Nutrition intervention: a prospective randomised controlled trial in colorectal cancer patients undergoing radiotherapy

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EUROPEAN

sued REE. Level of agreement at the individual level is indicated in the table Predicted Prediction

REE compared Equation

Harris-Benedict

to measured

REE (kJ)

Mean

Bias

Limits

of Agreement

22

1717

1995

2105

Schofield

26X

2134

Owen

60

1574

Mifflin

-22x

1x10

Cunningham

-117

12x0

15

12x0

-227

1889

Harris-Benedict

Wang 20kcaVkg

x 1.3

(& 2SD)

Conclusions: The best combination of low bias and nzuxowest limits of agreement was observed in the prediction of REE from the Wang equation based on fat free mass and the Han&Benedict equation based on weight and height. For an individual the limits of agreement for all equations anz wide and clinically important differences in predictions of REE would be obtained. Clinicians need to be aware of the limitations of the use of REE prediction equations for individuals.

230-P. INTESTAMIN@ INHIBITS PROLIFERATION AND INDUCES DIFFERENTIATION IN COLORECTAL CARCINOMA AND ADENOMA CELL LINES T. Kudlich Division of Gastroenterology, Department of Medicine, University of Wuerzburg, Wuerzburg, Germany Rationale: Intestamin@, a new immunoenhancing enteral nutrition supplement for critically ill patients, contains high amounts of glutaminedipeptides and antioxidants as well as tributyrine. The effects of Intestamin@ on proliferation, differentiation and apoptosis and the underlying intracel1~1~ mechanisms were investigated in colorectal cell lines. Method: The colorectal carcinoma cell lines HT29 and SW620 and the adenoma cell line Geki-2 were incubated with standxd medium supplemented with Intestamin (1.25%-10%) for 24h to 72h. Proliferation was assessedby cell counts. Cell cycle distribution and rate of apoptotic cells were determined by FACS. Cell&u differentiation was estimated by alkaline phosphatase (AP) levels. In addition, the expression of various factors of cell cycle control and apoptosis were investigated by westeln blot. Results: Proliferation was inhibited in time and dose dependently. Compxed to untreated controls, treatment with Intestamin@ (5% Vol, 24h) I-esuited in a decrease in proliferation to 68%f5% (HT29) and 74%f7% (SW620). However, this was neither reflected in changes of the cell cycle distribution nor in an increased rate of apoptotic cells. In HT29 and SW620 cells, AP levels increased time and dose dependently from 3U/I to 30U/I and 28U/I to 71U/I in HT29 (10% vol, 72h) and SW620 (2.5% vol, 72h), indicating an increase in cell&u differentiation. Except for an increase of p21 protein levels in HT29 and SW620 cells, no modulation of the examined factors (PCNA, ~53, cdk-2, bcl-2, and bax) could be detected. Conclusions: Intestamin@ did not have proliferative effects on the investigated cell lines. On the contrxy, a decrease of proliferation and an increase of cellular differentiation were noted. Further studies xe needed to dissect the differential effects of the various substances included in the preparation.

SOCIETY

OF PARENTERAL

AND

ENTERAL

NUTRlTION

231-P. CYTOKINE SERUM CONCENTRATION FOLLOWING SURGERY FOR ESOPHAGEAL CARCINOMA IN PATIENS W ITH PERIOPERATIVE NUTRITIONAL SUPPORT R. Slotwinski’, B. Szczygie 3~2, A. Szawlowski3, M. Talarek4, W .L. 01szewski~ ’Dept.of Surgical Research and Transplantology, Medical Research Center, Polish Academy of Sciences, ‘Dept. of Human Nutrition, The Medical University of Warsaw, 3Dept.of Upper DigestiveTract Cancer, 4Dept. of Upper Digestive Tract Cancer; M.C-S Memorial Cancer Center-Institute, ‘Dept.of Surgical Research and Transplantology, Polish Academy of Sciences, Warsaw, Poland Rationale: It is still uncle= what kind of p&operative feeding with specific nutrients alters cytokine production and down-regulates inflammatory response to surgical trauma. Method: In 9 patients with severe postoperative complications changes in systemic production of IL-6, sTNFR1, IL-lra and nutritional status were evaluated preoperatively before and after nutritional support (N&drink, Nutrison) and on day 4,lO and 14 following esophagectomy. In all patients early enteral nutrition (Peptisorb, N&son, Stresson) was introduced after surgery. Results: In the preoperative period 10 days nutritional supplementation increased serum IL-6 concentration from 47.1f14 to 74.0f50 pg/ml, (p=O.O4). There was increase of IL-1Rafrom 503.57f456 to 997.35f1137 pg/ml but no significant changes in sTNF-RI level. In the postoperative period IL-6 raised significantly (74.0f50 vs. 107.7fl1, p=O.O2) only on day 4. Thele was a significant increase in serum concentrations of IL-1Ra on day 4 and 14 when compared with preoperative levels before nutrition (503.57f456 pg/ml vs. 1474 f706, p=O.Ol and 1935f1506 pg/ml, p=O.Ol). Serum sTNR-RI concentration was significantly elevated on day 4 and 10 (1179.16f503 pg/ml vs. 1693.75f603 pg/ml, p=O.O3 and 1691.07f625 pg/ml, p=O.Ol) in compz&on with the preoperative level following nutritional supplementation. Nutritional status was not improved before operation and decreased postoperatively. Conclusions: Perioperative nutrition in patients with esophageal czucinoma significantly increases production of pro- and anti-inflammatory cytokines.

232-P. NUTRITION INTERVENTION: A PROSPECTIVE RANDOMISED CONTROLLED TRIAL IN COLORECTAL CANCER PATIENTS UNDERGOING RADIOTHERAPY P. Ravasco t , I. Monteiro Grille’ , P. Marques Vidal t , M. Camilo t ’ Centre Nutrition Metabolism, IMM, Faculty Medicine University Lisbon, ‘Radiotherapy Department, Hospital Santa Maria, Lisbon, Portugal Rationale: In cancer, the benefit of nutrition with or without supplementation is as yet unproven. Method: In a prospective block randomised controlled trial, the effect of individualised nutritional counselling or commercial supplements on oral intake was investigated. There were 111 colorectal cancer outpatients (pts), 7OM:41F, age 66+/-10(33-94), stratified by cancer stage; 37 (Gl) were assigned to individualised nutritional counselling based on foodstuffs, 37 (G2) to high protein liquid supplements and 37 (G3) to ad lib intake. Compliance was weekly monitored. Nutritional intake was assessed by a 24b recall questionnaire at the onset, at the end and 3 months after RT; total energy requirements (ER) were = estimated basal requirementsxl.2 activity factor, protein intake was compxed to reference. ANOVA stratified by stage, adjusted for symptoms was used for comparisons. Results: Baseline intake was sirnil= in all groups; energy was > ER (NS), protein was 5 needs, p=O.O6. During RT, >90% pts experienced increased diarrhcea (p=O.O09),nausea (p=O.O03), anorexia (p=O.O02); symptoms wele worse in stage III/IV, p=O.Ol. At the end of RT by compz&on to the onset, energy intake increased in Gl (555 kcal/d, p=O.O02) and G2 (296 kcal/d, p=O.O4); Gl>G2, p=O.OOl; protein intake increased in Gl (27g/d, p=O.O07) and G2 (3Og/d, p=O.OOl); Gl iG2, NS; the increase was always higher in stage I/II, p=O.O5. Energy/protein intake decreased in G3, piO.001. At 3 months follow-up, Gl pts still complied with nutritional recommendations and maintained energy/protein intake; in G2/G3 intake decreased, either to baseline (stage I/II) or below baseline, p=O.O56 (stage III/IV).

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MALIGNANCIES

Conclusions: Despite the RT induced symptoms, counselling and supplementation did improve patients’ intake, though more effectively in early stages. During RT, both interventions were effective protein intake restorers; individualised counselling and education was the optimal nutrition intelyention, and the only to assure a sustained adequate diet in the medium-telm.

233-P. NUTRITION & PATIENT OUTCOMES: PROSPECTIVE RANDOMISED CONTROLLED TRIAL IN HEAD-NECK CANCER PATIENTS UNDERGOING RADIOTHERAPY P. Ravasco t , I. Monteiro Grill0 ‘, P. Mxques Vidal t , M. Camilo t ’Centre Nutrition Metabolism, IMM, Faculty Medicine University Lisbon, 2Radiotherapy eprtment, Santa Maria Hospital, Lisbon, Portugal Rationale: In a prospective randomised controlled trial we have shown that nutrition intervention significantly increases oral intake. We further investigated whether nutritional counselling or commercial supplements affected predefined patients’ outcomes: nutritional status & Quality of Life

(QoL). Method: Sample size determined for 85% power, 1% significance. There were 75 head-neck cancer outpatients (pts) stratified by cancer staging: 25 (Gl) received individualised nutritional counselling with foodstuffs, 25 (G2) high protein liquid supplements & 25 (G3) an ad lib intake. Compliante was weekly monitored. Nutritional status (Ottery’s Subjective Global Assessment) and QoL (EORTC) were evaluated at the onset, at the end and 3 months after radiotherapy (RT). ANOVA stratified by stage, adjusted for symptoms & disease outcome was used for comparisons. Results: At baseline malnutrition was observed in 56% stage III/IV and 4% I/II pts, p=O.O04. During RT nutritional deterioration occurred in 29% Gl & 37% G2, aheady malnourished, & 96% G3 pts. In Gl, all QoL scores improved (piO.001) proportionally to energy/protein intake increase (piO.O03), yet pain/discomfort worsened in association with anorexia (p=O.O7) and dysphagia/odynophagia (p=O.O5). In G2, all function scores improved (piO.03); pain/discomfort worsened in association with anorexia (piO.001) and dysphagia/odynophagia (p=O.OOS).All QoL scores worsened in G3. At 3-months follow-up nutritional status maintained/improved in 88% Gl, good QoL was reported by all Gl pts. Only 59% G2 & 31% G3 maintained nutritional status, overall QoL deteriorated in G2 (p=O.O5) & G3 (p=O.OOl). Conclusions: During RT individualised counselling and supplements improved nutritional status & QoL. In the medium telm, patient outcomes were only consistently improved by individualised nutrition education and adherence to adequate diets.

234-P. NUTRITION & PATIENT OUTCOMES: A PROSPECTIVE RANDOMISED CONTROLLED TRIAL IN COLORECTAL CANCER PATIENTS UNDERGOING RADIOTHERAPY P. Ravasco ‘, I. Monteiro Grille’, P. Mxques Vidal ’, M. Camilo ’ ’Centre Nutrition Metabolism, IMM, Faculty Medicine University Lisbon, ‘Radiotherapy Department, Santa Maria Hospital, Lisbon, Portugal Rationale: We have previously shown in a prospective randomised controlled trial that nutrition intervention significantly increases oral intake. We further investigated whether nutritional counselling or commercial supple__ merits affected predefined patients’ outcomes: nub-itional status & Quality of Life (QoL). Method: Sample size was determined for 85% power, 1% significance. There were 111 colorectal cancer outpatients (pts) stratified by staging: 37 (Gl) received individualised counselling with foodstuffs, 37 (G2) high protein liquid supplements & 37 (G3) an ad lib intake. Compliance was weekly monitored. Nutritional status (Ottery’s Subjective Global Assessment) and QoL (EORTC) were evaluated at the onset, at the end and 3 months after radiotherapy (RT). ANOVA stratified by stage, adjusted for symptoms & disease outcome was used for compz&ons. Results: At baseline malnutrition was only observed in 39% stage III/IV pts. During RT, nutritional deterioration occurred in 18% Gl and 36% G2 malnourished pts, &in 92%G3. All QoL scores improved in Gl (piO.002) proportionally to energy/protein intake (piO.OOl), yet pain/discomfolt wors-

ened in association with anorexia (p=O.O6),nausea/vomiting (p=O.O7),diavrhcea (p=O.O5).In G2, only 3/5 function sconz~ improved (piO.06) proportionally to protein intake (p=O.O4); worse fatigue and pain/discomfort were associated with anorexia (piO.OOl), nausea/vomiting (piO.O4), diarrhoea (piO.002). All QoL scores worsened in G3. At 3-months follow-up nutritional status maintained/improved in 72% Gl, good QoL was reported by all Gl pts. Only 49% G2 and 42% G3 maintained nutritional status, overall QoL worsened (piO.05). Conclusions: During RT both interventions prevented nutritional deterioration, QoL was only influenced by counselling. In the medium tern, patient outcomes were only improved by individualised nutrition education.

235-P. LEPTIN LEVELS AND ITS RELATION CANCER CACHEXIA

TO LUNG

T.O.S.R. Bzu~os’, L. Kent-Smith’, L.L. Santos3, J.D. Silva4 ‘Nutrition Service, Port0 Cancer Centre, 2Nutrition Faculty, Port0 University, 31CU, 4Medical Oncology, Port0 Cancer Centre, Porte, Portugal Rationale: Lung cancer has a major impact on nutritional status. With the disease progression, the deterioration of the nutritional and immunological status xe evident and significantly affect the patient’s condition. Leptin represents the afferent signal in a feedback mechanism regulating fat mass. In advanced-stage cancer, Leptin values xe normally high and it is thought that these values can lead to anorexia and hypelmetabolism, worsening the malnomishment of patients. 15 patients with Non-small cell lung cancer wele evaluated. Method: Anthropometrical, biochemical and immunology parameters ineluded: weight, height, BMI, NRI, TSF and MAMC, total protein, albumin, pre-albumin, transferrin, Leptin, CRP, TLC, IL21, IL6, ILS, TNF and Cd4/CdS. Side effects for decreased food intake and diminished activity were identified. Patients were assessed prior to CT treatment. Descriptive statistics and Mann Whitney U test were used. Results: Weight loss at diagnosis was found in almost all patients: NRI, prealbumin and transferrin were low and immune function was compromised as shown by high values of IL21 and IL6. The population was divided according to their Leptin values that were high in 4 malnourished patients. Comparing both groups, Leptin values were significantly related to: preillness weight loss (p=O,O31), weight (p=O,O43), BMI (p=O,O19) and IL6 (p=O,O33). 5 patients referred anorexia and 9 refemzd having diminished their usual activity. Conclusions: Cancer cachexia may have a relation with Leptin, but no evidence was shown that, in lung cancer patients, Leptin’s normal role is not accomplished.

236-P. NUTRITIONAL COUNSELLING vs SUPPLEMENTS: PROSPECTIVE RANDOMISED CONTROLLED TRIAL IN HEAD-NECK CANCER PATIENTS UNDERGOING RADIOTHERAPY

A

P. Ravasco ‘, I. Monteiro Grille’ , P. Marques Vidal ’, M. Camilo ’ ~ ’ Centre Nutrition Metabolism, IMM, Faculty Medicine University Lisbon, ‘Radiotherapy Department, Hospital Santa Maria, Lisbon, Portugal Rationale: Evidence ascribing benefits to nutritional counselling with or without supplementation in cancer is as yet lacking. Method: In a prospective block randomised controlled trial, the effect of individualised nutritional counselling or commercial supplements on oral intake was investigated. There wele 75 head-neck cancer outpatients (pts), 6OM:15F, age 60+/-11(36-84), stratified by cancer staging; 25 (Gl) were assigned to individualised nutritional counselling based on current foodstuffs, 25 (G2) to high protein liquid supplements and 25 (G3) to ad lib intake. Compliance was weekly monitored. Nutritional intake was assessed by a 24hr recall questionnaire at the onset, at the end and 3 months after RT, total energy requirements (ER) were = estimated basal requirementsxl.2 activity factor, protein intake was compxed to reference. ANOVA stratified by staging and adjusted for symptoms was used for group comparisons. Results: Baseline nutritional intake was similar in the 3 groups; energy