ObjectiveTo determine whether resting energy expenditure (REE) is increased in cachectic patients with pancreatic cancer and to define the relation of tumor necrosis factor (TNF) and production to the acute-phase response and to REE. MethodsMeasurement of REE (indirect calorimetry) and assessment of body composition (bioelectrical impedance analysis) were done in 21 patients with unresectable pancreatic cancer and on 16 age-related controls. The systemic inflammatory response in peripheral blood of the cancer patients was assessed using the acute-phase protein, C-reactive protein, and the cytokines TNF and IL-6. Production of these cytokines by peripheral blood mononuclear cells in vitro was also measured. ResultsPatients with pancreatic cancer had an elevated REE when compared with controls (73.4 ± 5.0 vs. 53.5 ± 1.6 kcal/kg body cell mass; p < 0.003). Resting energy expenditure was significantly greater in cancer patients with an acute-phase response (C-reactive protein > 10 mg/L) than in those who did not have such a response (85.5 ± 10.0 [n = 9] vs. 64.3 ± 3.0 [n = 12] kcal/kg body cell mass; p < 0.04). Tumor necrosis factor was not detected in the serum of any of the cancer patients. Serum IL-6 was detected but levels were not significantly different among cancer patients with or without an acute-phase response. In contrast, spontaneous production of TNF and IL-6 by isolated peripheral blood mononuclear cells was significantly greater in cancer patients with an acute-phase response than in those without (TNF: 1231 ± 244 vs. 210 ± 54 pg/ mL/105 cells; p < 0.001; IL-6: 11.5 ± 1.7 vs. 3.6 ± 1.4 ng/mL/1 05 cells; p < 0.003). ConclusionsIn pancreatic cancer at least a component of weight loss is due to increased REE. Furthermore, the presence of an acute-phase response identifies a group of patients who are markedly hypermetabolic. The serum concentration of TNF or IL-6 does not correlate with the presence of an acute-phase response, whereas rates of cytokine production by peripheral blood mononuclear cells are significantly greater in patients with such a response. This suggests that local rather than systemic cytokine production may be important in regulating the acute-phase response.325

Summary Weight loss is common in patients with pancreatic cancer; however, the nature and progress of their nutritional depletion are not well documented. In this study, pre-illness weight and duration of weight loss were recorded in 20 patients with histologically confirmed unresectable cancer of the pancreas. Patients then underwent nutritional analysis at monthly intervals until death. The median period of assessment was 27 weeks (interquartile range 22.5-38.0 weeks). At the time of diagnosis, all patients had lost weight [median 14.2%(10.0-20.0%) of pre-illness stable weight], and this weight loss was progressive, increasing to a median of 24.5% by the time of the last assessment (P =0.0004). Body mass index was significantly reduced from a pre-illness median value of 24.9 kg m-2 (22.4-27.4 kg m-2) to 20.7 kg m-2 (19.5-23.6 kg m-2) at the time of diagnosis and further to 17.7 kg m-2 (16.6-23.1 kg m-2) just before death (P =0.0003). Further evidence of tissue depletion was evident from the significant reductions in lean body mass [43.4 kg (36.9-53.0 kg) to 40.1 kg (33.5-50.7 kg) P =0.008] and fat mass [12.5 kg (8.9-17.8 kg) to 9.6 kg (6.3-15.1 kg) P =0.03). This study confirms that the majority of patients with unresectable pancreatic cancer have already undergone significant weight loss by the time of diagnosis and that the natural history of this process is one of inexorable progression. These results highlight the need for selective non-toxic therapeutic intervention to attenuate cachexia and indicate that such interventions should be instituted early in the course of the disease.

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1. Multi-frequency bio-impedance analysis has been used to estimate extracellular and total body water in a heterogeneous group of 43 surgical patients (23 males, 20 females). 2. Radioisotope-dilution methods were used for the measurement of extracellular and total body water. 3. Resistance and reactance were measured between wrist and ankle at frequencies from 5 kHz to 1 MHz. 4. Extracellular and total body water were estimated by multiple stepwise regression using the radioisotope values as the dependent variables. The parameters included in the regression were: resistance and reactance at each frequency, body habitus parameters, plasma albumin and plasma sodium. 5. The standard errors of the estimates between the measured and estimated values were 1.73 litres (coefficient of variation 9.6%) and 2.17 litres (coefficient of variation 6.0%) for extracellular and total body water, respectively. 6. These errors represent a useful improvement relative to those obtained from anthropometric estimates. However, the improvements relative to the use of a single frequency (50 kHz) are not clinically significant.

1. Measurements of extracellular and total body water provide useful information on the nutritional status of surgical patients and may be estimated from whole-body bio-impedance measurements at different frequencies. 2. Resistance and reactance were measured at 50 frequencies from 5kHz to 1MHz in 29 surgical patients (17 males, 12 females) with a wide range of extracellular to total body water ratios. 3. A fit to the spectrum of reactance versus resistance data gave predicted resistances at frequencies zero and infinity. Values of extracellular and total body water determined by this bio-impedance spectroscopy technique were regressed against values obtained from radioisotope dilution. The standard errors of the estimate were 1.8931 and 3.2591 respectively. 4. Resistance indices (height2/resistance) at selected frequencies gave the highest correlations with extracellular and total body water at 5kHz and 200kHz respectively, and prediction equations derived from multiple stepwise regressions also showed these to be the optimum frequencies. The standard errors of the estimate for this multi-frequency bio-impedance analysis method were 1.9371 and 2.6061 for extracellular and total body water respectively. 5. To assess the ability of the two methods to measure changes in extracellular and total body water, reproducibility was assessed from repeat measurements 10 min apart in a subgroup of 15 patients. Bio-impedance spectroscopy gave mean coefficients of variation for extracellular and total body water of 0.9% and 3.0% respectively. For multi-frequency bio-impedance analysis the corresponding coefficients of variation were 0.9% and 0.6%. 6. It is concluded that a simple impedance analyser operating at only two frequencies compares favourably with the more complex spectroscopy technique for the determination of extracellular and total body water in surgical patients.