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Surgical Management of the Colorectal Cancer Patient with Simultaneous Liver and Lung Metastases

  • Colorectal Cancer Hepatic Metastases (MA Choti, Section Editor)
  • Published:
Current Colorectal Cancer Reports

Abstract

Although the liver and lung are the two most common sites of metastatic disease for colon and rectal cancer, management of simultaneous liver and lung metastases is ill-defined. The objective of this review is not only to review long-term outcomes after resection of simultaneous colorectal liver and lung metastases but also apply recent data regarding the (1) evolution of indeterminate pulmonary nodules discovered during staging evaluation of colorectal liver metastases, (2) impact of genetic mutations in colorectal cancer on disease outcomes, and (3) influence of lung metastases on overall survival outcomes to the management of patients with simultaneous colorectal liver and lung metastases.

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References

Papers of particular interest, published recently, have been highlighted as: • Of importance

  1. Carpizo DR, D’Angelica M. Liver resection for metastatic colorectal cancer in the presence of extrahepatic disease. Ann Surg Oncol. 2009;16:2411–21.

    Article  PubMed  Google Scholar 

  2. de Haas RJ, Wicherts DA, Adam R. Resection of colorectal liver metastases with extrahepatic disease. Dig Surg. 2008;25:461–6.

    Article  PubMed  Google Scholar 

  3. Nordholm-Carstensen A, Jorgensen LN, Wille-Jørgensen PA, Hansen H, Harling H. Indeterminate pulmonary nodules in colorectal-cancer: do radiologists agree? Ann Surg Oncol. 2015;22:543–9.

    Article  PubMed  Google Scholar 

  4. Brent A, Talbot R, Coyne J, Nash G. Should indeterminate lung lesions reported on staging CT scans influence the management of patients with colorectal cancer? Colorectal Dis. 2007;9:816–8.

    Article  CAS  PubMed  Google Scholar 

  5. Christofferson MW, Bulut O, Jess P. The diagnostic value of indeterminate lung lesions on staging chest computed tomographies in patients with colorectal cancer. Dan Med Bull. 2010;57:A4093.

    Google Scholar 

  6. Choi DJ, Kwak JM, Kim J, Woo SU, Kim SH. Preoperative chest computerized tomography in patients with locally advanced mid or lower rectal cancer: its role in staging and impact on treatment strategy. J Surg Oncol. 2010;102:588–92.

    Article  PubMed  Google Scholar 

  7. Restivo A, Zorcolo L, Piga S, Cocco IMF, Casula G. Routine preoperative chest computed tomography does not influence therapeutic strategy in patients with colorectal cancer. Colorectal Dis. 2012;14:e216–21.

    Article  CAS  PubMed  Google Scholar 

  8. McQueen AS, Scott J. CT staging of colorectal cancer: what do you find in the chest? Clin Radiol. 2012;67:352–8.

    Article  CAS  PubMed  Google Scholar 

  9. Pomerri F, Pucciarelli S, Maretto I, Perrone E, Pintacuda G, Lonardi S, et al. Significance of pulmonary nodules in patients with colorectal cancer. Eur Radiol. 2012;22:1680–6.

    Article  PubMed  Google Scholar 

  10. Karagkounis G, Torbenson MS, Daniel HD, Azad NS, Diaz LA, Donehower RC, et al. Incidence and prognostic impact of KRAS and BRAF mutation in patients undergoing surgery for liver metastasis. Cancer. 2013;119:4137–44.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Maithel SK, Ginsberg MS, D’Amico F, DeMatteo RP, Allen PJ, Fong Y, et al. Natural history of patients with subcentimeter pulmonary nodules undergoing hepatic resection for metastatic colorectal cancer. J Am Coll Surg. 2010;210:31–8.

    Article  PubMed  Google Scholar 

  12. Varol Y, Varol U, Karaca B, Karabulut B, Sezgin C, Uslu R. The frequency and significance of radiologically detected indeterminate pulmonary nodules in patients with colorectal cancer. Med Princ Pract. 2012;21:457–61.

    Article  PubMed  Google Scholar 

  13. Quyn AJ, Matthews A, Daniel T, Amin AI, Yalamarthi S. The clinical significance of radiologically detected indeterminate pulmonary nodules in colorectal cancer. Colorectal Dis. 2012;14:828–31.

    Article  CAS  PubMed  Google Scholar 

  14. Downs-Canner S, Bahar R, Reddy SK, Cardinal JS, Marsh JW, Geller DA, et al. Indeterminate pulmonary nodules represent lung metastases in a significant portion of patients undergoing liver resection for malignancy. J Gastrointest Surg. 2012;16:2256–9.

    Article  PubMed  Google Scholar 

  15. Gomez D, Kamali D, Dunn WK, Beckingham IJ, Brooks A, Cameron IC. Outcomes in patients with indeterminate pulmonary nodules undergoing resection for colorectal liver metastases. HPB (Oxford). 2012;14:448–54.

    Article  Google Scholar 

  16. Knijn N, Mekenkamp LJ, Klomp M, Vink-Borger ME, Tol J, Teerenstra S, et al. KRAS mutation analysis: a comparison between primary tumours and matched liver metastases in 305 colorectal cancer patients. Br J Cancer. 2011;104:1020–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Kim CH, Huh JW, Kim HR, Kim YJ. Indeterminate pulmonary nodules in colorectal cancer: follow-up guidelines based on a risk predictive model. Ann Surg. 2015;261:1145–52.

    Article  PubMed  Google Scholar 

  18. Nordholm-Carstensen A, Wille-Jørgensen PA, Jorgensen LN, Harling H. Indeterminate pulmonary nodules at colorectal cancer staging: a systematic review of predictive parameters for malignancy. Ann Surg Oncol. 2013;20:4022–30.

    Article  PubMed  Google Scholar 

  19. Grossman I, Avenarius JKA, Mastboom WJB, Klaase JM. Preoperative staging with chest CT in patients with colorectal carcinoma: not as a routine procedure. Ann Surg Oncol. 2010;17:2045–50.

    Article  Google Scholar 

  20. Karagkounis G, Cai G, Johnson PT, Pawlik TM, Fishman EK, Choti MA. The role of neoadjuvant chemotherapy in characterizing indeterminate lung lesions in patients with resectable colorectal liver metastases. Ann Surg Oncol. 2015;22:2201–8. Retrospective study showing that the concordance and disocordance of response to chemotherapy of liver and simultaneous indeterminate lung nodules accurately predicts malignant potential.

    Article  PubMed  Google Scholar 

  21. Mao C, Wu XY, Yang ZY, Threapleton DE, Yuan JQ, Yu YY, et al. Concordant analysis of KRAS, BRAF, PIK3CA mutations and PTEN expression between primary colorectal cancer and matched metastases. Sci Rep. 2015;5:8065.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Cejas P, López-Gómez M, Aguayo C, Madero R, de Castro CJ, Belda-Iniesta C, et al. KRAS mutations in primary colorectal cancer tumors and related metastases: a potential role in prediction of lung metastasis. PLoS One. 2009;4(12), e8199.

    Article  PubMed  PubMed Central  Google Scholar 

  23. Modest DP, Stintzing S, Laubender RP, Neumann J, Jung A, Giessen C, et al. Clinical characterization of patients with metastatic colorectal cancer depending on the KRAS status. Anticancer Drugs. 2011;22(9):913–8.

    Article  CAS  PubMed  Google Scholar 

  24. Kim MJ, Lee HS, Kim JH, Kim YJ, Kwon JH, Lee JO, et al. Different metastatic pattern according to the KRAS mutational status and site-specific discordance of KRAS status in patients with colorectal cancer. BMC Cancer. 2012;12:347.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Yaeger R, Cercek A, Chou JF, Sylvester BE, Kemeny NE, Hechtman JF, et al. BRAF mutation predicts for poor outcomes after metastasectomy in patients with metastatic colorectal cancer. Cancer. 2014;120(15):2316–24.

    Article  CAS  PubMed  Google Scholar 

  26. Yaeger R, Cowell E, Chou JF, Gewirtz AN, Borsu L, Vakiani E, et al. RAS mutations affect pattern of metastatic spread and increase propensity for brain metastasis in colorectal cancer. Cancer. 2015;121(8):1195–203.

    Article  CAS  PubMed  Google Scholar 

  27. Schirripa M, Cremolini C, Loupakis F, Morvillo M, Bergamo F, Zoratto F, et al. Role of NRAS mutations as prognostic and predictive markers in metastatic colorectal cancer. Int J Cancer. 2015;136(1):83–90.

    Article  CAS  PubMed  Google Scholar 

  28. Tie J, Lipton L, Desai J, Gibbs P, Jorissen RN, Christie M, et al. KRAS mutation is associated with lung metastasis in patients with curatively resected colorectal cancer. Clin Cancer Res. 2011;17(5):1122–30.

    Article  CAS  PubMed  Google Scholar 

  29. Vauthey JN, Zimmitti G, Kopetz SE, Shindoh J, Chen SS, Andreou A, et al. RAS mutation status predicts survival and patterns of recurrence in patients undergoing hepatectomy for colorectal liver metastases. Ann Surg. 2013;258(4):619–26. discussion 626–7.

    Article  PubMed  Google Scholar 

  30. Kemeny NE, Chou JF, Capanu M, Gewirtz AN, Cercek A, Kingham TP, et al. KRAS mutation influences recurrence patterns in patients undergoing hepatic resection of colorectal metastases. Cancer. 2014;120(24):3965–71.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Schweiger T, Hegedüs B, Nikolowsky C, Hegedüs Z, Szirtes I, Mair R, et al. BRAF and KRAS status in patients undergoing pulmonary metastasectomy from primary colorectal carcinoma: a prospective follow-up study. Ann Surg Oncol. 2014;21(3):946–54.

    Article  PubMed  Google Scholar 

  32. Zabaleta J, Aguinagalde B, Izquierdo JM, Bazterargui N, Laguna SM, Martin-Arruti M, Lobo C, Emparanza JI. The presence of mutations in the K-RAS gene does not affect survival after resection of pulmonary metastases from colorectal cancer. 3. ISRN Surg. 2014; 2014: 157586.

  33. Renaud S, Romain B, Falcoz PE, Olland A, Santelmo N, Brigand C, et al. KRAS and BRAF mutations are prognostic biomarkers in patients undergoing lung metastasectomy of colorectal cancer. Br J Cancer. 2015;112(4):720–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Margonis GA, Spolverato G, Kim Y, Karagkounis G, Choti MA, Pawlik TM. Effect of KRAS mutation on long-term outcomes of patients undergoing hepatic resection for colorectal liver metastases. Ann Surg Oncol. 2015;22(13):4158–65.

    Article  PubMed  Google Scholar 

  35. Pereira AA, Rego JF, Morris V, Overman MJ, Eng C, Garrett CR, et al. Association between KRAS mutation and lung metastasis in advanced colorectal cancer. Br J Cancer. 2015;112(3):424–8.

    Article  CAS  PubMed  Google Scholar 

  36. Hutchins G, Southward K, Handley K, Magill L, Beaumont C, Stahlschmidt J, et al. Value of mismatch repair, KRAS, and BRAF mutations in predicting recurrence and benefits from chemotherapy in colorectal cancer. J Clin Oncol. 2011;29:1261–70.

    Article  PubMed  Google Scholar 

  37. Morris V, Overman MJ, Jiang ZQ, Garrett C, Agarwal S, Eng C, et al. Progression-free survival remains poor over sequential lines of systemic therapy in patients with BRAF-mutated colorectal cancer. Clin Colorectal Cancer. 2014;13(3):164–71.

    Article  PubMed  PubMed Central  Google Scholar 

  38. Tran B, Kopetz S, Tie J, Gibbs P, Jiang ZQ, Lieu CH, et al. Impact of BRAF mutation and microsatellite instability on the pattern of metastatic spread and prognosis in metastatic colorectal cancer. Cancer. 2011;117:4623–32.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Stremitzer S, Stift J, Gruenberger B, Tamandl D, Aschacher T, Wolf B, et al. KRAS and outcome of liver resection after neoadjuvant chemotherapy including bevacizumab. Br J Surg. 2012;99:1575–83.

    Article  CAS  PubMed  Google Scholar 

  40. Conlin A, Smith G, Carey FA, Wolf CR, Steele RJC. The prognostic significance of K-ras, p53, and APC mutations in colorectal carcinoma. Gut. 2005;54:1283–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Petrowsky H, Sturm I, Graubitz O, Kooby DA, Staib-Sebler E, Gog C. Relevance of Ki-67 antigen expression and K-ras mutation in colorectal liver metastases. Eur J Surg Oncol. 2001;27:80–7.

    Article  CAS  PubMed  Google Scholar 

  42. Price TJ, Hardingham JE, Lee CK, Weickhardt A, Townsend AR, Wrin JW, et al. Impact of KRAS and BRAF gene mutation status on outcomes from the phase III AGITG MAX Trial of capecitabine alone or in combination with bevacizumab and mitomycin in advanced colorectal cancer. J Clin Oncol. 2011;29:2675–82.

    Article  CAS  PubMed  Google Scholar 

  43. Ogino S, Nosho K, Kirkner GJ, Shima K, Irahara N, Kure S, et al. PIK3CA mutation is associated with poor prognosis among patients with curatively resected colon cancer. J Clin Oncol. 2009;27:1477–84.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Teng HW, Huang YC, Lin JK, Chen WS, Lin TC, Jiang JK, et al. BRAF mutation is a prognostic biomarker for colorectal liver metastasectomy. J Surg Oncol. 2012;106(2):123–9.

    Article  CAS  PubMed  Google Scholar 

  45. Tol J, Dijkstra JR, Klomp M, Teerenstra S, Dommerholt M, Vink-Borger ME, et al. Markers for EGFR pathway activation as predictor of outcome in metastatic colorectal cancer patients with or without cetuximab. Eur J Cancer. 2010;46:1997–2009.

    Article  CAS  PubMed  Google Scholar 

  46. Samowitz WS, Sweeney C, Herrick J, Albersen H, Levin TR, Murtaugh MA, et al. Poor survival associated with the BRAF V600E mutation in microsatellite-stable colon cancers. Cancer Res. 2005;65:6063–9.

    Article  CAS  PubMed  Google Scholar 

  47. Brouquet A, Vauthey JN, Contreras CM, Walsh GL, Vaporciyan AA, Swisher SG, et al. Improved survival after resection of liver and lung colorectal metastases compared with liver-only metastases: a study of 112 patients with limited lung metastatic disease. J Am Coll Surg. 2011;213:62–71.

    Article  PubMed  Google Scholar 

  48. Nojiri K, Tanaka K, Nagano Y, Ueda M, Matsuo K, Ota M, et al. Efficacy of surgery for lung metastases from colorectal cancer synchronous to or following that for liver metastases. Anticancer Res. 2011;31:1049–54.

    PubMed  Google Scholar 

  49. Sakamoto Y, Sakaguchi Y, Oki E, Minami K, Toh Y, Okamura T. Surgical outcomes after resection of both hepatic and pulmonary metastases from colorectal cancer. World J Surg. 2012;36:2708–13.

    Article  PubMed  Google Scholar 

  50. Meinmarakis G, Angele M, Conrad C, Schauer R, Weidenhagen R, Crispin A, et al. Combined resection of colorectal hepatic-pulmonary metastases shows improved outcome over chemotherapy alone. Langenbecks Arch Surg. 2013;398:265–76.

    Article  Google Scholar 

  51. Chua TC, Saxena A, Liauw W, Chu F, Morris DL. Hepatectomy and resection of concomitant extrahepatic disease for colorectal liver metastases—a systematic review. Eur J Cancer. 2012;48:1757–65.

    Article  PubMed  Google Scholar 

  52. Hwang M, Jayakrishnan TT, Green DE, George B, Thomas JP, Groeschl RT, et al. Eur J Cancer. 2014;50:1747–57.

    Article  PubMed  Google Scholar 

  53. Pulitano C, Bodingbauer M, Aldrighetti L, de Jong MC, Castillo F, Schulick RD, et al. Liver resection for colorectal metastases in presence of extra-hepatic disease: results form an international multi-institutional analysis. Ann Surg Oncol. 2011;18:1380–8.

    Article  PubMed  Google Scholar 

  54. Andres A, Mentha G, Adam R, Gerstel E, Skipenko OG, Barroso E, et al. Surgical management of patients with colorectal cancer and simultaneous liver and lung metastases. Br J Surg. 2015;102:691–9. The largest study reporting survival outcomes after resection of simultaneous liver and lung colorectal metastases.

    Article  CAS  PubMed  Google Scholar 

  55. Dave RV, Pathak S, White AD, Hidalgo E, Prasad KR, Lodge JP, et al. Outcome after liver resection in patients presenting with simultaneous hepatopulmonary colorectal metastases. Br J Surg. 2015;102:261–8.

    Article  CAS  PubMed  Google Scholar 

  56. Mise Y, Mehran RJ, Aloia TA, Vauthey JN. Simultaneous lung resection via a transdiaphragmatic approach in patients undergoing liver resection for synchronous liver and lung metastases. Surgery. 2014;156:1197–203.

    Article  PubMed  PubMed Central  Google Scholar 

  57. Mise Y, Kopetz S, Mehran RJ, Aloia TA, Conrad C, Brudvik KW, et al. Is complete liver resection without resection of synchronous lung metastases justified? Ann Surg Oncol. 2015;22:1585–92. The only recent study comparing long-term outcomes among patients with synchronous liver and lung colorectal liver metastases who underwent resection of liver and lung and only liver disease. Also demonstrates the important of KRAS mutation on long-term outcomes.

    Article  PubMed  Google Scholar 

  58. Miller G, Biernacki P, Kemeny NE, Gonen M, Downey R, Jarnagin WR, et al. Outcomes after resection of synchronous or metachronous hepatic and pulmonary colorectal metastases. J Am Coll Surg. 2007;205:231–8.

    Article  PubMed  Google Scholar 

  59. Adam R, de Haas RJ, Wicherts DA, Vibert E, Salloum C, Azoulay D, et al. Concomitant extrahepatic disease in patients with colorectal liver metastases: when is there a place for surgery? Ann Surg. 2011;253:349–59.

    Article  PubMed  Google Scholar 

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Correspondence to Srinevas K. Reddy.

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This article is part of the Topical Collection on Colorectal Cancer Hepatic Metastases

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Reddy, S.K., Al-Sukhni, E. Surgical Management of the Colorectal Cancer Patient with Simultaneous Liver and Lung Metastases. Curr Colorectal Cancer Rep 12, 201–207 (2016). https://doi.org/10.1007/s11888-016-0325-6

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  • DOI: https://doi.org/10.1007/s11888-016-0325-6

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