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Published in: Journal of Gastrointestinal Surgery 7/2007

01-07-2007

Preoperative Chemotherapy for Colorectal Liver Metastases: Impact on Hepatic Histology and Postoperative Outcome

Authors: Timothy M. Pawlik, Kelly Olino, Ana Luiza Gleisner, Michael Torbenson, Richard Schulick, Michael A. Choti

Published in: Journal of Gastrointestinal Surgery | Issue 7/2007

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Abstract

Some investigators have suggested that preoperative chemotherapy for hepatic colorectal metastases may cause hepatic injury and increase perioperative morbidity and mortality. The objective of the current study was to examine whether treatment with preoperative chemotherapy was associated with hepatic injury of the nontumorous liver and whether such injury, if present, was associated with increased morbidity or mortality after hepatic resection. Two-hundred and twelve eligible patients who underwent hepatic resection for colorectal liver metastases between January 1999 and December 2005 were identified. Data on demographics, clinicopathologic characteristics, and preoperative chemotherapy details were collected and analyzed. The majority of patients received preoperative chemotherapy (n = 153; 72.2%). Chemotherapy consisted of fluoropyrimidine-based regimens: 5-FU monotherapy, 31.6%; irinotecan, 25.9%; and oxaliplatin, 14.6%. Among those patients who received chemotherapy, the type of chemotherapy regimen predicted distinct patterns of liver injury. Oxaliplatin was associated with increased likelihood of grade 3 sinusoidal dilatation (p = 0.017). Steatosis >30% was associated with irinotecan (27.3%) compared with no chemotherapy, 5-FU monotherapy, and oxaliplatin (all p < 0.05). Irinotecan also was associated with steatohepatitis, as two of the three patients with steatohepatitis had received irinotecan preoperatively. Overall, the perioperative complication rate was similar between the no-chemotherapy group (30.5%) and the chemotherapy group (35.3%) (p = 0.79). Preoperative chemotherapy was also not associated with 60-day mortality. In patients with hepatic colorectal metastases, preoperative chemotherapy is associated with hepatic injury in about 20 to 30% of patients. Furthermore, the type of hepatic injury after preoperative chemotherapy was regimen-specific.
Literature
1.
go back to reference Colucci G, Maiello E, Leo S, Giuliani F, Pedicini A, Pezzella G, Valori V, Galetta D, Contillo A, Prete F. Biochemical modulation of fluorouracil with high dose methotrexate or folinic acid in advanced colorectal cancer patients. Gruppo Oncologico dell’ Italia Meridionale (GOIM). Anticancer Res 1994;14:2157–2162.PubMed Colucci G, Maiello E, Leo S, Giuliani F, Pedicini A, Pezzella G, Valori V, Galetta D, Contillo A, Prete F. Biochemical modulation of fluorouracil with high dose methotrexate or folinic acid in advanced colorectal cancer patients. Gruppo Oncologico dell’ Italia Meridionale (GOIM). Anticancer Res 1994;14:2157–2162.PubMed
2.
go back to reference Saltz LB, Cox JV, Blanke C, Rosen LS, Fehrenbacher L, Moore MJ, Maroun JA, Ackland SP, Locker PK, Pirotta N, Elfring GL, Miller LL. Irinotecan plus fluorouracil and leucovorin for metastatic colorectal cancer. Irinotecan Study Group. N Engl J Med 2000;343:905–914.PubMedCrossRef Saltz LB, Cox JV, Blanke C, Rosen LS, Fehrenbacher L, Moore MJ, Maroun JA, Ackland SP, Locker PK, Pirotta N, Elfring GL, Miller LL. Irinotecan plus fluorouracil and leucovorin for metastatic colorectal cancer. Irinotecan Study Group. N Engl J Med 2000;343:905–914.PubMedCrossRef
3.
go back to reference Leichman CG, Fleming TR, Muggia FM, Tangen CM, Ardalan B, Doroshow JH, Meyers FJ, Holcombe RF, Weiss GR, Mangalik A, et al. Phase II study of fluorouracil and its modulation in advanced colorectal cancer: a Southwest Oncology Group study. J Clin Oncol 1995;13:1303–1311.PubMed Leichman CG, Fleming TR, Muggia FM, Tangen CM, Ardalan B, Doroshow JH, Meyers FJ, Holcombe RF, Weiss GR, Mangalik A, et al. Phase II study of fluorouracil and its modulation in advanced colorectal cancer: a Southwest Oncology Group study. J Clin Oncol 1995;13:1303–1311.PubMed
4.
go back to reference Buroker TR, O’Connell MJ, Wieand HS, Krook JE, Gerstner JB, Mailliard JA, Schaefer PL, Levitt R, Kardinal CG, Gesme DH, Jr. Randomized comparison of two schedules of fluorouracil and leucovorin in the treatment of advanced colorectal cancer. J Clin Oncol 1994;12:14–20.PubMed Buroker TR, O’Connell MJ, Wieand HS, Krook JE, Gerstner JB, Mailliard JA, Schaefer PL, Levitt R, Kardinal CG, Gesme DH, Jr. Randomized comparison of two schedules of fluorouracil and leucovorin in the treatment of advanced colorectal cancer. J Clin Oncol 1994;12:14–20.PubMed
5.
go back to reference Modulation of fluorouracil by leucovorin in patients with advanced colorectal cancer: evidence in terms of response rate. Advanced Colorectal Cancer Meta-Analysis Project. J Clin Oncol 1992;10:896–903. Modulation of fluorouracil by leucovorin in patients with advanced colorectal cancer: evidence in terms of response rate. Advanced Colorectal Cancer Meta-Analysis Project. J Clin Oncol 1992;10:896–903.
6.
go back to reference de Gramont A, Figer A, Seymour M, Homerin M, Hmissi A, Cassidy J, Boni C, Cortes-Funes H, Cervantes A, Freyer G, Papamichael D, Le Bail N, Louvet C, Hendler D, de Braud F, Wilson C, Morvan F, Bonetti A. Leucovorin and fluorouracil with or without oxaliplatin as first-line treatment in advanced colorectal cancer. J Clin Oncol 2000;18:2938–2947.PubMed de Gramont A, Figer A, Seymour M, Homerin M, Hmissi A, Cassidy J, Boni C, Cortes-Funes H, Cervantes A, Freyer G, Papamichael D, Le Bail N, Louvet C, Hendler D, de Braud F, Wilson C, Morvan F, Bonetti A. Leucovorin and fluorouracil with or without oxaliplatin as first-line treatment in advanced colorectal cancer. J Clin Oncol 2000;18:2938–2947.PubMed
7.
go back to reference Giacchetti S, Perpoint B, Zidani R, Le Bail N, Faggiuolo R, Focan C, Chollet P, Llory JF, Letourneau Y, Coudert B, Bertheaut-Cvitkovic F, Larregain-Fournier D, Le Rol A, Walter S, Adam R, Misset JL, Levi F. Phase III multicenter randomized trial of oxaliplatin added to chronomodulated fluorouracil-leucovorin as first-line treatment of metastatic colorectal cancer. J Clin Oncol 2000;18:136–147.PubMed Giacchetti S, Perpoint B, Zidani R, Le Bail N, Faggiuolo R, Focan C, Chollet P, Llory JF, Letourneau Y, Coudert B, Bertheaut-Cvitkovic F, Larregain-Fournier D, Le Rol A, Walter S, Adam R, Misset JL, Levi F. Phase III multicenter randomized trial of oxaliplatin added to chronomodulated fluorouracil-leucovorin as first-line treatment of metastatic colorectal cancer. J Clin Oncol 2000;18:136–147.PubMed
8.
go back to reference Goldberg RM, Sargent DJ, Morton RF, Fuchs CS, Ramanathan RK, Williamson SK, Findlay BP, Pitot HC, Alberts SR. A randomized controlled trial of fluorouracil plus leucovorin, irinotecan, and oxaliplatin combinations in patients with previously untreated metastatic colorectal cancer. J Clin Oncol 2004;22:23–30.PubMedCrossRef Goldberg RM, Sargent DJ, Morton RF, Fuchs CS, Ramanathan RK, Williamson SK, Findlay BP, Pitot HC, Alberts SR. A randomized controlled trial of fluorouracil plus leucovorin, irinotecan, and oxaliplatin combinations in patients with previously untreated metastatic colorectal cancer. J Clin Oncol 2004;22:23–30.PubMedCrossRef
9.
go back to reference Tournigand C, Andre T, Achille E, Lledo G, Flesh M, Mery-Mignard D, Quinaux E, Couteau C, Buyse M, Ganem G, Landi B, Colin P, Louvet C, de Gramont A. FOLFIRI followed by FOLFOX6 or the reverse sequence in advanced colorectal cancer: a randomized GERCOR study. J Clin Oncol 2004;22:229–237.PubMedCrossRef Tournigand C, Andre T, Achille E, Lledo G, Flesh M, Mery-Mignard D, Quinaux E, Couteau C, Buyse M, Ganem G, Landi B, Colin P, Louvet C, de Gramont A. FOLFIRI followed by FOLFOX6 or the reverse sequence in advanced colorectal cancer: a randomized GERCOR study. J Clin Oncol 2004;22:229–237.PubMedCrossRef
10.
go back to reference Bismuth H, Adam R, Levi F, Farabos C, Waechter F, Castaing D, Majno P, Engerran L. Resection of nonresectable liver metastases from colorectal cancer after neoadjuvant chemotherapy. Ann Surg 1996;224:509–520; discussion 520–522.PubMedCrossRef Bismuth H, Adam R, Levi F, Farabos C, Waechter F, Castaing D, Majno P, Engerran L. Resection of nonresectable liver metastases from colorectal cancer after neoadjuvant chemotherapy. Ann Surg 1996;224:509–520; discussion 520–522.PubMedCrossRef
11.
go back to reference Adam R, Delvart V, Pascal G, Valeanu A, Castaing D, Azoulay D, Giacchetti S, Paule B, Kunstlinger F, Ghemard O, Levi F, Bismuth H. Rescue surgery for unresectable colorectal liver metastases downstaged by chemotherapy: a model to predict long-term survival. Ann Surg 2004;240:644–657; discussion 657–648.PubMedCrossRef Adam R, Delvart V, Pascal G, Valeanu A, Castaing D, Azoulay D, Giacchetti S, Paule B, Kunstlinger F, Ghemard O, Levi F, Bismuth H. Rescue surgery for unresectable colorectal liver metastases downstaged by chemotherapy: a model to predict long-term survival. Ann Surg 2004;240:644–657; discussion 657–648.PubMedCrossRef
12.
go back to reference Adam R, Avisar E, Ariche A, Giachetti S, Azoulay D, Castaing D, Kunstlinger F, Levi F, Bismuth F. Five-year survival following hepatic resection after neoadjuvant therapy for nonresectable colorectal. Ann Surg Oncol 2001;8:347–353.PubMedCrossRef Adam R, Avisar E, Ariche A, Giachetti S, Azoulay D, Castaing D, Kunstlinger F, Levi F, Bismuth F. Five-year survival following hepatic resection after neoadjuvant therapy for nonresectable colorectal. Ann Surg Oncol 2001;8:347–353.PubMedCrossRef
13.
go back to reference Parikh AA, Gentner B, Wu TT, Curley SA, Ellis LM, Vauthey JN. Perioperative complications in patients undergoing major liver resection with or without neoadjuvant chemotherapy. J Gastrointest Surg 2003;7:1082–1088.PubMedCrossRef Parikh AA, Gentner B, Wu TT, Curley SA, Ellis LM, Vauthey JN. Perioperative complications in patients undergoing major liver resection with or without neoadjuvant chemotherapy. J Gastrointest Surg 2003;7:1082–1088.PubMedCrossRef
14.
go back to reference Rubbia-Brandt L, Audard V, Sartoretti P, Roth AD, Brezault C, Le Charpentier M, Dousset B, Morel P, Soubrane O, Chaussade S, Mentha G, Terris B. Severe hepatic sinusoidal obstruction associated with oxaliplatin-based chemotherapy in patients with metastatic colorectal cancer. Ann Oncol 2004;15:460–466.PubMedCrossRef Rubbia-Brandt L, Audard V, Sartoretti P, Roth AD, Brezault C, Le Charpentier M, Dousset B, Morel P, Soubrane O, Chaussade S, Mentha G, Terris B. Severe hepatic sinusoidal obstruction associated with oxaliplatin-based chemotherapy in patients with metastatic colorectal cancer. Ann Oncol 2004;15:460–466.PubMedCrossRef
15.
go back to reference Fernandez FG, Ritter J, Goodwin JW, Linehan DC, Hawkins WG, Strasberg SM. Effect of steatohepatitis associated with irinotecan or oxaliplatin pretreatment on resectability of hepatic colorectal metastases. J Am Coll Surg 2005;200:845–853.PubMedCrossRef Fernandez FG, Ritter J, Goodwin JW, Linehan DC, Hawkins WG, Strasberg SM. Effect of steatohepatitis associated with irinotecan or oxaliplatin pretreatment on resectability of hepatic colorectal metastases. J Am Coll Surg 2005;200:845–853.PubMedCrossRef
16.
go back to reference Kooby DA, Fong Y, Suriawinata A, Gonen M, Allen PJ, Klimstra DS, DeMatteo RP, D’Angelica M, Blumgart LH, Jarnagin WR. Impact of steatosis on perioperative outcome following hepatic resection. J Gastrointest Surg 2003;7:1034–1044.PubMedCrossRef Kooby DA, Fong Y, Suriawinata A, Gonen M, Allen PJ, Klimstra DS, DeMatteo RP, D’Angelica M, Blumgart LH, Jarnagin WR. Impact of steatosis on perioperative outcome following hepatic resection. J Gastrointest Surg 2003;7:1034–1044.PubMedCrossRef
17.
go back to reference Martin RC, 2nd, Brennan MF, Jaques DP. Quality of complication reporting in the surgical literature. Ann Surg 2002;235:803–813.PubMedCrossRef Martin RC, 2nd, Brennan MF, Jaques DP. Quality of complication reporting in the surgical literature. Ann Surg 2002;235:803–813.PubMedCrossRef
18.
go back to reference Kleiner DE, Brunt EM, Van Natta M, Behling C, Contos MJ, Cummings OW, Ferrell LD, Liu YC, Torbenson MS, Unalp-Arida A, Yeh M, McCullough AJ, Sanyal AJ. Design and validation of a histological scoring system for nonalcoholic fatty liver disease. Hepatology 2005;41:1313–1321.PubMedCrossRef Kleiner DE, Brunt EM, Van Natta M, Behling C, Contos MJ, Cummings OW, Ferrell LD, Liu YC, Torbenson MS, Unalp-Arida A, Yeh M, McCullough AJ, Sanyal AJ. Design and validation of a histological scoring system for nonalcoholic fatty liver disease. Hepatology 2005;41:1313–1321.PubMedCrossRef
19.
go back to reference Adam R, Pascal G, Castaing D, Azoulay D, Delvart V, Paule B, Levi F, Bismuth H. Tumor progression while on chemotherapy: a contraindication to liver resection for multiple colorectal metastases? Ann Surg 2004;240:1052–1061; discussion 1061–1064.PubMedCrossRef Adam R, Pascal G, Castaing D, Azoulay D, Delvart V, Paule B, Levi F, Bismuth H. Tumor progression while on chemotherapy: a contraindication to liver resection for multiple colorectal metastases? Ann Surg 2004;240:1052–1061; discussion 1061–1064.PubMedCrossRef
20.
go back to reference Pawlik TM, Abdalla EK, Ellis LM, Vauthey JN, Curley SA. Debunking dogma: surgery for four or more colorectal liver metastases is justified. J Gastrointest Surg 2006;10:240–248.PubMedCrossRef Pawlik TM, Abdalla EK, Ellis LM, Vauthey JN, Curley SA. Debunking dogma: surgery for four or more colorectal liver metastases is justified. J Gastrointest Surg 2006;10:240–248.PubMedCrossRef
21.
go back to reference Vauthey JN, Pawlik TM, Ribero D, Wu TT, Hoff PM, Xiong H, Eng C, Curley SA, Risio M, Muratore A, Capussotti L, Abdalla E. Chemotherapy regimen predicts steatohepatitis and an increase in ninety-day mortality after resection of hepatic colorectal metastases. J Clin Oncol 2006;24:2065–2072PubMedCrossRef Vauthey JN, Pawlik TM, Ribero D, Wu TT, Hoff PM, Xiong H, Eng C, Curley SA, Risio M, Muratore A, Capussotti L, Abdalla E. Chemotherapy regimen predicts steatohepatitis and an increase in ninety-day mortality after resection of hepatic colorectal metastases. J Clin Oncol 2006;24:2065–2072PubMedCrossRef
22.
go back to reference Brunt EM. Nonalcoholic steatohepatitis. Semin Liver Dis 2004;24:3–20.PubMed Brunt EM. Nonalcoholic steatohepatitis. Semin Liver Dis 2004;24:3–20.PubMed
23.
go back to reference Farrell GC, Larter CZ. Nonalcoholic fatty liver disease: from steatosis to cirrhosis. Hepatology 2006;43:S99–S112.PubMedCrossRef Farrell GC, Larter CZ. Nonalcoholic fatty liver disease: from steatosis to cirrhosis. Hepatology 2006;43:S99–S112.PubMedCrossRef
24.
go back to reference Ratziu V, Charlotte F, Heurtier A, Gombert S, Giral P, Bruckert E, Grimaldi A, Capron F, Poynard T. Sampling variability of liver biopsy in nonalcoholic fatty liver disease. Gastroenterology 2005;128:1898–1906.PubMedCrossRef Ratziu V, Charlotte F, Heurtier A, Gombert S, Giral P, Bruckert E, Grimaldi A, Capron F, Poynard T. Sampling variability of liver biopsy in nonalcoholic fatty liver disease. Gastroenterology 2005;128:1898–1906.PubMedCrossRef
25.
go back to reference Bellentani S, Saccoccio G, Masutti F, Croce LS, Brandi G, Sasso F, Cristanini G, Tiribelli C. Prevalence of and risk factors for hepatic steatosis in Northern Italy. Ann Intern Med 2000;132:112–117.PubMed Bellentani S, Saccoccio G, Masutti F, Croce LS, Brandi G, Sasso F, Cristanini G, Tiribelli C. Prevalence of and risk factors for hepatic steatosis in Northern Italy. Ann Intern Med 2000;132:112–117.PubMed
26.
go back to reference Angulo P, Lindor KD. Treatment of non-alcoholic steatohepatitis. Best Pract Res Clin Gastroenterol 2002;16:797–810.PubMedCrossRef Angulo P, Lindor KD. Treatment of non-alcoholic steatohepatitis. Best Pract Res Clin Gastroenterol 2002;16:797–810.PubMedCrossRef
27.
go back to reference Clark JM, Brancati FL, Diehl AM. Nonalcoholic fatty liver disease. Gastroenterology 2002;122:1649–1657.PubMedCrossRef Clark JM, Brancati FL, Diehl AM. Nonalcoholic fatty liver disease. Gastroenterology 2002;122:1649–1657.PubMedCrossRef
28.
go back to reference Neuschwander-Tetri BA, Caldwell SH. Nonalcoholic steatohepatitis: summary of an AASLD Single Topic Conference. Hepatology 2003;37:1202–1219.PubMedCrossRef Neuschwander-Tetri BA, Caldwell SH. Nonalcoholic steatohepatitis: summary of an AASLD Single Topic Conference. Hepatology 2003;37:1202–1219.PubMedCrossRef
29.
go back to reference Petersen KF, Befroy D, Dufour S, Dziura J, Ariyan C, Rothman DL, DiPietro L, Cline GW, Shulman GI. Mitochondrial dysfunction in the elderly: possible role in insulin resistance. Science 2003;300:1140–1142.PubMedCrossRef Petersen KF, Befroy D, Dufour S, Dziura J, Ariyan C, Rothman DL, DiPietro L, Cline GW, Shulman GI. Mitochondrial dysfunction in the elderly: possible role in insulin resistance. Science 2003;300:1140–1142.PubMedCrossRef
30.
31.
go back to reference Kim JK, Fillmore JJ, Chen Y, Yu C, Moore IK, Pypaert M, Lutz EP, Kako Y, Velez-Carrasco W, Goldberg IJ, Breslow JL, Shulman GI. Tissue-specific overexpression of lipoprotein lipase causes tissue-specific insulin resistance. Proc Natl Acad Sci U S A 2001;98:7522–7527.PubMedCrossRef Kim JK, Fillmore JJ, Chen Y, Yu C, Moore IK, Pypaert M, Lutz EP, Kako Y, Velez-Carrasco W, Goldberg IJ, Breslow JL, Shulman GI. Tissue-specific overexpression of lipoprotein lipase causes tissue-specific insulin resistance. Proc Natl Acad Sci U S A 2001;98:7522–7527.PubMedCrossRef
33.
go back to reference Browning JD, Horton JD. Molecular mediators of hepatic steatosis and liver injury. J Clin Invest 2004;114:147–152.PubMedCrossRef Browning JD, Horton JD. Molecular mediators of hepatic steatosis and liver injury. J Clin Invest 2004;114:147–152.PubMedCrossRef
34.
go back to reference Farrell GC. Signalling links in the liver: knitting SOCS with fat and inflammation. J Hepatol 2005;43:193–196.PubMedCrossRef Farrell GC. Signalling links in the liver: knitting SOCS with fat and inflammation. J Hepatol 2005;43:193–196.PubMedCrossRef
35.
go back to reference Behrns KE, Tsiotos GG, DeSouza NF, Krishna MK, Ludwig J, Nagorney DM. Hepatic steatosis as a potential risk factor for major hepatic resection. J Gastrointest Surg 1998;2:292–298.PubMedCrossRef Behrns KE, Tsiotos GG, DeSouza NF, Krishna MK, Ludwig J, Nagorney DM. Hepatic steatosis as a potential risk factor for major hepatic resection. J Gastrointest Surg 1998;2:292–298.PubMedCrossRef
36.
go back to reference Belghiti J, Hiramatsu K, Benoist S, Massault P, Sauvanet A, Farges O. Seven hundred forty-seven hepatectomies in the 1990s: an update to evaluate the actual risk of liver resection. J Am Coll Surg 2000;191:38–46.PubMedCrossRef Belghiti J, Hiramatsu K, Benoist S, Massault P, Sauvanet A, Farges O. Seven hundred forty-seven hepatectomies in the 1990s: an update to evaluate the actual risk of liver resection. J Am Coll Surg 2000;191:38–46.PubMedCrossRef
Metadata
Title
Preoperative Chemotherapy for Colorectal Liver Metastases: Impact on Hepatic Histology and Postoperative Outcome
Authors
Timothy M. Pawlik
Kelly Olino
Ana Luiza Gleisner
Michael Torbenson
Richard Schulick
Michael A. Choti
Publication date
01-07-2007
Publisher
Springer-Verlag
Published in
Journal of Gastrointestinal Surgery / Issue 7/2007
Print ISSN: 1091-255X
Electronic ISSN: 1873-4626
DOI
https://doi.org/10.1007/s11605-007-0149-4

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