Attenuated metabolic response to surgery in tumor-bearing rats.
BACKGROUND
During cancer, proteins are chronically wasted, including proteins of the gut. Surgical stress acutely increases protein breakdown of the gut. Surgery in cancer patients may thus have a double effect on the gut and lead to exhaustion and functional loss of the gut.


METHODS
Female Lewis rats (+/-200 g) were studied bearing a subcutaneous tumor or after sham implantation. Hysterectomy was performed in half of the rats as a standardized operative procedure. Postoperative protein kinetics of the gut were determined using a primed constant infusion of L-[2,6-(3)H]-phenylalanine. Gut function was assessed by testing its permeability for sugar probes lactulose and L-rhamnose. Villus height and crypt depth were measured and polyamine concentrations were measured as markers for mucosal proliferation and differentiation.


RESULTS
In control rats, gut protein breakdown increased from 6 +/- 3 to 32 +/- 8 nmol phenylalanine x 100 g body wt x min after hysterectomy. This was accompanied by increased amino acid membrane transport rates and metabolic shunting. In tumor-bearing rats, increased protein breakdown in response to surgery was attenuated (8 +/- 4 vs 17 +/- 4 nmol x 100 g body wt x min). Surgery increased the lactulose/L-rhamnose recovery ratio, indicating increased gut permeability. In the presence of a tumor gut permeability also increased and it increased further after surgery. No changes in villus height or polyamine levels could explain the increased permeability of the gut.


CONCLUSIONS
The study shows that a mild surgical trauma increases protein breakdown of the gut and simultaneously increases gut permeability. In the presence of a tumor the metabolic response to surgery is attenuated. Gut barrier loss was highest in the combined presence of cancer and the surgical insult.
de Blaauw
Ivo
I
Department of Surgery, Maastricht University, Maastricht, The Netherlands. deblaauw@wxs.nl
Deutz
Nicolaas E P
NE
Hulsewe
Karel W
KW
von Meyenfeldt
Maarten F
MF
D000818:Animals; D005260:Female; D007044:Hysterectomy / Q000009:adverse effects; D007421:Intestine, Small / Q000378:metabolism* / Q000503:physiopathology; D023421:Models, Animal; D009374:Neoplasms, Experimental / Q000150:complications / Q000378:metabolism*; D010539:Permeability; D011504:Protein-Losing Enteropathies / Q000209:etiology / Q000378:metabolism*; D011506:Proteins / Q000378:metabolism; D051381:Rats; D011917:Rats, Inbred Lew; D013312:Stress, Physiological / Q000209:etiology / Q000378:metabolism*; D013514:Surgical Procedures, Operative / Q000009:adverse effects*
D011506:Proteins