Blood transfusions and steatohepatitis are independent risk factors for complications following liver resection for colorectal cancer liver metastases

Massani,Marco; Capovilla,Giovanni; Ruffolo,Cesare; Bonariol,Roberta; Maccatrozzo,Paola; Tuci,Francesco; Battistella,Giuseppe; Grazi,Gian  Luca; Bassi,Nicolò

doi:10.3892/mco.2017.1358

Blood transfusions and steatohepatitis are independent risk factors for complications following liver resection for colorectal cancer liver metastases

Authors:
- Marco Massani
- Giovanni Capovilla
- Cesare Ruffolo
- Roberta Bonariol
- Paola Maccatrozzo
- Francesco Tuci
- Giuseppe Battistella
- Gian Luca Grazi
- Nicolò Bassi
View Affiliations

Affiliations: Department of Surgery, Regional Center for HPB Surgery, Regional Hospital of Treviso, I-31100 Treviso, Italy, Department of Surgical, Oncological and Gastroenterological Sciences, Padova University Hospital, University of Padova, I-35128 Padova, Italy, Department of Statistics and Epidemiology, Azienda ULSS 9, I-31100 Treviso, Italy, Department of Surgery, Regina Elena National Cancer Institute, I-00144 Rome, Italy
Published online on: August 1, 2017 https://doi.org/10.3892/mco.2017.1358
Pages: 529-538
Copyright: © Massani et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

The aim of the present study was to evaluate the risk factors for postoperative complications following liver resection for colorectal cancer liver metastases. Patients who underwent hepatic resection for colorectal cancer liver metastases were stratified according to chemotherapy administration and body mass index (BMI) to eliminate potential confounding factors. A univariate analysis was conducted to identify potential risk factors for postoperative complications following liver resection. Variables that exhibited a potential association were evaluated by multivariable logistic regression analysis to identify those independently associated with postoperative morbidity. Between January 2012 and March 2012, 100 patients underwent hepatic resection for liver metastases from colorectal carcinoma at the Treviso Regional Hospital (Treviso, Italy) and at the Regina Elena National Cancer Institute (Rome, Italy). Of the 100 patients, 61 received preoperative oxaliplatin‑ or irinotecan‑based chemotherapy. A total of 25 the patients had a BMI of ≥28 kg/m2. On univariate analysis, BMI ≥28 kg/m2 was found to be positively correlated with the presence of steatosis (P<0.01) and steatohepatitis (P<0.01). The administration of preoperative chemotherapy was correlated with the development of steatosis (P<0.01), steatohepatitis (P=0.02) and postoperative complications (P=0.03). Even following stratification for the use of preoperative chemotherapy, BMI ≥28 kg/m2 maintained its positive association with steatohepatitis. On multivariate analysis, steatohepatitis (P=0.005, HR=0.118, 95% CI: 0.027‑0.518) and blood transfusions (P=0.001, HR=0.131, 95% CI: 0.038‑0.452) were independently associated with postoperative complications. BMI ≥28 kg/m2 (P=0.004, HR=8.30, 95% CI: 2.39‑28.7) and irinotecan treatment (P=0.016, HR=0.16, 95% CI: 0.037‑0.711) were independent risk factors for steatohepatitis. In conclusion, steatohepatitis and perioperative blood transfusions were found to be the main determinant of postoperative complications following liver resection for colorectal liver metastases. Overweight patients may be more prone to the cytotoxic effects of irinotecan, harboring a higher risk of developing steatohepatitis.

View Figures

View References

1	Tomlinson JS, Jarnagin WR, DeMatteo RP, Fong Y, Kornprat P, Gonen M, Kemeny N, Brennan MF, Blumgart LH and D'Angelica M: Actual 10-year survival after resection of colorectal liver metastases defines cure. J Clin Oncol. 25:4575–4580. 2007. View Article : Google Scholar : PubMed/NCBI
2	Parks R, Gonen M, Kemeny N, Jarnagin W, D'Angelica M, DeMatteo R, Garden OJ, Blumgart LH and Fong Y: Adjuvant chemotherapy improves survival after resection of hepatic colorectal metastases: Analysis of data from two continents. J Am Coll Surg. 204:753–763. 2007. View Article : Google Scholar : PubMed/NCBI
3	Nordlinger B, Sorbye H, Glimelius B, Poston GJ, Schlag PM, Rougier P, Bechstein WO, Primrose JN, Walpole ET and Finch-Jones M: Perioperative chemotherapy with FOLFOX4 and surgery versus surgery alone for resectable liver metastases from colorectal cancer (EORTC Intergroup trial 40983): A randomised controlled trial. Lancet. 371:1007–1016. 2008. View Article : Google Scholar : PubMed/NCBI
4	Khatri VP, Petrelli NJ and Belghiti J: Extending the frontiers of surgical therapy for hepatic colorectal metastases: Is there a limit? J Clin Oncol. 23:8490–8499. 2005. View Article : Google Scholar : PubMed/NCBI
5	Leonard GD, Brenner B and Kemeny NE: Neoadjuvant chemotherapy before liver resection for patients with unresectable liver metastases from colorectal carcinoma. J Clin Oncol. 23:2038–2048. 2005. View Article : Google Scholar : PubMed/NCBI
6	Rubbia-Brandt L, Audard V, Sartoretti P, Roth AD, Brezault C, Le Charpentier M, Dousset B, Morel P, Soubrane O and Chaussade S: Severe hepatic sinusoidal obstruction associated with oxaliplatin-based chemotherapy in patients with metastatic colorectal cancer. Ann Oncol. 15:460–466. 2004. View Article : Google Scholar : PubMed/NCBI
7	Nakano H, Oussoultzoglou E, Rosso E, Casnedi S, Chenard-Neu MP, Dufour P, Bachellier P and Jaeck D: Sinusoidal injury increases morbidity after major hepatectomy in patients with colorectal liver metastases receiving preoperative chemotherapy. Ann Surg. 247:118–124. 2008. View Article : Google Scholar : PubMed/NCBI
8	Wolf PS, Park JO, Bao F, Allen PJ, DeMatteo RP, Fong Y, Jarnagin WR, Kingham TP, Gönen M and Kemeny N: Preoperative chemotherapy and the risk of hepatotoxicity and morbidity after liver resection for metastatic colorectal cancer: A single institution experience. J Am Coll Surg. 216:41–49. 2013. View Article : Google Scholar : PubMed/NCBI
9	Vauthey JN, Pawlik TM, Ribero D, Wu TT, Zorzi D, Hoff PM, Xiong HQ, Eng C, Lauwers GY and Mino-Kenudson M: Chemotherapy regimen predicts steatohepatitis and an increase in 90-day mortality after surgery for hepatic colorectal metastases. J Clin Oncol. 24:2065–2072. 2006. View Article : Google Scholar : PubMed/NCBI
10	Karoui M, Penna C, Amin-Hashem M, Mitry E, Benoist S, Franc B, Rougier P and Nordlinger B: Influence of preoperative chemotherapy on the risk of major hepatectomy for colorectal liver metastases. Ann Surg. 243:1–7. 2006. View Article : Google Scholar : PubMed/NCBI
11	Kooby DA, Fong Y, Suriawinata A, Gonen M, Allen PJ, Klimstra DS, DeMatteo RP, D'Angelica M, Blumgart LH and Jarnagin WR: Impact of steatosis on perioperative outcome following hepatic resection. J Gastrointest Surg. 7:1034–1044. 2003. View Article : Google Scholar : PubMed/NCBI
12	Renfro LA, Loupakis F, Adams RA, Seymour MT, Heinemann V, Schmoll HJ, Douillard JY, Hurwitz H, Fuchs CS and Diaz-Rubio E: Body mass index is prognostic in metastatic colorectal cancer: Pooled analysis of patients from first-line clinical trials in the ARCAD database. J Clin Oncol. 34:144–150. 2016. View Article : Google Scholar : PubMed/NCBI
13	Balzan S, Nagarajan G, Farges O, Galleano CZ, Dokmak S, Paugam C and Belghiti J: Safety of liver resections in obese and overweight patients. World J Surg. 34:2960–2968. 2010. View Article : Google Scholar : PubMed/NCBI
14	Viganò L, Kluger MD, Laurent A, Tayar C, Merle JC, Lauzet JY, Andreoletti M and Cherqui D: Liver resection in obese patients: Results of a case-control study. HPB (Oxford). 13:103–111. 2011. View Article : Google Scholar : PubMed/NCBI
15	Pi-Sunyer FX: Medical hazards of obesity. Ann Intern Med. 119:655–660. 1993. View Article : Google Scholar : PubMed/NCBI
16	Veteläinen R, van Vliet A, Gouma DJ and van Gulik TM: Steatosis as a risk factor in liver surgery. Ann Surg. 245:20–30. 2007. View Article : Google Scholar : PubMed/NCBI
17	André T, Louvet C, Maindrault-Goebel F, Couteau C, Mabro M, Lotz JP, Gilles-Amar V, Krulik M, Carola E, Izrael V and de Gramont A: CPT-11 (irinotecan) addition to bimonthly, high-dose leucovorin and bolus and continuous-infusion 5-fluorouracil (FOLFIRI) for pretreated metastatic colorectal cancer. GERCOR. Eur J Cancer. 35:1343–1347. 1999. View Article : Google Scholar : PubMed/NCBI
18	André T, Boni C, Mounedji-Boudiaf L, Navarro M, Tabernero J, Hickish T, Topham C, Zaninelli M, Clingan P and Bridgewater J: Oxaliplatin, fluorouracil, and leucovorin as adjuvant treatment for colon cancer. N Engl J Med. 350:2343–2351. 2004. View Article : Google Scholar : PubMed/NCBI
19	Pang YY: The Brisbane 2000 terminology of liver anatomy and resections. HPB 2000. 2:333–339, HPB (Oxford) 4: 99–100. 2002.
20	Kleiner DE, Brunt EM, Van Natta M, Behling C, Contos MJ, Cummings OW, Ferrell LD, Liu YC, Torbenson MS and Unalp-Arida A: Design and validation of a histological scoring system for nonalcoholic fatty liver disease. Hepatology. 41:1313–1321. 2005. View Article : Google Scholar : PubMed/NCBI
21	World Health Organization Europe: Obesity. Data and Statistic - 2015. http://www.euro.who.int/en/health-topics/noncommunicable-diseases/obesity/data-and-statisticsAccessed. August 28–2016.
22	Dindo D, Demartines N and Clavien PA: Classification of surgical complications: A new proposal with evaluation in a cohort of 6336 patients and results of a survey. Ann Surg. 240:205–213. 2004. View Article : Google Scholar : PubMed/NCBI
23	Capussotti L, Ferrero A, Viganò L, Sgotto E, Muratore A and Polastri R: Bile leakage and liver resection: Where is the risk? Arch Surg. 141:690–695. 2006. View Article : Google Scholar : PubMed/NCBI
24	Balzan S, Belghiti J, Farges O, Ogata S, Sauvanet A, Delefosse D and Durand F: The ‘50-50 criteria’ on postoperative day 5: An accurate predictor of liver failure and death after hepatectomy. Ann Surg. 242:824–829. 2005. View Article : Google Scholar : PubMed/NCBI
25	Bellomo R, Ronco C, Kellum JA, Mehta RL and Palevsky P: Acute Dialysis Quality Initiative workgroup: Acute renal failure-definition, outcome measures, animal models, fluid therapy and information technology needs: The second international consensus conference of the acute dialysis quality initiative (ADQI) Group. Crit Care. 8:R204–R212. 2004. View Article : Google Scholar : PubMed/NCBI
26	Reissfelder C, Brand K, Sobiegalla J, Rahbari NN, Bork U, Schirmacher P, Büchler MW, Weitz J and Koch M: Chemotherapy-associated liver injury and its influence on outcome after resection of colorectal liver metastases. Surgery. 155:245–254. 2014. View Article : Google Scholar : PubMed/NCBI
27	Behrns KE, Tsiotos GG, DeSouza NF, Krishna MK, Ludwig J and Nagorney DM: Hepatic steatosis as a potential risk factor for major hepatic resection. J Gastrointest Surg. 2:292–298. 1998. View Article : Google Scholar : PubMed/NCBI
28	Schaffner F and Thaler H: Nonalcoholic fatty liver disease. Prog Liver Dis. 8:283–298. 1986.PubMed/NCBI
29	Brouquet A, Benoist S, Julie C, Penna C, Beauchet A, Rougier P and Nordlinger B: Risk factors for chemotherapy-associated liver injuries: A multivariate analysis of a group of 146 patients with colorectal metastases. Surgery. 145:362–371. 2009. View Article : Google Scholar : PubMed/NCBI
30	Fernandez FG, Ritter J, Goodwin JW, Linehan DC, Hawkins WG and Strasberg SM: Effect of steatohepatitis associated with irinotecan or oxaliplatin pretreatment on resectability of hepatic colorectal metastases. J Am Coll Surg. 200:845–853. 2005. View Article : Google Scholar : PubMed/NCBI
31	Pawlik TM, Olino K, Gleisner AL, Torbenson M, Schulick R and Choti MA: Preoperative chemotherapy for colorectal liver metastases: Impact on hepatic histology and postoperative outcome. J Gastrointest Surg. 11:860–868. 2007. View Article : Google Scholar : PubMed/NCBI
32	Mathur AK, Ghaferi AA, Sell K, Sonnenday CJ, Englesbe MJ and Welling TH: Influence of body mass index on complications and oncologic outcomes following hepatectomy for malignancy. J Gastrointest Surg. 14:849–857. 2010. View Article : Google Scholar : PubMed/NCBI
33	Langella S, Russolillo N, Forchino F, Lo Tesoriere R, D'Eletto M and Ferrero A: Impact of obesity on postoperative outcome of hepatic resection for colorectal metastases. Surgery. 158:1521–1529. 2015. View Article : Google Scholar : PubMed/NCBI
34	Bower M, Wunderlich C, Brown R, Scoggins CR, McMasters KM and Martin RC: Obesity rather than neoadjuvant chemotherapy predicts steatohepatitis in patients with colorectal metastasis. Am J Surg. 205:685–690. 2013. View Article : Google Scholar : PubMed/NCBI
35	Day CP and James OF: Steatohepatitis: A tale of two ‘hits’? Gastroenterology. 114:842–845. 1998. View Article : Google Scholar : PubMed/NCBI
36	Gascón P, Zoumbos NC and Young NS: Immunologic abnormalities in patients receiving multiple blood transfusions. Ann Intern Med. 100:173–177. 1984. View Article : Google Scholar : PubMed/NCBI
37	Tadros T, Wobbes T and Hendriks T: Blood transfusion impairs the healing of experimental intestinal anastomoses. Ann Surg. 215:276–281. 1992. View Article : Google Scholar : PubMed/NCBI
38	Fujimoto J, Okamoto E, Yamanaka N, Tanaka T and Tanaka W: Adverse effect of perioperative blood transfusions on survival after hepatic resection for hepatocellular carcinoma. Hepatogastroenterology. 44:1390–1396. 1997.PubMed/NCBI
39	Kooby DA, Stockman J, Ben-Porat L, Gonen M, Jarnagin WR, Dematteo RP, Tuorto S, Wuest D, Blumgart LH and Fong Y: Influence of transfusions on perioperative and long-term outcome in patients following hepatic resection for colorectal metastases. Ann Surg. 237:860–870. 2003. View Article : Google Scholar : PubMed/NCBI