Marine phospholipids—a promising new dietary approach to tumor-associated weight loss Tolerance and incorporation of a high-dose eicosapentaenoic acid diester emulsion by patients with pancreatic cancer cachexia 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 Investigating the utility of serum cytokine measurements in a multi-institutional cancer anorexia/weight loss trial Reduced total energy expenditure and physical activity in cachectic patients with pancreatic cancer can be modulated by an energy and protein dense oral supplement enriched with n-3 fatty acids Randomized phase III clinical trial of five different arms of treatment for patients with cancer cachexia: interim results. The Clinical Value of Parenteral Immunonutrition in Surgical Patients 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 Nutrition intervention using an eicosapentaenoic acid (EPA)-containing supplement in patients with advanced colorectal cancer. Effects on nutritional and inflammatory status: a phase II trial Compliance with nutrition prescription improves outcomes in patients with unresectable 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. Favorable Effects of Preoperative Enteral Immunonutrition on a Surgical Site Infection in Patients with Colorectal Cancer Without Malnutrition Double-blind, placebo-controlled, randomized study of eicosapentaenoic acid diester in patients with cancer cachexia. Effect of early postoperative enteral immunonutrition on wound healing in patients undergoing surgery for gastric 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. 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. Eicosapentaenoic acid ethyl ester supplementation in cachectic cancer patients and healthy subjects: effects on lipolysis and lipid oxidation. Impact of fish oil and melatonin on cachexia in patients with advanced gastrointestinal cancer: a randomized pilot study. Enteral Nutrition Enriched With Eicosapentaenoic Acid (EPA) Preserves Lean Body Mass Following Esophageal Cancer Surgery: Results of a Double-Blinded Randomized Controlled Trial Early enteral feeding in postsurgical cancer patients. Fish oil structured lipid-based polymeric formula versus a standard polymeric formula. Immunoenhanced enteral nutrition formulas in head and neck cancer surgery: a prospective, randomized clinical trial. Immune and nutritional effects of early enteral nutrition after major abdominal operations. A Phase II Study with Antioxidants, Both in the Diet and Supplemented, Pharmaconutritional Support, Progestagen, and Anti-Cyclooxygenase-2 Showing Efficacy and Safety in Patients with Cancer-Related Anorexia/Cachexia and Oxidative Stress Phase II study of high‐dose fish oil capsules for patients with cancer‐related cachexia
Goals of workAdvanced tumor disease very often evokes excessive loss of body weight . Among others , fish oil or marine fatty acid ethyl esters were investigated for treatment of cancer cachexia with controversial results . In this study , a new formulation of marine fatty acids was investigated , the marine phospholipids , with more than 50 % of phospholipid-bound fatty acids being eicosapentaenoic and docosahexaenoic acid . Material s and methods Thirty-one tumor patients with various tumor entities suffering from weight loss were asked to take marine phospholipids ( 1.5 g/day ) as softgel capsules for a period of 6 weeks . Compliance , body weight , appetite , and quality of life as well as the fatty acid profile in plasma and blood cells were monitored ; 17 patients could be analyzed . Main results Marine phospholipids were very well accepted ; low-dose supplementation result ed in a significant increase of eicosapentaenoic and docosahexaenoic acid in plasma phospholipids ; therefore , significantly reducing the n − 6 to n − 3 fatty acid ratio . A stabilization of body weight was achieved ( median weight change of + 0.6 % after 6 weeks ) , while appetite and quality of life improved . Conclusions These promising first results encourage further investigation of marine phospholipids in cancer care 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 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 Background Interleukin-1 beta ( IL-1β ) , tumor necrosis factor alpha ( TNFα ) , and interleukin-6 ( IL-6 ) have been implicated in the cancer anorexia/weight loss syndrome . However , previous smaller studies have yielded conflicting results as to whether circulating , serum concentrations of these cytokines are in fact elevated . As the translational component of a large multi-institutional trial , this study assessed the clinical value of serum concentrations of these cytokines in patients with this syndrome . Methods Patients with incurable cancer with anorexia and /or weight loss were eligible . All underwent weekly weight measurements and appetite assessment for the first month and then monthly assessment s thereafter . Serum was obtained at baseline and at 1 month , and all three cytokines were measured with the Immunolite assay . Results A total of 118 patients participated . At baseline , 99 % , 54 % , and 47 % of patients ’ sample s had undetectable IL-1β , TNFα , and IL-6 , respectively . Similar results were obtained at 1 month . No correlations were observed between serum cytokine concentrations and changes in weight or appetite . Baseline serum IL-6 predicted a diminished survival but only after adjustment for age and cancer site . ConclusionS erum concentrations of IL-1β , TNFα , and IL-6 , as measured in this study , provide data of limited clinical value for patients with the cancer anorexia/weight loss syndrome The aim of the study was to assess the total energy expenditure ( TEE ) , resting energy expenditure ( REE ) and physical activity level ( PAL ) in home-living cachectic patients with advanced pancreatic cancer . The influence of an energy and protein dense oral supplement either enriched with or without the n-3 fatty acid eicosapentaenoic acid ( EPA ) and administered over an 8-week period was also determined . In total , 24 patients were studied at baseline . The total energy expenditure was measured using doubly labelled water and REE determined by indirect calorimetry . Patients were studied at baseline and then r and omised to either oral nutritional supplement . Measurements were repeated at 8 weeks . At baseline , REE was increased compared with predicted values for healthy individuals ( 1387(42 ) vs 1268(32 ) kcal day−1 , P=0.001 ) , but TEE ( 1732(82 ) vs 1903(48 ) kcal day−1 , P=0.023 ) and PAL ( 1.24(0.04 ) vs 1.50 ) were reduced . After 8 weeks , the REE , TEE and PAL of patients who received the control supplement did not change significantly . In contrast , although REE did not change , TEE and PAL increased significantly in those who received the n-3 ( EPA ) enriched supplement . In summary , patients with advanced pancreatic cancer  were hypermetabolic . However , TEE was reduced and this was secondary to a reduction in physical activity . The control energy and protein dense oral supplement did not influence the physical activity component of TEE . In contrast , administration of the supplement enriched with EPA was associated with an increase in physical activity , which may reflect improved quality of life OBJECTIVE In April 2005 a phase III r and omized study was started to establish which was the most effective and safest treatment of cancer-related anorexia/cachexia syndrome and oxidative stress in improving identified primary endpoints : increase of lean body mass , decrease of resting energy expenditure ( REE ) , increase of total daily physical activity , decrease of interleukin-6 and tumor necrosis factor-alpha , and improvement of fatigue assessed by the Multidimensional Fatigue Symptom Inventory-Short Form ( MFSI-SF ) . METHODS All patients were given as basic treatment polyphenols plus antioxidant agents alpha-lipoic acid , carbocysteine , and vitamins A , C , and E , all orally . Patients were then r and omized to one of the following five arms : 1 ) medroxyprogesterone acetate/megestrol acetate ; 2 ) pharmacologic nutritional support containing eicosapentaenoic acid ; 3 ) L-carnitine ; 4 ) thalidomide ; or 5 ) medroxyprogesterone acetate/megestrol acetate plus pharmacologic nutritional support plus L-carnitine plus thalidomide . Treatment duration was 4 mo . The sample comprised 475 patients . RESULTS By January 2007 , 125 patients , well balanced for all clinical characteristics , were included . No severe side effects were observed . As for efficacy , an interim analysis on 125 patients showed an improvement of at least one primary endpoint in arms 3 , 4 , and 5 , whereas arm 2 showed a significant worsening of lean body mass , REE , and MFSI-SF . Analysis of variance comparing the change of primary endpoints between arms showed a significant improvement of REE in favor of arm 5 versus arm 2 and a significant improvement of MFSI-SF in favor of arms 1 , 3 , and 5 versus arm 2 . A significant inferiority of arm 2 versus arms 3 , 4 , and 5 for the primary endpoints lean body mass , REE , and MFSI-SF was observed on the basis of t test for changes . CONCLUSION The interim results obtained thus far seem to suggest that the most effective treatment for cancer-related anorexia/cachexia syndrome and oxidative stress should be a combination regimen . The study is still in progress and the final results should confirm these data Abstract Background & Aim : to analyze the clinical impact and cost-effectiveness of parenteral immunonutrition ( PN ) . Methods : prospect i ve clinical trial of a group of 105 patients operated on for gastric carcinoma between 2001 - 2003 . During the postoperative period , patients were r and omly allocated to one of three groups : st and ard PN ( A ) , PN + glu-tamine ( B ) and PN + omega-3-FA ( C ) . The rate and type of complications , hepatic and renal function , cost and treatment tolerance in all groups were analyzed . Results : postoperative complications were observed in 11 patients ( 36,6 % ) in group A , in 7 ( 23,3 % ) in B and in 8 ( 26,6 % ) in C. The most common complication was pneumonia . Prealbumin concentration and TLC increased faster in groups B and C. The length of hospital stay was significantly shorter in the immunonutrition groups . The cost of PN was highest in C group , while cost of hospital stay was longer in A. Conclusions : immunostimulating parenteral nutrition helps to reduce the number of infectious complications , improves the function of the immune system , and has no influence on surgical complications , hepatic and renal function and protein synthesis . The cost of immunostimulating treatment based on omega-3-unsaturated fatty acids is higher than st and ard 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 Goals The aim of the study was to assess the impact of an eicosapentanoic acid-containing protein and energy dense oral nutritional supplement ( EPA-ONS ) on nutritional and inflammatory status , quality of life ( QOL ) , plasma phospholipids ( PPL ) and cytokine profile , tolerance of irinotecan-containing chemotherapy and EPA-ONS in patients with advanced colorectal cancer ( CRC ) receiving chemotherapy . Material s and methods Patients with advanced CRC having one prior chemotherapy regimen received 480 ml of EPA-ONS daily for 3 weeks before commencing chemotherapy with folinic acid , 5-fluorouracil , irinotecan ( FOLFIRI ) , and continued for 3 cycles of treatment ( 9 weeks ) . All assessment s including weight , body composition , C-reactive protein ( CRP ) , QOL , dietary intake , PPL and cytokine analyses were performed at baseline , 3 and 9 weeks . Results Twenty-three patients were enrolled , 20 completed 3 weeks , and 15 completed 9 weeks . The mean EPA-ONS intake was 1.7 tetrapaks ( 408 ml ) daily . There was a significant increase in mean weight ( 2.5 kg ) at 3 weeks ( p = 0.03 ) . Lean body mass ( LBM ) was maintained . Protein and energy intake significantly decreased after the commencement of chemotherapy ( protein p = 0.003 , energy p = 0.02 ) . There was a significant increase in energy levels ( p = 0.03 ) , whilst all other QOL measures were maintained . PPL EPA levels increased significantly over the first 3 weeks . Mean CRP increased by 14.9 mg/L over the first 3 weeks ( p = 0.004 ) , but decreased to baseline levels by the end of the trial . There was a significant correlation between plasma IL-6 and IL-10 concentrations and survival , and between IL-12 and toxicity . Conclusion Dietary counseling and the provision of EPA-ONS may result in maintenance of nutritional status and QOL , however r and omized trials are required to evaluate the impact of EPA on toxicity from chemotherapy BACKGROUND & AIMS There are few well- design ed studies evaluating the effect of oral nutrition supplements in patients with cancer cachexia . The aim of this study , in a posthoc analysis , was to examine the effect of dietary compliance on intake and body composition in patients with unresectable pancreatic cancer . METHODS Two hundred patients were r and omised to receive 2 cans/day of a protein and energy dense , oral nutrition supplement+/-n-3 fatty acids in an international , multi-centre r and omised trial over 8 weeks . Dietary compliance was defined a priori as consumption of a minimum of 1.5 cans/day of either supplement . Body composition , dietary intake and quality of life were measured at baseline , 4 and 8 weeks . RESULTS On average , there were significant differences in energy intake ( 501 kcal ) , protein intake ( 25.4 g ) and weight ( 1.7 kg ) between patients who were compliant with the nutrition prescription compared to noncompliant patients controlling for n-3 fatty acid r and omisation , baseline weight and quality of life . Over the 8-week period , there was significant improvement in weight only . There was no significant difference in the energy intake from meals of the total group over the 8 weeks . CONCLUSIONS Compliance with the prescription of 1.5 cans of a protein and energy dense , oral nutrition supplement + /-n-3 fatty acids improved nutrition related outcomes in untreated pancreatic cancer patients . This level of supplement intake does not inhibit meal intake 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 ) Purpose A prospect i ve study was conducted to ascertain the effects of preoperative enteral immunonutrition on a surgical site infection ( SSI ) in patients with colorectal cancer without malnutrition . Methods Patients with colorectal cancer undergoing elective surgery without malnutrition , bowel obstruction , severe cardiopulmonary complications , diabetes , collagen disease , or renal failure were sequentially divided into an immunonutrition group ( n = 33 ) and a control group  ( n = 34 ) . In the immunonutrition group , an enteral diet supplemented with arginine , dietary nucleotides , and ω-3 fatty acids was administered for 5 days ( 750 ml/day ) prior to surgery . Results The mean age was slightly higher in the immunonutrition group ( 69 ± 9 years ) than in the control group ( 63 ± 11 years ; P < 0.05 ) , but no significant differences between the groups were noted for the body mass index , total protein , albumin , hemoglobin , surgical methods , operation time , or volume of intraoperative bleeding . The frequencies of superficial incisional SSI , deep incisional SSI and organ/space SSI in the immunonutrition and control groups were 0 % and 11.8 % ( 4/34 ; P < 0.05 ) , 0 % and 0 % , and 0 % and 2.9 % ( 1/34 ) , respectively . Conclusion Preoperative enteral immunonutrition appears to be effective for preventing SSI in patients with colorectal cancer without malnutrition PURPOSE Eicosapentaenoic acid ( EPA ) has been proposed to have specific anticachectic effects . This trial compared EPA diethyl ester with placebo in cachectic cancer patients for effects on weight and lean body mass . PATIENTS AND METHODS Five hundred eighteen weight-losing patients with advanced gastrointestinal or lung cancer were studied in a multicenter , double-blind , placebo controlled trial . Patients were r and omly assigned to receive a novel preparation of pure EPA at a dose of 2 g or 4 g daily or placebo ( 2 g EPA , n = 175 ; 4 g EPA , n = 172 ; placebo , n = 171 ) . Patients were assessed at 4 weeks and 8 weeks . RESULTS The groups were well balanced at baseline . Mean weight loss at baseline was 18 % ( n = 518 ) . Over the 8-week treatment period , both intention-to-treat analysis and per protocol analysis revealed no statistically significant improvements in survival , weight , or other nutritional variables . There was , however , a trend in favor of EPA with analysis of the primary end point , weight , at 8 weeks showing a borderline , nonsignificant treatment effect ( P = .066 ) . Relative to placebo , mean weight increased by 1.2 kg with 2 g EPA ( 95 % CI , 0 kg to 2.3 kg ) and by 0.3 kg with 4 g EPA ( -0.9 kg to 1.5 kg ) . CONCLUSION The results indicate no statistically significant benefit from single agent EPA in the treatment of cancer cachexia . Future studies should concentrate on other agents or combination regimens BACKGROUND & AIMS One of the most frequent complications in patients with cancer and malnutrition is the surgical wound healing delay or failure . Some studies have shown that arginine improves wound healing in rodents and in healthy human beings . The main objective of this study was to assess the effect of early postoperative enteral immunonutrition on the wound healing process in patients undergoing surgery for gastric cancer . METHODS Sixty six patients with gastric cancer were r and omized to receive early postoperative enteral immunonutrition ( formula supplemented with arginine , omega-3 fatty acids and ribonucleic acid ( RNA ) ) or an isocaloric-isonitrogenous control . Assessment of wound healing process : ( 1 ) Quantification of hydroxyproline deposition in a subcutaneously placed catheter , ( 2 ) occurrence of surgical wound healing complications . RESULTS Sixty patients were analyzed . Patients fed with immunonutrition ( n=30 ) showed higher local hydroxyproline levels ( 59.7 nmol ( 5.0 - 201.8 ) , vs. 28.0 nmol ( 5.8 - 89.6 ) P=0.0018 ) and significantly lower episodes of surgical wound healing complications ( 0 vs. 8 ( 26.7 % ) P=0.005 ) when compared to patients fed with the control formula ( n=30 ) . CONCLUSIONS Early postoperative enteral nutrition with a formula supplemented with arginine , omega 3 fatty acids and RNA increased hydroxyproline synthesis and improved surgical wound healing in patients undergoing gastrectomy for gastric cancer 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 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 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 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 : Esophagectomy represents an exemplar of controlled major trauma , with marked metabolic , immunologic , and physiologic changes as well as an associated high incidence of complications . Eicosapentaenoic acid ( EPA ) enriched enteral nutrition ( EN ) modulates immune function and limits catabolism in patients with advanced cancer , but its impact in the peri-operative period is unclear . Objectives : To examine the effects of perioperative EPA enriched EN on the metabolic , nutritional , and immuno-inflammatory response to esophagectomy , and on postoperative complications . Methods : In a double-blind design , patients were r and omized to a st and ard EN formula or a formula enriched with 2.2 g EPA/d for 5 days preoperatively ( orally ) and 21 days postoperatively ( jejunostomy ) . Segmental bioelectrical impedance analysis was performed preoperatively and on POD 21 . Postoperative complications were monitored , as well as the acute phase response , coagulation markers , and serum cytokines . Results : Fifty-three patients ( 28 EPA , 25 st and ard ) completed the study , and both groups were well matched . Serum and peripheral blood mononuclear cell ( P BMC ) membrane EPA levels were significantly increased in the EPA group . There was no difference in the incidence of major complications . The EPA group maintained all aspects of body composition postoperatively , whereas patients in the st and ard EN group lost significant amounts of fat-free mass ( 1.9 kg , P = 0.030 ) compared with the EPA group [ leg ( 0.3 kg , P = 0.05 ) , arm ( 0.17 kg , P = 0.01 ) , and trunk ( 1.44 kg , P = 0.03 ) ] . The EPA group had a significantly ( P < 0.05 ) attenuated stress response for TNFα , IL-10 , and IL-8 compared with the st and ard group . Conclusions : EPA supplemented early EN is associated with preservation of lean body mass post esophagectomy compared with a st and ard EN . These properties may merit longer-term study to address its impact on recovery of function and quality of life in models of complex surgery or multimodal cancer treatment regimens OBJECTIVES The authors compared the safety , gastrointestinal tolerance , and clinical efficacy of feeding an enteral diet containing a fish oil/medium-chain triglyceride structured lipid ( FOSL-HN ) versus an isonitrogenous , isocaloric formula ( O-HN ) in patients undergoing major abdominal surgery for upper gastrointestinal malignancies . SUMMARY BACKGROUND DATA Previous studies suggest that feeding with n-3 fatty acids from fish oil can alter eicosanoid and cytokine production , yielding an improved immunocompetence and a reduced inflammatory response to injury . The use of n-3 fatty acids as a structured lipid can improve long-chain fatty acid absorption . METHODS This prospect i ve , blinded , r and omized trial was conducted in 50 adult patients who were jejunally fed either FOSL-HN or O-HN for 7 days .  Serum chemistries , hematology , urinalysis , gastrointestinal complications , liver and renal function , plasma and erythrocyte fatty acid analysis , urinary prostagl and ins , and outcome parameters were measured at baseline and on day 7 . Comparisons were made in 18 and 17 evaluable patients based a priori on the ability to reach a tube feeding rate of 40 mL/hour . RESULTS Patients receiving FOSL-HN experienced no untoward side effects , significant incorporation of eicosapentaenoic acid into plasma and erythrocyte phospholipids , and a 50 % decline in the total number of gastrointestinal complications and infections compared with patients given O-HN . The data strongly suggest improved liver and renal function during the postoperative period in the FOSL-HN group . CONCLUSION Early enteral feeding with FOSL-HN was safe and well tolerated . Results suggest that the use of such a formula during the postoperative period may reduce the number of infections and gastrointestinal complications per patient , as well as improve renal and liver function through modulation of urinary prostagl and in levels . Additional clinical trials to fully quantify clinical benefits and optimize nutritional support with FOSL-HN should be undertaken INTRODUCTION Significant malnutrition exists in a high percentage of patients with head and neck cancer . Malnutrition is associated with defects in immune function that may impair the host response to malignancy . Malnutrition and immunosupression make patients highly susceptible to postoperative infections and complications . OBJECTIVES Compare two immunoenhanced enteral nutritions with a control diet , and evaluate the effect in postoperative infections , length of stay and inflammatory markers . PATIENTS A population of 44 patients with oral and laryngeal cancer was enrolled in a r and omized trial . At surgery , patients were r and omly allocated to three groups : ( group I ) ; patients receiving an arginine-enhanced formula ( group II ) ; patients receiving a st and ard polymeric formula , and ( group III ) patients receiving an arginine , RNA and omega-3 fatty acids enhanced formula , in an isonitrogenous way . RESULTS The duration of enteral nutrition in the three groups was similar with an average duration of 14,5 + /- 8 days . The length of postoperative stay was similar , with an average of 19,8 + /- 8,5 days . Wound infections and general infections were more frequent in the control group . Fistula rates were not improved in the enhanced diet groups . No significant intergroup differences in the trend of the two plasma proteins ( albumin , transferrin ) , lymphocytes , weight , IL-6 , CPR and TNFalpha were detected . The control group showed the highest levels of TNFalpha at the fourteenth postoperative day . Gastrointestinal tolerance and diarrhoea rate were similar in all the patients . CONCLUSIONS Immunoenhanced enteral nutrition formulas improved the infection rate in the postoperative of head and neck cancer patients . In the fistula rates , we observed that technical problems and nutritional status might have played an equally important role , and therefore the positive effect of immunonutrition in this parameter might have been overestimated 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 Purpose : To test the efficacy and safety of an integrated treatment based on a pharmaconutritional support , antioxidants , and drugs , all given orally , in a population of advanced cancer patients with cancer-related anorexia/cachexia and oxidative stress . Patients and Methods : An open early-phase II study was design ed according to the Simon two-stage design . The integrated treatment consisted of diet with high polyphenols content ( 400 mg ) , antioxidant treatment ( 300 mg/d α-lipoic acid + 2.7 g/d carbocysteine lysine salt + 400 mg/d vitamin E + 30,000 IU/d vitamin A + 500 mg/d vitamin C ) , and pharmaconutritional support enriched with 2 cans per day (n-3)-PUFA ( eicosapentaenoic acid and docosahexaenoic acid ) , 500 mg/d medroxyprogesterone acetate , and 200 mg/d selective cyclooxygenase-2 inhibitor celecoxib . The treatment duration was 4 months . The following variables were evaluated : ( a ) clinical ( Eastern Cooperative Oncology Group performance status ) ; ( b ) nutritional [ lean body mass ( LBM ) , appetite , and resting energy expenditure ] ; ( c ) laboratory [ proinflammatory cytokines and leptin , reactive oxygen species ( ROS ) and antioxidant enzymes ] ; ( d ) quality of life ( European Organization for Research and Treatment of Cancer QLQ-C30 , Euro QL-5D , and MFSI-SF ) . Results : From July 2002 to January 2005 , 44 patients were enrolled . Of these , 39 completed the treatment and were assessable . Body weight increased significantly from baseline as did LBM and appetite . There was an important decrease of proinflammatory cytokines interleukin-6 ( IL-6 ) and tumor necrosis factor-α , and a negative relationship worthy of note was only found between LBM and IL-6 changes . As for quality of life evaluation , there was a marked improvement in the European Organization for Research and Treatment of Cancer QLQ-C30 , Euro QL-5DVAS , and multidimensional fatigue symptom inventory-short form scores . At the end of the study , 22 of the 39 patients were “ responders ” or “ high responders . ” The minimum required was 21 ; therefore , the treatment was effective and more importantly was shown to be safe . Conclusion : The efficacy and safety of the treatment have been shown by the study ; therefore , a r and omized phase III study is warranted . ( Cancer Epidemiol Biomarkers Prev 2006;15(5):1030–4 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
Background : The European Palliative Care Research Collaboration is developing clinical guidelines on cachexia in patients with advanced cancer .
A systematic review on the use of fish oil/omega-3-fatty acids (n-3-FA)/eicosapentaenoic acids ( EPA ) in advanced cancer patients suffering from cancer cachexia was performed as part of the guideline development .