Recent studies have suggested that circulating concentrations of leptin might play a role in cancer cachexia. In the first part of the study, we compared circulating concentrations of free and total leptin, percent fat mass, and the inflammatory markers C-reactive protein (CRP) and interleukin-6 (IL-6), together with appetite score, in age- and gender-matched healthy controls (n = 11) and advanced gastrointestinal cancer patients (n = 26). In the second part of the study, the same measurements were repeated before and after megestrol acetate treatment of weight-losing gastrointestinal cancer patients (n = 10). Body mass index and percent fat mass were significantly lower (P < 0.05) and IL-6 and CRP were significantly higher (P < 0.05) in cancer patients than in controls. There was no difference in the percentage of leptin bound in the circulation between controls and cancer patients. Circulating "free" leptin concentrations correlated with percent fat mass in controls (r = 0.745, P = 0.008) and cancer patients (r = 0.600, P = 0.001). In cancer patients, circulating leptin concentrations, either free or total, were not correlated with IL-6 or CRP concentrations. When adjusted for fat mass, the circulating concentrations of free and total leptin were significantly lower in the cancer patients (P < 0.01). Megestrol acetate treatment significantly increased circulating free and total leptin concentrations in the cancer patients (P < 0.05). There was a significant positive correlation between the change in circulating concentrations of free and total leptin and the change in percent fat mass (r = 0.685, P < 0.05 and r = 0.661, P < 0.05, respectively). The results of the present study indicate that the proportions of free and bound leptin in the circulation do not differ between normal subjects and patients with gastrointestinal cancer and in both groups are related to fat mass. Furthermore, the increase in circulating leptin concentrations after megestrol acetate treatment is not associated with any alteration in leptin binding.
The authors assessed the relative value of Dukes' staging and Doppler perfusion index (DPI) as prognostic indices of early death in patients with colorectal cancer who have had apparently curative surgery.Dukes' classification is recognized as the gold standard against which other prognostic factors should be compared; however, its discriminatory power is limited. No established method exists for accurately identifying patients who, despite having undergone an apparently curative resection for colorectal carcinoma, are at high risk.Eighty consecutive patients undergoing apparently curative surgery for colorectal cancer were staged using Dukes' classification. In addition, DPI (ratio of hepatic arterial to total liver blood flow) was measured before surgery by means of a duplex/color Doppler sonography.On the basis of 2-year follow-up data, Dukes' classification failed to define clearly those patients who died or who developed recurrent disease. In contrast, DPI clearly identified two groups of patients: 78% of patients with an abnormally elevated DPI value developed recurrent disease or died, whereas 97% of patients with a normal DPI value survived.This technique can identify patients at high risk for colorectal cancer, after having undergone apparently curative resection, who would be suitable for adjuvant therapy.
In the advanced cancer patient, performance status has considerable prognostic power. Karnofsky performance status, together with variables reported to influence its score, was measured in advanced gastrointestinal cancer patients (n = 148). For male and female patients, age, body mass index, weight loss, triceps skinfold thickness, mid-upper arm circumference, albumin, C-reactive protein, and tumor type and stage were regressed against Karnofsky performance status. On multiple regression analysis, only mid-upper arm circumference and log10 C-reactive protein in men (r2 = 0.462, P < 0.0001) and only mid-upper arm circumference and weight loss in women (r2 = 0.485, P < 0.01) were independent predictors of Karnofsky performance status. There was a significant partial correlation, with gender as a covariable, between log10 C-reactive protein and albumin (r = -0.530, P < 0.0001) and mid-upper arm circumference (r = -0.269, P = 0.035) and weight loss (r = 0.286, P = 0.024). The results of the present study indicate that mid-upper arm circumference is a major factor that influences performance status in male and female patients with advanced gastrointestinal cancer.
Abstract There is recent evidence that the inflammatory response may be important in the disproportionate loss of body cell mass in cancer patients. To examine this further, 18 male patients with lung or gastrointestinal cancer were studied over a 12‐week period. In addition to weight, anthropometry, C‐reactive protein (marker of the inflammatory response), albumin, and total body potassium were measured at baseline and 12 weeks. When those patients who lost total body potassium were compared with those who had not, there was a significant increase in the baseline and 12‐week C‐reactive protein concentrations (p < 0.05). The reduction in total body potassium was also associated with a reduction in triceps skinfold thickness (p < 0.05). There were significant correlations between the mean C‐reactive protein concentration and the relative (r = ‐0.846, p < 0.001) and absolute (r = ‐0.806, p < 0.001) change in total body potassium over the follow‐up period. This study demonstrates the association of a chronic inflammatory response with the rate of loss of body cell mass observed in cancer patients.
An 18-yr-old woman with primary amenorrhea, anosmia, and total lack of secondary sexual development was treated for 230 days using sc pulsatile GnRH. GnRH testing with 100 micrograms, sc, initially revealed a peak FSH to LH ratio greater than 1. After 28 days of treatment, this ratio had reversed. A dosage of 20 micrograms/2 h for 200 days resulted in a LH to FSH ratio greater than 2. Widening the interval to 20 micrograms/3 h significantly lowered LH, but not FSH, levels. Increasing the frequency to 20 micrograms/90 min again increased the LH to FSH ratio. Twenty-four-hour testing revealed a sleep-entrained PRL rise both during and after GnRH therapy, but no sleep-entrained rise in LH. Ultrasound monitoring revealed cyclic changes in ovarian diameter at 30- to 60-day intervals that coincided with cyclic increases in LH and estradiol. The uterine fundus doubled in length between days 50 and 110 of treatment. The patient progressed from Tanner pubic hair and breast stage I to stage II during treatment, which was terminated due to an allergic reaction to GnRH. This study provides the first report of hormonal and ultrasound events surrounding puberty induction with GnRH in the female. We conclude widening the interval of GnRH administration can reduce LH levels while maintaining FSH levels, cyclic changes in ovarian diameter, LH, and estradiol occur before menarche, and although pulsatile GnRH provides a fascinating model for the study of puberty in the female, the chronicity of therapy needed and its potential for allergic reaction make this method of inducing puberty suboptimal.
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