Cecilia Gavazzi

Perioperative Total Parenteral Nutrition in Malnourished, Gastrointestinal Cancer Patients: A Randomized, Clinical Trial

BACKGROUNDnClinical trials investigating the potential benefits of perioperative total parenteral nutrition (TPN) for reducing the risk of surgery in malnourished cancer patients have yielded controversial results.nnnMETHODSnNinety elective surgical patients with gastric or colorectal tumors and weight loss of 10% or more of usual body weight were randomly assigned to 10 days of preoperative and 9 days of postoperative nutrition vs a simple control group. The daily per kilogram body weight TPN regimen included 34.6 +/- 6.3 kcal nonprotein and 0.25 +/- 0.04 g nitrogen per kilogram in a volume of 42.6 +/- 7.3 mL of fluid. The glucose-to-fat calorie ratio was 70:30. Control patients did not receive preoperative nutrition but received 940 kcal nonprotein plus 85 g amino acids postoperatively.nnnRESULTSnComplications occurred in 37% of the patients receiving TPN vs 57% of the control patients (p = .03). Noninfectious complications mainly accounted for this difference, which was 12% vs 34%, respectively (p = .02). Mortality occurred in only 5 of the control group patients (p = .05). The total length of hospitalization for TPN patients was longer than for control (p = .00), whereas the length of postoperative stay in the two groups did not differ significantly.nnnCONCLUSIONSnThis study shows that 10 days of preoperative TPN that is continued postoperatively is able to reduce the complication rate by approximately one third and to prevent mortality in severely malnourished patients with gastrointestinal cancer.

Role of home parenteral nutrition in chronic radiation enteritis

OBJECTIVES:The management of chronic radiation enteritis (CRE) is difficult and often controversial. The aim of the study was to compare long-term outcome of patients with radiation-induced intestinal obstruction treated either surgically or with intestinal rest and home parenteral nutrition (HPN).METHODS:Thirty patients, with mechanical bowel obstruction due to CRE, were retrospectively included in the study and divided in two groups according to the first treatment approach. Seventeen patients underwent surgery (S group) and 13 patients were supported with HPN (HPN group). Survival, nutrition autonomy, number of surgeries, related complications and persistence of symptoms were evaluated in the two groups. Associations between factors and treatment group were assessed by means of the Wilcoxon rank sum test for continuous variables and the Fisher exact test for categorical variables. Overall survival was calculated using the Kaplan-Meier method.RESULTS:The two groups were similar in terms of age, dose of radiation therapy, time of occurrence and degree of signs and symptoms. 7/13 patients in the HPN group resolved the obstruction without surgery. 10/17 patients of the S group developed intestinal failure which required HPN. Nutrition autonomy was achieved in 100% and 58.8% of HPN and S group respectively (p = 0.01). The overall five-year survival was 90.0% and 68.4% respectively in the HPN and S group (p = 0.0231).CONCLUSIONS:Both HPN and surgery are often necessary in patients with chronic radiation-induced intestinal obstruction. However, the long term nutrition autonomy and survival seem to be better in patients initially treated with intestinal rest and HPN.

Artificial Nutrition in Cancer Patients: Which Route, What Composition?

Abstract. The state of art of artificial nutrition in depleted cancer patients is reviewed in brief. Because cancer cachexia cannot be equated to simple nutrient deficiency but is due instead to complex metabolic abnormalities, the nutritional effects of total parenteral (TPN) and enteral (EN) nutrition are more limited than in starving subjects. TPN and EN usually prevent further deterioration of the nutritional status, although they are not able to fully reverse a state of depletion. There is evidence that quantitative and qualitative modulation of certain nutrients may obtain better results because of a favorable impact on host metabolism. Research in this field is fully warranted. Moreover, the effects of some substrates on tumor metabolism and tumor growth require further investigation to define a nutritional regimen able to maintain the host metabolism with minimum stimulation of tumor growth.

Effect of total parenteral nutrition on the protein kinetics of patients with cancer cachexia.

Aims and background The question of whether TPN is able to reverse lean body mass depletion in cachectic cancer patients and, in particular, its effect on protein kinetics is a matter of some controversy. This study investigates the impact of TPN on protein kinetics in patients with gastric cancer. Methods The study involved three patients with 14–30% weight loss. They were administered a TPN regimen including 33–40 kcal/kg/day and 1.4–1.7 g amino acid/kg/day. The protein metabolism was studied before and during TPN using a stable amino acid isotope. Results Whole body protein turnover and breakdown did not change during TPN, whereas whole body protein synthesis increased from 3.39 ± 1.04 to 6.05 ± 0.48 g/kg/day (P = 0.03). However, the net balance, which was slightly negative prior to TPN, became positive during nutritional support. In the skeletal muscle compartment the synthesis improved with TPN (from 9.38 ± 2.6 nmol/100 mL/min to 35.95 ± 3.4 nmol/100 mL/min; P = 0.0143), whereas breakdown did not change significantly. Conclusions TPN triggers a positive metabolic response in cachectic cancer patients. Whether this results in a clinical benefit for the patient requires further investigation.

Total nutritional manipulation in humans: report of acancer patient

We report here on a patient requiring home total parenteral nutrition (TPN) for a huge intra-abdominal desmoid associated with chronic small bowel pseudo-obstruction who was kept on a special lipid-based calorie regimen for 5 months. The rationale was to attempt to feed the host with a minimal stimulation of tumour growth by using lipid as caloric substrate instead of glucose which is utilized by the tumour. Gluconeogenesis was tentatively inhibited at the level of phosphoenolpyruvate-carboxy-kinase through the oral intake of hydrazine sulphate. The regimen consisted of 28 non-protein lipid Kcal/kg/day plus 1.5 g amino acid per kg/day. Only a small amount of glucose (approx. 40 g/day) was allowed. Tolerance to the regimen was good and body weight maintained. Liver enzymes remained within the normal range and liver sonography was normal throughout the 5 months therapy and there were no episodes of symptomatic hypoglycaemia. The tumour volume did not substantially change.

Urn models for response-adaptive randomized designs: a simulation study based on a non-adaptive randomized trial

ABSTRACT Recently, response-adaptive designs have been proposed in randomized clinical trials to achieve ethical and/or cost advantages by using sequential accrual information collected during the trial to dynamically update the probabilities of treatment assignments. In this context, urn models—where the probability to assign patients to treatments is interpreted as the proportion of balls of different colors available in a virtual urn—have been used as response-adaptive randomization rules. We propose the use of Randomly Reinforced Urn (RRU) models in a simulation study based on a published randomized clinical trial on the efficacy of home enteral nutrition in cancer patients after major gastrointestinal surgery. We compare results with the RRU design with those previously published with the non-adaptive approach. We also provide a code written with the R software to implement the RRU design in practice. In detail, we simulate 10,000 trials based on the RRU model in three set-ups of different total sample sizes. We report information on the number of patients allocated to the inferior treatment and on the empirical power of the t-test for the treatment coefficient in the ANOVA model. We carry out a sensitivity analysis to assess the effect of different urn compositions. For each sample size, in approximately 75% of the simulation runs, the number of patients allocated to the inferior treatment by the RRU design is lower, as compared to the non-adaptive design. The empirical power of the t-test for the treatment effect is similar in the two designs.