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Missing colorectal liver metastases: the surgical challenge

  • Systematic Reviews and Meta-analyses
  • Published:
Langenbeck's Archives of Surgery Aims and scope Submit manuscript

Abstract

Background

New chemotherapy schemes have allowed for a better radiological response of unresectable colorectal liver metastases, leading to an interesting scenario known as a complete radiological response. The aim of this study was to review the current management of missing liver metastases (MLM) from the liver surgeon’s point of view.

Methods

A systematic search was conducted on all publications of PubMed and Embase between 2003 and 2018. Meta-analysis was performed on MLM resected/unresected. Residual tumor or regrowth and relapse-free survival were used as evaluation indices.

Results

After literature search, 18 original articles were included for analysis. The predictive factors for MLM are type and duration of chemotherapy and size and number of lesions. Magnetic resonance is the most sensitive preoperative technique. Regarding clinical management, liver surgery is deemed the fundamental pillar in the therapeutic strategy of these patients. Meta-analysis due to data heterogeneity was inconclusive.

Conclusions

Depending on the clinical context, MLM monitoring appears to be a valid therapeutic alternative. Nevertheless, prospective randomized clinical studies are needed.

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Abbreviations

CE-IOUS:

Contrast intra-operative ultrasound

CRLM:

Colorectal liver metastases

CPR:

Complete pathological response

CRR:

Complete radiological response

CT:

Computer tomography

HAI:

Hepatic arterial infusion

IOUS:

Intra-operative ultrasound

MLM:

Missing liver metastases

MRI:

Magnetic resonance

SC:

Systemic chemotherapy

SCR:

Sustained clinical response

References

  1. van Kessel CS, Buckens CFM, van den Bosch MAAJ, van Leeuwen MS, van Hillegersberg R, Verkooijen HM (2012) Preoperative imaging of colorectal liver metastases after neoadjuvant chemotherapy: a meta-analysis. Ann Surg Oncol 19:2805–2813. https://doi.org/10.1245/s10434-012-2300-z

    Article  PubMed  PubMed Central  Google Scholar 

  2. Zendel A, Laat E, Dreznik Y, Zakai B, Eshkenazy R, Ariche A (2014) “Vanishing liver metastases” - a real challenge for liver surgeons. Hepatobiliary Surg Nutr 3(5):295–302. https://doi.org/10.3978/j.issn.2304-3881.2014.09.13

    Article  PubMed  PubMed Central  Google Scholar 

  3. Kuhlmann K, van Hilst J, Fisher S, Poston G (2016) Management of disappearing colorectal liver metastases. Eur J Surg Oncol 42(12):1798–1805. https://doi.org/10.1016/j.ejso.2016.05.005

    Article  CAS  PubMed  Google Scholar 

  4. Lucidi V, Hendlisz A, Van Laethem JL, Donckler V (2016) Missing metastases as a model to challenge current therapeutic algorithms in colorectal liver metastases. World J Gastroenterol 22(15):3937–3944. https://doi.org/10.3748/wjg.v22.i15.3937

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Bischof DA, Clara BM, Mantel SK, Pawlik T (2013) Surgical management of disappearing colorectal liver metastases. Br J Surg 100(11):1414–1420. https://doi.org/10.1002/bjs.9213

    Article  CAS  PubMed  Google Scholar 

  6. Elias D, Youssef O, Sideris L, Dromain C, Baton O, Boige V et al (2004) Evolution of missing colorectal liver metastases following inductive chemotherapy and hepatectomy. J Surg Oncol 86(1):4–9. https://doi.org/10.1002/jso.20039

    Article  PubMed  Google Scholar 

  7. Benoist S, Brouquet A, Penna C, Julié C, El Hajjam M, Chagnon S et al (2006) Complete response of colorectal liver metastases after chemotherapy: does it mean cure? J Clin Oncol 24(24):3939–3945. https://doi.org/10.1200/JCO.2006.05.8727

    Article  PubMed  Google Scholar 

  8. Dy GK, Krook JE, Green EM, Sargent DJ, Delaunoit T, Morton RF et al (2007) Impact of complete response to chemotherapy on overall survival in advanced colorectal cancer: results from intergroup N9741. J Clin Oncol 25(23):3469–3474. https://doi.org/10.1200/JCO.2007.10.7128

    Article  PubMed  Google Scholar 

  9. Elias D, Goere D, Boige V, Kohnen-Sharhi N, Malka D, Tomasic G et al (2007) Outcome of posthepatectomy-missing colorectal liver metastases after complete response to chemotherapy: impact of adjuvant intra-arterial hepatic oxaliplatin. Ann Surg Oncol 14(11):3188–3194. https://doi.org/10.1245/s10434-007-9482-9

    Article  PubMed  Google Scholar 

  10. Adam R, Wicherts DA, de Hass RJ, Aloia T, Lévi F, Paule B et al (2008) Complete pathologic response after preoperative chemotherapy for colorectal liver metastases: myth or reality? J Clin Oncol 26(10):1635–1641. https://doi.org/10.1200/JCO.2007.13.7471

    Article  PubMed  Google Scholar 

  11. Tanaka K, Takakura H, Takeda K, Matsuo K, Nagano Y, Endo I (2009) Importance of complete pathologic response to prehepatectomy chemotherapy in treating colorectal cancer metastases. Ann Surg 250:935–942

    Article  Google Scholar 

  12. van Vledder MG, de Jong MC, Pawlik TM, Schulick RD, Diaz LA, Choti MA (2010) Disappearing colorectal liver metastases after chemotherapy: should we be concerned? J Gastrointest Surg 14:1691–1700. https://doi.org/10.1007/s11605-010-1348-y

    Article  PubMed  Google Scholar 

  13. Auer RC, White RR, Kemeny NE, Schwartz LH, Shia J, Blumgart LH et al (2010) Predictors of a true complete response among disappearing liver metastases from colorectal cancer after chemotherapy. Cancer 116(6):1502–1509. https://doi.org/10.1002/cncr.24912

    Article  PubMed  Google Scholar 

  14. Goèré D, Gaujoux S, Deschamps F, Dumont F, Soukada A, Dromain C et al (2011) Patients operated on for initially unresectable colorectal liver metastases with missing metastases experience a favorable long-term outcome. Ann Surg 254:114–118. https://doi.org/10.1097/SLA.0b013e31821ad704

    Article  PubMed  Google Scholar 

  15. Ferrero A, Langella S, Russolillo N, Vigano L, Lo Tesoriere R, Capussotti L (2012) Intraoperative detection of disappearing colorectal liver metastases as a predictor of residual disease. J Gastrointest Surg 16:806–814. https://doi.org/10.1007/s11605-011-1810-5

    Article  PubMed  Google Scholar 

  16. Ono T, Ishida H, Kumamoto K, Okada N, Ishibashi K (2012) Outcome in disappearing colorectal cancer liver metastases during oxaliplatin-based chemotherapy. Oncol Lett 4(5):905–909. https://doi.org/10.3892/ol.2012.842

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Arita J, Ono Y, Takahashi M, Inoue Y, Takahashi Y, Saiura A (2014) Usefulness of contrast-enhanced intraoperative ultrasound in identifying disappearing liver metastases from colorectal carcinoma after chemotherapy. Ann Surg Oncol Suppl 3:s390–s397. https://doi.org/10.1245/s10434-014-3576-y

  18. Owen JW, Fowler KJ, Doyle MB, Saad NE, Linehan DC, Chapman WC (2016) Colorectal liver metastases: disappearing lesions in the era or Evorist hepatobiliary magnetic resonance imaging. HBP 18:296–303. https://doi.org/10.1016/j.hpb.2015.10.009

    Article  Google Scholar 

  19. Sturesson C, Nilsson J, Lindell G, Andersson RG, Kepsen I (2015) Disappearing liver metastases from colorectal cancer: impact of modern imaging modalities. HBP 17:983–987. https://doi.org/10.1111/hpb.12476

    Article  Google Scholar 

  20. Passot G, Odisio BC, Zorzi D, Mahvash A, Gupta S, Wallace MJ et al (2016) Eradication of missing liver metastases after fiducial placement. J Gastrointest Surg 20(6):1173–1178. https://doi.org/10.1007/s11605-016-3079-1

    Article  PubMed  Google Scholar 

  21. Park MJ, Hong N, Han K, Kim MJ, Lee JJ, Park JS et al (2017) Use of imaging to predict complete response of colorectal liver metastases after chemotherapy: MR imaging versus CT imaging. Radiology 284(2):423–431. https://doi.org/10.1148/radiol.2017161619

    Article  PubMed  Google Scholar 

  22. Tani K, Shindoh J, Akamatsu N, Arita J, Kaneko J, Sakamoto Y et al (2018) Managment of disappearing lesions after chemotherapy for colorectal liver metastases: relation between detectability and residual tumors. J Surg Oncol 117(2):191–197. https://doi.org/10.1002/jso.24805

    Article  CAS  PubMed  Google Scholar 

  23. Oba A, Mise Y, Ito H, Hiratsuka M, Inoue Y, Ishizawa T et al (2018) Clinical implications of disappearing colorectal liver metastases have changed in the era of hepatocyte-specific MRI and contrast-enhanced intraoperative ultrasonography. HBP 20:708–714. https://doi.org/10.1016/j.hpb.2018.02.377

    Article  Google Scholar 

  24. Carpenter S, Fong Y (2010) Management of disappearing colorectal hepatic metastases. Adv Surg 44:269–279

    Article  Google Scholar 

  25. Moher D, Liberati A, Tetzlaff J, Altman DG, PRISMA Group (2009) Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. J Clin Epidemiol 62(10):1006–1012. https://doi.org/10.1016/j.jclinepi.2009.06.005

    Article  PubMed  Google Scholar 

  26. von Elm E, Altman DG, Egger M, Pocock SJ, Gotzsche PC, Vandenbroucke JP et al (2007) The strengthening the reporting of observational studies in epidemiology (STROBE) statement guidelines for reporting observational studies. Lancet 370(9596):1453–1457. https://doi.org/10.1016/S0140-6736(07)61602-X

    Article  Google Scholar 

  27. Guyatt CH, Oxmann AD, Vist GE, Kunz R, Falck-Ytter Y, Alonso-Coello P et al (2008) GRADE: an emerging consensus on rating quality of evidence and strength of recommendations. BMJ 336:924–926. https://doi.org/10.1136/bmj.39489.470347.AD

    Article  PubMed  PubMed Central  Google Scholar 

  28. Higgins J, Thompson SG, Deeks JJ, Altman DG (2003) Measuring inconsistency in meta-analyses. BMJ. 327:557–560. https://doi.org/10.1136/bmj.327.7414.557

    Article  PubMed  PubMed Central  Google Scholar 

  29. Walter H, Thomas AL (2013) Liver resection following FOLFOXIRI plus bevacizumab: a detailed pathological review. Br J Cancer 108:2417. https://doi.org/10.1038/bjc.2013.244

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Fiorentini G, Sarti D, Aliberti C, Carandina R, Mambrini A, Guadagni S (2017) Multidisciplinary approach of colorectal cancer liver metastases. World J Clin Oncol 8(3):190–202. https://doi.org/10.5306/wjco.v8.i3.190

    Article  PubMed  PubMed Central  Google Scholar 

  31. Peppercorn PD, Reznek RH, Wilson P, Slevin ML, Gupta RK (1998) Demonstration of hepatic steatosis by computerized tomography in patients receiving 5-luorouracil-based therapy for advanced colorectal cancer. Br J Cancer 77:2008–2011

    Article  CAS  Google Scholar 

  32. Vauthey JN, Pwlik TM, Ribero D, Wu TT, Zorzi D, Hoff PM et al (2006) Chemotherapy regimen predicts steatohepatitis and an increase in 90-day mortality after surgery for hepatic colorectal metastases. J Clin Oncol 24:2065–2072. https://doi.org/10.1200/JCO.2005.05.3074

    Article  CAS  PubMed  Google Scholar 

  33. Pawlik TM, Olino K, Gleisner AL, Torbenson M, Schluck R, Choti MA (2007) Preoperative chemotherapy for colorectal liver metastases: impact on hepatic histology and postoperative outcome. J Gastrontest Sure 11:860–868. https://doi.org/10.1007/s11605-007-0149-4

    Article  Google Scholar 

  34. Gaujoux S, Goèré D, Dumont F, Souadka A, Dromain C, Ducreux M et al (2011) Complete radiological response of colorectal liver metastases after chemotherapy: what can we expect? Dig Surg 28:114–120. https://doi.org/10.1159/000323819

    Article  CAS  PubMed  Google Scholar 

  35. Fowler KJ, Linehan DC, Tenias CO (2013) Colorectal liver metastases: state of the art imaging. Ann Surg Oncol 20:1185–1193. https://doi.org/10.1245/s10434-012-2730-7

    Article  PubMed  Google Scholar 

  36. Thomay AA, Charpentier KP (2010) Optimizing resection for “responding” hepatic metastases after me-adjuvant chemotherapy. J Surg Oncol 102(8):1002–1008. https://doi.org/10.1002/jso.21694

    Article  PubMed  Google Scholar 

  37. Bipat S, van Leeuwen MS, Comans EF, Piji ME, Bossuyt PM, Zwlnderman AH et al (2005) Colorectal liver metastases: CT, MR imaging and PET for diagnosis - meta-analysis. Radiology 237(1):123–131. https://doi.org/10.1148/radiol.2371042060

    Article  PubMed  Google Scholar 

  38. Benson AB, Venook AP, Cederquist L, Chan E, Chen YJ, Cooper HS et al (2017) National comprehensive cancer network clinical practice guidelines in oncology. Colon cancer, versión 1.2017. J Natl Compr Canc Netw 15:370–98

    Article  CAS  Google Scholar 

  39. Wagle P, Ananthakrishnan L, Coppa CP (2017) Imaging liver metastases. Dig Dis Interv 01(03):147–154. https://doi.org/10.1016/j.ejrad.2005.11.041

    Article  Google Scholar 

  40. Adams RB, Aloia TA, Loyer E, Pawlik TM, Taouli B, Choti MA (2013) Selection for hepatic resection of colorectal liver metastases: expert consensus statement. HBP 15:91–103. https://doi.org/10.1111/j.1477-2574.2012.00557.x

    Article  Google Scholar 

  41. Shah AJ, Callaway M, Thomas MG, Finch-Jones MD (2010) Contrast-enhanced intraoperative ultrasound improves detection of liver metastases during surgery for primary colorectal cancer. HBP 12:181–187. https://doi.org/10.1111/j.1477-2574.2009.00141.x

    Article  Google Scholar 

  42. Zalinski S, Abdalla EK, Manvash A, Vauthey JN (2009) A marking technique for intraoperative localization of small liver metastases before systemic chemotherapy. Ann Sure Oncol 16:1208–1211. https://doi.org/10.1245/s10434-009-0328-5

    Article  Google Scholar 

  43. Page AJ, Cosgrove DC, Herman JM, Pawlik TM (2015) Advances in understanding of colorectal liver metastases and implications for the clinic. Expert Rev Gastroenterol Hepatol 9(2):245–259. https://doi.org/10.1586/17474124.2014.940897

    Article  CAS  PubMed  Google Scholar 

  44. Goldberg SN, Charboneau JW, Dodd GD 3rd, Dupuy DE, Gervais DA, Gillams RA et al (2003) Image-guided tumor ablation: proposal for standardization of terms and reporting criteria. Radiology 228:335–345. https://doi.org/10.1148/radiol.2282021787

    Article  PubMed  Google Scholar 

  45. Erce C, Parks W (2003) Interstitial ablative techniques for hepatic tumours. Br J Surg 90:272–289. https://doi.org/10.1002/bjs.4091

    Article  CAS  PubMed  Google Scholar 

  46. Lencioni R (2008) What is the long-term survival benefit of radiofrequency ablation in patients with colorectal liver metastases? Nat Clin Pract Gastroenterol Hepatol 5:246–247. https://doi.org/10.1038/ncpgasthep1103

    Article  PubMed  Google Scholar 

  47. Gillams AR (2004) Liver ablation therapy. Br J Radiol 77:713–723. https://doi.org/10.1259/bjr/86761907

    Article  CAS  PubMed  Google Scholar 

  48. Gilams A, Goldberg N, Ahmed M, Bale R, Breen D, Callstrom M et al (2015) Thermal ablation of colorectal liver metastases: a position paper by an international panel of ablation experts, The interventional oncology sans frontières meeting 2013. Eur Radiol 25:3438–3454. https://doi.org/10.1007/s00330-015-3779-z

    Article  Google Scholar 

  49. Ruers T, Van Coevorden F, Punt CJ, Pierie JE, Borel-Rinkes I, Ledermann JA et al (2017) Local treatment of unresectable colorectal liver metastases: results of a randomized phase II trial. J Natl Cancer Inst 109(9). https://doi.org/10.1093/jnci/djx015

  50. Goèré D, Benhaim L, Bonnet S, Malka D, Faron M, Elias D et al (2013) Adjuvant chemotherapy after resection of colorectal liver metastases in patients at high risk of hepatic recurrence. A comparative study between hepatic arterial infusion of oxaliplatin and modern systemic chemotherapy. Ann Surg 257:114–20. https://doi.org/10.1097/SLA.0b013e31827b9005

    Article  PubMed  Google Scholar 

  51. Wimmer K, Schwartz C, Szabo C, Bodingbauer M, Tamandl D, Mittböck M et al (2017) Impact of neoadjuvant chemotherapy on clinical risk scores and survival in patients with colorectal liver metastases. Ann Surg Oncol 24:236–243. https://doi.org/10.1245/s10434-016-5615-3

    Article  PubMed  Google Scholar 

  52. Ribeiro HS, Torres OJ, Marques MC, Herman P, Kalil AN, Fernandes ES et al (2016) I Brazilian consensus on multimodal treatment of colorectal liver metastases. Module 2: approach to resectable metastases. Arq Bras Cir Dig 29(1):9–13. https://doi.org/10.1590/0102-6720201600010003

    Article  PubMed  PubMed Central  Google Scholar 

  53. Karanikolas PJ, Metrakos P, Chan K, Asmis T, Chen E, Kingham TP et al (2014) Hepatic arterial infusion pump chemotherapy in the management of colorectal liver metastases: expert consensus statement. Curr Oncol 21:e129–e136. https://doi.org/10.3747/co.21.1577

    Article  Google Scholar 

  54. Japan Clinical Oncology Group / European Society of Surgical Oncology. European Organization for Research and Treatment of Cancer. Diffusion-Weighted MRI for liver metastasis (DREAM). Identifier: NCT02781935. ClinicalTrials.gov. First posted: May 25, 2016

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Acknowledgements

We thank Dr. Junichi Arita, Dr. Stephane Benoist, Dr. Alessandro Ferrero, Dr. Akio Saiura, and Dr. Atsushi Oba for their invaluable comments.

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Authors and Affiliations

  1. General and Digestive Surgery Department - Hospital Clínic, IDIBAPS, CIBERHD, University of Barcelona, Carrer Villarroel 170, 08036, Barcelona, Spain

    Elena Ramírez-Maldonado, Rocío García-Pérez, Joana Ferrer-Fàbrega, Josep Fuster & Juan Carlos García-Valdecasas

  2. Medical Statistics Core Facility, Institut D´Investigacions Biomédiques August Pi I Sunyer (IDIBAPS), Hospital Clinic Barcelona, Barcelona, Spain

    Victor Sapena

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  1. Elena Ramírez-Maldonado
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  2. Rocío García-Pérez
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Contributions

Elena Ramírez-Maldonado, Rocío García-Pérez, and Joana Ferrer-Fàbrega participated in all phases of the study. Victor Sapena participated in the statistical methodology and results of the meta-analysis. Josep Fuster and Juan Carlos García-Valdecasas participated in the analysis and interpretation of data and critical revision of the manuscript.

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Correspondence to Elena Ramírez-Maldonado.

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Ramírez-Maldonado, E., García-Pérez, R., Ferrer-Fàbrega, J. et al. Missing colorectal liver metastases: the surgical challenge. Langenbecks Arch Surg 406, 2163–2175 (2021). https://doi.org/10.1007/s00423-021-02297-4

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