Metabolic signature of electrosurgical liver dissection.
OBJECTIVE
High frequency electrosurgery has a key role in the broadening application of liver surgery. Its molecular signature, i.e. the metabolites evolving from electrocauterization which may inhibit hepatic wound healing, have not been systematically studied.


METHODS
Human liver samples were thus obtained during surgery before and after electrosurgical dissection and subjected to a two-stage metabolomic screening experiment (discovery sample: N = 18, replication sample: N = 20) using gas chromatography/mass spectrometry.


RESULTS
In a set of 208 chemically defined metabolites, electrosurgical dissection lead to a distinct metabolic signature resulting in a separation in the first two dimensions of a principal components analysis. Six metabolites including glycolic acid, azelaic acid, 2-n-pentylfuran, dihydroactinidiolide, 2-butenal and n-pentanal were consistently increased after electrosurgery meeting the discovery (p<2.0 × 10(-4)) and the replication thresholds (p<3.5 × 10(-3)). Azelaic acid, a lipid peroxidation product from the fragmentation of abundant sn-2 linoleoyl residues, was most abundant and increased 8.1-fold after electrosurgical liver dissection (preplication = 1.6 × 10(-4)). The corresponding phospholipid hexadecyl azelaoyl glycerophosphocholine inhibited wound healing and tissue remodelling in scratch- and proliferation assays of hepatic stellate cells and cholangiocytes, and caused apoptosis dose-dependently in vitro, which may explain in part the tissue damage due to electrosurgery.


CONCLUSIONS
Hepatic electrosurgery generates a metabolic signature with characteristic lipid peroxidation products. Among these, azelaic acid shows a dose-dependent toxicity in liver cells and inhibits wound healing. These observations potentially pave the way for pharmacological intervention prior liver surgery to modify the metabolic response and prevent postoperative complications.
Department of General and Thoracic Surgery, University Hospital Schleswig-Holstein, Kiel, Germany.
Witigo
W
von Schönfels
Oliver
O
von Kampen
Eleonora
E
Patsenker
Felix
F
Stickel
Bodo
B
Schniewind
Sebastian
S
Hinz
Markus
M
Ahrens
Katharina
K
Balschun
Jan-Hendrik
JH
Egberts
Klaus
K
Richter
Andreas
A
Landrock
Bence
B
Sipos
Olga
O
Will
Patrizia
P
Huebbe
Stefan
S
Schreiber
Michael
M
Nothnagel
Christoph
C
Röcken
Gerald
G
Rimbach
Thomas
T
Becker
Jochen
J
Hampe
Clemens
C
Schafmayer
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis / Q000187:drug effects; D002460:Cell Line; D003998:Dicarboxylic Acids / Q000302:isolation & purification / Q000378:metabolism / Q000494:pharmacology*; D004210:Dissection / Q000379:methods; D004305:Dose-Response Relationship, Drug; D004598:Electrosurgery; D005260:Female; D055166:Hepatic Stellate Cells / Q000166:cytology / Q000187:drug effects; D006801:Humans; D015227:Lipid Peroxidation; D008099:Liver / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D008297:Male; D055442:Metabolome; D008875:Middle Aged; D010767:Phosphorylcholine / Q000031:analogs & derivatives* / Q000302:isolation & purification / Q000378:metabolism / Q000494:pharmacology; D025341:Principal Component Analysis; D014945:Wound Healing / Q000187:drug effects*
C543859:1-0-hexadecyl-2-azelaoyl-sn-glycero-3-phosphocoline; D003998:Dicarboxylic Acids; D010767:Phosphorylcholine; C010038:azelaic acid