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Liver Injury Due to Chemotherapy-induced Sinusoidal Obstruction Syndrome Is Associated with Sinusoidal Capillarization

  • Hepatobiliary Tumors
  • Published:
Annals of Surgical Oncology Aims and scope Submit manuscript

Abstract

Background

Indocyanine green (ICG) retention is a validated test of hepatic function in patients with chronic liver disease. The underlying mechanism for the impairment of ICG retention in patients undergoing chemotherapy for colorectal liver metastases (CLM) remains unclear. We sought to elucidate the mechanism for impairment of ICG retention in patients with CLM.

Methods

Clinicopathologic data of 98 patients with CLM undergoing hepatectomy were analyzed. The archived nontumoral liver parenchyma bearing no CLM were immunostained with CD34 antibody to determine the sinusoidal capillarization.

Results

Of 98 patients, 80 received preoperative chemotherapy. Sinusoidal obstruction syndrome (SOS) occurred in 39 patients (39.8%). The development of SOS in patients receiving oxaliplatin-based chemotherapy was significantly higher compared to those receiving non-oxaliplatin-based chemotherapy (P = 0.003). SOS was independently associated with abnormal ICG retention rate at 15 minutes (ICG-R15) (odds ratio 3.45, 95% confidence interval 1.31–9.04, P = 0.012) and CD 34 overexpression (odds ratio 18.76, 95% confidence interval 4.58–76.81, P < 0.001). ICG-R15 correlated with CD34 expression within the nontumoral liver parenchyma (r = 0.707, P < 0.001) and severity of SOS (r = 0.423, P < 0.001). CD34 positive areas were likely situated at the peripheral area of SOS, and both SOS score and number of cycles of oxaliplatin-based chemotherapy significantly correlated with CD34 expression (r = 0.629, P < 0.001 and r = 0.522, P < 0.001, respectively).

Conclusions

These results suggest that the deterioration of hepatic functional reserve due to SOS is associated with sinusoidal capillarization, indicated by CD34 overexpression within nontumoral liver parenchyma adjacent to SOS.

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Acknowledgment

The authors thank Professor Bertrand Ludes and Professor Gilbert Vicente for their help, Eliane Supper, Fabienne Reymann, and Martine Muckensturm, who performed immunohistochemistry.

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Authors and Affiliations

  1. Centre de Chirurgie Viscérale et de Transplantation, Hôpital de Hautepierre, Hôpitaux Universitaires de Strasbourg, Strasbourg, France

    Masato Narita MD, PhD, Elie Oussoultzoglou MD, Muddasar Rather MD, Edoardo Rosso MD, Pietro Addeo MD, Daniel Jaeck MD, PhD, FRCS & Philippe Bachellier MD, PhD

  2. Service d’Anatomie Pathologique, Hôpital de Hautepierre, Hôpitaux Universitaires de Strasbourg, Strasbourg, France

    Marie-Pierre Chenard MD, PhD

  3. Department of Surgical Oncology, The Permanente Medical Group, Walnut Creek, CA, USA

    Pascal Fuchshuber MD, PhD, FACS

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  1. Masato Narita MD, PhD
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  2. Elie Oussoultzoglou MD
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  3. Marie-Pierre Chenard MD, PhD
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  4. Pascal Fuchshuber MD, PhD, FACS
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  5. Muddasar Rather MD
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  6. Edoardo Rosso MD
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  8. Daniel Jaeck MD, PhD, FRCS
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  9. Philippe Bachellier MD, PhD
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Corresponding author

Correspondence to Philippe Bachellier MD, PhD.

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Narita, M., Oussoultzoglou, E., Chenard, MP. et al. Liver Injury Due to Chemotherapy-induced Sinusoidal Obstruction Syndrome Is Associated with Sinusoidal Capillarization. Ann Surg Oncol 19, 2230–2237 (2012). https://doi.org/10.1245/s10434-011-2112-6

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  • DOI: https://doi.org/10.1245/s10434-011-2112-6

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