Patryk Kambakamba1, Michael Linecker1, Marcel Schneider1, Cäcilia S Reiner2, Thi Dan Linh Nguyen-Kim2, Perparim Limani1, Ivan Romic3, Joan Figueras4, Henrik Petrowsky1, Pierre-Alain Clavien1, Mickaël Lesurtel5. 1. Department of Visceral and Transplant Surgery, University and University Hospital Zurich, Zürich, Switzerland. 2. Department of Radiology, University Hospital Zurich, Zürich, Switzerland. 3. Department of Surgery, University Hospital Zagreb, Zagreb, Croatia. 4. Department of Surgery, University Hospital Dr. Josep Trueta Girona, Girona, Spain. 5. Department of Visceral and Transplant Surgery, University and University Hospital Zurich, Zürich, Switzerland; Department of General Surgery and Liver Transplantation, Croix-Rousse University Hospital, Hospices Civils de Lyon, University of Lyon I, Lyon, France. Electronic address: mickael.lesurtel@chu-lyon.fr.
Abstract
BACKGROUND: Associating liver partition and portal vein ligation for staged hepatectomy induces an unprecedented liver hypertrophy and enables resection of otherwise unresectable liver tumors. The effect of associating liver partition and portal vein ligation for staged hepatectomy on tumor proliferation, however, remains a concern. This study investigated the impact of associating liver partition and portal vein ligation for staged hepatectomy on growth of colorectal metastases in mice and in humans. METHODS: The effect of associating liver partition and portal vein ligation for staged hepatectomy and 90% portal vein ligation on colorectal liver and lung metastases was investigated in mice. In vivo tumor progression was assessed by magnetic resonance imaging, histology, and survival experiments. The effects of associating liver partition and portal vein ligation for staged hepatectomy, portal vein ligation, and control sera on cultures of several colorectal cancer cell lines (MC38 and CT26) were tested in vitro. Additionally, the international associating liver partition and portal vein ligation for staged hepatectomy registry enabled us to identify patients with remaining tumor in the future liver remnant after associating liver partition and portal vein ligation for staged hepatectomy stage 1. RESULTS: Two and 3 weeks after associating liver partition and portal vein ligation for staged hepatectomy stage 1, portal vein ligation, or sham surgery, liver magnetic resonance images showed similar numbers (P=.14/0.82), sizes (P=.45/0.98), and growth kinetics (P=.58/0.68) of intrahepatic tumor. Tumor growth was not different between the associating liver partition and portal vein ligation for staged hepatectomy and portal vein ligation groups after completion of stage 2. Median survival after tumor cell injection was similar after sham surgery (36 days; 95% confidence interval; 27-57 days), completion of associating liver partition and portal vein ligation for staged hepatectomy (42 days; 95% confidence interval; 35-49 days), and portal vein ligation (39 days; 95% confidence interval; 34-43 days, P=.237). Progression of pulmonary metastases and in vitro cell proliferation were comparable among groups. Observations in humans failed to identify any accelerated tumor growth in the future liver remnant within the regenerative phase after associating liver partition and portal vein ligation for staged hepatectomy stage 1. CONCLUSION: The accelerated regeneration process associated with associating liver partition and portal vein ligation for staged hepatectomy does not appear to enhance growth of colorectal metastases.
BACKGROUND: Associating liver partition and portal vein ligation for staged hepatectomy induces an unprecedented liver hypertrophy and enables resection of otherwise unresectable liver tumors. The effect of associating liver partition and portal vein ligation for staged hepatectomy on tumor proliferation, however, remains a concern. This study investigated the impact of associating liver partition and portal vein ligation for staged hepatectomy on growth of colorectal metastases in mice and in humans. METHODS: The effect of associating liver partition and portal vein ligation for staged hepatectomy and 90% portal vein ligation on colorectal liver and lung metastases was investigated in mice. In vivo tumor progression was assessed by magnetic resonance imaging, histology, and survival experiments. The effects of associating liver partition and portal vein ligation for staged hepatectomy, portal vein ligation, and control sera on cultures of several colorectal cancer cell lines (MC38 and CT26) were tested in vitro. Additionally, the international associating liver partition and portal vein ligation for staged hepatectomy registry enabled us to identify patients with remaining tumor in the future liver remnant after associating liver partition and portal vein ligation for staged hepatectomy stage 1. RESULTS: Two and 3 weeks after associating liver partition and portal vein ligation for staged hepatectomy stage 1, portal vein ligation, or sham surgery, liver magnetic resonance images showed similar numbers (P=.14/0.82), sizes (P=.45/0.98), and growth kinetics (P=.58/0.68) of intrahepatic tumor. Tumor growth was not different between the associating liver partition and portal vein ligation for staged hepatectomy and portal vein ligation groups after completion of stage 2. Median survival after tumor cell injection was similar after sham surgery (36 days; 95% confidence interval; 27-57 days), completion of associating liver partition and portal vein ligation for staged hepatectomy (42 days; 95% confidence interval; 35-49 days), and portal vein ligation (39 days; 95% confidence interval; 34-43 days, P=.237). Progression of pulmonary metastases and in vitro cell proliferation were comparable among groups. Observations in humans failed to identify any accelerated tumor growth in the future liver remnant within the regenerative phase after associating liver partition and portal vein ligation for staged hepatectomy stage 1. CONCLUSION: The accelerated regeneration process associated with associating liver partition and portal vein ligation for staged hepatectomy does not appear to enhance growth of colorectal metastases.