Friday, April 10, 2015

Transplantation for liver cancer: current thinking

Though it seems to be a logical option to treat liver cancer by liver transplantation, there are several issues that affects the long term disease free survival.  The only statistically proven and internationally accepted indication (Milan criteria) is as follows- Patients with single tumour less than 5 cm in size or multiple tumours none more than 3 cm and the total diameter not exceeding 5 cm with absence of gross invasion of blood vessels and having no spread outside the confines of the liver have 5 year survival that is comparable to patients with no cancer (around 82% five year survival).

Several issues about liver cancer are poorly understood.  Most importantly the biology of these cancers are as variable as ones finger print. The aggressiveness of the cancer measured as tumour grade varies from person to person.  Their host interaction and immune responses vary widely.  The tumour antigens that are expressed and tumour markers detected in the blood vary too.  This clearly makes decision to transplant extremely difficult. There is no perfect technology till date to detect microscopic spread of cancer outside the liver.  PET scan is all that we have and the specificty of this technique is limited. the recurrence of cancer after transplant depends on the presence of micro-metastasis. It seems grossly unscientific to carryout transplants for patients who fail to meet the so called Milan criteria.  What then should be the approach?

The only reason that transplant ever became an option to treat liver cancers is because majority of cancers occurred in diseased cirrhotic livers. Liver was viewed as precancerous in cirrhosis.  However it seems that the only way to understand the biology of individual tumours is to give it time and watch the evolution. Hence it is better to treat the cancer in the liver than to treat the liver with cancer, strategies should aim at cancer control unless the patient suffers from advanced liver failure (ie; those with high MELD score).  By adopting cancer control with tumour resection, ablation, chemo-embolization or radio-embolization, one gets the opportunity to see if there are new foci of cancer that crops up or if there is an extrahepatic focus of cancer.

This strategy helps to super select patients with good tumour biology who would also have good outcome after transplantation. Hence the focus should be to use tumour control strategies before recommending transplantation.  This is the hunch I had in 2010 when the first post was made in this blog. subsequently this thought process has been proven by the elegant study done at University of California, San Francisco.  The study by John P.Roberts clearly shows that survival of patients with beyond Milan criteria were significantly better when they waited to have tumour control before transplant than otherwise, as waiting allowed to cull patients with poor tumour biology from the transplant list.

Atigens = immunity stimulating proteins
PET = Positron Emission Tomography
Metastasis = tumour clumps spreading through blood
MELD = Modified Endstage Liver Disease score
Embolization = technique of cutting blood supply to the tumour

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