J Korean Surg Soc.  2011 Jan;80(1):36-42. 10.4174/jkss.2011.80.1.36.

Is Preoperative Chemotherapy Safe for Patients with Colorectal Liver Metastases Undergoing Metastasectomy?

• Park JM
• Kim BW
• Kim YB
• Seok JY
• Paek OJ
• Oh SY
• Suh KW

• KMID: 2096617
• DOI: http://doi.org/10.4174/jkss.2011.80.1.36

Abstract

PURPOSE
Controversies regarding preoperative versus postoperative chemotherapy for patients having hepatic metastases of colorectal primary made us elucidate the safety of chemotherapy. By examining the histopathologic changes in the liver following preoperative chemotherapy and analyzing the relation between surgical outcomes and preoperative chemotherapy, we were able to answer whether preoperative chemotherapy is safe.
METHODS
We analyzed 38 patients who underwent chemotherapy before resection of hepatic metastasis from colorectal primary, retrospectively. Types of chemotherapy regimen were FL (5-FU+leucovorin), FOLFOX4 (oxaliplatin+5-FU+leucovorin), and FOLFIRI (irinotecan+5-FU+leucovorin). Results of liver function tests were compared before and after preoperative chemotherapy. One pathologist reviewed the degree of hepatic injury from resected specimens. Associations between the histological findings of hepatic injury and surgical outcomes and chemotherapeutic agents were examined.
RESULTS
Histopathologic analysis revealed severe liver injury was present in 12 patients (31.6%). In further detail, moderate to severe sinusoidal dilatation was found in 3 patients (25%), steatosis of more than 30% was identified in 9 patients (75%), and steatohepatitis Kleiner score of > or =4 in 5 patients (41.7%). Preoperative chemotherapy did not affect the biochemical profiles of liver function. The overall perioperative complication rate was 5.3% (n=2). There was no difference in postoperative morbidity or mortality from reported results following hepatectomy.
CONCLUSION
We found preoperative chemotherapy definitely induced histopathologic changes of hepatotoxicities. Even so, preoperative chemotherapy did not increase morbidity or mortality after hepatic metastasectomy. Preoperative chemotherapy seems to be safe in performing curative hepatic resection for the metastases.

Keyword

Chemotherapy; Colon cancer; Metastasis

MeSH Terms

Colonic Neoplasms
Dilatation
Fatty Liver
Humans
Liver
Liver Function Tests
Metastasectomy
Neoplasm Metastasis
Retrospective Studies

Figure

• 

  Fig. 1. Examples of the liver injury. (A) Sinusoidal dilatation. Moderate centrilobular sinusoidal distention is observed in a patient who received oxaliplatin, and the hepatic cords are atrophic due to the dilated sinusoids (H&E stain, ×400). (B) Moderate steatosis. Macrovesicular and microvesicular steatosis is observed in the hepatic lobule over a half of the area (H&E stain, ×400). (C) Steatohepatitis. The hepatocytes show ballooning degeneration, lobular inflammation, macrovesicular and microvesicular steatosis (Kleiner score 5) (H&E stain, ×400).

Reference

References

1. Benoist S, Nordlinger B. The role of preoperative chemotherapy in patients with resectable colorectal liver metastases. Ann Surg Oncol. 2009; 16:2385–90.

2. Small R, Lubezky N, Ben-Haim M. Current controversies in the surgical management of colorectal cancer metastases to the liver. Isr Med Assoc J. 2007; 9:742–7.

3. Reddy SK, Zorzi D, Lum YW, Barbas AS, Pawlik TM, Ribero D, et al. Timing of multimodality therapy for resectable synchronous colorectal liver metastases: a retrospective multi-in-stitutional analysis. Ann Surg Oncol. 2009; 16:1809–19.

4. Abdalla EK, Adam R, Bilchik AJ, Jaeck D, Vauthey JN, Mahvi D. Improving resectability of hepatic colorectal metastases: expert consensus statement. Ann Surg Oncol. 2006; 13:1271–80.

5. Tomlinson JS, Jarnagin WR, DeMatteo RP, Fong Y, Kornprat P, Gonen M, et al. Actual 10-year survival after resection of colorectal liver metastases defines cure. J Clin Oncol. 2007; 25:4575–80.

6. Aloia TA, Vauthey JN, Loyer EM, Ribero D, Pawlik TM, Wei SH, et al. Solitary colorectal liver metastasis: resection determines outcome. Arch Surg. 2006; 141:460–6. discussion. 6–7.

7. Lubezky N, Geva R, Shmueli E, Nakache R, Klausner JM, Figer A, et al. Is there a survival benefit to neoadjuvant versus adjuvant chemotherapy, combined with surgery for resectable colorectal liver metastases? World J Surg. 2009; 33:1028–34.

8. Pawlik TM, Olino K, Gleisner AL, Torbenson M, Schulick R, Choti MA. Preoperative chemotherapy for colorectal liver metastases: impact on hepatic histology and postoperative outcome. J Gastrointest Surg. 2007; 11:860–8.

9. Martin RC 2nd, Brennan MF, Jaques DP. Quality of complication reporting in the surgical literature. Ann Surg. 2002; 235:803–13.

10. Kleiner DE, Brunt EM, Van Natta M, Behling C, Contos MJ, Cummings OW, et al. Design and validation of a histological scoring system for nonalcoholic fatty liver disease. Hepatology. 2005; 41:1313–21.

11. Vauthey JN, Pawlik TM, Ribero D, Wu TT, Zorzi D, Hoff PM, et al. Chemotherapy regimen predicts steatohepatitis and an increase in 90-day mortality after surgery for hepatic colorectal metastases. J Clin Oncol. 2006; 24:2065–72.

12. Rubbia-Brandt L, Audard V, Sartoretti P, Roth AD, Brezault C, Le Charpentier M, et al. Severe hepatic sinusoidal obstruction associated with oxaliplatin-based chemotherapy in patients with metastatic colorectal cancer. Ann Oncol. 2004; 15:460–6.

13. Sitzmann JV, Greene PS. Perioperative predictors of morbidity following hepatic resection for neoplasm. A multivariate analysis of a single surgeon experience with 105 patients. Ann Surg. 1994; 219:13–7.

14. Tsao JI, Loftus JP, Nagorney DM, Adson MA, Ilstrup DM. Trends in morbidity and mortality of hepatic resection for malignancy. A matched comparative analysis. Ann Surg. 1994; 220:199–205.

15. Schroeder RA, Marroquin CE, Bute BP, Khuri S, Henderson WG, Kuo PC. Predictive indices of morbidity and mortality after liver resection. Ann Surg. 2006; 243:373–9.

16. Weber SM, Jarnagin WR, DeMatteo RP, Blumgart LH, Fong Y. Survival after resection of multiple hepatic colorectal metastases. Ann Surg Oncol. 2000; 7:643–50.

17. Bolton JS, Fuhrman GM. Survival after resection of multiple bilobar hepatic metastases from colorectal carcinoma. Ann Surg. 2000; 231:743–51.

18. Lorenz M, Muller HH, Schramm H, Gassel HJ, Rau HG, Ridwelski K, et al. Randomized trial of surgery versus surgery followed by adjuvant hepatic arterial infusion with 5-fluorour-acil and folinic acid for liver metastases of colorectal cancer. German Cooperative on Liver Metastases (Arbeitsgruppe Lebermetastasen). Ann Surg. 1998; 228:756–62.

19. Bradley AL, Chapman WC, Wright JK, Marsh JW, Geevar-ghese S, Blair KT, et al. Surgical experience with hepatic colorectal metastasis. Am Surg. 1999; 65:560–6. discussion. 6–7.

20. Nordlinger B, Sorbye H, Glimelius B, Poston GJ, Schlag PM, Rougier P, et al. 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. 2008; 371:1007–16.

21. Scoggins CR, Campbell ML, Landry CS, Slomiany BA, Woodall CE, McMasters KM, et al. Preoperative chemotherapy does not increase morbidity or mortality of hepatic resection for colorectal cancer metastases. Ann Surg Oncol. 2009; 16:35–41.

22. Tanaka K, Adam R, Shimada H, Azoulay D, Levi F, Bismuth H. Role of neoadjuvant chemotherapy in the treatment of multiple colorectal metastases to the liver. Br J Surg. 2003; 90:963–9.

23. Kemeny N. Presurgical chemotherapy in patients being considered for liver resection. Oncologist. 2007; 12:825–39.

24. 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; 200:845–53.

25. Aloia T, Sebagh M, Plasse M, Karam V, Levi F, Giacchetti S, et al. Liver histology and surgical outcomes after preoperative chemotherapy with fluorouracil plus oxaliplatin in colorectal cancer liver metastases. J Clin Oncol. 2006; 24:4983–90.

26. Hebbar M, Pruvot FR, Romano O, Triboulet JP, de Gramont A. Integration of neoadjuvant and adjuvant chemotherapy in patients with resectable liver metastases from colorectal cancer. Cancer Treat Rev. 2009; 35:668–75.

27. Cummings LC, Payes JD, Cooper GS. Survival after hepatic resection in metastatic colorectal cancer: a population-based study. Cancer. 2007; 109:718–26.