Hepatic cryoablation-induced acute lung injury: Histopathologic findings

Kay Washington, Jacob P. Debelak, Caroline Gobbell, Dora R. Sztipanovits, Yu Shyr, Sandy Olson, William C. Chapman

Research output: Contribution to journalArticle

36 Scopus citations

Abstract

We have previously shown that hepatic cryoablation (cryo), but not partial hepatectomy, induces a systemic inflammatory response, with distant organ injury and overproduction of NF-κB-dependent cytokines. Serum tumor necrosis factor-α (TNF-α) and macrophage inflammatory protein-2 (MIP-2) levels are markedly increased 1 h and beyond after cryo compared with partial hepatectomy where no elevation occurs. NF-κB activation (by electrophoretic mobility shift assay) is strikingly increased in the noncryo liver (but not in the lung) at 30 min and in both the liver and lung tissue 1 h after cryo, returning to the baseline by 2 h and beyond. The current study investigated the histopathologic changes associated with cryoablation-induced acute lung injury. Animals underwent 35% hepatic resection or a similar volume hepatic cryo and were sacrificed at 1, 2, 6, and 24 h. Pulmonary histologic features were assessed using hematoxylin and eosin and immunoperoxidase staining with a macrophage-specific antibody (anti-lysozyme, 1:200 dilution, Dako, Carpinteria, CA). The following features were graded semiquantitatively (0-3): perivascular lymphoid cuffs, airspace edema and hemorrhage, margination of neutrophils within pulmonary vasculature, and the presence of macrophages with foamy cytoplasm in the pulmonary interstitium. Hepatic resection (n = 21) resulted in slight perivascular edema at 1, 2, 6, and 24 h post-resection, but there were no other significant changes. Pulmonary findings after hepatic cryo (n = 22) included prominent perivascular lymphoid cuffs 1 and 2 h following hepatic injury that were not present at any other time point (P 0.01). Marginating PMNs and foamy macrophages were more common after cryo at all time points (P < 0.05, cryo vs resection). Severe lung injury, as evidenced by airspace edema and parenchymal hemorrhage, was present in four of six (67%) animals at 24 h (P 0.03). In follow-up studies immediate resection (n = 15) of the cryo-treated liver prior to thawing prevented the pulmonary changes. The findings of pulmonary perivascular interstitial macrophages 2 h following hepatic cryo suggests that hepatic cytokine production may induce downstream recruitment of pulmonary macrophages, which may contribute to subsequent severe lung injury. This study suggests that a soluble mediator from direct liver injury leads to neutrophilic lung inflammation and this is associated with the thawing phase of cryoablation.

Original languageEnglish
Pages (from-to)1-7
Number of pages7
JournalJournal of Surgical Research
Volume95
Issue number1
DOIs
StatePublished - Jan 1 2001
Externally publishedYes

Keywords

  • Critical care
  • Cryoablation
  • Liver tumor
  • Lung inflammation
  • Sepsis
  • Shock
  • Trauma

Fingerprint Dive into the research topics of 'Hepatic cryoablation-induced acute lung injury: Histopathologic findings'. Together they form a unique fingerprint.

  • Cite this

    Washington, K., Debelak, J. P., Gobbell, C., Sztipanovits, D. R., Shyr, Y., Olson, S., & Chapman, W. C. (2001). Hepatic cryoablation-induced acute lung injury: Histopathologic findings. Journal of Surgical Research, 95(1), 1-7. https://doi.org/10.1006/jsre.2000.5976