hepatectomy?

Findings  In this randomized clinical trial including 80 participants, no statistically significant difference in tumor cell dissemination (5 of 21 [24%] vs 6 of 22 [27%]) and overall (median, 73 vs 55 months) and disease-free (median, 48 vs 40 months) survival was found between conventional hepatectomy and the anterior approach.

Meaning  These findings suggest that both techniques offer safe and comparable postoperative and survival outcomes in patients undergoing right-sided hepatectomy for colorectal cancer.


Importance  Tumor relapse after partial hepatectomy for colorectal liver metastasis (CRLM) remains an unsolved issue. Intraoperative manipulation of the liver during conventional hepatectomy might enhance hematogenous tumor cell spread. The anterior approach is an alternative approach that may reduce intraoperative tumor cell dissemination.

Objective  To determine the efficacy and safety of the anterior approach compared with conventional hepatectomy in patients undergoing resection for CRLM.

Design, Setting, and Participants  This randomized clinical study evaluated the efficacy and safety of the anterior approach compared with conventional hepatectomy in adult patients with CRLM who were scheduled for hepatectomy from February 1, 2003, to March 31, 2012, at a tertiary-care hospital. A total of 80 patients with CRLM were randomized to the anterior approach and conventional hepatectomy groups in a 1:1 ratio. Bone marrow and blood samples were analyzed for disseminated tumor cells and circulating tumor cells (CTC) using cytokeratin 20 reverse transcriptase–polymerase chain reaction analysis. Data were analyzed from April 1 to December 1, 2018, using intention to treat.

Interventions  Anterior approach vs conventional hepatectomy.

Main Outcomes and Measures  The primary end point was intraoperative CTC detection in central blood samples after liver resection. Secondary end points included postoperative morbidity, mortality, and long-term survival.

Results  Among the 80 patients included in the analysis (48 men [60%]; mean [SD] age, 61 [10] years), baseline characteristics, including preoperative CTC detection, were comparable between both groups. There was no statistically significant difference in intraoperative CTC detection between patients in the conventional hepatectomy (5 of 21 [24%]) and anterior approach (6 of 22 [27%]) groups (P > .99). Except for a longer operating time in the anterior approach group (mean [SD], 171 [53] vs 221 [53] minutes; P < .001), there were no significant differences in intraoperative and postoperative outcomes between both study groups. Although detection of CTC was associated with poor overall (median, 46 [95% CI, 40-52] vs 81 [95% CI, 54-107] months; P = .03) and disease-free (median, 40 [95% CI, 34-46] vs 60 [95% CI, 46-74] months; P = .04) survival, there was no significant difference in overall (median, 73 [95% CI, 42-104] vs 55 [95% CI, 35-75] months; P = .43) and disease-free (median, 48 [95% CI, 40-56] vs 40 [95% CI, 28-52] months; P = .88) survival between the conventional hepatectomy and anterior approach groups. Also, there was no significant difference in patterns of recurrence between both groups.

Conclusions and Relevance  This randomized clinical trial found that the anterior approach was not superior to conventional hepatectomy in reducing intraoperative tumor cell dissemination in patients undergoing resection of CRLM.

Trial Registration Identifier: ISRCTN45066244

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CME Disclosure Statement: Unless noted, all individuals in control of content reported no relevant financial relationships. If applicable, all relevant financial relationships have been mitigated.

Article Information

Accepted for Publication: July 30, 2020.

Published Online: November 4, 2020. doi:10.1001/jamasurg.2020.5050

Correction: This article was corrected on May 26, 2021, to fix the P value for the detection of preoperative and intraoperative tumor cells in the Abstract, main text, and Table 3, and to fix an error in the numbers at risk in Figure 2A.

Corresponding Author: Jürgen Weitz, MD, Department of Gastrointestinal, Thoracic and Vascular Surgery, University Hospital Carl Gustav Carus at the Technische Universität Dresden, Fetscherstraße 74, 01307 Dresden, Germany (

Author Contributions: Drs Rahbari and Birgin contributed equally to this study. Drs Rahbari and Birgin had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

Concept and design: Weitz.

Acquisition, analysis, or interpretation of data: All authors.

Drafting of the manuscript: Rahbari, Birgin.

Critical revision of the manuscript for important intellectual content: All authors.

Statistical analysis: Rahbari, Birgin.

Administrative, technical, or material support: Bork, Mehrabi, Weitz.

Supervision: Rahbari, Bork, Reißfelder.

Conflict of Interest Disclosures: None reported.

Funding/Support: This study was supported by the Department of Surgery, University of Heidelberg.

Role of the Funder/Sponsor: The sponsor had no role in the design and conduct of the study; interpretation of the data; and preparation, review, or approval of the manuscript. The sponsor was involved in the collection, management, and analysis of the data and granted approval to submit the manuscript for publication.

Data Sharing Statement: See Supplement 3.

Creasy  JM , Sadot  E , Koerkamp  BG ,  et al.  Actual 10-year survival after hepatic resection of colorectal liver metastases: what factors preclude cure?   Surgery. 2018;163(6):1238-1244. doi:10.1016/j.surg.2018.01.004 PubMedGoogle ScholarCrossref
de Jong  MC , Mayo  SC , Pulitano  C ,  et al.  Repeat curative intent liver surgery is safe and effective for recurrent colorectal liver metastasis: results from an international multi-institutional analysis.   J Gastrointest Surg. 2009;13(12):2141-2151. doi:10.1007/s11605-009-1050-0 PubMedGoogle ScholarCrossref
de Jong  MC , Pulitano  C , Ribero  D ,  et al.  Rates and patterns of recurrence following curative intent surgery for colorectal liver metastasis: an international multi-institutional analysis of 1669 patients.   Ann Surg. 2009;250(3):440-448. doi:10.1097/SLA.0b013e3181b4539b PubMedGoogle ScholarCrossref
Rahbari  NN , D’Angelica  MI .  Surgical salvage of recurrence after resection of colorectal liver metastases: incidence and outcomes.   Hepat Oncol. 2017;4(1):25-33. doi:10.2217/hep-2017-0002 PubMedGoogle Scholar
Bork  U , Rahbari  NN , Schölch  S ,  et al.  Circulating tumour cells and outcome in non-metastatic colorectal cancer: a prospective study.   Br J Cancer. 2015;112(8):1306-1313. doi:10.1038/bjc.2015.88 PubMedGoogle ScholarCrossref
Groot Koerkamp  B , Rahbari  NN , Büchler  MW , Koch  M , Weitz  J .  Circulating tumor cells and prognosis of patients with resectable colorectal liver metastases or widespread metastatic colorectal cancer: a meta-analysis.   Ann Surg Oncol. 2013;20(7):2156-2165. doi:10.1245/s10434-013-2907-8 PubMedGoogle ScholarCrossref
Rahbari  NN , Aigner  M , Thorlund  K ,  et al.  Meta-analysis shows that detection of circulating tumor cells indicates poor prognosis in patients with colorectal cancer.   Gastroenterology. 2010;138(5):1714-1726. doi:10.1053/j.gastro.2010.01.008 PubMedGoogle ScholarCrossref
Rahbari  NN , Bork  U , Schölch  S ,  et al.  Metastatic spread emerging from liver metastases of colorectal cancer: does the seed leave the soil again?   Ann Surg. 2016;263(2):345-352. doi:10.1097/SLA.0000000000001341 PubMedGoogle ScholarCrossref
Iwatsuki  S , Esquivel  CO , Gordon  RD , Starzl  TE .  Liver resection for metastatic colorectal cancer.   Surgery. 1986;100(4):804-810.PubMedGoogle Scholar
Weitz  J , Koch  M , Kienle  P ,  et al.  Detection of hematogenic tumor cell dissemination in patients undergoing resection of liver metastases of colorectal cancer.   Ann Surg. 2000;232(1):66-72. doi:10.1097/00000658-200007000-00010 PubMedGoogle ScholarCrossref
Hao  S , Chen  S , Tu  C , Huang  T .  Anterior approach to improve the prognosis in HCC patients via decreasing dissemination of EpCAM+ circulating tumor cells.   J Gastrointest Surg. 2017;21(7):1112-1120. doi:10.1007/s11605-017-3410-5 PubMedGoogle ScholarCrossref
Liu  CL , Fan  ST , Cheung  ST , Lo  CM , Ng  IO , Wong  J .  Anterior approach versus conventional approach right hepatic resection for large hepatocellular carcinoma: a prospective randomized controlled study.   Ann Surg. 2006;244(2):194-203. doi:10.1097/01.sla.0000225095.18754.45 PubMedGoogle ScholarCrossref
Schmidt  T , Koch  M , Antolovic  D ,  et al.  Influence of two different resection techniques (conventional liver resection versus anterior approach) of liver metastases from colorectal cancer on hematogenous tumor cell dissemination: prospective randomized multicenter trial.   BMC Surg. 2008;8:6. doi:10.1186/1471-2482-8-6 PubMedGoogle ScholarCrossref
Weitz  J , Kienle  P , Magener  A ,  et al.  Detection of disseminated colorectal cancer cells in lymph nodes, blood and bone marrow.   Clin Cancer Res. 1999;5(7):1830-1836.PubMedGoogle Scholar
Ozawa  K .  Nonconventional Approaches to Advanced Liver Cancer: Liver Surgery Approached Through the Mitochondria. Medical Tribune; 1992:117-165.
Liddo  G , Buc  E , Nagarajan  G , Hidaka  M , Dokmak  S , Belghiti  J .  The liver hanging manoeuvre.   HPB (Oxford). 2009;11(4):296-305. doi:10.1111/j.1477-2574.2009.00068.x PubMedGoogle ScholarCrossref
Li  Y , Xu  KS , Li  JS ,  et al.  The research of no-touch isolation technique on the prevention of postoperative recurrence and metastasis of hepatocellular carcinoma after hepatectomy.   Hepatogastroenterology. 2014;61(131):784-791.PubMedGoogle Scholar
Arrazubi  V , Mata  E , Antelo  ML ,  et al.  Circulating tumor cells in patients undergoing resection of colorectal cancer liver metastases: clinical utility for long-term outcome: a prospective trial.   Ann Surg Oncol. 2019;26(9):2805-2811. doi:10.1245/s10434-019-07503-8 PubMedGoogle ScholarCrossref
Seeberg  LT , Waage  A , Brunborg  C ,  et al.  Circulating tumor cells in patients with colorectal liver metastasis predict impaired survival.   Ann Surg. 2015;261(1):164-171. doi:10.1097/SLA.0000000000000580 PubMedGoogle ScholarCrossref
Gasch  C , Bauernhofer  T , Pichler  M ,  et al.  Heterogeneity of epidermal growth factor receptor status and mutations of KRAS/PIK3CA in circulating tumor cells of patients with colorectal cancer.   Clin Chem. 2013;59(1):252-260. doi:10.1373/clinchem.2012.188557 PubMedGoogle ScholarCrossref
Mostert  B , Jiang  Y , Sieuwerts  AM ,  et al.  KRAS and BRAF mutation status in circulating colorectal tumor cells and their correlation with primary and metastatic tumor tissue.   Int J Cancer. 2013;133(1):130-141. doi:10.1002/ijc.27987 PubMedGoogle ScholarCrossref
Soler  A , Cayrefourcq  L , Mazard  T ,  et al.  Autologous cell lines from circulating colon cancer cells captured from sequential liquid biopsies as model to study therapy-driven tumor changes.   Sci Rep. 2018;8(1):15931. doi:10.1038/s41598-018-34365-z PubMedGoogle ScholarCrossref
She  WH , Chan  ACY , Ma  KW ,  et al.  Anterior approach to major resection for colorectal liver metastasis.   J Gastrointest Surg. 2018;22(11):1928-1938. doi:10.1007/s11605-018-3840-8 PubMedGoogle ScholarCrossref
Llado  L , Muñoz  A , Ramos  E , Torras  J , Fabregat  J , Rafecas  A .  The anterior hanging-approach improves postoperative course after right hepatectomy in patients with colorectal liver metastases: results of a prospective study with propensity-score matching comparison.   Eur J Surg Oncol. 2016;42(2):176-183. doi:10.1016/j.ejso.2015.11.009 PubMedGoogle ScholarCrossref
Fritzmann  J , Kirchberg  J , Sturm  D ,  et al.  Randomized clinical trial of stapler hepatectomy versus LigaSure™ transection in elective hepatic resection.   Br J Surg. 2018;105(9):1119-1127. doi:10.1002/bjs.10902 PubMedGoogle ScholarCrossref
Fretland  AA , Dagenborg  VJ , Bjørnelv  GMW ,  et al.  Laparoscopic versus open resection for colorectal liver metastases: the OSLO-COMET randomized controlled trial.   Ann Surg. 2018;267(2):199-207. doi:10.1097/SLA.0000000000002353 PubMedGoogle ScholarCrossref
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.   Ann Surg. 2012;255(3):405-414. doi:10.1097/SLA.0b013e31824856f5 PubMedGoogle ScholarCrossref
Capussotti  L , Ferrero  A , Russolillo  N , Langella  S , Lo Tesoriere  R , Viganò  L .  Routine anterior approach during right hepatectomy: results of a prospective randomised controlled trial.   J Gastrointest Surg. 2012;16(7):1324-1332. doi:10.1007/s11605-012-1894-6 PubMedGoogle ScholarCrossref
Coppa  J , Citterio  D , Cotsoglou  C ,  et al.  Transhepatic anterior approach to the inferior vena cava in large retroperitoneal tumors resected en bloc with the right liver lobe.   Surgery. 2013;154(5):1061-1068. doi:10.1016/j.surg.2013.05.027 PubMedGoogle ScholarCrossref
Hinz  S , Hendricks  A , Wittig  A ,  et al.  Detection of circulating tumor cells with CK20 RT-PCR is an independent negative prognostic marker in colon cancer patients: a prospective study.   BMC Cancer. 2017;17(1):53. doi:10.1186/s12885-016-3035-1 PubMedGoogle ScholarCrossref
Koch  M , Kienle  P , Hinz  U ,  et al.  Detection of hematogenous tumor cell dissemination predicts tumor relapse in patients undergoing surgical resection of colorectal liver metastases.   Ann Surg. 2005;241(2):199-205. doi:10.1097/01.sla.0000151795.15068.27 PubMedGoogle ScholarCrossref
Soeth  E , Vogel  I , Röder  C ,  et al.  Comparative analysis of bone marrow and venous blood isolates from gastrointestinal cancer patients for the detection of disseminated tumor cells using reverse transcription PCR.   Cancer Res. 1997;57(15):3106-3110.PubMedGoogle Scholar
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