Abdominal Radiology

, Volume 43, Issue 11, pp 2991–3000 | Cite as

Correlation between CT morphologic appearance and histologic findings in colorectal liver metastasis after preoperative chemotherapy

  • Kazuyuki IshidaEmail author
  • Akio Tamura
  • Kenichi Kato
  • Noriyuki Uesugi
  • Mitsumasa Osakabe
  • Makoto Eizuka
  • Yasushi Hasegawa
  • Hiroyuki Nitta
  • Koki Otsuka
  • Akira Sasaki
  • Shigeru Ehara
  • Tamotsu Sugai



Radiological evaluation of the efficacy of preoperative chemotherapy for colorectal liver metastasis (CRLM) is the most important tool for determining treatment strategies. The aim of this study was to identify a correlation between morphologic appearance on computed tomography (CT) and histologic findings of CRLM after preoperative chemotherapy.


We examined 47 patients who had undergone a first hepatic resection for CRLM after preoperative chemotherapy and had received contrast-enhanced CT scans. We assessed the morphologic appearance of the overall attenuation based on metastases changing from heterogeneous to mixed and homogenous lesions, the tumor–liver interface, and the peripheral rim enhancement on CT. Histologic parameters included usual necrosis (UN), infarct-like necrosis (ILN), three-zonal change, dangerous halo, mucous lake, shape of ILN, dominant type of necrosis, and presence of viable tumor cells. The relationship between morphologic appearance and histologic findings was evaluated.


CT overall attenuation revealed that UN predominance was more common in the heterogeneous group than in the mixed and homogeneous groups (P = 0.011). The frequency of ILN increased sequentially from ill-defined to variable and sharp at the tumor–liver interface (P = 0.038), and the frequency of UN decreased sequentially from present to partially resolved and completely resolved in the peripheral rim enhancement (P = 0.023). The histologic presence of viable tumor cells was closely associated with the tumor–liver interface (P = 0.0003) and the peripheral rim enhancement (P = 0.004).


CT morphologic appearance of CRLM after preoperative chemotherapy is correlated with histologic findings regarding necrosis.


Colorectal carcinoma Metastasis Liver neoplasms Computed tomography X-ray Comparative histology 



This work was supported by JSPS KAKENHI Grant Number JP16K08655.

Compliance with ethical standards

Disclosures of conflicts of interest

All authors disclosed no relevant relationships.


  1. 1.
    Stangl R, Altendorf-Hofmann A, Charnley RM, Scheele J (1994) Factors influencing the natural history of colorectal liver metastases. Lancet 343:1405–1410CrossRefGoogle Scholar
  2. 2.
    Steele G Jr, Ravikumar TS (1989) Resection of hepatic metastases from colorectal cancer. Biol Perspect Ann Surg 210:127–138CrossRefGoogle Scholar
  3. 3.
    Scheele J, Stangl R, Altendorf-Hofmann A (1990) Hepatic metastases from colorectal carcinoma: impact of surgical resection on the natural history. Br J Surg 77:1241–1246CrossRefGoogle Scholar
  4. 4.
    Weber JC, Bachellier P, Oussoultzoglou E, Jaeck D (2003) Simultaneous resection of colorectal primary tumour and synchronous liver metastases. Br J Surg 90:956–962CrossRefGoogle Scholar
  5. 5.
    Andres A, Majno PE, Morel P, et al. (2008) Improved long-term outcome of surgery for advanced colorectal liver metastases: reasons and implications for management on the basis of a severity score. Ann Surg Oncol 15:134–143CrossRefGoogle Scholar
  6. 6.
    Wagner JS, Adson MA, Van Heerden JA, Adson MH, Ilstrup DM (1984) The natural history of hepatic metastases from colorectal cancer. A comparison with resective treatment. Ann Surg 199:502–508CrossRefGoogle Scholar
  7. 7.
    Giacchetti S, Itzhaki M, Gruia G, et al. (1999) Long-term survival of patients with unresectable colorectal cancer liver metastases following infusional chemotherapy with 5-fluorouracil, leucovorin, oxaliplatin and surgery. Ann Oncol 10:663–669CrossRefGoogle Scholar
  8. 8.
    Adam R, Delvart V, Pascal G, et al. (2004) Rescue surgery for unresectable colorectal liver metastases downstaged by chemotherapy: a model to predict long-term survival. Ann Surg 240:644–657CrossRefGoogle Scholar
  9. 9.
    Alberts SR, Horvath WL, Sternfeld WC, et al. (2005) Oxaliplatin, fluorouracil, and leucovorin for patients with unresectable liver-only metastases from colorectal cancer: a North Central Cancer Treatment Group phase II study. J Clin Oncol 23:9243–9249CrossRefGoogle Scholar
  10. 10.
    Therasse P, Arbuck SG, Eisenhauer EA, et al. (2000) New guidelines to evaluate the response to treatment in solid tumors. European Organization for Research and Treatment of Cancer, National Cancer Institute of the United States, National Cancer Institute of Canada. J Natl Cancer Inst 92:205–216CrossRefGoogle Scholar
  11. 11.
    Eisenhauer EA, Therasse P, Bogaerts J, et al. (2009) New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer 45:228–247CrossRefGoogle Scholar
  12. 12.
    Saltz LB, Clarke S, Diaz-Rubio E, et al. (2008) Bevacizumab in combination with oxaliplatin-based chemotherapy as first-line therapy in metastatic colorectal cancer: a randomized phase III study. J Clin Oncol 26:2013–2019CrossRefGoogle Scholar
  13. 13.
    Sathornsumetee S, Cao Y, Marcello JE, et al. (2008) Tumor angiogenic and hypoxic profiles predict radiographic response and survival in malignant astrocytoma patients treated with bevacizumab and irinotecan. J Clin Oncol 26:271–278CrossRefGoogle Scholar
  14. 14.
    Grothey A, Hedrick EE, Mass RD, et al. (2008) Response-independent survival benefit in metastatic colorectal cancer: a comparative analysis of N9741 and AVF2107. J Clin Oncol 26:183–189CrossRefGoogle Scholar
  15. 15.
    Chun YS, Vauthey JN, Boonsirikamchai P, et al. (2009) Association of computed tomography morphologic criteria with pathologic response and survival in patients treated with bevacizumab for colorectal liver metastases. JAMA 302:2338–2344CrossRefGoogle Scholar
  16. 16.
    Shindoh J, Loyer EM, Kopetz S, et al. (2012) Optimal morphologic response to preoperative chemotherapy: an alternate outcome end point before resection of hepatic colorectal metastases. J Clin Oncol 30:4566–4572CrossRefGoogle Scholar
  17. 17.
    Yoshita H, Hosokawa A, Ueda A, et al. (2014) Predictive value of optimal morphologic response to first-line chemotherapy in patients with colorectal liver metastases. Digestion 89:43–48CrossRefGoogle Scholar
  18. 18.
    Nishioka Y, Shindoh J, Yoshioka R, et al. (2015) Radiological morphology of colorectal liver metastases after preoperative chemotherapy predicts tumor viability and postoperative outcomes. J Gastrointest Surg 19:1653–1661CrossRefGoogle Scholar
  19. 19.
    Rubbia-Brandt L, Giostra E, Brezault C, et al. (2007) Importance of histological tumor response assessment in predicting the outcome in patients with colorectal liver metastases treated with neo-adjuvant chemotherapy followed by liver surgery. Ann Oncol 18:299–304CrossRefGoogle Scholar
  20. 20.
    Blazer DG 3rd, Kishi Y, Maru DM, et al. (2008) Pathologic response to preoperative chemotherapy: a new outcome end point after resection of hepatic colorectal metastases. J Clin Oncol 26:5344–5351CrossRefGoogle Scholar
  21. 21.
    Klinger M, Tamandl D, Eipeldauer S, et al. (2010) Bevacizumab improves pathological response of colorectal cancer liver metastases treated with XELOX/FOLFOX. Ann Surg Oncol 17:2059–2065CrossRefGoogle Scholar
  22. 22.
    Chang HH, Leeper WR, Chan G, Quan D, Driman DK (2012) Infarct-like necrosis: a distinct form of necrosis seen in colorectal carcinoma liver metastases treated with perioperative chemotherapy. Am J Surg Pathol 36:570–576CrossRefGoogle Scholar
  23. 23.
    Ishida K, Uesugi N, Hasegawa Y, et al. (2015) Proposal for novel histological findings of colorectal liver metastases with preoperative chemotherapy. Pathol Int 65:367–373CrossRefGoogle Scholar
  24. 24.
    Loupakis F, Schirripa M, Caparello C, et al. (2013) Histopathologic evaluation of liver metastases from colorectal cancer in patients treated with FOLFOXIRI plus bevacizumab. Br J Cancer 108:2549–2556CrossRefGoogle Scholar
  25. 25.
    Aloysius MM, Zaitoun AM, Beckingham IJ, et al. (2007) The pathological response to neoadjuvant chemotherapy with FOLFOX-4 for colorectal liver metastases: a comparative study. Virchows Arch 451:943–948CrossRefGoogle Scholar
  26. 26.
    Mentha G, Terraz S, Morel P, et al. (2009) Dangerous halo after neoadjuvant chemotherapy and two-step hepatectomy for colorectal liver metastases. Br J Surg 96:95–103CrossRefGoogle Scholar
  27. 27.
    Bibeau F, Gil H, Castan F, Boissiere-Michot F (2013) Comment on ‘Histopathologic evaluation of liver metastases from colorectal cancer in patients treated with FOLFOXIRI plus bevacizumab’. Br J Cancer 109:3127–3129CrossRefGoogle Scholar
  28. 28.
    Ribero D, Wang H, Donadon M, et al. (2007) Bevacizumab improves pathologic response and protects against hepatic injury in patients treated with oxaliplatin-based chemotherapy for colorectal liver metastases. Cancer 110:2761–2767CrossRefGoogle Scholar
  29. 29.
    Lam VW, Spiro C, Laurence JM, et al. (2012) A systematic review of clinical response and survival outcomes of downsizing systemic chemotherapy and rescue liver surgery in patients with initially unresectable colorectal liver metastases. Ann Surg Oncol 19:1292–1301CrossRefGoogle Scholar
  30. 30.
    Ng JK, Urbanski SJ, Mangat N, et al. (2008) Colorectal liver metastases contract centripetally with a response to chemotherapy: a histomorphologic study. Cancer 112:362–371CrossRefGoogle Scholar
  31. 31.
    Folprecht G, Gruenberger T, Bechstein WO, et al. (2010) Tumour response and secondary resectability of colorectal liver metastases following neoadjuvant chemotherapy with cetuximab: the CELIM randomised phase 2 trial. Lanc Oncol 11:38–47CrossRefGoogle Scholar
  32. 32.
    Ng F, Ganeshan B, Kozarski R, Miles KA, Goh V (2013) Assessment of primary colorectal cancer heterogeneity by using whole-tumor texture analysis: contrast-enhanced CT texture as a biomarker of 5-year survival. Radiology 266:177–184CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Kazuyuki Ishida
    • 1
    Email author
  • Akio Tamura
    • 2
  • Kenichi Kato
    • 2
  • Noriyuki Uesugi
    • 1
  • Mitsumasa Osakabe
    • 1
  • Makoto Eizuka
    • 1
  • Yasushi Hasegawa
    • 3
  • Hiroyuki Nitta
    • 3
  • Koki Otsuka
    • 3
  • Akira Sasaki
    • 3
  • Shigeru Ehara
    • 2
  • Tamotsu Sugai
    • 1
  1. 1.Department of Molecular Diagnostic PathologyIwate Medical UniversityMoriokaJapan
  2. 2.Department of RadiologyIwate Medical UniversityMoriokaJapan
  3. 3.Department of SurgeryIwate Medical UniversityMoriokaJapan

Personalised recommendations