[1600] Capillarization of Hepatic Sinusoids after Neoadjuvant Therapy

PW Klonowski, B Tan, DC Linehan, MR Porembka, EM Brunt. Washington University School of Medicine, St. Louis, MO

Background: Oxaliplatin-based neoadjuvant therapy for hepatic colorectal metastasis (HCM) has been associated with hepatic injury including sinusoidal ectasia, peliosis and nodular regenerative hyperplasia. Currently, there exists no method to grade the injury. Aim: To further characterize the sinusoidal lesions and create a vascular injury scoring system.
Design: Forty patients who underwent neoadjuvant treatment and resection for HCM were retrospectively selected by an oncologist; 26 received oxaliplatin-based therapy (ox+), 14 did not (ox-). Samples of non-tumor liver were blindly evaluated by H&E, trichrome, and anti-CD34 immunostain (CD34).
Results: The injury patterns noted were hepatocellular anisonucleosis, varying degrees of sinusoidal disruption and cord atrophy, peliosis and steatosis. Steatosis, present in 16/40 (40%) total cases, did not correlate with neoadjuvant treatment. Thirteen of 40 (33%) cases showed injury; 10 were ox+. Hepatocyte anisonucleosis, peliosis and hemorrhage were only seen in ox+ cases. CD34 (score 0-2, based on low power extent) showed a trend of aberrant expression, focally in areas of damage as well as sinusoids not visibly injured in 22/25 (88%) ox+ vs 9/13 (69%) ox- cases; ≥2+ CD34 (multifocal, extensive) was present in 8 (32%) ox+ and 2 (15%) ox- cases. One ox+ patient died of liver failure 10 months post-op. Table 1 lists the proposed vascular injury score based on H&E and trichrome findings.
Conclusions: By blinded analysis, the majority of cases (62% ox+, 79% ox-) had no vascular findings. However, anisonucleosis and severe microvascular injury occurred in ox+ treated livers. Aberrant CD34 expression suggests more extensive injury than is observed by routine stains; altered endothelium in the parenchyma could result from unopposed arterial pressure in the damaged sinusoids. Anisonucleosis in ox+ cases warrants further study.

Table 1. Vascular Injury Score
Vascular Injury ScoreH&ETrichrome
0None ± anisonucleosisNegative
1AnisonucleosisDelicate PSF; suggestive sinusoidal ectasia
2Extensive anisonucleosisAs above + clusters of deep basophilic hepatocytes
3aSinusoidal prominence + RBCs in sinusoidsAs above + PSF outlines affected sinusoids
3bz3 sinusoidal ectasia + cord atrophyz3 PSF
3cAs above + early peliosisTrichrome negative in peliosis
4aDefinite peliosis, extensiveAs above
4bSinusoidal disruption + cord atrophy, hemorrhage, multifocalPSF + intrasinusoidal debris
4cAs above + outflow vein obliterationAs above + terminal hepatic venule fibrosis
PSF=perisinusoidal fibrosis; z3=zone 3

Category: Liver & Pancreas

Monday, March 22, 2010 1:00 PM

Poster Session II # 176, Monday Afternoon


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