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Evaluation of mechanisms behind elevated energy expenditure in cancer patients
NUTRITION AND CANCER
0.32 Balances of energy-yielding subtrates across malignantgastric tumors in man M. GrescW, H.-D.Saeger, M Barfh,H.Leweling and E. Ho/m Dept. of Pathophysiology, Medical Clinic I Mannheim and Surgical Clinic Mannheim, University of Heideibetg, Mannheim, FRG In vitro-observations have supported the hypothesis that glutamine is a major substrate for energy metabolism of malignant tumors. Arguments against this hypothesis came from studies of human tumors grafted on animals. Because of possible differences between the experimental setting of cancer xenografts and the human in viva-condition with regard to blood flow and the biochemical environment, gastric carcinomas of 9 patients (mean age 62 years) were investigated during ‘curative’ operations. We measured the balance of glutamine (Gln), glucose (Glc), lactate &act), free fatty acids (FFA), 3-hydroxybutyrate (3-OHB), and acetoacetate (AcAc) across the tumors. A-V substrate differences were obtained by drawing blood samples from the femoral artery and-by cannulation - from either the left gastric or the gastroepiploic vein. Tumor blood flow was determined by a direct venous outffow technique. To compare the metabolism of the carcinomas with that of peripheral tissues, the leg exchange of substrates was also studied (femoral A-V differences, venous occlusion plethysmo-
0.34 The nutritional status of the cancer patient does not affect the tumour growth F.Bcuzetli,P. Boracchi, 1. Cozzagllio and A. Costa lstituto Nazionae Tumori, Milano, Italy
graphy). Reauftw (mean k SEM) pwphwv
GM Gk Lacl FFA 3-ctiB A& Eidwge(mnMWgxmh);
T’p<
composition biochemical tests and tumor stage. Resting energy expenditure was measured by indirect calorimetry after an overnight fast before treatment, and all measurements were repeated after 5 days of drug treatment. Reeults: The groups were well-balanced according to all stratification variables. Liver and kidney function tests were normal in all patients. Mean weight loss was 14.5 f 1.3kg during the last 3 months. 8-blockade decreased energy expenditure by 10 i 3% (- 159 ? 59 kcal/day) vs controls (23 _+25 kcsl/day) @ < 0.05). Indomethacin, morphine and placebo had no effect on resting energy expenditure in cancer patients. Conclusion: This study confirms that elevated adrenergic activity explains increased metabolic rate in cancer disease. Inflammation and pain are less significant factors.
cu&unas
-12f59 -57t20 t1152~556 +254+134 (6t3%) (4i1%) -713+26x -96?91 -168+236 -236i76 t753t417 +141t74 (llS%) (14f6%) +309+_165 1150f46 (10+6%)" (si+lo%)t carchcmswpenphery:t~
Blood flow was markedly greater in the carcinomas (4.3 ? 0.4ml/109g x min) than in the peripheral tissues (1.5 + 0.2). The metabolic balances across the tumors and the periphery are presented in the table, net uptake rates as percentage of supply being listed in brackets. Summary and conclusions: 1) On average no net uptake of Gln occurred in the tumors investigated. 2) Glc and Lact were more intensively exchanged by the tumors than by the peripheral tissues. 3) Gastric carcinomas appear to utilize Glc as a major energy source, although - as related to Glc uptake these tumors release more Lact than the periphery. 4) The contribution of the ketone bodies to the energy supply of the tumors was, in part, neutralized by a release of FFA. 5) Concerning the uptake rates as percentage of supply, AcAc was less accessible to the tumors than to the periphery and was - in the periphery - extracted to a higher degree than Glc.
There is considerable evidence from studies on tumour bearing animals that nutritional support aiming at maintaining a good nutritional status (NS), can promote the tumour growth (TG). The experience in humans is however scanty and controversial and this issue has never been investigated extensively. We have therefore analysed in cancer patients whether there is a relationship between the NS and TG. The hypothesis behind it was that if it is true that a generous availability of substrates promote the TG, the better the NS the higher the tumour cells proliferation. Two hundred and forty six aduft patients with non-Hodgkin’s lymphoma were characterized by the NS (weight loss (WL), serum albumin (SA) serum cholinesterase (SChe), no. lymphocytes(L)) and by the rate of incorporation of 3H thymidine (labelling index (Ll)) in the tumoral tissue. The values of SA, SChe and L were subdivided in 3 classes adopting as cut points the tertiles values of their distribution while WL wasdicotomized in NO and YES. The association between nutritional parameters and LI was evaluated by a univariate analysis (X2 test and Mantel-Haenszel X2 test and the odd ratio) and by a logistic multiple regression model. The results of univariate analysis show a statistically significant association between ‘poor’ NS (depressed nutritional indexes) and ‘high’ LI (increased TG), while the multiple regression analysis found that the only significant association was that between low SChe and high LI. In conclusion these data show for the first time in a large series of patients that maintenance of a good NS does not have any deleterious effect on the TG.
0.35 Effect of low-lactose/low-fat diet during pelvic radiotherapy A. Bye, T: Ose, K Sundf0r, S. Kaaea and C. Tropk The Norwegian Radium Hospital, Oslo, Norway
0.33 Evaluation of mechanisms behind elevated energy expendiire in cancer patients A. Hyftander, U. KLkner and K. Lundholm
In a prospective clinical trial 138 women undergoing pelvic radiotherapy for gynaecological malignancies, were randomized to receive either a regular diet (group I) or a low-lactose/low-fat diet (group II) in order to evaluate a possible impact of diet therapy on radiation induced diarrftoea, nausea, vomiting and wellbeing. Methods: Daily number and consistency of stcols, use of antidiietics and patients’ wellbeing (measured by the EORTC core quality of life questionnaire) were registered before start of therapy (week 0), in the last week (week 8) and 6 weeks after end of therapy (week 12). BeauB: Group I used twice as much antidiaretics (Loperamid) as group II in week 6, (mean 1.1 tablets pr. day versus 0.6, p = 0.096). Thirty-two (48%) patients in group I reported diarrhoea, versus 14 (23%) in group II (p = 0.805, Mann-Whitney U-test). In week 12 there were no difference in use of antidiaretics (mean 0.1 tablets pr. day, p r 0.05). Three patients in each group still had diarrhoea (p > 0.05). Only 6 patients in each group
Department of Surgery, Sah&enska Hospital. Gbteborg, Sweden Cancer patients have increased energy expenditure. This is associated with an increased adrenergic activity and includes elevated sensitivity to 6-adrenergic agonists in both human and experimental models. Afm: To evaluate whether either increased adrenergic activity or activation of inflammatory pathways explain increased energy expenditure in cancer cachexia. Metho& Weight-losing cancer patients were randomized to receive one of four drug treatments for five days: a) propranolol8Omg x 2, b) indomethacin 54fmg x 2, c) morphine 5mg x 3 or 4) placebo x 2. All patients were randomized by a computer-based algorfthm. Randomization accounted for stratification according to measured resting energy expendiiure, body 12
0.32 Balances of energy-yielding subtrates across malignantgastric tumors in man M. GrescW, H.-D.Saeger, M Barfh,H.Leweling and E. Ho/m Dept. of Pathophysiology, Medical Clinic I Mannheim and Surgical Clinic Mannheim, University of Heideibetg, Mannheim, FRG In vitro-observations have supported the hypothesis that glutamine is a major substrate for energy metabolism of malignant tumors. Arguments against this hypothesis came from studies of human tumors grafted on animals. Because of possible differences between the experimental setting of cancer xenografts and the human in viva-condition with regard to blood flow and the biochemical environment, gastric carcinomas of 9 patients (mean age 62 years) were investigated during ‘curative’ operations. We measured the balance of glutamine (Gln), glucose (Glc), lactate &act), free fatty acids (FFA), 3-hydroxybutyrate (3-OHB), and acetoacetate (AcAc) across the tumors. A-V substrate differences were obtained by drawing blood samples from the femoral artery and-by cannulation - from either the left gastric or the gastroepiploic vein. Tumor blood flow was determined by a direct venous outffow technique. To compare the metabolism of the carcinomas with that of peripheral tissues, the leg exchange of substrates was also studied (femoral A-V differences, venous occlusion plethysmo-
0.34 The nutritional status of the cancer patient does not affect the tumour growth F.Bcuzetli,P. Boracchi, 1. Cozzagllio and A. Costa lstituto Nazionae Tumori, Milano, Italy
graphy). Reauftw (mean k SEM) pwphwv
GM Gk Lacl FFA 3-ctiB A& Eidwge(mnMWgxmh);
T’p<
composition biochemical tests and tumor stage. Resting energy expenditure was measured by indirect calorimetry after an overnight fast before treatment, and all measurements were repeated after 5 days of drug treatment. Reeults: The groups were well-balanced according to all stratification variables. Liver and kidney function tests were normal in all patients. Mean weight loss was 14.5 f 1.3kg during the last 3 months. 8-blockade decreased energy expenditure by 10 i 3% (- 159 ? 59 kcal/day) vs controls (23 _+25 kcsl/day) @ < 0.05). Indomethacin, morphine and placebo had no effect on resting energy expenditure in cancer patients. Conclusion: This study confirms that elevated adrenergic activity explains increased metabolic rate in cancer disease. Inflammation and pain are less significant factors.
cu&unas
-12f59 -57t20 t1152~556 +254+134 (6t3%) (4i1%) -713+26x -96?91 -168+236 -236i76 t753t417 +141t74 (llS%) (14f6%) +309+_165 1150f46 (10+6%)" (si+lo%)t carchcmswpenphery:t~
Blood flow was markedly greater in the carcinomas (4.3 ? 0.4ml/109g x min) than in the peripheral tissues (1.5 + 0.2). The metabolic balances across the tumors and the periphery are presented in the table, net uptake rates as percentage of supply being listed in brackets. Summary and conclusions: 1) On average no net uptake of Gln occurred in the tumors investigated. 2) Glc and Lact were more intensively exchanged by the tumors than by the peripheral tissues. 3) Gastric carcinomas appear to utilize Glc as a major energy source, although - as related to Glc uptake these tumors release more Lact than the periphery. 4) The contribution of the ketone bodies to the energy supply of the tumors was, in part, neutralized by a release of FFA. 5) Concerning the uptake rates as percentage of supply, AcAc was less accessible to the tumors than to the periphery and was - in the periphery - extracted to a higher degree than Glc.
There is considerable evidence from studies on tumour bearing animals that nutritional support aiming at maintaining a good nutritional status (NS), can promote the tumour growth (TG). The experience in humans is however scanty and controversial and this issue has never been investigated extensively. We have therefore analysed in cancer patients whether there is a relationship between the NS and TG. The hypothesis behind it was that if it is true that a generous availability of substrates promote the TG, the better the NS the higher the tumour cells proliferation. Two hundred and forty six aduft patients with non-Hodgkin’s lymphoma were characterized by the NS (weight loss (WL), serum albumin (SA) serum cholinesterase (SChe), no. lymphocytes(L)) and by the rate of incorporation of 3H thymidine (labelling index (Ll)) in the tumoral tissue. The values of SA, SChe and L were subdivided in 3 classes adopting as cut points the tertiles values of their distribution while WL wasdicotomized in NO and YES. The association between nutritional parameters and LI was evaluated by a univariate analysis (X2 test and Mantel-Haenszel X2 test and the odd ratio) and by a logistic multiple regression model. The results of univariate analysis show a statistically significant association between ‘poor’ NS (depressed nutritional indexes) and ‘high’ LI (increased TG), while the multiple regression analysis found that the only significant association was that between low SChe and high LI. In conclusion these data show for the first time in a large series of patients that maintenance of a good NS does not have any deleterious effect on the TG.
0.35 Effect of low-lactose/low-fat diet during pelvic radiotherapy A. Bye, T: Ose, K Sundf0r, S. Kaaea and C. Tropk The Norwegian Radium Hospital, Oslo, Norway
0.33 Evaluation of mechanisms behind elevated energy expendiire in cancer patients A. Hyftander, U. KLkner and K. Lundholm
In a prospective clinical trial 138 women undergoing pelvic radiotherapy for gynaecological malignancies, were randomized to receive either a regular diet (group I) or a low-lactose/low-fat diet (group II) in order to evaluate a possible impact of diet therapy on radiation induced diarrftoea, nausea, vomiting and wellbeing. Methods: Daily number and consistency of stcols, use of antidiietics and patients’ wellbeing (measured by the EORTC core quality of life questionnaire) were registered before start of therapy (week 0), in the last week (week 8) and 6 weeks after end of therapy (week 12). BeauB: Group I used twice as much antidiaretics (Loperamid) as group II in week 6, (mean 1.1 tablets pr. day versus 0.6, p = 0.096). Thirty-two (48%) patients in group I reported diarrhoea, versus 14 (23%) in group II (p = 0.805, Mann-Whitney U-test). In week 12 there were no difference in use of antidiaretics (mean 0.1 tablets pr. day, p r 0.05). Three patients in each group still had diarrhoea (p > 0.05). Only 6 patients in each group
Department of Surgery, Sah&enska Hospital. Gbteborg, Sweden Cancer patients have increased energy expenditure. This is associated with an increased adrenergic activity and includes elevated sensitivity to 6-adrenergic agonists in both human and experimental models. Afm: To evaluate whether either increased adrenergic activity or activation of inflammatory pathways explain increased energy expenditure in cancer cachexia. Metho& Weight-losing cancer patients were randomized to receive one of four drug treatments for five days: a) propranolol8Omg x 2, b) indomethacin 54fmg x 2, c) morphine 5mg x 3 or 4) placebo x 2. All patients were randomized by a computer-based algorfthm. Randomization accounted for stratification according to measured resting energy expendiiure, body 12