Increased vascular endothelial growth factor transcription in residual hepatocellular carcinoma after open versus laparoscopic hepatectomy in a small animal model.
BACKGROUND
Vascular endothelial growth factor (VEGF) is overexpressed in hepatocellular carcinoma (HCC), and findings have shown that its upregulation in these tumors has an impact on tumor growth. The authors hypothesized that compared with open liver resection, laparoscopic hepatectomy would result in a decreased local angiogenic response in residual tumor cells.


METHODS
Right- and left-lobe hepatomas were induced in Buffalo rats via laparoscopically guided subcapsular injection of Morris hepatoma cells. After 1 week, the animals were randomized to laparoscopic or open left lateral hepatectomy. In 14 days after resection, the rats were killed, the residual right lobe tumors were measured, and tissue was procured for RNA extraction. Transcript levels of VEGF messenger RNA (mRNA) were quantified with reverse transcriptase-polymerase chain reaction (RT-PCR), and VEGF serum levels were measured by enzyme-linked immunoassay (ELISA) both before resection and at the time of tissue harvest.


RESULTS
None of the animals had development satellite liver lesions or distant metastases in the abdomen or thorax. The median residual tumor volume was 320 mm(3) in the open group compared with 180 mm(3) in the laparoscopic group (p = 0.164). The animals that underwent open resection had a 1.3-fold increase in VEGF mRNA transcript levels compared with the laparoscopic resection group (p = 0.008). The serum VEGF levels were not significantly different between the laparoscopic and open groups at baseline (open tumor resection [OR], 23.7 +/- 12.0 pg/ml; laparoscopic tumor resection [LR], 30.7 +/- 15.5 pg/ml; p = 0.334) nor at the time of tissue harvest (OR, 19.9 +/- 19.6 pg/ml; LR, 26.9 +/- 34.5 pg/ml; p = 0.549).


CONCLUSIONS
Laparoscopic hepatic resection produces decreased VEGF mRNA expression in residual hepatoma cells compared with open resection. Decreased stimulation of angiogenesis promoters in the tumor microenvironment after minimally invasive liver resection may contribute to a lower residual disease burden and ultimately lead to a lower recurrence rate.
Perry
Kyle A
KA
Department of Surgery, Oregon Health and Science University, Mail Code L223A, 3181 Sam Jackson Park Road, Portland, OR 97239, USA.
Enestvedt
C Kristian
CK
Hosack
Luke W
LW
Pham
Thai H
TH
Diggs
Brian S
BS
Teh
Swee
S
Orloff
Susan
S
Winn
Shelly
S
Hunter
John G
JG
Sheppard
Brett C
BC
D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000097:blood / Q000235:genetics* / Q000601:surgery; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006498:Hepatectomy / Q000379:methods*; D010535:Laparoscopy; D007813:Laparotomy; D008099:Liver / Q000473:pathology / Q000601:surgery; D008114:Liver Neoplasms, Experimental / Q000097:blood / Q000235:genetics* / Q000601:surgery; D009389:Neovascularization, Pathologic; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics*; D051381:Rats; D011915:Rats, Inbred BUF; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis / Q000235:genetics*
D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A