The prognosis of incurable cachectic cancer patients on home parenteral nutrition: a multi-centre observational study with prospective follow-up of 414 patients.

BACKGROUND: The role of home parenteral nutrition (HPN) in incurable cachectic cancer patients unable to eat is extremely controversial. The aim of this study is to analyse which factors can influence the outcome. PATIENTS AND METHODS: We studied prospectively 414 incurable cachectic (sub)obstructed cancer patients receiving HPN and analysed the association between patient or clinical characteristics and surviving status. RESULTS: Median weight loss, versus pre-disease and last 6-month period, was 24% and 16%, respectively. Median body mass index was 19.5, median KPS was 60, median life expectancy was 3 months. Mean/median survival was 4.7/3.0 months; 50.0% and 22.9% of patients survived 3 and 6 months, respectively. At the multivariable analysis, the variables significantly associated with 3- and 6-month survival were Glasgow Prognostic Score (GPS) and KPS, and GPS, KPS and tumour spread, respectively. By the aggregation of the significant variables, it was possible to dissect several classes of patients with different survival probabilities. CONCLUSIONS: The outcome of cachectic incurable cancer patients on HPN is not homogeneous. It is possible to identify groups of patients with a ≥6-month survival (possibly longer than that allowed in starvation). The indications for HPN can be modulated on these clinical/biochemical indices.

Natural killer cell activity and sensitivity to positive and negative modulation in uncomplicated obese subjects: relationships to leptin and diet composition.

BACKGROUND: Natural killer (NK) cells are a key component of innate immunity; their activity is modulated by cytokines and hormones and is influenced by diet. In obesity, a higher risk of cancer and infections has been demonstrated. Studies on NK cell activity have yielded inconsistent results; NK cell sensitivity to modulators has not been assessed before. OBJECTIVE: In this case-control study, we assessed both spontaneous NK cell activity and responsiveness to positive (interleukin (IL)-2) and negative (cortisol) modulators in uncomplicated obesity; we searched for correlations between NK cell activity and anthropometric, dietary and metabolic variables. METHODS: In all, 21 obese (six males/15 females) and 21 age- and sex-matched healthy nonobese subjects underwent clinical examination and dietary and laboratory analyses. Spontaneous and modulated NK activities of peripheral blood mononuclear cells were measured by enzyme-release cytotoxicity assay. RESULTS: Spontaneous NK cell activity was not different in obese subjects vs controls. IL-2 stimulated and cortisol inhibited NK cell activity in both populations. Cortisol-dependent inhibition was lower in the obese than in the control group (-24.4+/-2.9 vs -38.6+/-3.3%, P=0.002), but decreased sensitivity was restricted to women (P=0.0007). In obese subjects, cortisol-dependent inhibition negatively correlated with serum leptin levels (r=-0.54, P=0.02) and, in women, with body mass index (r=-0.63, P=0.01); IL-2-dependent stimulation positively correlated with dietary carbohydrates (r=0.61, P=0.005) and serum LDL levels (r=0.55, P=0.009) and negatively correlated with dietary lipids (r=-0.71, P=0.0006). CONCLUSION: Spontaneous and IL-2-inducible NK cell activity is normal in uncomplicated obesity. Sensitivity to IL-2 correlates with fat and carbohydrate intake. Sensitivity to glucocorticoids negatively correlates with serum leptin levels and is significantly diminished in obese women, in whom it correlates with body mass index.

Time-dependent modifications of splanchnic circulation in female pigs submitted to end-to-side portacaval anastomosis.

Fractional systemic bioavailability of orally administered drugs was found to be unexpectedly low in liver cirrhosis, even after surgical portal-systemic shunting. Fecal loss or intestinal first-pass elimination were assumed to explain the finding. In this paper we evaluated alternative pathophysiological interpretations relating low bioavailability to adaptive circulatory modifications. D-Sorbitol was used because its hepatic extraction is very high and hepatic removal follows a flow-dependent clearance regimen. D-Sorbitol bioavailability was measured at steady state in pigs submitted to end-to-side portacaval anastomosis, immediately after surgery and four weeks later. Intestinal first-pass elimination dependent on fecal loss and intraluminal degradation was excluded by administering D-sorbitol into the superior mesenteric artery. Almost complete bioavailability was observed immediately after surgery (N = 6, 0.96+/-0.08); four weeks later the bioavailability dropped (-36.8+/-18.7%; P < 0.001) while hepatic clearance significantly increased (+83.6+/-47.9%; P < 0.01). Experimental data support the hypothesis that adaptive circulatory changes spontaneously occur after some time, leading to a lower than expected portal bioavailability.

[Evaluation of malnutrition risk in adult hospital patients]. / Valutazione del rischio di malnutrizione in pazienti adulti ospedalizzati.

BACKGROUND: The aim of the study was to evaluate the validity and reliability of a risk of malnutrition screening tool (MST) proposed by Ferguson et al. for adult hospital patients. METHODS: The study included 207 consecutive patients admitted to a Hospital (118 males, 89 females, aged 61+/-16 years) including internal medicine (89), lung (60) and surgical (58) patients. The MST, consisting of three questions regarding appetite and recent unintentional weight loss, was applied to each patients. Peripheral lymphocytes and serum albumin considered as predictor of nutritional status were also evaluated. RESULTS: Forty-two patients (20% of overall population) resulted malnourished at admission and nutrition support was rapidly established. Of the remaining, 141 (85%), according to the score of MST were not at risk of malnutrition, while 24 (15%) were classified at risk. Peripheral lymphocytes and serum albumin were unable to discriminate the risk in well-nourished patients. CONCLUSIONS: The proposed MST is confirmed as strongly predictor of nutritional status. It is a simple, quick, reliable, valid tool and can be carried out nursing staff. Its routine application will consistently identify patients at risk of malnutrition so that nutrition care can be promptly started.

Brain manganese deposition and blood levels in patients undergoing home parenteral nutrition.

BACKGROUND: Extrapyramidal syndrome and alterations in brain magnetic resonance images are described in patients undergoing long-term home parenteral nutrition (HPN) and in cholestatic patients. These abnormalities have been correlated to basal ganglia manganese (Mn) accumulation. METHODS: A longitudinal 1-year study was conducted on 15 patients undergoing HPN (median duration, 3.8 years; range, 1.7-10; median Mn parenteral supplementation, 0.1 mg/d). Whole-blood, plasma, intra-erythrocytes, and urinary Mn concentrations were measured and brain magnetic resonance was performed at the beginning (time 0) and after 1 year of Mn intravenous supplementation withdrawal (time 1). No patients showed psychosis, extrapyramidal syndrome, or cholestasis. RESULTS: At time zero, 10 of 15 patients (67%) showed paramagnetic accumulation on cerebral magnetic resonance images; at time 1 there was a reduction of cerebral Mn accumulation. In all patients, blood-Mn levels were significantly reduced after 1 year of Mn intravenous supplementation withdrawal. CONCLUSIONS: Patients receiving long-term HPN showed an elevated incidence of alterations in brain magnetic resonance images with a median Mn intravenous supplementation of 0.1 mg/d. Mn supplementation withdrawal significantly decreased metal levels in blood and brain storage. We noticed that the intra-erythrocyte Mn level was a good index of Mn status.

Assessment of functional liver mass and plasma flow in acromegaly before and after long-term treatment with octreotide.

Functional liver mass and functional liver plasma flow (FLPF) were assessed in 11 patients with clinical features of acromegaly by determining galactose elimination capacity (GEC) and extrarenal clearance of sorbitol, before and 5 to 7 months after treatment with the long-acting somatostatin analog, octreotide (150 to 600 micrograms/d in three subcutaneous injections). Growth hormone (GH) and insulin-like growth factor-I (IGF-I) levels, as well as liver size by ultrasound, were also recorded. Baseline GEC was increased in every patient but one, for a mean of 0.78 +/- 0.10 g/min (normal, 0.53 +/- 0.07; P < .01). At reevaluation after 5 to 7 months of octreotide treatment, a significant reduction of GEC was observed (0.62 +/- 0.08 g/min, P < .001). Changes of GEC paralleled those of GH (38.6 +/- 34.4 v 11.7 +/- 15.2 micrograms/L, P < .01) and IGF-I (5.0 +/- 1.7 v 2.7 +/- 2.2 U/ml, P < .001). Significant correlations were found between GEC and GH (r = .50, P < .05) and between GEC and IGF-I (r = .55, P < .01). FLPF, assessed by extrarenal clearance of sorbitol, was within the normal limit in all cases (0.98 +/- 0.19 v 0.97 +/- 0.12 L/min, NS) and remained normal after 5 to 7 months of octreotide treatment (0.99 +/- 0.11 L/min). Hepatic structure determined with ultrasonic scanning and conventional liver-function tests were basally normal in all patients, with a slight increase of liver volume in three cases. No change of biochemical and/or morphological features occurred during follow-up evaluation. The results support the hypothesis that GH and especially IGF-I enhance liver metabolic capacity; conversely, functional liver perfusion is largely independent of their actions. Our data also suggest that octreotide is unable to produce well-structured changes of liver circulation when administered long-term.

Effects of nifedipine on functional liver plasma flow in normal subjects and in patients with cirrhosis.

The short-term effects of nifedipine (10 mg administered sublingually) on functional liver plasma flow, measured by calculating the extrarenal clearance of sorbitol, were investigated in 12 normal volunteers and 40 patients with cirrhosis scored according to Child-Pugh classification. Nifedipine significantly increased functional liver plasma flow in healthy subjects (23%, p < 0.0001) and in patients with cirrhosis in the Child-Pugh class A group (19%, p < 0.001); in patients in the Child-Pugh class B group functional liver plasma flow was not modified, whereas in the patients in the Child-Pugh class C group it was significantly reduced (-7%, p < 0.02). The mean arterial pressure showed a significant reduction in all groups studied. According to the pathophysiologic meaning of functional liver plasma flow, it is suggested that nifedipine meets criteria for an ideal test substance to evaluate the functional reserve of the liver. Furthermore, when used with the Child-Pugh classification, its effect on functional liver plasma flow may be useful to improve the efficiency of the Child-Pugh classification, in establishing the prognosis of patients with cirrhosis.