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Right portal vein ligation: reply
332
Letters to the Editor
to resect tumors involving all three hepatic veins.3 Both authors use portal vein embolization extensively and have not described abnormal growth of tumors in the nonembolized liver segments during the waiting time of liver regeneration. Liver metastases are supplied mainly by the hepatic artery, whereas normal liver is primarily perfused by the portal vein.4,5 After portal vein embolization, arterial flow in the embolized hemiliver increases significantly,6 resulting in a potential risk for increased tumor progression in the ligated liver segments. Remarkably, because small liver metastases are primarily vascularized by the portal vein,7,8 and left portal flow increases markedly after right portal vein ligation or embolization,6 no intrahepatic recurrences in the left liver are reported in this series.1 This may be an indirect sign that surgery in this cohort was indeed radical, and no microscopic metastatic foci were present in the left lobe. Some concerns may be raised about pharmacokinetics of oral capecitabine in these patients. This drug passes rapidly and extensively through the intestinal membrane as an intact molecule,9 and it is then activated in tumor tissue.10 Ligation of the portal vein of the hemiliver harboring the residual metastases might impair its clinical efficacy if administered as adjuvant treatment after the primary procedure in these patients. Though promising, this new technique might need further studies in animal models to investigate the kinetics of liver tumor growth after portal vein ligation and embolization before being routinely applied in humans. REFERENCES 1. Kianmanesh R, Farges O, Abdalla EK, et al. Right portal vein ligation: a new planned two-step all-surgical approach for complete resection of primary gastrointestinal tumors with multiple bilateral liver metastases. J Am Coll Surg 2003;197:164–170. 2. Minagawa M, Makuuchi M, Torzilli G, et al. Extension of the frontiers of surgical indications in the treatment of liver metastases from colorectal cancer: long-term results. Ann Surg 2000; 231:487–499. 3. Nagino M, Yamada T, Kamiya J, et al. Left hepatic trisegmentectomy with right hepatic vein resection after right hepatic vein embolization. Surgery 2003;133:580–582. 4. Breedis C, Young C. The blood supply of neoplasms in the liver. Am J Pathol 1954;30:969. 5. Kemeny N, Fata F. Arterial, portal, or systemic chemotherapy for patients with hepatic metastasis of colorectal carcinoma. J Hepatobiliary Pancreat Surg 1999;6:39–49. 6. Kito Y, Nagino M, Nimura Y. Doppler sonography of hepatic arterial blood flow velocity after percutaneous transhepatic por-
J Am Coll Surg
7. 8. 9.
10.
tal vein embolization. AJR Am J Roentgenol 2001;176:909– 912. Ackermann NB. The blood supply of experimental liver metastasis. IV. Changes in vascularity with increasing tumor growth. Surgery 1974;2:589–597. Bassermann R. Changes of vascular pattern of tumors and surrounding tissue during different phases of metastatic growth. Cancer Res 1986;100:256–264. Schu¨ ller J, Cassidy J, Dumont E, et al. Preferential activation of capecitabine in tumor following oral administration to colorectal cancer patients. Cancer Chemother Pharmacol 2000;45: 291–297. Miwa M, Ura M, Nishida M, et al. Design of a novel oral fluoropyrimidine carbamate, capecitabine, which generates 5-fluorouracil selectively in tumors by enzyme concentrated in human liver and cancer tissue. Eur J Cancer 1998;34:1274– 1281.
Reply Reza Kianmanesh, MD Jacques Belghiti, MD Clichy, France We thank Dr Papadia for his comments concerning our described two-step all-surgical technique, which is a new strategy for achievement of “macroscopic cure” in patients with primary intact gross gastrointestinal tumors and diffuse bilobar liver metastases. Concerning the definition of “unresectable” liver metastases, we consider as “unresectable” in whom all of the liver metastases cannot be removed at one-step surgery and those who require extensive complex resections, not leaving behind sufficient functional liver parenchyma with adequate inflow and outflow pedicles. As is mentioned in our article, this is a rare situation, and the studied population represented less than 10% of the whole population of liver resection for gastrointestinal metastases (both from neuroendocrine or colorectal origin) in our center. Dr Papadia is concerned about the eventual growth of tumors in both left and right liver after portal ligation. This concern led us to remove all detected left liver metastases (including those in segments 1 and 4). This is part of the concept of bringing to hypertrophy a “cleared” left liver after right portal vein ligation. Additionally, to avoid right liver tumor growth (and possibly left liver micrometastases), we routinely propose systemic chemotherapy after the first step, especially if the
Vol. 198, No. 2, February 2004
period before the planned second step (right or extended right hepatectomy) is estimated to be longer than 6 to 8 weeks. As mentioned in the discussion section of our article, more and more patients receive preoperative chemotherapy and might have an injured liver parenchyma.
Letters to the Editor
333
The risk of major liver resection in these patients justifies differing major complex liver resections and gastrointestinal surgery and performing portal vein ligation to increase tolerance and safety of the major liver resection planned at the second step.
Letters to the Editor
to resect tumors involving all three hepatic veins.3 Both authors use portal vein embolization extensively and have not described abnormal growth of tumors in the nonembolized liver segments during the waiting time of liver regeneration. Liver metastases are supplied mainly by the hepatic artery, whereas normal liver is primarily perfused by the portal vein.4,5 After portal vein embolization, arterial flow in the embolized hemiliver increases significantly,6 resulting in a potential risk for increased tumor progression in the ligated liver segments. Remarkably, because small liver metastases are primarily vascularized by the portal vein,7,8 and left portal flow increases markedly after right portal vein ligation or embolization,6 no intrahepatic recurrences in the left liver are reported in this series.1 This may be an indirect sign that surgery in this cohort was indeed radical, and no microscopic metastatic foci were present in the left lobe. Some concerns may be raised about pharmacokinetics of oral capecitabine in these patients. This drug passes rapidly and extensively through the intestinal membrane as an intact molecule,9 and it is then activated in tumor tissue.10 Ligation of the portal vein of the hemiliver harboring the residual metastases might impair its clinical efficacy if administered as adjuvant treatment after the primary procedure in these patients. Though promising, this new technique might need further studies in animal models to investigate the kinetics of liver tumor growth after portal vein ligation and embolization before being routinely applied in humans. REFERENCES 1. Kianmanesh R, Farges O, Abdalla EK, et al. Right portal vein ligation: a new planned two-step all-surgical approach for complete resection of primary gastrointestinal tumors with multiple bilateral liver metastases. J Am Coll Surg 2003;197:164–170. 2. Minagawa M, Makuuchi M, Torzilli G, et al. Extension of the frontiers of surgical indications in the treatment of liver metastases from colorectal cancer: long-term results. Ann Surg 2000; 231:487–499. 3. Nagino M, Yamada T, Kamiya J, et al. Left hepatic trisegmentectomy with right hepatic vein resection after right hepatic vein embolization. Surgery 2003;133:580–582. 4. Breedis C, Young C. The blood supply of neoplasms in the liver. Am J Pathol 1954;30:969. 5. Kemeny N, Fata F. Arterial, portal, or systemic chemotherapy for patients with hepatic metastasis of colorectal carcinoma. J Hepatobiliary Pancreat Surg 1999;6:39–49. 6. Kito Y, Nagino M, Nimura Y. Doppler sonography of hepatic arterial blood flow velocity after percutaneous transhepatic por-
J Am Coll Surg
7. 8. 9.
10.
tal vein embolization. AJR Am J Roentgenol 2001;176:909– 912. Ackermann NB. The blood supply of experimental liver metastasis. IV. Changes in vascularity with increasing tumor growth. Surgery 1974;2:589–597. Bassermann R. Changes of vascular pattern of tumors and surrounding tissue during different phases of metastatic growth. Cancer Res 1986;100:256–264. Schu¨ ller J, Cassidy J, Dumont E, et al. Preferential activation of capecitabine in tumor following oral administration to colorectal cancer patients. Cancer Chemother Pharmacol 2000;45: 291–297. Miwa M, Ura M, Nishida M, et al. Design of a novel oral fluoropyrimidine carbamate, capecitabine, which generates 5-fluorouracil selectively in tumors by enzyme concentrated in human liver and cancer tissue. Eur J Cancer 1998;34:1274– 1281.
Reply Reza Kianmanesh, MD Jacques Belghiti, MD Clichy, France We thank Dr Papadia for his comments concerning our described two-step all-surgical technique, which is a new strategy for achievement of “macroscopic cure” in patients with primary intact gross gastrointestinal tumors and diffuse bilobar liver metastases. Concerning the definition of “unresectable” liver metastases, we consider as “unresectable” in whom all of the liver metastases cannot be removed at one-step surgery and those who require extensive complex resections, not leaving behind sufficient functional liver parenchyma with adequate inflow and outflow pedicles. As is mentioned in our article, this is a rare situation, and the studied population represented less than 10% of the whole population of liver resection for gastrointestinal metastases (both from neuroendocrine or colorectal origin) in our center. Dr Papadia is concerned about the eventual growth of tumors in both left and right liver after portal ligation. This concern led us to remove all detected left liver metastases (including those in segments 1 and 4). This is part of the concept of bringing to hypertrophy a “cleared” left liver after right portal vein ligation. Additionally, to avoid right liver tumor growth (and possibly left liver micrometastases), we routinely propose systemic chemotherapy after the first step, especially if the
Vol. 198, No. 2, February 2004
period before the planned second step (right or extended right hepatectomy) is estimated to be longer than 6 to 8 weeks. As mentioned in the discussion section of our article, more and more patients receive preoperative chemotherapy and might have an injured liver parenchyma.
Letters to the Editor
333
The risk of major liver resection in these patients justifies differing major complex liver resections and gastrointestinal surgery and performing portal vein ligation to increase tolerance and safety of the major liver resection planned at the second step.