The Roles of Laparoscopic Liver Resection and Hypoxia Inducible Factor in the Pathophysiology of Liver cancer
Author(s)
Healey, Andrew James
Type
Thesis
Abstract
In the last 20 years laparoscopic liver resection has been increasingly practised. However its
role in the treatment of liver cancer remains under scrutiny. I performed a pilot study at a
specialist HPB unit assessing the results of the laparoscopic resections of one surgeon and
comparing them to the results of matched cases on whom he had performed open
resection. The resection technique was radiofrequency assisted resection pioneered in this
unit. I also analysed the resected tissue to investigate any differential effect on cell
characteristics of the 2 operative techniques. Operative time was significantly longer in
laparoscopic cases and time to recurrence of R0 resections significantly shorter. Resected
tissue demonstrated significantly higher levels of the hypoxia inducible factor-2 and CD10, a
recognised poor prognostic marker in primary colorectal tumours.
I hypothesised that livers resected laparoscopically are under a relative hypoxia because of
the increased intraabdominal pressure associated with the pneumoperitoneum and tumours
cells therefore have a positive selection advantage. In the setting of longer resection times
this may compromise the oncological result of the surgery causing earlier recurrence. Using
a established model of HIF activation, I showed that poor prognostic marker CD10 may be a
function of hypoxia inducible regulation. Certainly I was able to replicate data from cervical
squamous epithelia demonstrating that both in benign, dysplastic and malignant tissue, HIF
expression corresponded to a reduced cell E-cadherin expression that may allow a more
malignant potential.
I also analysed the effect of RF ablation on circulating tumour cells in palliative irresectable
cancers and in the context of both open and laparoscopic liver resection. This showed only a
transient rise in both resectional techniques, (open and lap) that would unlikely count for
the differential oncological outcome previously demonstrated in the pilot study.
In keeping with current international opinion, further work is required to verify the role of
laparoscopic liver resection in liver cancer.
role in the treatment of liver cancer remains under scrutiny. I performed a pilot study at a
specialist HPB unit assessing the results of the laparoscopic resections of one surgeon and
comparing them to the results of matched cases on whom he had performed open
resection. The resection technique was radiofrequency assisted resection pioneered in this
unit. I also analysed the resected tissue to investigate any differential effect on cell
characteristics of the 2 operative techniques. Operative time was significantly longer in
laparoscopic cases and time to recurrence of R0 resections significantly shorter. Resected
tissue demonstrated significantly higher levels of the hypoxia inducible factor-2 and CD10, a
recognised poor prognostic marker in primary colorectal tumours.
I hypothesised that livers resected laparoscopically are under a relative hypoxia because of
the increased intraabdominal pressure associated with the pneumoperitoneum and tumours
cells therefore have a positive selection advantage. In the setting of longer resection times
this may compromise the oncological result of the surgery causing earlier recurrence. Using
a established model of HIF activation, I showed that poor prognostic marker CD10 may be a
function of hypoxia inducible regulation. Certainly I was able to replicate data from cervical
squamous epithelia demonstrating that both in benign, dysplastic and malignant tissue, HIF
expression corresponded to a reduced cell E-cadherin expression that may allow a more
malignant potential.
I also analysed the effect of RF ablation on circulating tumour cells in palliative irresectable
cancers and in the context of both open and laparoscopic liver resection. This showed only a
transient rise in both resectional techniques, (open and lap) that would unlikely count for
the differential oncological outcome previously demonstrated in the pilot study.
In keeping with current international opinion, further work is required to verify the role of
laparoscopic liver resection in liver cancer.
Date Issued
2011
Date Awarded
2012-03
Copyright Statement
Attribution NoDerivatives 4.0 International Licence (CC BY-ND)
Advisor
Jiao, Long
Sponsor
Royal College of Surgeons of Edinburgh
Creator
Healey, Andrew James
Publisher Department
Medicine
Publisher Institution
Imperial College London
Qualification Level
Doctoral
Qualification Name
Doctor of Medicine (Research) MD (Res)