Tolerance and incorporation of a high-dose eicosapentaenoic acid diester emulsion by patients with pancreatic cancer cachexia Plasma and neutrophil fatty acid composition in advanced cancer patients and response to fish oil supplementation Effect of a protein and energy dense n-3 fatty acid enriched oral supplement on loss of weight and lean tissue in cancer cachexia: a randomised double blind trial Early postoperative enteral nutrition with arginine-omega-3 fatty acids and ribonucleic acid-supplemented diet versus placebo in cancer patients: an immunologic evaluation of Impact. Early postoperative enteral immunonutrition: clinical outcome and cost-comparison analysis in surgical patients. Reduced postoperative infections with an immune-enhancing nutritional supplement. Outcome and cost-effectiveness of perioperative enteral immunonutrition in patients undergoing elective upper gastrointestinal tract surgery: a prospective randomized study. Dietary omega‐3 polyunsaturated fatty acids plus vitamin E restore immunodeficiency and prolong survival for severely ill patients with generalized malignancy The effect of an oral nutritional supplement enriched with fish oil on weight-loss in patients with pancreatic cancer Phase I clinical study of fish oil fatty acid capsules for patients with cancer cachexia: cancer and leukemia group B study 9473. Cancer-related anorexia/cachexia syndrome and oxidative stress: an innovative approach beyond current treatment. Perioperative immunonutrition in patients undergoing cancer surgery: results of a randomized double-blind phase 3 trial. Gut function and immune and inflammatory responses in patients perioperatively fed with supplemented enteral formulas. A prospective, randomized trial of early enteral feeding after resection of upper gastrointestinal malignancy. Weight stabilisation is associated with improved survival duration and quality of life in unresectable pancreatic cancer. Modulation of the liver export protein synthetic response to feeding by an n-3 fatty-acid-enriched nutritional supplement is associated with anabolism in cachectic cancer patients. Effect of Oral Eicosapentaenoic Acid on Weight Loss in Patients With Pancreatic Cancer Effect of a fish oil structured lipid-based diet on prostaglandin release from mononuclear cells in cancer patients after surgery. Effect of fish oil on appetite and other symptoms in patients with advanced cancer and anorexia/cachexia: a double-blind, placebo-controlled study. An eicosapentaenoic acid supplement versus megestrol acetate versus both for patients with cancer-associated wasting: a North Central Cancer Treatment Group and National Cancer Institute of Canada collaborative effort. Effect of route of delivery and formulation of postoperative nutritional support in patients undergoing major operations for malignant neoplasms. A randomized controlled trial of preoperative oral supplementation with a specialized diet in patients with gastrointestinal cancer. Preoperative oral supplement with immunonutrients in cancer patients. Complications of Pancreatic Surgery and the Role of Perioperative Nutrition Eicosapentaenoic acid ethyl ester supplementation in cachectic cancer patients and healthy subjects: effects on lipolysis and lipid oxidation. Omega-3 fatty acids improve liver and pancreas function in postoperative cancer patients. Impact of fish oil and melatonin on cachexia in patients with advanced gastrointestinal cancer: a randomized pilot study. A prospective, randomized clinical trial on perioperative feeding with an arginine-, omega-3 fatty acid-, and RNA-enriched enteral diet: effect on host response and nutritional status. Effect of dietary counseling on food intake, body weight, response rate, survival, and quality of life in cancer patients undergoing chemotherapy: a prospective, randomized study. Enteral Nutrition During Multimodality Therapy in Upper Gastrointestinal Cancer Patients Immune and nutritional effects of early enteral nutrition after major abdominal operations. Benefits of early postoperative enteral feeding in cancer patients. Phase II study of high‐dose fish oil capsules for patients with cancer‐related cachexia Influence of a pre-operative enteral supplement on functional activities of peripheral leukocytes from patients with major surgery.
Chemotherapy and radiotherapy offer little benefit to patients with advanced pancreatic cancer .  Eicosapentaenoic acid ( EPA ) has anticancer effects both in vitro and in animal models . The dose of EPA that can be administered to cancer patients has previously been limited by the low purity of available preparations and the tolerability of large capsules . A high-purity preparation of EPA as a 20 % oil-in-water diester emulsion allowed a small study of the tolerance , incorporation , and effects of EPA in high doses in five patients with advanced pancreatic cancer . Patients underwent assessment at baseline and every 4 wk thereafter . All patients managed to tolerate a dose providing 18 g EPA per day , with doses between 9 and 27 g daily being taken for at least a month . Dosage was limited by a sensation of fullness , cramping abdominal pain , steatorrhea , and nausea . All such symptoms were controlled by dose reduction or pancreatic enzyme supplements . No other adverse effects attributable to the trial agent were observed . Plasma phospholipid EPA content increased from around 1 % at baseline to 10 % at 4 wk and 20 % at 8 wk . Incorporation of EPA into red blood cell phospholipids reached levels of around 10 % . The present study has shown that a novel , high-purity , EPA diester emulsion can be tolerated at a dose providing around 18 g EPA per day with side-effects being easily controlled . The acceptibility of large doses of oral EPA should allow larger controlled clinical studies into potential anticancer effects of EPA Metabolic dem and and altered supply of essential nutrients is poorly characterised in patients with advanced cancer . A possible imbalance or deficiency of essential fatty acids is suggested by reported beneficial effects of fish oil supplementation . To assess fatty acid status ( composition of plasma and neutrophil phospholipids ) in advanced cancer patients before and after 14 days of supplementation ( 12±1 g day−1 ) with fish ( eicosapentaenoic acid , and docosahexaenoic acid ) or placebo ( olive ) oil . Blood was drawn from cancer patients experiencing weight loss of > 5 % body weight ( n=23 ) . Fatty acid composition of plasma phospholipids and the major phospholipid classes of isolated neutrophils were determined using gas liquid chromatography . At baseline , patients with advanced cancer exhibited low levels ( < 30 % of normal values ) of plasma phospholipids and constituent fatty acids and elevated 20:4 n-6 content in neutrophil phospholipids . High n-6/n-3 fatty acid ratios in neutrophil and plasma phospholipids were inversely related to body mass index . Fish oil supplementation raised eicosapentaenoic acid and docosahexaenoic acid content in plasma but not neutrophil phospholipids . 20:4 n-6 content was reduced in neutrophil PI following supplementation with fish oil . Change in body weight during the supplementation period related directly to increases in eicosapentaenoic acid in plasma . Advanced cancer patients have alterations in lipid metabolism potentially due to nutritional status and /or chemotherapy . Potential obstacles in fatty acid utilisation must be addressed in future trials aim ing to improve outcomes using nutritional intervention with fish oils Aim : N-3 fatty acids , especially eicosapentaenoic acid ( EPA ) , may possess anticachectic properties . This trial compared a protein and energy dense supplement enriched with n-3 fatty acids and antioxidants ( experimental : E ) with an isocaloric isonitrogenous control supplement ( C ) for their effects on weight , lean body mass ( LBM ) , dietary intake , and quality of life in cachectic patients with advanced pancreatic cancer . Methods : A total of 200 patients ( 95 E ; 105 C ) were r and omised to consume two cans/day of the E or C supplement ( 480 ml , 620 kcal , 32 g protein ± 2.2 g EPA ) for eight weeks in a multicentre , r and omised , double blind trial . Results : At enrolment , patients ’ mean rate of weight loss was 3.3 kg/month . Intake of the supplements ( E or C ) was below the recommended dose ( 2 cans/day ) and averaged 1.4 cans/day . Over eight weeks , patients in both groups stopped losing weight ( Δ weight E : −0.25 kg/month versus C : −0.37 kg/month ; p = 0.74 ) and LBM ( Δ LBM E : + 0.27 kg/month versus C : + 0.12 kg/month ; p = 0.88 ) to an equal degree ( change from baseline E and C , p<0.001 ) . In view of evident non-compliance in both E and C groups , correlation analyses were undertaken to examine for potential dose-response relationships . E patients demonstrated significant correlations between their supplement intake and weight gain ( r = 0.50 , p<0.001 ) and increase in LBM ( r = 0.33 , p = 0.036 ) . Such correlations were not statistically significant in C patients . The relationship of supplement intake with change in LBM was significantly different between E and C patients ( p = 0.043 ) . Increased plasma EPA levels in the E group were associated with weight and LBM gain ( r = 0.50 , p<0.001 ; r = 0.51 , p = 0.001 ) . Weight gain was associated with improved quality of life ( p<0.01 ) only in the E group . Conclusion : Intention to treat group comparisons indicated that at the mean dose taken , enrichment with n-3 fatty acids did not provide a therapeutic advantage and that both supplements were equally effective in arresting weight loss . Post hoc dose-response analysis suggests that if taken in sufficient quantity , only the n-3 fatty acid enriched energy and protein dense supplement results in net gain of weight , lean tissue , and improved quality of life . Further trials are required to examine the potential role of n-3 enriched supplements in the treatment of cancer cachexia OBJECTIVE To evaluate the effect of early postoperative feeding with a nutritionally complete enteral diet supplemented with the nutrients arginine , ribonucleic acid ( RNA ) , and omega-3 fatty acids on the immune function in patients undergoing surgery for upper gastrointestinal ( GI ) malignancies . DESIGN Prospect i ve , r and omized , placebo-controlled , double-blind study . SETTING Surgical intensive care unit ( ICU ) in a German university hospital . PATIENTS Forty-two consecutive patients receiving an enteral diet via needle catheter jejunostomy after GI surgery for cancer . INTERVENTIONS Patients were r and omized to receive either the arginine , RNA , and omega-3 fatty acids supplemented diet or an isocaloric and isonitrogenous placebo diet . Early enteral nutrition was started on postoperative day 1 in the surgical ICU with 20 mL/hr and progressed to the optimal goal of 80 mL/hr by postoperative day 5 . MEASUREMENTS AND MAIN RESULTS Clinical examination and adverse GI symptoms were recorded on a daily basis . Body weight was determined twice weekly . Immunoglobulin concentrations were determined by laser nephelometry . Interferon-gamma concentrations were measured with a modified enzyme-linked immunosorbent assay method . Fluorescence-activated cell scan flow cytometry was performed to analyze B cells , T lymphocytes and their subsets . Clinical patient characteristics and mean caloric intake were similar between the two groups and both formulas were well tolerated . The number of T lymphocytes and their subsets , helper T cells ( CD4 ) and activated T cells ( CD3 , HLA-DR ) , were significantly higher in the supplemented diet group on postoperative days 10 and 16 ( p < .05 ) . Mean interferon-gamma concentration after phytohemagglutinin stimulation was higher in the supplemented diet group on postoperative day 16 . In the supplemented diet group , mean immunoglobulin M concentrations were significantly higher on postoperative day 10 and mean immunoglobulin G concentrations were higher on postoperative day 16 ( p < .05 ) compared with the results in the placebo group . B-lymphocyte indices were significantly higher in the supplemented vs. the placebo diet group on postoperative days 7 and 10 ( p < .05 ) . CONCLUSIONS Supplementation of enteral diet with arginine , RNA , and omega-3 fatty acids in the early postoperative time period improves postoperative immunologic responses and helps to overcome more rapidly the immunologic depression after surgical trauma OBJECTIVE To determine if early postoperative feeding of patients with upper gastrointestinal malignancy , using an enteral diet supplemented with arginine , dietary nucleotides , and omega-3 fatty acids ( IMPACT , S and oz Nutrition , Bern , Switzerl and ) results in an improved clinical outcome , i.e. , reduced infectious and wound complications and decreased treatment costs when compared with an isocaloric , isonitrogenous control diet . DESIGN A prospect i ve , r and omized , placebo-controlled , double-blind , multicenter trial of the clinical outcome and a retrospective cost-comparison analysis . SETTING Surgical intensive care units in three different German university hospitals . PATIENTS Of 164 patients enrolled in the study , 154 patients were eligible for analysis . They were admitted to the intensive care unit after upper gastrointestinal surgery for cancer and they received an enteral diet via needle catheter jejunostomy .  Infectious complications were defined as sepsis or systemic inflammatory response syndrome , pneumonia , urinary tract infection , central venous catheter sepsis , wound infection , and anastomotic leakage . The complication events were prospect ively divided into two groups : early ( postoperative days 1 to 5 ) and late ( after the fifth postoperative day ) postoperative complications . The treatment costs of each complication were analyzed and compared in both groups . INTERVENTIONS Patients were r and omized to receive either the immunonutritional diet ( n = 77 ) or an isocaloric and isonitrogenous placebo diet ( n = 77 ) . Enteral feeding was initiated 12 to 24 hrs after surgery , starting with 20 mL/hr and advanced to a target volume of 80 mL/hr by postoperative day 5 . MEASUREMENTS AND MAIN RESULTS Clinical examination and adverse gastrointestinal symptoms were recorded on a daily basis . Both groups tolerated early enteral feeding well , and the rate of tube feeding-related complications was low . Postoperative complications occurred in 17 patients in the immunonutrition group vs. 24 patients in the control group ( NS ) . Further , in the early phase ( postoperative day 1 to 5 ) , complications occurred to a similar extent in both groups ( 12 patients in the immunonutritional group vs. 11 patients in the control group ) . However , in the late phase ( after postoperative day 5 ) , considerably fewer patients in the experimental diet group experienced complications compared with the control group ( 5 vs. 13 , p < .05 ) . In addition , the frequency rate of complicating events were recorded in each group . In the experimental diet group , a total of 22 complicating events were recorded vs. a total of 32 events in the placebo diet group ( NS ) . However , the occurrence of late complicating events , i.e. , complicating events after the fifth postoperative day , was significantly reduced in the immunonutrition group when compared with the control group ( 8 vs. 17 events , p < .05 ) . The total costs for the treatment of the complications were 83,563 German marks in the experimental diet group vs. 122,430 German marks in the control group , result ing in a cost-reduction of 38,867 German marks . ( At the end of December 1995 , the conversion rate from German marks to U.S. dollars was 1.4365 German marks to $ 1.00 . ) CONCLUSIONS Early enteral feeding with an arginine , dietary nucleotides , and omega-3 fatty acids supplemented diet , as well as an isonitrogenous , isocaloric control diet ( placebo ) were well tolerated in patients who underwent upper gastrointestinal surgery . In patients who received the supplemented diet , a significant reduction in the frequency rate of late postoperative infectious and wound complications was observed . Thereby , the treatment costs were substantially reduced in the immunonutrition group as compared with the control group OBJECTIVES /HYPOTHESIS Malnutrition is a significant risk factor for postoperative infections in patients undergoing oncologic surgery . This study was undertaken to determine if perioperative nutritional supplementation with an immune-enhancing formula is superior to st and ard formula in the prevention of postoperative infectious complications . STUDY DESIGN This was a prospect i ve , r and omized , double-blind trial comparing perioperative nutritional supplementation with Impact and st and ard nutritional formulas . METHODS Following stratification , 136 patients undergoing oncologic head and neck surgery were r and omly assigned to one of four treatment groups : preoperative/postoperative Impact , postoperative Impact , preoperative/postoperative st and ard formula , and postoperative st and ard formula . Outcome measures included laboratory evaluations of nutritional status , infectious and wound healing complications , and duration of hospitalization . Statistical analysis was performed using chi2 or two-tailed Fisher Exact Tests , when appropriate . RESULTS Intent-to-treat ( P = .02 ) and actual therapy ( P = .04 ) analyses revealed a significant decrease in the incidence of postoperative infectious complications ( all sites ) in patients who received Impact . There was no significant difference in wound healing problems or duration of hospitalization . Postoperative measures of nutrition status demonstrated a higher serum albumin ( P = .05 ) in patients who received Impact compared with st and ard formula . CONCLUSIONS Compared with st and ard formula , perioperative nutritional supplementation with Impact significantly reduced the incidence of infectious complications . The length of hospitalization was significantly prolonged in patients with postoperative infections , suggesting potential cost savings with the use of immune-enhancing formulas such as Impact HYPOTHESIS Perioperatively administered enteral immunonutrition will improve early postoperative morbidity and cost-effectiveness after gastrointestinal tract surgery . DESIGN A prospect i ve , r and omized , double-blind , multicenter clinical trial . SETTING Surgical departments in German university and teaching hospitals . PATIENTS One hundred fifty-four patients with upper gastrointestinal tract malignant neoplasms who were eligible for analysis . INTERVENTION Preoperatively , patients received 5 days of oral immunonutrition ( an arginine- , RNA- , and omega3 fatty acid-supplemented diet ) or an isoenergetic control diet ( 1 L/d ) . Early postoperative enteral feeding with immunonutrition or an isoenergetic , isonitrogenous control diet using a catheter jejunostomy was performed for 10 days . MAIN OUTCOME MEASURES Postoperative infectious complications , their treatment costs , and cost-effectiveness of immunonutrition were analyzed . Plasma levels of the fatty acids eicosapentaenoic acid and docosahexaenoic acid were measured . RESULTS In the immunonutrition group , significantly fewer infectious complication events occurred ( 14 vs 27 ; P = .05 ) . The number of patients with complications was significantly lower in the supplemented diet group after postoperative day 3 ( 7 vs 16 ; P = .04 ) . The treatment costs of complications in the supplemented diet group were suggestively lower than in the control diet group ( DM 75172 vs DM 204273 ) . Cost-effectiveness was DM 1503 in the experimental group vs DM 3587 in the control group , where DM denotes deutsche mark ( German currency ) . CONCLUSION The perioperative administration of an enteral immunonutrition significantly ( P = .05 ) decreased the early occurrence of postoperative infections and reduced substantially the treatment costs of the complications after major upper gastrointestinal tract surgery The aim of the current prospect i ve , r and omized control study was to investigate the effect of dietary omega‐3 polyunsaturated fatty acids plus vitamin E on the immune status and survival of well‐nourished and malnourished patients with generalized malignancy Summary Previous studies have suggested that administration of oral eicosapentaenoic acid ( EPA ) will stabilize weight in patients with advanced pancreatic cancer . The aim of the present study was to determine if a combination of EPA with a conventional oral nutritional supplement could produce weight gain in these patients . Twenty patients with unresectable pancreatic adenocarcinoma were asked to consume two cans of a fish oil-enriched nutritional supplement per day in addition to their normal food intake . Each can contained 310 kcal , 16.1 g protein and 1.09 g EPA . Patients were assessed for weight , body composition , dietary intake , resting energy expenditure ( REE ) and performance status . Patients consumed a median of 1.9 cans day–1 . All patients were losing weight at baseline at a median rate of 2.9 kg month–1 . After administration of the fish oil-enriched supplement , patients had significant weight-gain at both 3 ( median 1 kg , P = 0.024 ) and 7 weeks ( median 2 kg , P = 0.033 ) . Dietary intake increased significantly by almost 400 kcal day–1 ( P = 0.002 ) . REE per kg body weight and per kg lean body mass fell significantly . Performance status and appetite were significantly improved at 3 weeks . In contrast to previous studies of oral conventional nutritional supplements in weight-losing cancer patients , this study suggests that an EPA-enriched supplement may reverse cachexia in advanced pancreatic cancer The purpose of this study was to determine the maximum tolerated dose and dose-limiting toxicities of fish oil fatty acid capsules containing omega-3 fatty acid ethyl esters .  Twenty-two patients with neoplastic disease not amenable to curative therapy who had lost 2 % of body weight over a previous 1 month time period were given an escalating dose of fish oil fatty acids . The maximum tolerated dose was found to be 0.3 g/kg per day of this preparation . This means that a 70-kg patient can generally tolerate up to 21 1-g capsules/day containing 13.1 g of eicosapentaenoic acid + docosahexaenoic acid , the two major omega-3 fatty acids .  Dose-limiting toxicity was gastrointestinal , mainly diarrhea , and a poorly described toxicity design ated as " unable to tolerate in esophagus or stomach . " A patient with chronic lymphocytic leukemia taking the fish oil provided an unusual opportunity to perform a detailed biochemical study of the effect of fish oil capsules on the lipids of malignant cells at several sequential time points in treatment . Studies of the malignant lymphocytes , serum , and whole blood of this one patient revealed an increase in eicosapentaenoic acid , the major component of the fish oil capsules , during fish oil capsule treatment . This study provides a scientific basis for the selection of omega-3 fatty acid doses for future studies in cancer . The maximum tolerated dose found is considerably higher than anticipated from published studies of many human diseases . The observation of a modification of the lipids of leukemic cells , serum , and blood in a patient with chronic leukemia provides a biochemical basis for a possible effect of fish oil supplements on cancer cachexia and tumor growth OBJECTIVE Cancer-related anorexia/cachexia syndrome and oxidative stress play a key role in the progression and outcome of neoplastic disease . PATIENTS AND METHODS On the basis of our previously published studies and clinical experience , we have developed an innovative approach consisting of diet with high polyphenol content ( 400 mg ) , p.o . pharmaconutritional support enriched with n - 3 fatty acids ( eicosapentaenoic acid and docosahexaenoic acid ) 2 cans ( 237 mL each ) per day , medroxiprogesterone acetate 500 mg/d , antioxidant treatment with alpha-lipoic acid 300 mg/d plus carbocysteine lysine salt 2.7 g/d plus vitamin E 400 mg/d plus vitamin A 30,000 IU/d plus vitamin C 500 mg/d , and selective cyclooxygenase-2 inhibitor Celecoxib 200 mg/d . The treatment is administered for 16 weeks . The following variables are evaluated : ( a ) clinical variables ( stage and Eastern Cooperative Oncology Group performance status ) ; ( b ) nutritional variables ( lean body mass , appetite , and resting energy expenditure ) ; ( c ) laboratory variables ( serum levels of proinflammatory cytokines , C-reactive protein , and leptin and blood levels of reactive oxygen species and antioxidant enzymes ) ; and ( d ) quality of life variables ( European Organization for Research and Treatment of Cancer QLQ-C30 , EQ-5Dindex , and EQ-5DVAS ) . A phase II nonr and omized study has been design ed to enroll 40 patients with advanced cancer at different sites with symptoms of cancer-related anorexia/cachexia syndrome and oxidative stress . RESULTS As of January 2004 , 28 patients have been enrolled : 25 patients were evaluable and 14 of them have completed the treatment ( 20 patients have completed 2 months of treatment ) . As for clinical response , five patients improved , three patients remained unchanged , and six patients worsened . The Eastern Cooperative Oncology Group performance status ( grade ) 1 remained unchanged . As for nutritional/functional variables , the lean body mass increased significantly at 2 and 4 months . As for laboratory variables , reactive oxygen species decreased significantly and proinflammatory cytokines interleukin-6 and tumor necrosis factor-alpha decreased significantly . As for quality of life , it comprehensively improved after treatment . CONCLUSIONS The treatment has been shown to be effective for clinical response , increase of lean body mass , decrease of reactive oxygen species and proinflammatory cytokines , and improvement of quality of life . The treatment has been shown to be safe with good compliance of patients . The study is in progress ( 14 further patients will be included ) HYPOTHESIS Perioperative administration of a supplemented enteral formula may reduce the rate of postoperative infections . DESIGN Prospect i ve , r and omized , double-blind clinical trial . SETTING Department of surgery at a university hospital . PATIENTS Two hundred six patients with neoplasm of colorectum , stomach , or pancreas . INTERVENTION Patients were r and omized to drink 1 L/d of either a control enteral formula ( n = 104 ) or the same formula enriched with arginine , RNA , and omega3 fatty acids ( n = 102 ) for 7 consecutive days before surgery . The 2 diets were isoenergetic and isonitrogenous . Jejunal infusion with the same formulas was started 6 hours after operation and continued until postoperative day 7 . MAIN OUTCOME MEASURES Rate of postoperative infectious complications and length of hospital stay . RESULTS Both groups were comparable for age , sex , weight loss , Karnofsky scale score , nutritional status , hemoglobin level , duration of surgery , blood loss , and rate of homologous transfusion . Intent-to-treat analysis showed a 14 % ( 14/102 ) infectious complication rate in the supplemented group vs 30 % ( 31/104 ) in the control group ( P = .009 ) . In the eligible population , the postoperative infection rate was 11 % ( 9/85 ) in the supplemented group vs. 24 % ( 21/86 ) in the control group ( P = .02 ) . The mean + /- SD length of postoperative stay was 11.1+/-4.4 days in the supplemented group and 12.9+/-4.6 in the control group ( P = .01 ) . CONCLUSION Perioperative administration of a supplemented enteral formula significantly reduced postoperative infections and length of stay in patients undergoing surgery for cancer OBJECTIVE To evaluate if the perioperative administration of a supplemented enteral formula modulates selective inflammatory and immune variables and gut function after surgery . DESIGN Prospect i ve , r and omized , double-blind , clinical trial . SETTING Department of surgery , university hospital . PATIENTS Forty patients with neoplasm of the colorectum or stomach . INTERVENTION Seven days before surgery , the patients drank 1 L/d of a control enteral formula ( n = 20 ) or the same formula enriched with arginine , RNA , and omega-3 fatty acids ( n = 20 ) . Jejunal infusion with the same formulas was started 6 hours after operation and continued until day 7 . MAIN OUTCOME MEASURES Immune response was determined by phagocytosis ability and respiratory burst of polymorphonuclear cells , and inflammatory response by plasma levels of C-reactive protein . Operative intestinal microperfusion , postoperative intestinal mucosa oxygen metabolism , and plasma intestinal isoenzyme of alkaline phosphatase were used as indicators of gut function . Plasma nitric oxide also was determined . RESULTS In the enriched group , phagocytosis ability and respiratory burst after surgery was higher ( P < .01 ) and C-reactive protein level was lower ( P < .05 ) than in the control group . The enriched group had higher mean ( + /-SD ) intestinal microperfusion ( 180 + /- 46 vs 146 + /- 59 perfusion units , P < .05 ) , intestinal mucosa oxygen metabolism ( pHi 7.39 + /- 0.2 vs pHi 7.33 + /- 0.1 , P < .05 ) , and 5-fold lower levels of intestinal isoenzyme of alkaline phosphatase ( P < .05 ) . Postoperative levels of nitric oxide were higher in the enriched group ( P < .05 , analysis of variance ) . CONCLUSION The perioperative administration of an enriched enteral formula significantly improved gut function and positively modulated postsurgical immunosuppressive and inflammatory responses OBJECTIVE The purpose of the study was to determine whether early postoperative enteral feeding with an immune-enhancing formula ( IEF ) decreases morbidity , mortality , and length of hospital stay in patients with upper gastrointestinal ( GI ) cancer . SUMMARY BACKGROUND DATA Early enteral feeding with an IEF has been associated with improved outcome in trauma and critical care patients . Evaluable data documenting reduced complications after major upper GI surgery for malignancy with early enteral feeding are limited . METHODS Between March 1994 and August 1996 , 195 patients with a preoperative diagnosis of esophageal ( n = 23 ) , gastric ( n = 75 ) , peripancreatic ( n = 86 ) , or bile duct ( n = 11 ) cancer underwent resection and were r and omized to IEF via jejunostomy tube or control ( CNTL ) .  Tube feedings were supplemented with arginine , RNA , and omega-3 fatty acids , begun on postoperative 1 , and advanced to a goal of 25 kcal/kg per day . The CNTL involved intravenous crystalloid solutions . Statistical analysis was by t test , chi square , or logistic regression . RESULTS Patient demographics , nutritional status , and operative factors were similar between the groups . Caloric intake was 61 % and 22 % of goal for the IEF and CNTL groups , respectively . The IEF group received significantly more protein , carbohydrate , lipids and immune-enhancing nutrients than did the CNTL group . There were no significant differences in the number of minor , major , or infectious wound complications between the groups . There was one bowel necrosis associated with IEF requiring reoperation . Hospital mortality was 2.5 % and median length of hospital stay was 11 days , which was not different between the groups . CONCLUSION Early enteral feeding with an IEF was not beneficial and should not be used in a routine fashion after surgery for upper GI malignancies BACKGROUND & AIMS Cancer-induced weight loss is associated with poor outcomes and is common in pancreatic cancer . The aims were to determine whether stabilising weight loss for patients with unresectable pancreatic cancer was associated with improved survival and quality of life ( QoL ) and to identify determinants of weight stabilisation . METHODS A post hoc analysis was performed using data from 107 patients in a multicentre trial . Patients were categorised as weight losing ( > 1 kg lost ) or weight stable ( < or = 1 kg lost ) after an 8 week nutrition intervention period . Group survival duration ( Kaplan Meier ) and QoL ( EORTC QLQ-C30 ) were compared . Predictors of weight stability were determined using logistic regression analysis . RESULTS Patients with weight stabilisation survived longer from baseline ( log rank test 5.53 , P = 0.019 ) . They also reported higher QoL scores ( P = 0.037 ) and a greater mean energy intake ( P < 0.001 ) at Week 8 than those who continued to lose weight . The absence of nausea and vomiting ( OR 6.5 , P = 0.010 ) and female gender ( OR 5.2 , P = 0.020 ) were independent determinants of weight stabilisation . CONCLUSIONS Weight stabilisation over an 8 week period in weight-losing patients with unresectable pancreatic cancer was associated with improved survival duration and The acute-phase protein response is associated with accelerated weight loss and shortened survival in cancer . This may be due to hepatic protein synthesis increasing dem and for amino acids . An n -3 fatty-acid-enriched nutritional supplement will moderate aspects of cachexia in cancer patients . The present study examined the effect of such a supplement on hepatic synthesis of albumin and fibrinogen . Albumin and fibrinogen synthesis were measured in the fed and fasting state in eight weight-losing patients with pancreatic cancer by an intravenous flooding dose technique . Tracer incorporation into proteins was measured by GC/MS . Patients were restudied after 3 weeks of oral supplement enriched with fish oil ( providing 2510 kJ/day and 2 g of eicosapentaenoic acid/day ) . At baseline , all patients were losing weight ( median , 2.4 kg/month ) . After 3 weeks of consumption of the fish-oil-enriched nutritional supplement , patients ' weight stabilized ( median change , + 1 kg ; P = 0.01 ) . At baseline , albumin and fibrinogen synthesis rates were stimulated in the fed compared with the fasting state [ 14.2 compared with 11.3 g/day ( 29 % rise ; P = 0.01 ) and 4.5 compared with 3.3 g/day ( 38 % rise ; P = 0.01 ) respectively ] . After 3 weeks of the supplement , this stimulation in the fed state was no longer observed for albumin and was reduced for fibrinogen [ 11.2 compared with 10.5 g/day ( 3 % rise ; P = 0.21 ) and 3.7 compared with 2.9 g/day ( 17 % rise ; P = 0.01 ) respectively ] . After 3 weeks , the combined albumin plus fibrinogen synthetic rate tended to fall in the fasting state ( 14.7 compared with 12.3 g/day ; P = 0.09 ) and was significantly reduced in the fed state ( 18.7 compared with 14.6 g/day ; P = 0.01 ) . Modulation of hepatic export protein synthesis with feeding may have contributed to the net whole-body anabolism observed with administration of the n -3 fatty-acid-enriched oral supplement Abstract : Eicosapentaenoic acid ( EPA ) has been shown to modulate aspects of the inflammatory response that may contribute to weight loss in cancer . This study aim ed to evaluate the acceptability and effects of oral supplementation with high-purity EPA in weight-losing patients with advanced pancreatic cancer . Twenty-six patients were entered into the study .  EPA ( 95 % pure ) was administered as free acid starting at 1 g/day ; the dose was increased to 6 g/day over four weeks , and then a maintenance dose of 6 g/day was administered . Patients were assessed before EPA and at 4 , 8 , and 12 weeks while receiving EPA , for weight , body composition , hematologic and clinical chemistry variables , acute-phase protein response , and performance status . Overall survival was noted . Supplementation was well tolerated , with only five patients experiencing side effects possibly attributable to the EPA . Before starting EPA , all patients had been losing weight at a median rate of 2 kg/mo . In general , after EPA supplementation , weight was stable . After four weeks of EPA supplementation , patients had a median weight gain of 0.5 kg ( p = 0.0009 vs. rate of weight loss at baseline ) , and this stabilization of weight persisted over the 12-week study period . Total body water as a percentage of body weight remained stable , as did the proportion of patients with an acute-phase protein response , patients ' nutritional intake , and performance status . Overall median survival from diagnosis in this study was 203 days . This study suggests that EPA is well tolerated , may stabilize weight in cachectic pancreatic cancer patients , and should be tested as an anticachectic agent in controlled trials BACKGROUND The authors compared the effect on eicosanoid production ( prostagl and in E2 [ PGE2 ] , 6-keto PGF 1 alpha , and thromboxane B2 ) from peripheral blood mononuclear cells ( P BMC ) of feeding an enteral diet containing a fish oil/medium-chain triglyceride structured lipid ( FOSL-HN ) vs an isonitrogenous , isocaloric formula ( O-HN ) in patients undergoing major abdominal surgery for upper gastrointestinal malignancies . A previous study , which used the same formulas and experimental design , suggested improved renal and liver function as well as a reduced number of gastrointestinal and infectious complications with the use of fish oil structured lipids . This study sought to investigate the potential mechanism for these effects by assessing eicosanoid production from P BMC with the two diets . METHODS This prospect i ve , blinded , r and omized trial was conducted in 20 patients who were jejunally fed either FOSL-HN or O-HN for 7 days .  Serum chemistries , hematology , urinalysis , gastrointestinal complications , liver and renal function , and eicosanoid production from isolated P BMC , either unstimulated or stimulated with endotoxin , were measured at endotoxin baseline and on day 7 . Comparisons were made in 10 and 8 evaluable patients based a priori on the ability to reach a tube feeding rate of > 40 mL/h . RESULTS Patients receiving FOSL-HN experienced no untoward side effects compared with patients given O-HN and demonstrated the same general trend toward improved hepatic , renal and immune function found in the previous study . There was a significant reduction in PGE2 ( p < .03 ) and 6-keto PGF 1 alpha ( p < .01 ) production from P BMC with endotoxin stimulation in patients receiving FOSL-HN . CONCLUSIONS The results of early enteral feeding with FOSL-HN after surgery in this follow-up study provide further support to cl aims of safety , tolerance , and improved physiologic function . There was an associated reduction in eicosanoid production from P BMC s , which is presumed to be the principal mechanism for these effects PURPOSE To determine whether high doses of fish oil , administered over 2 weeks , improve symptoms in patients with advanced cancer and decreased weight and appetite . PATIENTS AND METHODS Sixty patients were r and omly assigned to fish oil capsules or placebo .  Appetite , tiredness , nausea , well-being , caloric intake , nutritional status , and function were prospect ively assessed at days 1 and 14 . RESULTS The baseline weight loss was 16 + /- 11 and 16 + /- 8 kg in the fish oil ( n = 30 ) and placebo ( n = 30 ) group respectively , whereas the baseline appetite ( 0 mm = best and 10 mm = worst ) was 58 + /- 24 mm and 67 + /- 19 mm , respectively ( P = not significant ) . The mean daily dose was 10 + /- 4 ( fish oil group ) and 9 + /- 3 ( placebo group ) capsules , which provided 1.8 g of eicosapentaenoic acid and 1.2 g of docosahexaenoic acid in the fish oil group . No significant differences in symptomatic or nutritional parameters were found ( P < .05 ) , and there was no correlation between changes in different variables between days 1 and 14 and the fish oil doses . Finally , the majority of the patients were not able to swallow more than 10 fish oil capsules per day , mainly because of burping and aftertaste . CONCLUSION Fish oil did not significantly influence appetite , tiredness , nausea , well-being , caloric intake , nutritional status , or function after 2 weeks compared with placebo in patients with advanced cancer and loss of both weight and appetite PURPOSE Studies suggest eicosapentaenoic acid ( EPA ) , an omega-3 fatty acid , augments weight , appetite , and survival in cancer-associated wasting . This study determined whether an EPA supplement-administered alone or with megestrol acetate (MA)-was more effective than MA . PATIENTS AND METHODS Four hundred twenty-one assessable patients with cancer-associated wasting were r and omly assigned to an EPA supplement 1.09 g administered bid plus placebo ; MA liquid suspension 600 mg/d plus an isocaloric , isonitrogenous supplement administered twice a day ; or both .  Eligible patients reported a 5-lb , 2-month weight loss and /or intake of less than 20 calories/kg/d . RESULTS A smaller percentage taking the EPA supplement gained > or= 10 % of baseline weight compared with those taking MA : 6 % v 18 % , respectively ( P = .004 ) . Combination therapy result ed in weight gain of > or= 10 % in 11 % of patients ( P = .17 across all arms ) . The percentage of patients with appetite improvement ( North Central Cancer Treatment Group Question naire ) was not statistically different : 63 % , 69 % , and 66 % , in EPA- , MA- , and combination-treated arms , respectively ( P = .69 ) . In contrast , 4-week Functional Assessment of Anorexia/Cachexia Therapy scores suggested MA-containing arms experienced superior appetite stimulation compared with the EPA arm , with scores of 40 , 55 , and 55 in EPA- , MA- , and combination-treated arms , respectively ( P = .004 ) . Survival was not significantly different among arms . Global quality of life was not significantly different among groups . With the exception of increased impotence in MA-treated patients , toxicity was comparable . CONCLUSION This EPA supplement , either alone or in combination with MA , does not improve weight or appetite better than MA alone OBJECTIVE To study the effect of the route of delivery and formulation of postoperative nutritional support on host defense , protein metabolism , infectious complications , and outcome . DESIGN Prospect i ve , r and omized , clinical trial . SETTING Department of Surgery at a university hospital . PATIENTS Two hundred sixty c and i date s for pancreaticoduodenectomy or gastrectomy for cancer . INTERVENTIONS Patients were r and omly allocated into 3 groups during surgery . Starting 6 hours after operation , the first group received a st and ard enteral formula ( st and ard group ; n = 87 ) ; the second , the same enteral formula enriched with arginine , omega-3 fatty acids , and RNA ( immunonutrition group ; n = 87 ) ; and the third , total parenteral nutrition ( parenteral group ; n = 86 ) . The 3 regimens were isocaloric and isonitrogenous . The nutritional goal was 105 kJ/kg per day . MAIN OUTCOME MEASURES Immune response by phagocytosis ability of polymorphonuclear cells , interleukin (IL)-2 receptor levels , and delayed hypersensitivity response ; protein synthesis by IL-6 and prealbumin ; tolerance of enteral feeding ; incidence of postoperative complications ; and length of hospital stay . RESULTS The immunonutrition group had a significantly better recovery of the immune parameters on postoperative day 8 compared with the other groups . Linear regression analysis showed an inverse correlation between IL-6 and preambulin levels ( r = 0.766 ) only in the immunonutrition group . Only 11 patients ( 6.3 % ) in both enteral groups did not reach the nutritional goal . Postoperative infection rate was 14.9 % ( 13/87 ) in the immunonutrition group , 22.9 % ( 20/87 ) in the st and ard group , and 27.9 % ( 24/86 ) in the parenteral group ( P = .06 ) . Mean + /- SD length of hospital stay was 16.1 + /- 6.2 , 19.2 + /- 7.9 , and 21.6 + /- 8.9 days in the immunonutrition , st and ard , and parenteral groups , respectively ( P = .01 vs st and ard group ; P = .004 vs parenteral group ) . CONCLUSIONS Early postoperative enteral feeding is a valid alternative to parenteral feeding in patients undergoing major surgery . Immunonutrition enhances the host response , induces a switch from acute-phase to constitutive proteins , and improves outcome BACKGROUND & AIMS Perioperative nutrition with specialized enteral diets improves outcome when compared with st and ard formulas . A post-hoc analysis suggested preoperative administration as the most important period . Thus , we design ed a study to underst and prospect ively whether preoperative supplementation could be as efficacious as the perioperative approach and superior to a conventional treatment ( no artificial nutrition ) in reducing postoperative infections and length of hospital stay . METHODS A total of 305 patients with preoperative weight loss < 10 % and cancer of the gastrointestinal tract were r and omized to receive the following : ( 1 ) oral supplementation for 5 days before surgery with 1 L/day of a formula enriched with arginine , omega-3 fatty acids , and RNA , with no nutritional support given after surgery ( preoperative group , n = 102 ) ; ( 2 ) the same preoperative treatment plus postoperative jejunal infusion with the same enriched formula ( perioperative group , n = 101 ) ; and ( 3 ) no artificial nutrition before and after surgery ( conventional group ; n = 102 ) . RESULTS The 3 groups were comparable for all baseline and surgical characteristics . Intention-to-treat analysis showed a 13.7 % incidence of postoperative infections in the preoperative group , 15.8 % in the perioperative group , and 30.4 % in the conventional group ( P = 0.006 vs. preoperative ; P = 0.02 vs. perioperative ) . Length of hospital stay was 11.6 + /- 4.7 days in the preoperative group , 12.2 + /- 4.1 days in the perioperative group , and 14.0 + /- 7.7 days in the conventional group ( P = 0.008 vs. preoperative and P = 0.03 vs. perioperative ) . CONCLUSIONS Preoperative supplementation is as effective as perioperative administration in improving outcome . Both strategies seem superior to the conventional approach BACKGROUND Early postoperative enteral nutrition with immune-enhancing supplements has helped to restore immune function and reduce infectious complications in patients with cancer undergoing major gastrointestinal operations . The aim of this study was to evaluate the effectiveness of similar supplements ( containing arginine and arginine plus omega-3 fatty acids ) given preoperatively for 1 week before cancer surgery . METHODS In this r and omized , double-blinded study , patients scheduled to undergo elective resection of upper gastrointestinal tumors were given one of three different oral liquid supplemental diets ( control , arginine , arginine plus omega-3 fatty acids ) to be taken each day for 7 days before surgery . Blood sample s were obtained upon enrollment , on the morning of surgery , and on postoperative day 1 for analysis of immunologic function . RESULTS Mean serum ornithine ( a metabolite of arginine ) levels were significantly higher compared with controls , but no significant increase in mean serum arginine levels was noted on the morning of surgery for those patients who received arginine as part of the supplement . In conjunction with these findings , there were no differences among groups in mean lymphocyte mitogenesis , mean peripheral blood mononuclear cell production of cytokines , or clinical outcomes . CONCLUSIONS Use of oral liquid supplements in this fashion did not improve lymphocyte proliferation or monocyte functions in patients with cancer undergoing major surgery Background : According to international guidelines , artificial nutrition may be indicated after pancreaticoduodenectomy ( PD ) . This clinical study was design ed to evaluate whether the route of administration and the composition of the postoperative nutritional support could affect outcome . Methods : One hundred patients who underwent PD for cancer of the pancreatic head were prospect ively studied . Patients were r and omized to receive a st and ard enteral formula ( SEN ; n = 35 ) or immunonutrition with an enteral formula enriched with arginine , ω-3 fatty acids , and RNA ( IEN group ; n = 33 ) , or total parenteral nutrition ( TPN ; n = 32 ) . Postoperative feeding was started within 12 h after surgery . The three regimens were isoenergetic and isonitrogenous . Tolerance of enteral feeding , rate and severity of postoperative complications , and length of hospital stay ( LOS ) were evaluated . Results : Full nutritional goal ( 25 kcal/kg ) was achieved in 84 % of enterally fed patients versus 96 % in the parenteral group ( p = NS ) . The rate of postoperative complications was lower in the IEN group ( 33 % ) than in the SEN ( 40 % ) and TPN groups ( 59 % ) . The severity of infectious complications ( sepsis score ) was lower in the IEN ( 5.5 ) than the SEN ( 7.9 ) and TPN groups ( 10.4 ; p < 0.05 ) . LOS was shorter in the IEN than in the SEN and TPN groups ( 16.3 vs. 17.8 vs. 19.3 days , respectively ; p < 0.05 ) . Conclusions : In patients undergoing PD the established nutritional goal can be obtained by enteral feeding . Immunonutrition seems to improve outcome BACKGROUND & AIMS Recent reports suggest that weight loss in cachectic cancer patients may be inhibited by supplementation of the n-3 fatty acid eicosapentaenoic acid ( 20:5n-3 ; EPA ) , presumably due to inhibition of lipolysis . The aim of the present double-blind , r and omized trial was to assess whether short-term oral EPA ethyl ester ( EE ) supplementation inhibits lipolysis and lipid oxidation in weight-losing cancer patients and in healthy subjects . METHODS Seventeen weight-losing , cancer patients of different tumor types , and 16 healthy subjects were r and omized to receive EPA-EE ( 6 g/d ) or placebo ( oleic acid (OA)-EE ; 6 g/d ) for seven days . At baseline ( day 0 ) and during supplementation ( days 2 and 7 ) whole-body lipolysis and palmitic acid release were measured in the overnight fasting state using [ 1 , 1 , 2 , 3 , 3-(2)H(5)]glycerol and [1-(13)C]palmitic acid . Palmitate oxidation was determined by measuring(13)CO(2)enrichment in expired breath . RESULTS No significant effects of EPA-EE on whole-body lipolysis , palmitic acid release , or palmitate oxidation were detected in cancer patients nor in healthy subjects in comparison with OA-EE . EPA-EE supplementation reduced plasma-free fatty acid and triacylglycerol concentrations significantly in healthy subjects but not in cancer patients . CONCLUSION We conclude that supplementation of EPA-EE does not significantly inhibit lipolysis or lipid oxidation in weight-losing cancer patients or in healthy subjects during short-term supplementation when using OA-EE as a placebo supplement Epidemiologic studies have indicated that high intake of saturated fat and /or animal fat increases the risk of colon and breast cancer . Omega-3 PUFAs in fish oil ( FO ) can inhibit the growth of human cancer cells in vitro and in vivo . These effects are related to the uptake of eicosapentaenoic acid ( EPA ) and docosahexaenoic acid ( DHA ) into the cellular substrate pool and their competitive metabolism with arachidonic acid ( AA ) at the cyclooxygenase and 5-lipoxygenase levels . The metabolites of EPA and DHA have less inflammatory and immunosuppressant potency than the substances derived from AA . Based on previous experimental data , we hypothesized that FO supplementation after major abdominal cancer surgery would improve hepatic and pancreatic function . Ours was a prospect i ve , r and omized , double-blinded clinical trial on 44 patients undergoing elective major abdominal surgery , r and omly assigned to receive total parenteral nutrition ( TPN ) supplemented with either soybean oil ( SO 1.0 g/kg body weight daily , n = 20 ) for 5 days or a combination of FO and SO ( FO 0.2 + SO 0.8 g/kg body weight daily , n = 24 ) . Compared to pure SO supplementation in the postoperative period , FO significantly reduced ASAT [ 0.8 + /- 0.1 vs. 0.5 + /- 0.1 mmol/(l . sec ) ] , ALAT [ 0.9 + /- 0.1 vs. 0.6 + /- 0.1 mmol/(l . sec ) ] , bilirubin ( 16.1 + /- 5.3 vs. 6.9 + /- 0.6 mmol/l ) , LDH ( 7.7 + /- 0.4 vs. 6.7 + /- 0.4 mmol/(l . sec ) and lipase ( 0.6 + /- 0.1 vs. 0.4 + /- 0.1 micromol/(l . sec ) in the postoperative course . Moreover , patients with increased risk of sepsis ( IL-6/IL-10 ratio > 8) showed a tendency to shorter ICU stay ( 18 hr ) under omega-3 PUFA treatment . Weight loss as encountered after the SO emulsion of 1.1 + /- 2.2 kg was absent in the FO group . After major abdominal tumor surgery , FO supplementation improved liver and pancreas function , which might have contributed to the faster recovery of patients OBJECTIVE The effect of fish oil ( FO ) , melatonin ( MLT ) , or their combination and dietary advice on cachexia and biochemistry variables reflecting cachexia were investigated in patients with advanced gastrointestinal cancer . METHODS Twenty-four patients not amenable to st and ard anticancer treatment and with documented weight loss and /or decreased serum albumin were included . They were r and omized to 30 mL/d of FO , which provided 4.9 g of eicosapentaenoic acid and 3.2 g of docosahexanoic acid , or 18 mg/d of MLT for 4 wk . During the next 4 wk , all patients had FO and MLT .  Serum or plasma was analyzed for tumor necrosis factor-alpha , interleukin-1beta , soluble interleukin-2 receptor , interleukin-6 , and interleukin-8 and the fatty acids eicosapentaenoic acid , docosahexanoic acid , arachidonic acid , and linoleic acid . RESULTS Serum levels of eicosapentaenoic acid and docosahexanoic acid increased as expected with FO . No major changes in biochemical variables and cytokines were observed with any intervention . In the FO group , 5 of 13 patients ( 38 % ) showed weight stabilization or gain compared with 3 of 11 patients ( 27 % ) in the MLT group . After combining interventions , approximately 63 % of patients showed such responses . CONCLUSIONS FO , MLT , or their combination did not induce major biochemical changes indicative of a strong anticachectic effect . Nonetheless , the interventions used may have produced a weight-stabilizing effect BACKGROUND The use of immune-enhancing enteral diets in the postoperative period has given contrasting results . The purpose of this prospect i ve , r and omized , double-blinded clinical study was to evaluate the effect of immunonutrition given perioperatively on cytokine release and nutritional parameters . METHODS Patients with cancer of the stomach or colo-rectum were eligible . Subjects consumed 1 L/d of either a control enteral formula ( n = 25 ; control group ) or a formula supplemented with arginine , omega-3 fatty acids , and RNA ( n = 25 ; verum group ) for 1 week before surgery . Both formulas were given by mouth . Six hours after the operation , jejunal infusion with the same diets was started and maintained for 7 days . Blood was drawn at different time points to assess albumin , prealbumin ( PA ) , transferrin , cholinesterase activity , retinol binding protein ( RBP ) , interleukin-2 receptors alpha ( IL-2Ralpha ) , IL-6 , and IL-1 soluble receptors ( IL-1RII ) . The composite score of delayed hypersensitivity response ( DHR ) to skin test also was determined ( the higher the score , the lower the immune response ) . RESULTS During the 7 days of presurgical feeding , none of the above parameters changed in either group . Eight days after operation , in the control group , the concentration of PA and RBP was lower than in the verum group ( 0.18 vs 0.26 g/L for PA and 30.5 vs 38.7 mg/L for RBP ; p < .05 ) . IL-2Ralpha concentration was 507 pg/mL in the verum group vs 238 pg/mL in the control group ( p < .001 ) , whereas IL-6 and IL-1RII were higher in the control group than in the verum group ( 104 vs 49 and 328 vs 183 pg/mL , respectively ; p < .01 ) . The DHR score was 0.68 in the control group vs 0.42 in the verum group ( p < .05 ) . CONCLUSIONS Perioperative feeding with a supplemented enteral diet modulates cytokine production and enhances cell-mediated immunity and the synthesis of short half-life proteins PURPOSE This study examined the effect of frequent nutritional counseling on oral intake , body weight , response rate , survival , and quality of life in patients with cancer of the lung ( small-cell ) , ovary , or breast undergoing cyclic chemotherapy . PATIENTS AND METHODS Of 105 assessable patients , 57 were r and omized to receive nutritional counseling , and 48 to receive no nutritional counseling and consumption of an ad lib oral intake .  The intervention group was counseled to achieve a daily energy and protein intake according to recommended dietary allowances . Counseling was st and ardized and performed by a trained dietitian , and took place twice monthly during a 5-month period from start of chemotherapy . RESULTS Dietary counseling increased daily energy intake by approximately 1 MJ and protein intake by 10 g over the entire study period . There was no change in the control group . Counseling led to an insignificant increase in body weight , but triceps skinfold measurement increased significantly after 5 months . Response rate and overall survival did not differ between the groups . Quality of life measured by the Quality -of-Life index ( QL-index ) increased significantly in both groups , but did not differ between groups . CONCLUSION No clinical benefit could be demonstrated despite long-term and continuous improved food intake in cancer patients with solid tumors undergoing aggressive chemotherapy Objective The objective of this study was to evaluate long-term enteral nutrition support in postoperative cancer patients . Background Multimodality therapy of surgical patients with upper gastrointestinal malignancies may improve survival , but often results in substantial malnutrition , immunosuppression , and morbidity . The benefits of combined inpatient and outpatient enteral feeding with st and ard diets or diets supplemented with arginine , RNA + ω-3 fatty acids are unclear . Methods Sixty adult patients with esophageal ( 22 ) , gastric ( 16 ) , and pancreatic ( 22 ) lesions were stratified by disease site and percent usual weight and r and omized to receive supplemental or st and ard diet via jejunostomy beginning on the first postoperative day ( goal = 25 kcal/kg/day ) until hospital discharge . Patients also were r and omized to receive ( n = 37 ) or not receive ( n = 23 ) enteral jejunostomy feedings ( 1000 kcal/day overnight ) for the 12− to 16-week recovery and radiation/chemotherapy periods . Plasma and peripheral white blood cells were obtained for fatty acid levels and PGE2 production measurements . Results Mean plasma and cellular ω3/ω6 fatty acid levels ( percent composition ) increased significantly ( p < 0.05 ) in the arginine + ω-3 fatty acid group by postoperative day 7 ( 0.30 vs. 0.13 ) and ( 0.29 vs. 0.14 ) and continued to increase over time . Mean PGE2 production decreased significantly ( p < 0.05 ) from 2760 to 1600 ng/106 cells/mL at day 7 in the arginine + ω-3 fatty acid group , whereas no significant change over time was noted in the st and ard group . Infectious/wound complications occurred in 10 % of the supplemented group compared with 43 % of the st and ard group ( p < 0.05 ) ; mean length of hospital stay was 16 vs. 22 ( p < 0.05 ) days , respectively . Of the patients who received postoperative chemoradation therapy , only 1 ( 6 % ) of the 18 patients r and omized to receive tube feeding did not continue , whereas 8 ( 61 % ) of the 13 patients not r and omized to tube feedings required crossover to jejunostomy nutritional support . Conclusions Supplemental enteral feeding significantly increased plasma and peripheral white blood cell ω3/ω6 ratios and significantly decreased PGE2 production and postoperative AIM To investigate the effect of early postoperative enteral nutrition enriched with arginine , RNA and omega-3 fatty acids on immunological and nutritional variables  after elective curative operations for gastric or pancreatic cancer . DESIGN R and omised controlled trial . SETTING University hospital , Italy . SUBJECTS 78 Consecutive patients who were to undergo curative operations for gastric or pancreatic cancer , 60 of whom were suitable for the study . INTERVENTIONS Patients were r and omly allocated to three groups ( n = 20 each ) according to the type of postoperative nutritional support : st and ard enteral diet , the same diet enriched with arginine , RNA , and omega-3 fatty acids or total parenteral nutrition . The daily nutritional goal was 25 kcal ( 105 kJ)/kg and 0.25 g nitrogen/kg for all patients . MAIN OUTCOME MEASURES Serum concentrations of immunoglobulins , albumin , transferrin , prealbumin , retinol binding protein ( RBP ) ; cholinesterase activity , weight loss , duration of operation , operative blood loss ; blood transfusion ; delayed hypersensitivity responses , number of lymphocyte subsets , phagocytic ability of monocytes , number of interleukin-2 ( IL-2 ) plasma receptors , interleukin-6 ( IL-6 ) plasma concentrations , postoperative infections and sepsis scores . RESULTS All enterally fed patients but one completed the nutritional programme . There were significant postoperative reductions in both nutritional and immunological variables in all groups . On postoperative days 4 and 8 prealbumin concentration ( p < 0.05 ) , RBP concentration ( p < 0.05 ) , delayed hypersensitivity responses ( p < 0.05 ) , phagocytic ability of monocytes ( p < 0.01 ) and concentration of IL-2 receptors ( p < 0.009 ) had all recovered more in the group receiving the enriched solution . There was no difference in the postoperative infection rates among the three groups , but the infections were less severe in the enriched group ( p < 0.005 ) . CONCLUSION Early enteral feeding was well tolerated . Patients who received the enriched solution recovered both their nutritional and immunological status quicker than those in the other two groups OBJECTIVE To evaluate the effect of the early postoperative administration of an enriched enteral diet in cancer patients . DESIGN R and omised controlled study . SETTING Surgical intensive care unit of a university hospital . PATIENTS 77 consecutive patients undergoing curative surgery for gastric or pancreatic cancer . INTERVENTIONS Patients were r and omised into 3 groups to receive : a st and ard enteral formula ( n=24 ) ; the same formula enriched with arginine , RNA , and omega-3 fatty acids ( n = 26 ) , isonitrogen isocaloric total parenteral nutrition ( n = 27 ) . Enteral nutrition was started within 12 h following surgery . Infusion rate was progressively increased reaching the full regimen on postoperative day ( POD ) 4 . On admission and on POD 1 and 8 , the following measurements were performed : serum level of total iron-binding capacity , albumin , prealbumin , retinol-binding protein ( RBP ) , and cholinesterase . Delayed hypersensitivity response ( DHR ) , IgG , IgM , IgA , lymphocyte subsets . and monocyte phagocytosis ability were also evaluated . Bioelectrical impedance analysis was performed preoperatively and on POD 2 , 7 , and 11 . The rate and severity of postoperative infections and the length of hospital stay were evaluated . RESULTS In all patients , a significant drop of nutritional and immunologic parameters was observed on POD 1 . A significant increase of prealbumin ( p<0.02 ) , RBP ( p<0.005 ) , monocyte phagocytosis ability ( p<0.001 ) , and DHR ( p<0.005 ) was found on POD 8 only in the group fed with the enriched diet . A significant reduction of severity of postoperative infections and length of postoperative stay was found in the group with the enriched diet compared to the other groups . CONCLUSIONS These data are suggestive of an improvement of the nutritional and immunologic status and clinical outcome in cancer patients who receive an enriched enteral diet in the early postoperative course The authors undertook a multiinstitutional Phase II cooperative group study to examine the potential of oral fish oil fatty acid supplements administered at high doses to slow weight loss and to improve quality of life in patients with malignancy‐related cachexia Following severe trauma or major surgery patients develop functional alterations of host defense mechanisms which contribute an enhanced susceptibility towards microbial infections . Several studies have demonstrated that a specialized nutritional regimen may improve immune functions . We analyzed leukocyte functions from 40 patients undergoing major upper gastrointestinal surgery in a r and omized placebo-controlled double-blind study . Patients were divided into two groups , one received 5 days pre-operatively an orally given experimental supplement enriched with omega-3-fatty acids , arginine , and ribonucleic acid ( RNA ) , the other an isocaloric , control supplement . The experimental group generated significantly more leukotriene B(5 ) ( LTB(5 ) ) as compared to the control group . In contrast , the capacity to generate leukotriene B(4 ) ( LTB(4 ) ) as well as the synthesis of interleukin-8 ( IL-8 ) was not significantly different in both groups . Additionally , lymphocyte/monocyte proliferation was analyzed and donor specific heterogeneities were observed ; but no significant differences were found between the two nutritional regimens
BACKGROUND Cancer cachexia is a distressing weight loss syndrome commonly seen in advanced cancer patients .
It is associated with reduced quality of life and shorter survival time .
Eicosapentaenoic acid ( EPA ) is a long chain polyunsaturated fatty acid found naturally in some fish which has been used to decrease weight loss , promote weight gain and increase survival times in patients affected with cancer cachexia .
OBJECTIVES To evaluate the effectiveness and safety of EPA in relieving symptoms associated with the cachexia syndrome in patients with advanced cancer .