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The Roles of Laparoscopic Liver Resection and Hypoxia Inducible Factor in the Pathophysiology of Liver cancer

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Title: The Roles of Laparoscopic Liver Resection and Hypoxia Inducible Factor in the Pathophysiology of Liver cancer
Authors: Healey, Andrew James
Item Type: Thesis or dissertation
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.
Issue Date: 2011
Date Awarded: Mar-2012
URI: http://hdl.handle.net/10044/1/9319
DOI: https://doi.org/10.25560/9319
Supervisor: Jiao, Long
Sponsor/Funder: Royal College of Surgeons of Edinburgh
Author: Healey, Andrew James
Department: Medicine
Publisher: Imperial College London
Qualification Level: Doctoral
Qualification Name: Doctor of Medicine (Research) MD (Res)
Appears in Collections:Medicine PhD theses



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