Skip to main content

Defining Resectability of Colorectal Cancer Liver Metastases: Technical and Oncologic Perspectives

  • Chapter
  • First Online:
Colorectal Cancer Liver Metastases

Abstract

While liver metastases in colorectal cancer patients are common, only a small proportion of patients with colorectal liver metastases (CRLM) are considered resectable at presentation. Current treatment strategies associated with improved survival are limited, and efforts to increase resectability rates among patients with CRLM are warranted. Resectability of CRLM should be defined along three domains: from a medical standpoint, an oncologic standpoint, and finally a technical standpoint. Adherence to a stepwise protocol for preoperative evaluation of patients with CRLM is critical to ensure proper patient selection and to optimize outcomes.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 99.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 129.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 179.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Brouquet A, Abdalla EK, Kopetz S, et al. High survival rate after two-stage resection of advanced colorectal liver metastases: response-based selection and complete resection define outcome. J Clin Oncol. 2011;29:1083–90.

    Article  PubMed  PubMed Central  Google Scholar 

  2. Mise Y, Aloia TA, Brudvik KW, et al. Parenchymal-sparing hepatectomy in colorectal liver metastasis improves salvageability and survival. Ann Surg. 2016;263:146–52.

    Article  PubMed  Google Scholar 

  3. 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;24:4983–90.

    Article  PubMed  CAS  Google Scholar 

  4. Kooby DA, Fong Y, Suriawinata A, et al. Impact of steatosis on perioperative outcome following hepatic resection. J Gastrointest Surg. 2003;7:1034–44.

    Article  PubMed  Google Scholar 

  5. Parikh AA, Gentner B, Wu TT, et al. Perioperative complications in patients undergoing major liver resection with or without neoadjuvant chemotherapy. J Gastrointest Surg. 2003;7:1082–8.

    Article  PubMed  Google Scholar 

  6. 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;15:460–6.

    Article  PubMed  CAS  Google Scholar 

  7. Day RW, Cleeland CS, Wang XS, et al. Patient-reported outcomes accurately measure the value of an enhanced recovery program in liver surgery. J Am Coll Surg. 2015;221:1023–1030 e1021–1022.

    Article  PubMed  Google Scholar 

  8. Bilimoria KY, Liu Y, Paruch JL, et al. Development and evaluation of the universal ACS NSQIP surgical risk calculator: a decision aid and informed consent tool for patients and surgeons. J Am Coll Surg. 2013;217:833–842.e831–833.

    Article  PubMed  PubMed Central  Google Scholar 

  9. Reddy S, Contreras CM, Singletary B, et al. Timed stair climbing is the single strongest predictor of perioperative complications in patients undergoing abdominal surgery. J Am Coll Surg. 2016;222:559–66.

    Article  PubMed  PubMed Central  Google Scholar 

  10. Wagner D, Buttner S, Kim Y, et al. Clinical and morphometric parameters of frailty for prediction of mortality following hepatopancreaticobiliary surgery in the elderly. Br J Surg. 2016;103:e83–92.

    Article  PubMed  CAS  Google Scholar 

  11. Ballantyne GH, Quin J. Surgical treatment of liver metastases in patients with colorectal cancer. Cancer. 1993;71:4252–66.

    Article  PubMed  CAS  Google Scholar 

  12. Cady B, Stone MD, WV MD Jr, et al. Technical and biological factors in disease-free survival after hepatic resection for colorectal cancer metastases. Arch Surg. 1992;127:561–8; discussion 568–569

    Article  PubMed  CAS  Google Scholar 

  13. Tzeng CW, Cooper AB, Vauthey JN, et al. Predictors of morbidity and mortality after hepatectomy in elderly patients: analysis of 7621 NSQIP patients. HPB (Oxford). 2014;16:459–68.

    Article  Google Scholar 

  14. Tzeng CW, Cooper AB, Vauthey JN, et al. Predictors of morbidity and mortality after hepatectomy in elderly patients: analysis of 7621 NSQIP patients. HPB (Oxford). 2013;15:773.

    Article  PubMed Central  Google Scholar 

  15. Aloia TA, Zimmitti G, Conrad C, et al. Return to intended oncologic treatment (RIOT): a novel metric for evaluating the quality of oncosurgical therapy for malignancy. J Surg Oncol. 2014;110:107–14.

    Article  PubMed  PubMed Central  Google Scholar 

  16. Adam R, Pascal G, Castaing D, et al. Tumor progression while on chemotherapy: a contraindication to liver resection for multiple colorectal metastases? Ann Surg. 2004;240:1052–61; discussion 1061-1054

    Article  PubMed  PubMed Central  Google Scholar 

  17. Nordlinger B, Guiguet M, Vaillant JC, et al. Surgical resection of colorectal carcinoma metastases to the liver. A prognostic scoring system to improve case selection, based on 1568 patients. Association Francaise de Chirurgie. Cancer. 1996;77:1254–62.

    Article  PubMed  CAS  Google Scholar 

  18. Adam R, de Haas RJ, Wicherts DA, et al. Is hepatic resection justified after chemotherapy in patients with colorectal liver metastases and lymph node involvement? J Clin Oncol. 2008;26:3672–80.

    Article  PubMed  Google Scholar 

  19. Nanji S, Tsang ME, Wei X, Booth CM. Regional lymph node involvement in patients undergoing liver resection for colorectal cancer metastases. Eur J Surg Oncol. 2017;43:322–9.

    Article  PubMed  CAS  Google Scholar 

  20. Okuno M, Goumard C, Mizuno T, et al. Prognostic impact of perihepatic lymph node metastases in patients with resectable colorectal liver metastases. Br J Surg. 2018;105:1200.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  21. Pulitano C, Bodingbauer M, Aldrighetti L, et al. Colorectal liver metastasis in the setting of lymph node metastasis: defining the benefit of surgical resection. Ann Surg Oncol. 2012;19:435–42.

    Article  PubMed  Google Scholar 

  22. Fong Y, Fortner J, Sun RL, et al. Clinical score for predicting recurrence after hepatic resection for metastatic colorectal cancer: analysis of 1001 consecutive cases. Ann Surg. 1999;230:309–18; discussion 318–321

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  23. Rosen CB, Nagorney DM, Taswell HF, et al. Perioperative blood transfusion and determinants of survival after liver resection for metastatic colorectal carcinoma. Ann Surg. 1992;216:493–504. discussion 504-495

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  24. Scheele J, Stang R, Altendorf-Hofmann A, Paul M. Resection of colorectal liver metastases. World J Surg. 1995;19:59–71.

    Article  PubMed  CAS  Google Scholar 

  25. Vibert E, Bretagnol F, Alves A, et al. Multivariate analysis of predictive factors for early postoperative death after colorectal surgery in patients with colorectal cancer and synchronous unresectable liver metastases. Dis Colon Rectum. 2007;50:1776–82.

    Article  PubMed  Google Scholar 

  26. Abdalla EK, Adam R, Bilchik AJ, et al. Improving resectability of hepatic colorectal metastases: expert consensus statement. Ann Surg Oncol. 2006;13:1271–80.

    Article  PubMed  Google Scholar 

  27. 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;12:900.

    Article  PubMed  Google Scholar 

  28. Miller G, Biernacki P, Kemeny NE, 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 

  29. Mise Y, Kopetz S, Mehran RJ, et al. Is complete liver resection without resection of synchronous lung metastases justified? Ann Surg Oncol. 2015;22:1585–92.

    Article  PubMed  Google Scholar 

  30. Headrick JR, Miller DL, Nagorney DM, et al. Surgical treatment of hepatic and pulmonary metastases from colon cancer. Ann Thorac Surg. 2001;71:975–9; discussion 979–980.

    Article  PubMed  CAS  Google Scholar 

  31. Carpizo DR, Are C, Jarnagin W, et al. Liver resection for metastatic colorectal cancer in patients with concurrent extrahepatic disease: results in 127 patients treated at a single center. Ann Surg Oncol. 2009;16:2138–46.

    Article  PubMed  Google Scholar 

  32. Minagawa M, Makuuchi M, Torzilli G, et al. Extension of the frontiers of surgical indications in the treatment of liver metastases from colorectal cancer: long-term results. Ann Surg. 2000;231:487–99.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  33. Elias D, Ouellet JF, Bellon N, et al. Extrahepatic disease does not contraindicate hepatectomy for colorectal liver metastases. Br J Surg. 2003;90:567–74.

    Article  PubMed  CAS  Google Scholar 

  34. Bos JL, Fearon ER, Hamilton SR, et al. Prevalence of ras gene mutations in human colorectal cancers. Nature. 1987;327:293–7.

    Article  PubMed  CAS  Google Scholar 

  35. Amado RG, Wolf M, Peeters M, et al. Wild-type KRAS is required for panitumumab efficacy in patients with metastatic colorectal cancer. J Clin Oncol. 2008;26:1626–34.

    Article  PubMed  CAS  Google Scholar 

  36. Karapetis CS, Khambata-Ford S, Jonker DJ, et al. K-ras mutations and benefit from cetuximab in advanced colorectal cancer. N Engl J Med. 2008;359:1757–65.

    Article  PubMed  CAS  Google Scholar 

  37. Van Cutsem E, Kohne CH, Hitre E, et al. Cetuximab and chemotherapy as initial treatment for metastatic colorectal cancer. N Engl J Med. 2009;360:1408–17.

    Article  PubMed  Google Scholar 

  38. Peeters M, Price TJ, Cervantes A, et al. Randomized phase III study of panitumumab with fluorouracil, leucovorin, and irinotecan (FOLFIRI) compared with FOLFIRI alone as second-line treatment in patients with metastatic colorectal cancer. J Clin Oncol. 2010;28:4706–13.

    Article  PubMed  CAS  Google Scholar 

  39. Pereira AA, Rego JF, Morris V, et al. Association between KRAS mutation and lung metastasis in advanced colorectal cancer. Br J Cancer. 2015;112:424–8.

    Article  PubMed  CAS  Google Scholar 

  40. Vauthey JN, Kopetz S, Aloia TA, Andreou A. KRAS mutation in colorectal cancer metastases after adjuvant FOLFOX for the primary. Br J Cancer. 2012;107:1442–3; author reply 1444.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  41. Vauthey JN, Zimmitti G, Kopetz SE, et al. RAS mutation status predicts survival and patterns of recurrence in patients undergoing hepatectomy for colorectal liver metastases. Ann Surg. 2013;258:619–26; discussion 626–617.

    Article  PubMed  Google Scholar 

  42. Chun YS, Passot G, Yamashita S, et al. Deleterious effect of RAS and evolutionary high-risk TP53 double mutation in colorectal liver metastases. Ann Surg. 2019;269(5):917–23.

    Article  PubMed  Google Scholar 

  43. Yamashita S, Chun YS, Kopetz SE et al. APC and PIK3CA mutational cooperativity predicts pathologic response and survival in patients undergoing resection for colorectal liver metastases. Ann Surg. 2017. PMID: 28379870. [Epub ahead of print].

    Google Scholar 

  44. Vauthey JN, Kopetz SE. From multidisciplinary to personalized treatment of colorectal liver metastases: 4 reasons to consider RAS. Cancer. 2013;119:4083–5.

    Article  PubMed  Google Scholar 

  45. Kattan MW, Gonen M, Jarnagin WR, et al. A nomogram for predicting disease-specific survival after hepatic resection for metastatic colorectal cancer. Ann Surg. 2008;247:282–7.

    Article  PubMed  Google Scholar 

  46. Rees M, Tekkis PP, Welsh FK, et al. Evaluation of long-term survival after hepatic resection for metastatic colorectal cancer: a multifactorial model of 929 patients. Ann Surg. 2008;247:125–35.

    Article  PubMed  Google Scholar 

  47. Iwatsuki S, Dvorchik I, Madariaga JR, et al. Hepatic resection for metastatic colorectal adenocarcinoma: a proposal of a prognostic scoring system. J Am Coll Surg. 1999;189:291–9.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  48. Malik HZ, Prasad KR, Halazun KJ, et al. Preoperative prognostic score for predicting survival after hepatic resection for colorectal liver metastases. Ann Surg. 2007;246:806–14.

    Article  PubMed  Google Scholar 

  49. Zakaria S, Donohue JH, Que FG, et al. Hepatic resection for colorectal metastases: value for risk scoring systems? Ann Surg. 2007;246:183–91.

    Article  PubMed  PubMed Central  Google Scholar 

  50. Schussler-Fiorenza CM, Mahvi DM, Niederhuber J, et al. Clinical risk score correlates with yield of PET scan in patients with colorectal hepatic metastases. J Gastrointest Surg. 2004;8:150–7; discussion 157–158.

    Article  PubMed  Google Scholar 

  51. Jarnagin WR, Conlon K, Bodniewicz J, et al. A clinical scoring system predicts the yield of diagnostic laparoscopy in patients with potentially resectable hepatic colorectal metastases. Cancer. 2001;91:1121–8.

    Article  PubMed  CAS  Google Scholar 

  52. Chun YS, Vauthey JN, Ribero D, et al. Systemic chemotherapy and two-stage hepatectomy for extensive bilateral colorectal liver metastases: perioperative safety and survival. J Gastrointest Surg. 2007;11:1498–504; discussion 1504-1495.

    Article  PubMed  Google Scholar 

  53. Passot G, Chun YS, Kopetz SE, et al. Predictors of safety and efficacy of 2-stage hepatectomy for bilateral colorectal liver metastases. J Am Coll Surg. 2016;223:99–108.

    Article  PubMed  PubMed Central  Google Scholar 

  54. Cloyd JM, Aloia TA. Hammer versus Swiss Army knife: developing a strategy for the management of bilobar colorectal liver metastases. Surgery. 2017;162:12–7.

    Article  PubMed  Google Scholar 

  55. Gold JS, Are C, Kornprat P, et al. Increased use of parenchymal-sparing surgery for bilateral liver metastases from colorectal cancer is associated with improved mortality without change in oncologic outcome: trends in treatment over time in 440 patients. Ann Surg. 2008;247:109–17.

    Article  PubMed  Google Scholar 

  56. Torzilli G, Procopio F, Botea F, et al. One-stage ultrasonographically guided hepatectomy for multiple bilobar colorectal metastases: a feasible and effective alternative to the 2-stage approach. Surgery. 2009;146:60–71.

    Article  PubMed  Google Scholar 

  57. Passot G, Odisio BC, Zorzi D, et al. Eradication of missing liver metastases after fiducial placement. J Gastrointest Surg. 2016;20:1173–8.

    Article  PubMed  Google Scholar 

  58. Vigano L, Ferrero A, Amisano M, et al. Comparison of laparoscopic and open intraoperative ultrasonography for staging liver tumours. Br J Surg. 2013;100:535–42.

    Article  PubMed  CAS  Google Scholar 

  59. Abdalla EK, Vauthey JN, Ellis LM, et al. Recurrence and outcomes following hepatic resection, radiofrequency ablation, and combined resection/ablation for colorectal liver metastases. Ann Surg. 2004;239:818–25; discussion 825-817.

    Article  PubMed  PubMed Central  Google Scholar 

  60. Berber E, Pelley R, Siperstein AE. Predictors of survival after radiofrequency thermal ablation of colorectal cancer metastases to the liver: a prospective study. J Clin Oncol. 2005;23:1358–64.

    Article  PubMed  Google Scholar 

  61. Kennedy TJ, Cassera MA, Khajanchee YS, et al. Laparoscopic radiofrequency ablation for the management of colorectal liver metastases: 10-year experience. J Surg Oncol. 2013;107:324–8.

    Article  PubMed  Google Scholar 

  62. Stang A, Fischbach R, Teichmann W, et al. A systematic review on the clinical benefit and role of radiofrequency ablation as treatment of colorectal liver metastases. Eur J Cancer. 2009;45:1748–56.

    Article  PubMed  Google Scholar 

  63. Jaeck D, Oussoultzoglou E, Rosso E, et al. A two-stage hepatectomy procedure combined with portal vein embolization to achieve curative resection for initially unresectable multiple and bilobar colorectal liver metastases. Ann Surg. 2004;240:1037–49; discussion 1049-1051.

    Article  PubMed  PubMed Central  Google Scholar 

  64. Broering DC, Hillert C, Krupski G, et al. Portal vein embolization vs. portal vein ligation for induction of hypertrophy of the future liver remnant. J Gastrointest Surg. 2002;6:905–13; discussion 913.

    Article  PubMed  Google Scholar 

  65. Wilms C, Mueller L, Lenk C, et al. Comparative study of portal vein embolization versus portal vein ligation for induction of hypertrophy of the future liver remnant using a mini-pig model. Ann Surg. 2008;247:825–34.

    Article  PubMed  Google Scholar 

  66. Schnitzbauer AA, Lang SA, Goessmann H, et al. Right portal vein ligation combined with in situ splitting induces rapid left lateral liver lobe hypertrophy enabling 2-staged extended right hepatic resection in small-for-size settings. Ann Surg. 2012;255:405–14.

    Article  PubMed  Google Scholar 

  67. Ratti F, Schadde E, Masetti M, et al. Strategies to increase the resectability of patients with colorectal liver metastases: a multi-center case-match analysis of ALPPS and conventional two-stage hepatectomy. Ann Surg Oncol. 2015;22:1933–42.

    Article  PubMed  Google Scholar 

  68. Schadde E, Ardiles V, Robles-Campos R, et al. Early survival and safety of ALPPS: first report of the international ALPPS registry. Ann Surg. 2014;260:829–36; discussion 836-828.

    Article  PubMed  Google Scholar 

  69. Alvarez FA, Ardiles V, de Santibanes M, et al. Associating liver partition and portal vein ligation for staged hepatectomy offers high oncological feasibility with adequate patient safety: a prospective study at a single center. Ann Surg. 2015;261:723–32.

    Article  PubMed  Google Scholar 

  70. Oldhafer KJ, Donati M, Jenner RM, et al. ALPPS for patients with colorectal liver metastases: effective liver hypertrophy, but early tumor recurrence. World J Surg. 2014;38:1504–9.

    Article  PubMed  Google Scholar 

  71. Wicherts DA, Miller R, de Haas RJ, et al. Long-term results of two-stage hepatectomy for irresectable colorectal cancer liver metastases. Ann Surg. 2008;248:994–1005.

    Article  PubMed  Google Scholar 

  72. Kemeny N, Daly J, Reichman B, et al. Intrahepatic or systemic infusion of fluorodeoxyuridine in patients with liver metastases from colorectal carcinoma. A randomized trial. Ann Intern Med. 1987;107:459–65.

    Article  PubMed  CAS  Google Scholar 

  73. Boige V, Malka D, Elias D, et al. Hepatic arterial infusion of oxaliplatin and intravenous LV5FU2 in unresectable liver metastases from colorectal cancer after systemic chemotherapy failure. Ann Surg Oncol. 2008;15:219–26.

    Article  PubMed  Google Scholar 

  74. Ducreux M, Ychou M, Laplanche A, et al. Hepatic arterial oxaliplatin infusion plus intravenous chemotherapy in colorectal cancer with inoperable hepatic metastases: a trial of the gastrointestinal group of the Federation Nationale des Centres de Lutte Contre le Cancer. J Clin Oncol. 2005;23:4881–7.

    Article  PubMed  CAS  Google Scholar 

  75. Kemeny N, Gonen M, Sullivan D, et al. Phase I study of hepatic arterial infusion of floxuridine and dexamethasone with systemic irinotecan for unresectable hepatic metastases from colorectal cancer. J Clin Oncol. 2001;19:2687–95.

    Article  PubMed  CAS  Google Scholar 

  76. Kemeny NE, Melendez FD, Capanu M, et al. Conversion to resectability using hepatic artery infusion plus systemic chemotherapy for the treatment of unresectable liver metastases from colorectal carcinoma. J Clin Oncol. 2009;27:3465–71.

    Article  PubMed  PubMed Central  Google Scholar 

  77. Karanicolas PJ, Metrakos P, Chan K, et al. Hepatic arterial infusion pump chemotherapy in the management of colorectal liver metastases: expert consensus statement. Curr Oncol. 2014;21:e129–36.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  78. Zacharias AJ, Jayakrishnan TT, Rajeev R, et al. Comparative effectiveness of hepatic artery based therapies for unresectable colorectal liver metastases: a meta-analysis. PLoS One. 2015;10:e0139940.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  79. Nordlinger B, Sorbye H, Glimelius B, 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.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  80. Allen PJ, Kemeny N, Jarnagin W, et al. Importance of response to neoadjuvant chemotherapy in patients undergoing resection of synchronous colorectal liver metastases. J Gastrointest Surg. 2003;7:109–17.

    Article  PubMed  Google Scholar 

  81. Adams RB, Aloia TA, Loyer E, et al. Selection for hepatic resection of colorectal liver metastases: expert consensus statement. HPB (Oxford). 2013;15:91–103.

    Article  PubMed Central  Google Scholar 

  82. Blazer DG 3rd, Kishi Y, Maru DM, et al. Pathologic response to preoperative chemotherapy: a new outcome end point after resection of hepatic colorectal metastases. J Clin Oncol. 2008;26:5344–51.

    Article  PubMed  Google Scholar 

  83. Tuma RS. Sometimes size doesn’t matter: reevaluating RECIST and tumor response rate endpoints. J Natl Cancer Inst. 2006;98:1272–4.

    Article  PubMed  Google Scholar 

  84. Shindoh J, Loyer EM, Kopetz S, et al. Optimal morphologic response to preoperative chemotherapy: an alternate outcome end point before resection of hepatic colorectal metastases. J Clin Oncol. 2012;30:4566–72.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  85. Chun YS, Vauthey JN, Boonsirikamchai P, et al. Association of computed tomography morphologic criteria with pathologic response and survival in patients treated with bevacizumab for colorectal liver metastases. JAMA. 2009;302:2338–44.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Thomas A. Aloia .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2020 Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Marcus, R.K., Aloia, T.A. (2020). Defining Resectability of Colorectal Cancer Liver Metastases: Technical and Oncologic Perspectives. In: Correia, M., Choti, M., Rocha, F., Wakabayashi, G. (eds) Colorectal Cancer Liver Metastases. Springer, Cham. https://doi.org/10.1007/978-3-030-25486-5_11

Download citation

  • DOI: https://doi.org/10.1007/978-3-030-25486-5_11

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-030-25485-8

  • Online ISBN: 978-3-030-25486-5

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics