gastro-jРоссийский журнал гастроэнтерологии, гепатологии, колопроктологииRussian Journal of Gastroenterology, Hepatology, Coloproctology1382-43762658-6673«Gastro» LLCgastro-j-1723Research ArticleЛЕКЦИИ И ОБЗОРЫLECTURES AND REVIEWSГепатотоксичность химиотерапии колоректального рака: современное состояние проблемыHepatotoxic chemotherapy of colorectal cancer: state-of-the-artПолищукЛ. О.PolishchukL. O.КозминЛ. Д.KozminL. D.СтрояковскийД. Л.StroyakovskyD. L.ДоровскойЕ. С.DorovskoyYe. S.СкипенкоО. Г.SkipenkoO. G.2009051020091951019Copyright © Полищук Л.О., Козмин Л.Д., Строяковский Д.Л., Доровской Е.С., Скипенко О.Г., 20092009Полищук Л.О., Козмин Л.Д., Строяковский Д.Л., Доровской Е.С., Скипенко О.Г.Polishchuk L.O., Kozmin L.D., Stroyakovsky D.L., Dorovskoy Y.S., Skipenko O.G.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.gastro-j.ru/jour/article/view/1723

Цель обзора. Проанализировать современное состояние проблемы хирургического лечения больных после неоадъювантной химиотерапии.Основные положения. Печень – первый орган на пути гематогенного распространения опухоли. В настоящее время большинством онкологов принят тезис, что единственным лечением, определяющим высокие цифры выживаемости, является хирургическое. В последнее десятилетие все большее число больных оперируется после длительной химиотерапии. Учитывая системное воздействие цитостатиков, их выраженный иммуносупрессивный и гепатотоксичный характер, можно было ожидать резкого ухудшения показателя послеоперационной заболеваемости и летальности. Однако данные большинства исследований опровергают это предположение. Более того, изменения паренхимы печени и, как следствие, течение периоперационного периода может зависеть от состава и режима химиотерапии.Заключение. Знание спектра гепатотоксичности цитостатиков вместе с пониманием процессов, ответственных за функциональную и регенераторную способность печени, позволит выбирать оптимальную тактику комбинированного лечения больных с метастазами колоректального рака.

The aim of review

The aim of review. To analyze state-of-the-art of surgical treatment of patients after neoadjuvant chemotherapy.

Original positions

Original positions. Liver is the first organ on a way of hematogenous spread of tumor. Now the majority of oncologists accepted the point, that only treatment, that provide high survival rate, is surgical. In the last decade increasing numbers of patients are operated after a long-term chemotherapy. Taking into account systemic action of cytotoxic drugs, their severe immune-suppressive and hepatotoxic features, it was possible to expect dramatic deterioration of postoperative morbidity and mortality figures. However data of the majority of studies deny this assumption. Moreover, changes of hepatic parenchyma and as the consequence, course of perioperational period can depend on composition and mode of chemotherapy.

Conclusion

Conclusion. The knowledge of spectrum of hepatotoxic of cytotoxic drugs with comprehension of the processes, that determine functional and regenerative capacity of the liver, allows to choose optimal approach of the combined treatment of patients with colorectal cancer metastases.

метастазы колоректального рака печенихимиотерапиягепатологическая токсичностьсинусоидальная дилатациястеатозжировая дистрофияпослеоперационные осложненияliver metastases of colorectal cancerchemotherapyhepatological toxicitysinusoidal dilatationsteatosisfatty dystrophypostoperative complicationsReferencesAbad A., Anton A., Massuti B. et al. Resectability of liver metastases (LM) in patients with advanced colorectal cancer (ACRC) after treatment with the combination of oxaliplatin (OXA), irinotecan (IRI) and 5-FU: Final results of a phase II study // J. Clin. Oncol. – 2005. – Vol. 23 (suppl. 16). – P. 275 [Abstract 3618].Abad A., Anton A., Massuti B. et al. Resectability of liver metastases (LM) in patients with advanced colorectal cancer (ACRC) after treatment with the combination of oxaliplatin (OXA), irinotecan (IRI) and 5-FU: Final results of a phase II study // J. Clin. Oncol. – 2005. – Vol. 23 (suppl. 16). – P. 275 [Abstract 3618].Abdalla E.K., Vauthey J.N., Ellis L.M. et al. Recurrence and outcomes following hepatic resection, radiofrequency ablation, and combined resection/ablation for colorectal liver metastases // Ann. Surg. – 2004. – Vol. 239. – P. 818–827.Abdalla E.K., Vauthey J.N., Ellis L.M. et al. Recurrence and outcomes following hepatic resection, radiofrequency ablation, and combined resection/ablation for colorectal liver metastases // Ann. Surg. – 2004. – Vol. 239. – P. 818–827.Adam R., Aloia T., Levi F. et al. Hepatic resection after rescue cetuximab treatment for colorectal liver metastases previously refractory to conventional systemic therapy // J. Clin. Oncol. – 2007. – Vol. 25. – P. 4593–4602.Adam R., Aloia T., Levi F. et al. Hepatic resection after rescue cetuximab treatment for colorectal liver metastases previously refractory to conventional systemic therapy // J. Clin. Oncol. – 2007. – Vol. 25. – P. 4593–4602.Adam R., Avisar E., Ariche A. et al. Five-year survival following hepatic resection after neoadjuvant therapy for nonresectable colorectal [liver] metastases // Ann. Surg. Oncol. – 2001. – Vol. 8, N 4. – P. 347–353.Adam R., Avisar E., Ariche A. et al. Five-year survival following hepatic resection after neoadjuvant therapy for nonresectable colorectal [liver] metastases // Ann. Surg. Oncol. – 2001. – Vol. 8, N 4. – P. 347–353.Adam R., Delvart V., Pascal G. et al. Rescue surgery for unresectable colorectal liver metastases downstaged by chemotherapy: A model to predict long-term survival // Ann. Surg. – 2004. – Vol. 240. – P. 644–657.Adam R., Delvart V., Pascal G. et al. Rescue surgery for unresectable colorectal liver metastases downstaged by chemotherapy: A model to predict long-term survival // Ann. Surg. – 2004. – Vol. 240. – P. 644–657.Adam R., Wicherts D.A., de Haas R.J. et al. Complete pathologic response after preoperative chemotherapy for colorectal liver metastases: myth or reality? // J. Clin. Oncol. – 2008. – Vol. 26. – P. 1635–1641.Adam R., Wicherts D.A., de Haas R.J. et al. Complete pathologic response after preoperative chemotherapy for colorectal liver metastases: myth or reality? // J. Clin. Oncol. – 2008. – Vol. 26. – P. 1635–1641.Alberts S.R., Horvath W.L., Sternfeld W.C. et al. Oxaliplatin, fluorouracil, and leucovorin for patients with unresectable liver-only metastases from colorectal cancer: A North Central Cancer Treatment Group Phase II Study// J. Clin. Oncol. – 2005. – Vol. 23, N 36. – P. 1–7.Alberts S.R., Horvath W.L., Sternfeld W.C. et al. Oxaliplatin, fluorouracil, and leucovorin for patients with unresectable liver-only metastases from colorectal cancer: A North Central Cancer Treatment Group Phase II Study// J. Clin. Oncol. – 2005. – Vol. 23, N 36. – P. 1–7.Aloia T., Sebagh M., Plasse M. et al. Liver histology and surgical outcomes after preoperative chemotherapy with fluorouracil plus oxaliplatin in colorectal cancer liver metastases // J. Clin. Oncol. – 2006. – Vol. 24. – P. 4983–4990.Aloia T., Sebagh M., Plasse M. et al. Liver histology and surgical outcomes after preoperative chemotherapy with fluorouracil plus oxaliplatin in colorectal cancer liver metastases // J. Clin. Oncol. – 2006. – Vol. 24. – P. 4983–4990.Baron F., Deprez M., Beguin Y. The veno-occlusive disease of the liver // Haematologica. – 1997. – Vol. 82. – P. 718–725.Baron F., Deprez M., Beguin Y. The veno-occlusive disease of the liver // Haematologica. – 1997. – Vol. 82. – P. 718–725.Behrns K.E., Tsiotos G.G., DeSouza N.F. et al. Hepatic steatosis as a potential risk factor for major hepatic resection // J. Gastrointest. Surg. – 1998. – Vol. 2. – P. 292–298.Behrns K.E., Tsiotos G.G., DeSouza N.F. et al. Hepatic steatosis as a potential risk factor for major hepatic resection // J. Gastrointest. Surg. – 1998. – Vol. 2. – P. 292–298.Belghiti J., Hiramatsu K., Benoist S. et al. Seven hundred forty-seven hepatectomies in the 1990s: an update to evaluate the actual risk of liver resection // J. Am. Coll. Surg. – 2000. – Vol. 191. – P. 38–46.Belghiti J., Hiramatsu K., Benoist S. et al. Seven hundred forty-seven hepatectomies in the 1990s: an update to evaluate the actual risk of liver resection // J. Am. Coll. Surg. – 2000. – Vol. 191. – P. 38–46.Bellentani S., Saccoccio G., Masutti F. et al. Prevalence of and risk factors for hepatic steatosis in northern Italy // Ann. Intern. Med. – 2000. – Vol. 132. – P. 112–117.Bellentani S., Saccoccio G., Masutti F. et al. Prevalence of and risk factors for hepatic steatosis in northern Italy // Ann. Intern. Med. – 2000. – Vol. 132. – P. 112–117.Bengtsson G., Carlsson G., Hafstrom L., Jonsson P.E. Natural history of patients with untreated liver metastases from colorectal cancer // Am. J. Surg. – 1981. – Vol. 141. – P. 586–589.Bengtsson G., Carlsson G., Hafstrom L., Jonsson P.E. Natural history of patients with untreated liver metastases from colorectal cancer // Am. J. Surg. – 1981. – Vol. 141. – P. 586–589.Bilchik A.J., Poston G., Curley S.A. et al. Neoadjuvant chemotherapy for metastatic colon cancer: a cautionary note // J. Clin. Oncol. – 2005. – Vol. 23. – P. 9073–9078.Bilchik A.J., Poston G., Curley S.A. et al. Neoadjuvant chemotherapy for metastatic colon cancer: a cautionary note // J. Clin. Oncol. – 2005. – Vol. 23. – P. 9073–9078.Bodingbauer M., Tamandl D., Schmid K. et al. Size of surgical margin does not influence recurrence rates after curative liver resection for colorectal cancer liver metastases // Br. J. Surg. – 2007. – Vol. 94. – P. 1133–1138.Bodingbauer M., Tamandl D., Schmid K. et al. Size of surgical margin does not influence recurrence rates after curative liver resection for colorectal cancer liver metastases // Br. J. Surg. – 2007. – Vol. 94. – P. 1133–1138.Brunt E.M. Nonalcoholic steatohepatitis // Semin. Liver Dis. – 2004. – Vol. 24. – P. 3–20.Brunt E.M. Nonalcoholic steatohepatitis // Semin. Liver Dis. – 2004. – Vol. 24. – P. 3–20.Brunt E.M., Janney C.G., Di Bisceglie A.M. et al. Nonalcoholic steatohepatitis: a proposal for grading and staging the histological lesions // Am. J. Gastroenterol. – 1999. – Vol. 94. – P. 2467–2474.Brunt E.M., Janney C.G., Di Bisceglie A.M. et al. Nonalcoholic steatohepatitis: a proposal for grading and staging the histological lesions // Am. J. Gastroenterol. – 1999. – Vol. 94. – P. 2467–2474.Burkhardt A., Kloppel G. Unusual obliterative disease of the hepatic veins in an infant // Virchows Arch. – 1977. – Vol. 375. – P. 225–232.Burkhardt A., Kloppel G. Unusual obliterative disease of the hepatic veins in an infant // Virchows Arch. – 1977. – Vol. 375. – P. 225–232.Cervantes A., Casado E., van Cutsem E. et al. Cetuximab plus oxaliplatin/5-fluorouracil (5-FU)/folinic acid (FA) (FOLFOX-4) for the epidermal growth factor receptor (EGFR)-expressing metastatic colorectal cancer (mCRC) in the first-line setting: a phase II study // Eur. J. Cancer Suppl. – 2005. – Vol. 3, N 2. – P. 181 [Abstract 642].Cervantes A., Casado E., van Cutsem E. et al. Cetuximab plus oxaliplatin/5-fluorouracil (5-FU)/folinic acid (FA) (FOLFOX-4) for the epidermal growth factor receptor (EGFR)-expressing metastatic colorectal cancer (mCRC) in the first-line setting: a phase II study // Eur. J. Cancer Suppl. – 2005. – Vol. 3, N 2. – P. 181 [Abstract 642].Cohen A.D., Kemeny N.E. An update on hepatic arterial infusion chemotherapy for colorectal cancer // Oncologist. – 2003. – Vol. 8. – P. 553–566.Cohen A.D., Kemeny N.E. An update on hepatic arterial infusion chemotherapy for colorectal cancer // Oncologist. – 2003. – Vol. 8. – P. 553–566.Cure H., Chevalier V., Adenis A. et al. Phase II trial of chronomodulated infusion of high-dose fluorouracil and l-folinic acid in previously untreated patients with metastatic colorectal cancer // J. Clin. Oncol. – 2002. – Vol. 20, N 5. – P. 1175–1181.Cure H., Chevalier V., Adenis A. et al. Phase II trial of chronomodulated infusion of high-dose fluorouracil and l-folinic acid in previously untreated patients with metastatic colorectal cancer // J. Clin. Oncol. – 2002. – Vol. 20, N 5. – P. 1175–1181.DAngelica M., Kornprat P., Gonen M. et al. Lack of evidence for increased operative morbidity after hepatectomy with perioperative use of bevacizumab: a matched case-control study // Ann. Surg. Oncol. – 2007. – Vol. 14, N 2. – P. 759–765.DAngelica M., Kornprat P., Gonen M. et al. Lack of evidence for increased operative morbidity after hepatectomy with perioperative use of bevacizumab: a matched case-control study // Ann. Surg. Oncol. – 2007. – Vol. 14, N 2. – P. 759–765.De Gramont A., Cervantes A., Andre T. et al. OPTIMOX study: FOLFOX 7/LV5FU2 compared to FOLFOX 4 in patients with advanced colorectal cancer // Proc. Am. Soc. Clin. Oncol. – 2004. – Vol. 23. – [Abstract 3525].De Gramont A., Cervantes A., Andre T. et al. OPTIMOX study: FOLFOX 7/LV5FU2 compared to FOLFOX 4 in patients with advanced colorectal cancer // Proc. Am. Soc. Clin. Oncol. – 2004. – Vol. 23. – [Abstract 3525].De Gramont A., Figer A., Seymour M. et al. Leucovorin and fluorouracil with or without oxaliplatin as first-line treatment in advanced colorectal cancer // J. Clin. Oncol. – 2000. – Vol. 18. – P. 2938–2947.De Gramont A., Figer A., Seymour M. et al. Leucovorin and fluorouracil with or without oxaliplatin as first-line treatment in advanced colorectal cancer // J. Clin. Oncol. – 2000. – Vol. 18. – P. 2938–2947.Denk H., Stumptner C., Zatloukal K. Mallory body revisited // J. Hepatol. – 2000. – Vol. 32. – P. 689–702.Denk H., Stumptner C., Zatloukal K. Mallory body revisited // J. Hepatol. – 2000. – Vol. 32. – P. 689–702.Drixler T.A., Vogten M.J., Ritchie E.D. et al. Liver regeneration is an angiogenesis- associated phenomenon // Ann. Surg. – 2002. – Vol. 236. – P. 703–711.Drixler T.A., Vogten M.J., Ritchie E.D. et al. Liver regeneration is an angiogenesis- associated phenomenon // Ann. Surg. – 2002. – Vol. 236. – P. 703–711.Elias D., Liberale G., Vernerey D. et al. Hepatic and extrahepatic colorectal metastases: when resectable, their localization does not matter, but their total number has a prognostic effect // Ann. Surg. Oncol. – 2005. – Vol. 12, N 11. – P. 900–909.Elias D., Liberale G., Vernerey D. et al. Hepatic and extrahepatic colorectal metastases: when resectable, their localization does not matter, but their total number has a prognostic effect // Ann. Surg. Oncol. – 2005. – Vol. 12, N 11. – P. 900–909.Ensminger W.D., Rosowsky A., Raso V. A clinical pharmacological evaluation of hepatic arterial infusions of 5-fluoro-2-deoxyuridine and 5-fluorouracil // Cancer Res. – 1978. – Vol. 38. – P. 3784–3792.Ensminger W.D., Rosowsky A., Raso V. A clinical pharmacological evaluation of hepatic arterial infusions of 5-fluoro-2-deoxyuridine and 5-fluorouracil // Cancer Res. – 1978. – Vol. 38. – P. 3784–3792.Erlichman C., Fine S., Wong A. et al. A randomized trial of fluorouracil and folinic acid in patients with metastatic colorectal carcinoma // J. Clin. Oncol. – 1988. – Vol. 6. – P. 469–475.Erlichman C., Fine S., Wong A. et al. A randomized trial of fluorouracil and folinic acid in patients with metastatic colorectal carcinoma // J. Clin. Oncol. – 1988. – Vol. 6. – P. 469–475.Fernandez F.G., Ritter J., Goodwin J.W. et al. Effect of steatohepatitis associated with irinotecan or oxaliplatin pretreatment on respectability of hepatic colorectal metastases // J. Am. Coll. Surg. – 2005. – Vol. 200. – P. 845–853.Fernandez F.G., Ritter J., Goodwin J.W. et al. Effect of steatohepatitis associated with irinotecan or oxaliplatin pretreatment on respectability of hepatic colorectal metastases // J. Am. Coll. Surg. – 2005. – Vol. 200. – P. 845–853.Folprecht G., Lutz M.P., Schoffski P. et al. Cetuximab and irinotecan/5-fluorouracil/folinic acid is a safe combination for the first-line treatment of patients with epidermal growth factor receptor expressing metastatic colorectal carcinoma // Ann. Oncol. – 2006. – Vol. 17, N 3. – P. 450–456.Folprecht G., Lutz M.P., Schoffski P. et al. Cetuximab and irinotecan/5-fluorouracil/folinic acid is a safe combination for the first-line treatment of patients with epidermal growth factor receptor expressing metastatic colorectal carcinoma // Ann. Oncol. – 2006. – Vol. 17, N 3. – P. 450–456.Fong Y., Bentrem D.J. CASH (Chemotherapy-associated steatohepatitis) costs // Ann. Surg. – 2006. – Vol. 243. – P. 8–9.Fong Y., Bentrem D.J. CASH (Chemotherapy-associated steatohepatitis) costs // Ann. Surg. – 2006. – Vol. 243. – P. 8–9.Giacchetti S., Bjarnason G.A., Garufi C. et al. First line infusion of 5-fluorouracil, leucovorin and oxaliplatin for metastatic colorectal cancer: 4-day chronomodulated (FFL4-10) versus 2-day FOLFOX2. A multicenter randomized Phase III trial of the Chronotherapy Group of the European Organization for Research and Treatment of Cancer (EORTC 05963) // Proc. Am. Soc. Clin. Oncol. – 2004. – Vol. 23. – [Abstract 3526].Giacchetti S., Bjarnason G.A., Garufi C. et al. First line infusion of 5-fluorouracil, leucovorin and oxaliplatin for metastatic colorectal cancer: 4-day chronomodulated (FFL4-10) versus 2-day FOLFOX2. A multicenter randomized Phase III trial of the Chronotherapy Group of the European Organization for Research and Treatment of Cancer (EORTC 05963) // Proc. Am. Soc. Clin. Oncol. – 2004. – Vol. 23. – [Abstract 3526].Jaeck D., Bachellier P., Guiguet M. et al. Long-term survival following resection of colorectal metastases // Br. J. Surg. – 1997. – Vol. 84. – P. 977–980.Jaeck D., Bachellier P., Guiguet M. et al. Long-term survival following resection of colorectal metastases // Br. J. Surg. – 1997. – Vol. 84. – P. 977–980.Jaeck D., Nakano H., Bachellier P. et al. Significance of hepatic pedicle lymph node involvement in patients with colorectal liver metastases: a prospective study // Ann. Surg. Oncol. – 2002. – Vol. 9, N 5. – P. 430–438.Jaeck D., Nakano H., Bachellier P. et al. Significance of hepatic pedicle lymph node involvement in patients with colorectal liver metastases: a prospective study // Ann. Surg. Oncol. – 2002. – Vol. 9, N 5. – P. 430–438.Karoui M., Penna C., Amin-Hashem M. et al. Influence of preoperative chemotherapy on the risk of major hepatectomy for colorectal liver metastases // Ann. Surg. – 2006. – Vol. 243. – P. 1–7.Karoui M., Penna C., Amin-Hashem M. et al. Influence of preoperative chemotherapy on the risk of major hepatectomy for colorectal liver metastases // Ann. Surg. – 2006. – Vol. 243. – P. 1–7.Kemeny N., Fata F. Arterial, portal, or systemic chemotherapy for patients with hepatic metastasis of colorectal carcinoma // J. Hepatobil. Pancreat. Surg. – 1999. – Vol. 1. – P. 39–49.Kemeny N., Fata F. Arterial, portal, or systemic chemotherapy for patients with hepatic metastasis of colorectal carcinoma // J. Hepatobil. Pancreat. Surg. – 1999. – Vol. 1. – P. 39–49.Kleiner D.E., Brunt E.M., van Natta M. et al. Design and validation of a histological scoring system for nonalcoholic fatty liver disease // Hepatology. – 2005. – Vol. 41. – P. 1313–1321.Kleiner D.E., Brunt E.M., van Natta M. et al. Design and validation of a histological scoring system for nonalcoholic fatty liver disease // Hepatology. – 2005. – Vol. 41. – P. 1313–1321.Kohne C.H., van Cutsem E., Wils J.A. et al. Irinotecan improves the activity of the AIO regimen in metastatic colorectal cancer: Results of EORTC GI Group study 40986 // Proc. Am. Soc. Clin. Oncol. – 2003. – Vol. 22. – P. 254.Kohne C.H., van Cutsem E., Wils J.A. et al. Irinotecan improves the activity of the AIO regimen in metastatic colorectal cancer: Results of EORTC GI Group study 40986 // Proc. Am. Soc. Clin. Oncol. – 2003. – Vol. 22. – P. 254.Kooby D.A., Fong Y., Suriawinata A. et al. Impact of steatosis on perioperative outcome following hepatic resection // J. Gastrointest. Surg. – 2003. – Vol. 7. – P. 1034–1044.Kooby D.A., Fong Y., Suriawinata A. et al. Impact of steatosis on perioperative outcome following hepatic resection // J. Gastrointest. Surg. – 2003. – Vol. 7. – P. 1034–1044.Kopetz S., Abbruzzese J.L., Eng C. et al. Preliminary results from a phase II study of infusional 5-FU, leucovorin and irinotecan (FOLFIRI) plus bevacizumab as first-line treatment for metastatic colorectal cancer (mCRC) // J. Clin. Oncol. – 2006. – Vol. 24 (18S) [Abstract 3579].Kopetz S., Abbruzzese J.L., Eng C. et al. Preliminary results from a phase II study of infusional 5-FU, leucovorin and irinotecan (FOLFIRI) plus bevacizumab as first-line treatment for metastatic colorectal cancer (mCRC) // J. Clin. Oncol. – 2006. – Vol. 24 (18S) [Abstract 3579].Laurent C., Sa Cunha A., Couderc P. et al. Influence of postoperative morbidity on long-term survival following liver resection for colorectal metastases // Br. J. Surg. – 2003. – Vol. 90. – P. 1131–1136.Laurent C., Sa Cunha A., Couderc P. et al. Influence of postoperative morbidity on long-term survival following liver resection for colorectal metastases // Br. J. Surg. – 2003. – Vol. 90. – P. 1131–1136.Little S.A., Jarnagin W.R., DeMatteo R.P. et al. Diabetes is associated with increased perioperative mortality but equivalent long-term outcome after hepatic resection for colorectal cancer // J. Gastrointest. Surg. – 2002. – Vol. 6. – P. 88–94.Little S.A., Jarnagin W.R., DeMatteo R.P. et al. Diabetes is associated with increased perioperative mortality but equivalent long-term outcome after hepatic resection for colorectal cancer // J. Gastrointest. Surg. – 2002. – Vol. 6. – P. 88–94.Lortat-Jacob J.L., Robert H.G. Hepatectomie droite reglйe // Presse Med. – 1952. – Vol. 60. – P. 549.Lortat-Jacob J.L., Robert H.G. Hepatectomie droite reglйe // Presse Med. – 1952. – Vol. 60. – P. 549.Lucarelli G., Galimbert M., Delfini C. et al. Marrow transplantation for thalassaemia following busulfan and cyclophosphamide // Lancet. – 1985. – Vol. 325, N 8442. – P. 1355–1357.Lucarelli G., Galimbert M., Delfini C. et al. Marrow transplantation for thalassaemia following busulfan and cyclophosphamide // Lancet. – 1985. – Vol. 325, N 8442. – P. 1355–1357.Ludwig J., Viggiano T.R., McGill D.B., Oh B.J. Nonalcoholic steatohepatitis: Mayo clinic experiences with a hitherto unnamed disease // Mayo Clin. Proc. – 1980. – Vol. 55. – P. 434–438.Ludwig J., Viggiano T.R., McGill D.B., Oh B.J. Nonalcoholic steatohepatitis: Mayo clinic experiences with a hitherto unnamed disease // Mayo Clin. Proc. – 1980. – Vol. 55. – P. 434–438.McDonald G.B., Hinds M.S., Fisher L.D. et al. Veno-occlusive disease of the liver and multiorgan failure after done marrow transplantation: A cohort study of 355 patients // Ann. Intern. Med. – 1993. – Vol. 118. – P. 255–267.McDonald G.B., Hinds M.S., Fisher L.D. et al. Veno-occlusive disease of the liver and multiorgan failure after done marrow transplantation: A cohort study of 355 patients // Ann. Intern. Med. – 1993. – Vol. 118. – P. 255–267.McLean E.K. The toxic actions of pyrrolizidine (Senecio) alkaloids // Pharmacol. Rev. – 1970. – Vol. 22. – P. 429–483.McLean E.K. The toxic actions of pyrrolizidine (Senecio) alkaloids // Pharmacol. Rev. – 1970. – Vol. 22. – P. 429–483.Moertel C.G., Fleming T.R., Macdonald J.S. et al. Hepatic toxicity associated with fluorouracil plus levamisole adjuvant therapy // J. Clin. Oncol. – 1993. – Vol. 11. – P. 2386–2390.Moertel C.G., Fleming T.R., Macdonald J.S. et al. Hepatic toxicity associated with fluorouracil plus levamisole adjuvant therapy // J. Clin. Oncol. – 1993. – Vol. 11. – P. 2386–2390.Mynster T., Christensen I.J., Moesgaard F., Nielsen H.J. Effects of the combination of blood transfusion and postoperative infectious complications on prognosis after surgery for colorectal cancer. Danish RANXOS Colorectal Cancer Study Group // Br. J. Surg. – 2000. – Vol. 87. – P. 1553–1562.Mynster T., Christensen I.J., Moesgaard F., Nielsen H.J. Effects of the combination of blood transfusion and postoperative infectious complications on prognosis after surgery for colorectal cancer. Danish RANXOS Colorectal Cancer Study Group // Br. J. Surg. – 2000. – Vol. 87. – P. 1553–1562.Nordlinger B., Guiguet M., Vaillant J.C. et al. Surgical resection of colorectal carcinoma metastases to the liver a prognostic scoring system to improve case selection, based on 1568 patients // Cancer. – 1996. – Vol. 77. – P. 1254–1262.Nordlinger B., Guiguet M., Vaillant J.C. et al. Surgical resection of colorectal carcinoma metastases to the liver a prognostic scoring system to improve case selection, based on 1568 patients // Cancer. – 1996. – Vol. 77. – P. 1254–1262.Nordlinger B., Sorbye H., Debois M. et al. Feasibility and risks of pre-operative chemotherapy (CT) with Folfox 4 and surgery for resectable colorectal cancer liver metastases (LM). Interim results of the EORTC Intergroup randomized phase III study 40983 // Proc. Am. Soc. Clin. Oncol. – 2005. – Vol. 23 [Abstract 3528].Nordlinger B., Sorbye H., Debois M. et al. Feasibility and risks of pre-operative chemotherapy (CT) with Folfox 4 and surgery for resectable colorectal cancer liver metastases (LM). Interim results of the EORTC Intergroup randomized phase III study 40983 // Proc. Am. Soc. Clin. Oncol. – 2005. – Vol. 23 [Abstract 3528].Nordlinger B., van Cutsem E., Rougier P. et al. Does chemotherapy prior to liver resection increase the potential for cure in patients with metastatic colorectal cancer? A report from the European Colorectal Metastases Treatment Group // Eur. J. Cancer. – 2007. – Vol. 43. – P. 2037–2045.Nordlinger B., van Cutsem E., Rougier P. et al. Does chemotherapy prior to liver resection increase the potential for cure in patients with metastatic colorectal cancer? A report from the European Colorectal Metastases Treatment Group // Eur. J. Cancer. – 2007. – Vol. 43. – P. 2037–2045.Peeters M., Raoul J.L., van Laetham J.L. et al. Cetuximab in combination with irinotecan/5-fluorouracil (5-FU)/folinic acid (FA) (FOLFIRI) in the first-line treatment of metastatic colorectal cancer // Eur. J. Cancer Suppl. – 2005. – Vol. 3, N 2. – P. 188 [Abstract 664].Peeters M., Raoul J.L., van Laetham J.L. et al. Cetuximab in combination with irinotecan/5-fluorouracil (5-FU)/folinic acid (FA) (FOLFIRI) in the first-line treatment of metastatic colorectal cancer // Eur. J. Cancer Suppl. – 2005. – Vol. 3, N 2. – P. 188 [Abstract 664].Peppercorn P.D., Reznek R.H., Wilson P. et al. Demonstration of hepatic steatosis by computerized tomography in patients receiving 5-fluorouracil-based therapy for advanced colorectal cancer // Br. J. Cancer. – 1998. – Vol. 77. – P. 2008–2011.Peppercorn P.D., Reznek R.H., Wilson P. et al. Demonstration of hepatic steatosis by computerized tomography in patients receiving 5-fluorouracil-based therapy for advanced colorectal cancer // Br. J. Cancer. – 1998. – Vol. 77. – P. 2008–2011.Poon M.A., OўConnell M.J., Wieand H.S. et al. Biochemical modulation of fluorouracil with leucovorin: Confirmatory evidence of improved therapeutic efficacy in advanced colorectal cancer // J. Clin. Oncol. – 1991. – Vol. 9. – P. 1967–1972.Poon M.A., OўConnell M.J., Wieand H.S. et al. Biochemical modulation of fluorouracil with leucovorin: Confirmatory evidence of improved therapeutic efficacy in advanced colorectal cancer // J. Clin. Oncol. – 1991. – Vol. 9. – P. 1967–1972.Pozzo C., Basso M., Cassano A. et al. Neoadjuvant treatment of unresectable liver disease with irinotecan and 5-fluorouracil plus folinic acid in colorectal cancer patients // Ann. Oncol. – 2004. – Vol. 15. – P. 933–939.Pozzo C., Basso M., Cassano A. et al. Neoadjuvant treatment of unresectable liver disease with irinotecan and 5-fluorouracil plus folinic acid in colorectal cancer patients // Ann. Oncol. – 2004. – Vol. 15. – P. 933–939.Quenet F., Nordlinger B., Rivoire M. et al. Resection of previously unresectable liver metastases from colorectal cancer after chemotherapy with CPT-11/L-OHP/LV5FU (Folfirinox): A prospective phase II trial // Proc. Am. Soc. Clin. Oncol. – 2004. – Vol. 23 [Abstract 3613].Quenet F., Nordlinger B., Rivoire M. et al. Resection of previously unresectable liver metastases from colorectal cancer after chemotherapy with CPT-11/L-OHP/LV5FU (Folfirinox): A prospective phase II trial // Proc. Am. Soc. Clin. Oncol. – 2004. – Vol. 23 [Abstract 3613].Rees M., Plant G., Bygrave S. Late results justify resection for multiple hepatic metastases from colorectal cancer // Br. J. Surg. – 1997. – Vol. 84. – P. 1136–1140.Rees M., Plant G., Bygrave S. Late results justify resection for multiple hepatic metastases from colorectal cancer // Br. J. Surg. – 1997. – Vol. 84. – P. 1136–1140.Ribero D., Wang H., Donadon M. et al. Bevacizumab improves pathologic response and protects against hepatic injury in patients treated with oxaliplatin-based chemotherapy for colorectal liver metastases // Cancer. – 2007. – Vol. 110. – P. 2761–2767.Ribero D., Wang H., Donadon M. et al. Bevacizumab improves pathologic response and protects against hepatic injury in patients treated with oxaliplatin-based chemotherapy for colorectal liver metastases // Cancer. – 2007. – Vol. 110. – P. 2761–2767.Robertson G., Leclercq I., Farrell G.C. Nonalcoholic steatosis and steatohepatitis II. Cytochrome P-450 enzymes and oxidative stress // Am. J. Physiol. Gastrointest. Liver Physiol. – 2001. – Vol. 281. – P. 1135–1139.Robertson G., Leclercq I., Farrell G.C. Nonalcoholic steatosis and steatohepatitis II. Cytochrome P-450 enzymes and oxidative stress // Am. J. Physiol. Gastrointest. Liver Physiol. – 2001. – Vol. 281. – P. 1135–1139.Ruan D.T., Warren R.S. Liver-directed therapies in colorectal cancer // Semin. Oncol. – 2005. – Vol. 32. – P. 85–94.Ruan D.T., Warren R.S. Liver-directed therapies in colorectal cancer // Semin. Oncol. – 2005. – Vol. 32. – P. 85–94.Rubbia-Brandt L., Audard V., Sartoretti P. et al. Severe hepatic sinusoidal obstruction associated with oxaliplatin-based chemotherapy in patients with metastatic colorectal cancer // Ann. Oncol. – 2004. – Vol. 15. – P. 460–466.Rubbia-Brandt L., Audard V., Sartoretti P. et al. Severe hepatic sinusoidal obstruction associated with oxaliplatin-based chemotherapy in patients with metastatic colorectal cancer // Ann. Oncol. – 2004. – Vol. 15. – P. 460–466.Sahajpal A., Vollmer C.M., Dixon E. et al. Chemotherapy for colorectal cancer prior to liver resection for colorectal cancer hepatic metastases does not adversely affect peri-operative outcomes // J. Surg. Oncol. – 2007. – Vol. 95. – P. 22–27.Sahajpal A., Vollmer C.M., Dixon E. et al. Chemotherapy for colorectal cancer prior to liver resection for colorectal cancer hepatic metastases does not adversely affect peri-operative outcomes // J. Surg. Oncol. – 2007. – Vol. 95. – P. 22–27.Scheele J., Stangl R., Altendorf-Hofmann A. Hepatic metastases from colorectal carcinoma: impact of surgical resection on the natural history // Br. J. Surg. – 1990. – Vol. 77. – P. 1241–1246.Scheele J., Stangl R., Altendorf-Hofmann A. Hepatic metastases from colorectal carcinoma: impact of surgical resection on the natural history // Br. J. Surg. – 1990. – Vol. 77. – P. 1241–1246.Schmoll H.J., Cassidy J. Integrating oxaliplatin into the management of colorectal cancer // Oncologist. – 2001. – Vol. 6 (suppl. 4). – P. 24–28.Schmoll H.J., Cassidy J. Integrating oxaliplatin into the management of colorectal cancer // Oncologist. – 2001. – Vol. 6 (suppl. 4). – P. 24–28.Schroeder R.A., Marroquin C.E., Bute B.P. et al. Predictive Indices of morbidity and mortality after liver resection // Ann. Surg. – 2006. – Vol. 243. – P. 373–379.Schroeder R.A., Marroquin C.E., Bute B.P. et al. Predictive Indices of morbidity and mortality after liver resection // Ann. Surg. – 2006. – Vol. 243. – P. 373–379.Shulman H.M., Hinterberger W. Hepatic veno-occlusive disease – liver toxicity syndrome after bone marrow transplantation // Bone Marrow Transplant. – 1992. – Vol. 10. – P. 197–214.Shulman H.M., Hinterberger W. Hepatic veno-occlusive disease – liver toxicity syndrome after bone marrow transplantation // Bone Marrow Transplant. – 1992. – Vol. 10. – P. 197–214.Silverman J.F., OўBrien K.F., Long S. et al. Liver pathology in morbidly obese patients with and without diabetes // Am. J. Gastroenterol. – 1990. – Vol. 85. – P. 1349–1355.Silverman J.F., OўBrien K.F., Long S. et al. Liver pathology in morbidly obese patients with and without diabetes // Am. J. Gastroenterol. – 1990. – Vol. 85. – P. 1349–1355.Simmonds P.C., Primrose J.N., Colquitt J.L. et al. Surgical resection of hepatic metastases from colorectal cancer: a systematic review of published studies // Br. J. Cancer. – 2006. – Vol. 94. – P. 982–999.Simmonds P.C., Primrose J.N., Colquitt J.L. et al. Surgical resection of hepatic metastases from colorectal cancer: a systematic review of published studies // Br. J. Cancer. – 2006. – Vol. 94. – P. 982–999.Teufel A., Steinmann S., Siebler J. et al. Irinotecan plus folinic acid/continuous 5-fluorouracil as simplified bimonthly FOLFIRI regimen for first-line therapy of metastatic colorectal cancer // BMC Cancer. – 2004. – Vol. 4, N 38. – P. 1–8.Teufel A., Steinmann S., Siebler J. et al. Irinotecan plus folinic acid/continuous 5-fluorouracil as simplified bimonthly FOLFIRI regimen for first-line therapy of metastatic colorectal cancer // BMC Cancer. – 2004. – Vol. 4, N 38. – P. 1–8.Tournigand C., Andre T., Achille E. et al. FOLFIRI followed by FOLFOX6 or the reverse sequence in advanced colorectal cancer: A randomized GERCOR study // J. Clin. Oncol. – 2004. – Vol. 22. – P. 229–237.Tournigand C., Andre T., Achille E. et al. FOLFIRI followed by FOLFOX6 or the reverse sequence in advanced colorectal cancer: A randomized GERCOR study // J. Clin. Oncol. – 2004. – Vol. 22. – P. 229–237.Vauthey J.N., Pawlik T.M., Ribero D. et al. Chemotherapy regimen predicts steatohepatitis and an increase in 90-day mortality after surgery for hepatic colorectal metastases // J. Clin. Oncol. – 2006. – Vol. 24. – P. 2065–2072.Vauthey J.N., Pawlik T.M., Ribero D. et al. Chemotherapy regimen predicts steatohepatitis and an increase in 90-day mortality after surgery for hepatic colorectal metastases // J. Clin. Oncol. – 2006. – Vol. 24. – P. 2065–2072.Wanless I.R., Wong F., Blendis L.M. et al. Hepatic and portal vein thrombosis in cirrhosis: possible role in development of parenchymal extinction and portal hypertension // Hepatology. – 1995. – Vol. 21. – P. 1238–1247.Wanless I.R., Wong F., Blendis L.M. et al. Hepatic and portal vein thrombosis in cirrhosis: possible role in development of parenchymal extinction and portal hypertension // Hepatology. – 1995. – Vol. 21. – P. 1238–1247.Weber S.M., Jarnagin W.R., DeMatteo R.P. et al. Survival after resection of multiple hepatic colorectal metastases // Ann. Surg. Oncol. – 2000. – Vol. 7, N 9. – P. 643–650.Weber S.M., Jarnagin W.R., DeMatteo R.P. et al. Survival after resection of multiple hepatic colorectal metastases // Ann. Surg. Oncol. – 2000. – Vol. 7, N 9. – P. 643–650.Wold L.E., Ludwig J. Peliosis hepatis: two morphologic variants? // Hum. Pathol. – 1981. – Vol. 12. – P. 388–389.Wold L.E., Ludwig J. Peliosis hepatis: two morphologic variants? // Hum. Pathol. – 1981. – Vol. 12. – P. 388–389.Yoon S.S., Tanabe K.K. Surgical treatment and other regional treatments for colorectal cancer liver metastases // Oncologist. – 1999. – Vol. 4. – P. 197–208.Yoon S.S., Tanabe K.K. Surgical treatment and other regional treatments for colorectal cancer liver metastases // Oncologist. – 1999. – Vol. 4. – P. 197–208.Zafrani E.S. An additional argument for a toxic mechanism of peliosis hepatis in man // Hepatology. – 1990. – Vol. 11. – P. 322–323.Zafrani E.S. An additional argument for a toxic mechanism of peliosis hepatis in man // Hepatology. – 1990. – Vol. 11. – P. 322–323.Zeiss J., Merrick H.W., Savolaine E.R. et al. Fatty liver change as a result of hepatic artery infusion chemotherapy // Am. J. Clin. Oncol. – 1990. – Vol. 13. – P. 156–160.Zeiss J., Merrick H.W., Savolaine E.R. et al. Fatty liver change as a result of hepatic artery infusion chemotherapy // Am. J. Clin. Oncol. – 1990. – Vol. 13. – P. 156–160.Zorzi D., Chun Y.S., Madoff D.C. et al. Chemotherapy with bevacizumab does not affect liver regeneration after portal vein embolization in the treatment of colorectal liver metastases // Ann. Surg. Oncol. – 2008. – Vol. 15, N 10. – P. 2765–2772.Zorzi D., Chun Y.S., Madoff D.C. et al. Chemotherapy with bevacizumab does not affect liver regeneration after portal vein embolization in the treatment of colorectal liver metastases // Ann. Surg. Oncol. – 2008. – Vol. 15, N 10. – P. 2765–2772.Zorzi D., Laurent A., Pawlik T.M. et al. Chemotherapy-associated hepatotoxicity and surgery for colorectal liver metastases // Br. J. Surg. – 2007. – Vol. 94. – P. 274–286.Zorzi D., Laurent A., Pawlik T.M. et al. Chemotherapy-associated hepatotoxicity and surgery for colorectal liver metastases // Br. J. Surg. – 2007. – Vol. 94. – P. 274–286.

The authors declare that there are no conflicts of interest present.