Reference References

130

Letters to the Editor

Ann. Surg. * January 1997

multivariate models, the high percentage of rectal tumors in our study could not have influenced the findings on the association between blood transfusions and pattem of recurrence. Therefore, the association with local recurrence was true for rectal and for colon tumors. Fortunately, Amato et al. support our recommendations for meticulous surgery and strict indications for blood transfusions, which, in our opinion, is beneficial to all surgical patients, including those with colorectal cancer.

Reference 1. Busch ORC, Hop WCJ, Marquet RL, et al. Blood transfusions and local tumor recurrence in colorectal cancer: evidence of a noncausal relationship. Ann Surg 1994; 220:791-797.

OLIVIER R. C. BUSCH, PH.D. WIM C. J. Hop, M.Sc. RICHARD L. MARQUET, PH.D. JOHANNES JEEKEL, PH.D. Rotterdam, The Netherlands

Dear Editor: We read with great interest the recent article by Dr. Goeters and colleagues.' We would like to congratulate the authors for carrying out these complex metabolic studies in postoperative patients. However, before insulin-like growth factor-l (IGF-1) can be discounted as an anticatabolic hormone in surgical patients, we would like to point out certain features in this study that may have had an important bearing on the results. The IGF1 treatment only started the day after the surgical procedure. It has been well documented that plasma cytokine levels rise in the perioperative period.2'3 These cytokines have profound effects on metabolism and plasma hormonal concentrations.4'5 The patients already were in a catabolic state by the time they were given their first dose of IGF-1. It is far easier to stop the catabolic process in its initial stage than half-way through the full blown catabolic phase. The situation is analogous to preventing deep vein thrombosis and infection with preoperative subcutaneous heparin and prophylactic antibiotics respectively. It has been shown that IGF-1 suppresses plasma insulin in postoperative patients.6 In this study, plasma insulin concentrations may have been suppressed after IGF-l administration, but the sampling period of 24 hours probably was too infrequent to detect any early perturbations. We were surprised to find that growth hormone (GH) concentrations were not measured in this study. In healthy adults IGF-l administration reduces plasma GH concentration,7 and the direct anabolic effects of GH have been well documented in surgical patients.89 It has been postulated that in septic patients, GH resistance is accompanied by a switch from indirect to direct actions of GH. 0 If the patients in this study had reduced plasma GH concentrations, this may explain some of the findings. There is increased protein catabolism and synthesis in the postoperative period, and this response is tissue dependent. The increased synthesis of acute phase proteins in the visceral tissue may be offset by increased catabolism of myofibril proteins in the muscle. The half-life of these acute phase proteins is far shorter than that of the muscle proteins; thus, some of the nitrogen loss could be accounted

for by this shift. In most postoperative subjects, the skeletal muscle protein loss determines the rate of recovery. It has been shown that the urinary 3-methylhistidine loss does not correlate with skeletal muscle catabolism." It might have been more useful to measure the protein synthesis in the muscle or protein oxidation in addition to the whole body nitrogen balance.

References 1. Goeters C, Mertes N, Tacke J, et al. Repeated administration of recombinant human insulin-like growth factor-I in patients after gastric surgery: effect on metabolic and hormonal patterns. Ann Surg 1995; 222:646-653. 2. Cruickshank AM, Fraser WD, Burns HJG, et al. Response of serum interlukin-6 in patients undergoing elective surgery of varying severity. Clin Sci 1990; 79:161-165. 3. Baigrie RJ, Lamont PM, Kwiatkowski D, et al. Systemic cytokine response after major surgery. Br J Surg 1992; 79:757-760. 4. Spath-Schwalbe E, Born J, Schrezenmeier H, et al. Interleukin-6 stimulates the hypothalamus-pituitary-adrenocortical axis in man. J Clin Endocrinol Metab 1994; 79:1212-1214. 5. Stouthard JML, Romijn JA, van der Poll T, et al. Endocrinologic and metabolic effects of interlukin-6 in humans. Am J Physiol 1995; 268:E813-E819. 6. Miell JP, Taylor AM, Jones J, et al. Administration of human recombinant insulin-like growth factor-I to patients following major gastrointestinal surgery. Clin Endicrinol 1992; 37:542-551. 7. Zenobi PD, Graf S, Ursprung H, Froesch ER. Effects of insulinlike growth factor-I on glucose tolerance, insulin levels and insulin secretion. J Clin Invest 1992; 89:1908-1913. 8. Douglas RG, Humberstone DA, Haystead A, Shaw JHF. Metabolic effects of recombinant human growth hormone: isotopic studies in the post absorptive state and during total parenteral nutrition. Br J Surg 1990; 77:785-790. 9. Byrne TA, Morrissey TB, Gatzen C, et al. Anabolic therapy with growth hormone accelerates protein gain in surgical patients requiring nutritional rehabilitation. Ann Surg 1993; 218:400-418. 10. Ross R, Miell J, Freeman E, et al. Critically ill patients have high basal growth hormone levels with attenuated oscillatory activity associated with low levels of insulin-like growth factor-1. Clin Endocrinol 1991; 35:47-54. 11. Rennie MJ, Bennegard K, Eden E, et al. Urinary excretion and efflux from the leg of 3-methylhistidine before and after major surgical operation. Metabolism 1984; 33:250-256.

JASWINDER S. SAMRA, M.B., CH.B., F.R.C.S., D.PHIL. LUCINDA K. SUMMERS, M.B.B.S., B.Sc., M.R.C.P.

Oxford, England April 15, 1996 Dear Editor: We appreciate Dr. Samra's comments. Surgery and trauma induce well-known changes of the hormonal milieu and mediator deliberation causing protein breakdown. The objective of our study was to evaluate the effect of insulin-like growth factor-1 (IGF-1) on the established catabolic process. We did not assume that IGF-1 would modify neuroendocrine stress response and thus the catabolic process itself like, e.g., a2-agonists' or epidural anesthesia potentially. In this case it might have been sensible to apply the drug before surgery. We assumed that IGF-1 would improve protein economy and balance by its anabolic action. Thus, we started the study on the