Non-Gl-Malignancy-Related Malabsorption Leads to Malnutrition and Weight Loss

  • Susumu Suzuki
  • Carolina G. Goncalves
  • Eduardo J. B. Ramos
  • Akihiro Asakawa
  • Akio Inui
  • Michael M. Meguid


Approximately 80% of patients with advanced-stage cancer have cancer anorexia-cachexia syndrome (CACS), in which one of the main manifestations is malnutrition [1]. CACS is characterised by anorexia, decreased food intake, tissue wasting, and body weight loss. It is also associated with changes in lipid, protein, and carbohydrate metabolism, leading to a decrease in fat and muscle mass, which independently influence mortality in cancer patients [2] [5]. Anorexia and reduced food intake occur during growth of the tumour, thus compromising host defences which, in turn, detrimentally influences outcome [1]. Reduced food intake and malabsorption reduce energy intake, even though energy expenditure is increased [6] [8].


Gastric Emptying Cancer Cachexia Reduce Food Intake Meal Size Dorsal Motor Nucleus 
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  1. 1.
    Laviano A, Meguid MM, Rossi Fanelli F (2003) Cancer anorexia: clinical implications, pathogenesis, and therapeutic strategies. Lancet Oncol 4:686–694PubMedCrossRefGoogle Scholar
  2. 2.
    Mantovani G, Macciò A, Massa E, Madeddu C (2001) Managing cancer-related anorexia/cachexia. Drugs 61:499–514PubMedCrossRefGoogle Scholar
  3. 3.
    Inui A (1999) Cancer anorexia-cachexia syndrome: are neuropeptides the key? Cancer Res 59:4493–4501PubMedGoogle Scholar
  4. 4.
    Warren S (1932) The immediate cause of death in cancer. Am J Med Sci 184:610–615CrossRefGoogle Scholar
  5. 5.
    Lanzotti VJ, Thomas DR, Boyle LE et al (1977) Survival with inoperable lung cancer: an integration of prognostic variables based on simple clinical criteria. Cancer 39:303–313PubMedCrossRefGoogle Scholar
  6. 6.
    Staal van den Brekel AJ, Schols AM, ten Velde GP et al (1994) Analysis of the energy balance in lung cancer patients. Cancer Res 54:6430–6433Google Scholar
  7. 7.
    Wigmore SJ, Plester CE, Ross JA, Fearon KC (1997) Contribution of anorexia and hypermetabolism to weight loss in anicteric patients with pancreatic cancer. Br J Surg 84:196–197PubMedCrossRefGoogle Scholar
  8. 8.
    Inui A (2002) Cancer anorexia-cachexia syndrome: current issues in research and management. CA Cancer J Clin 52:72–91PubMedGoogle Scholar
  9. 9.
    Prima V, Tennant M, Gorbatyuk OS et al (2004) Differential modulation of energy balance by leptin, ciliary neurotrophic factor, and leukemia inhibitory factor gene delivery: microarray deoxyribonucleic acid-chip analysis of gene expression. Endocrinology 145:2035–2045PubMedCrossRefGoogle Scholar
  10. 10.
    Inui A(1999) Feeding and body-weight regulation by hypothalamic neuropeptides mediation of the actions of leptin. Trends Neurosci 22:62–67Google Scholar
  11. 11.
    Bruera E (1997) ABC of palliative care. Anorexia, cachexia, and nutrition. BMJ 315:1219–1222PubMedGoogle Scholar
  12. 12.
    Veerabagu MP, Meguid MM, Oler A, Levine RA (1996) Intravenous nucleosides and a nucleotide promote healing of small bowel ulcers in experimental enterocolitis. Dig Dis Sci 41:1452–1457PubMedCrossRefGoogle Scholar
  13. 13.
    Dymock IW, MacKay N, Miller V et al (1967) Small intestinal function in neoplastic disease. Br J Cancer 21:505–511PubMedGoogle Scholar
  14. 14.
    Parrilli G, Iaffaioli RV, Martorano M et al (1989) Effects of anthracycline therapy on intestinal absorption in patients with advanced breast cancer. Cancer Res 49:3689–3691PubMedGoogle Scholar
  15. 15.
    Coimbra CR, Plourde V (1996) Abdominal surgeryinduced inhibition of gastric emptying is mediated in part by interleukin-1 beta. Am J Physiol 270:R556–R560PubMedGoogle Scholar
  16. 16.
    Hardin J, Kroeker K, Chung B, Gall DG (2000) Effect of proinflammatory interleukins on jejunal nutrient transport. Gut 47:184–191PubMedCrossRefGoogle Scholar
  17. 17.
    Wise BE, Schwartz MW, Cummings DE (2003) Melanocortin signaling and anorexia in chronic disease states. Ann N Y Acad Sci 994:275–281Google Scholar
  18. 18.
    Emch GS, Hermann GE, Rogers RC (2000) TNFalpha activates solitary nucleus neurons responsive to gastric distension. Am J Physiol Gastrointest Liver Physiol 279:G582–G586PubMedGoogle Scholar
  19. 19.
    Cohen MA, Ellis SM, Le Roux CW et al (2003) Oxyntomodulin suppresses appetite and reduces food intake in humans. J Clin Endocrinol Metab 88:4696–4701PubMedCrossRefGoogle Scholar
  20. 20.
    Asakawa A, Inui A, Yuzuriha H et al (2003) Characterization of the effects of pancreatic polypeptide in the regulation of energy balance. Gastroenterology 124:1325–1336PubMedCrossRefGoogle Scholar
  21. 21.
    Tseng WW, Liu CD (2002) Peptide YY and cancer: current findings and potential clinical applications. Peptides 23:389–395PubMedCrossRefGoogle Scholar
  22. 22.
    Niijima A, Meguid MM (1998) Influence of systemic arginine-lysine on immune organ function: an electrophysiological study. Brain Res Bull 45:437–441PubMedCrossRefGoogle Scholar
  23. 23.
    Hunt JN (1980) A possible relation between the regulation of gastric emptying and food intake. Am J Physiol 239:G1–G4PubMedGoogle Scholar
  24. 24.
    Nelson KA, Walsh D, Sheehan FA (1994) The cancer anorexia-cachexia syndrome. J Clin Oncol 12:213–225PubMedGoogle Scholar
  25. 25.
    Bruera E, Catz Z, Hooper R et al (1987) Chronic nausea and anorexia in advanced cancer patients: a possible role for autonomic dysfunction. J Pain Symptom Manage 2:19–21PubMedCrossRefGoogle Scholar
  26. 26.
    Bruera E, MacDonald N, Brenneis C et al (1986) Metoclopramide infusion with a disposable portable pump. Ann Intern Med 104:896PubMedGoogle Scholar
  27. 27.
    Shivshanker K, Bennett RWJr, Haynie TP (1983) Tumor-associated gastroparesis: correction with metoclopramide. Am J Surg 145:221–225PubMedCrossRefGoogle Scholar
  28. 28.
    Meguid M, Landel AM, Lo CC, Rivera D (1987) Effect of tumor and tumor removal on DNA, RNA, protein tissue content and survival of methylcholanthrene sarcoma-bearing rat. Surg Res Commun 1:261–271Google Scholar
  29. 29.
    Landel AM, Lo CC, Meguid MM, Rivera D (2005) Effect of methylcholanthrene-induced sarcoma and its removal on rat plasma and intracellular free amino acid content. Surg Res Commun 1:273–287Google Scholar
  30. 30.
    Suzuki S, Ramos EJ, Goncalves CG et al (2006) Effect of peripheral sarcoma on gastric emptying and small bowel absorption in tumor bearing rats. Clinical Nutrition (in press)Google Scholar
  31. 31.
    Wingate D (1976) The eupeptide system: A general theory of gastrointestinal hormones. Lancet 1:529–532PubMedCrossRefGoogle Scholar
  32. 32.
    Mroz CT, Kelly KA (1977) The role of the extrinsic antral nerves in the regulation of gastric emptying. Surg Gynecol Obstet 145:369–377PubMedGoogle Scholar
  33. 33.
    Fujimiya M, Inui A (2000) Peptidergic regulation of gastrointestinal motility in rodents. Peptides 21:1565–1582PubMedCrossRefGoogle Scholar
  34. 34.
    Daun JM, McCarthy DO (1993) The role of cholecystokinin in interleukin-1-induced anorexia. Physiol Behav 54:237–241PubMedCrossRefGoogle Scholar
  35. 35.
    Giner M, Laviano A, Meguid MM, Gleason JR (1996) In 1995 a correlation between malnutrition and poor outcome in critically ill patients still exists. Nutrition 12:23–29PubMedCrossRefGoogle Scholar
  36. 36.
    Creamer B (1964) Malignancy and the small-intestinal mucosa. Br Med J 5422:1435–1436Google Scholar
  37. 37.
    Somayaji BN, Nelson RS, McGregor RF (1972) Small intestinal function in malignant neoplasia. Cancer 29:1215–1222PubMedCrossRefGoogle Scholar
  38. 38.
    Klipstein FA, Smarth G (1969) Intestinal structure and function in neoplastic disease. Am J Dig Dis 14:887–899PubMedCrossRefGoogle Scholar
  39. 39.
    Rubin H (2003) Cancer cachexia: its correlations and causes. Proc Natl Acad Sci 100:5384–5389PubMedCrossRefGoogle Scholar
  40. 40.
    Inui A(2001) Cytokines and sickness behavior: implications from knockout animal models. Trends Immunol 22:469–473Google Scholar
  41. 41.
    Plata-Salaman CR (2000) Central nervous system mechanisms contributing to the cachexia-anorexia syndrome. Nutrition 16:1009–1012PubMedCrossRefGoogle Scholar
  42. 42.
    Meguid MM, Ramos EJ, Laviano A et al (2004) Tumor anorexia: effects on neuropeptide Y and monoamines in paraventricular nucleus. Peptides 25:261–266PubMedCrossRefGoogle Scholar
  43. 43.
    Plata-Salaman CR(1996) Anorexia during acute and chronic disease. Nutrition 12:69–78Google Scholar
  44. 44.
    Sonti G, Ilyin SE, Plata-Salaman CR (1996) Neuropeptide Y blocks and reverses interleukin-1 beta-induced anorexia in rats. Peptides 17:517–520PubMedCrossRefGoogle Scholar
  45. 45.
    Opara El, Laviano A, Meguid MM, Yang ZJ (1995) Correlation between food intake and CSF IL-1 alpha in anorectic tumor bearing rats. Neuroreport 6:750–752PubMedCrossRefGoogle Scholar
  46. 46.
    Torelli GF, Meguid MM, Moldawer LL et al (1999) Use of recombinant human soluble TNF receptor in anorectic tumor-bearing rats. Am J Physiol 277:R850–R855PubMedGoogle Scholar
  47. 47.
    Yang ZJ, Koseki M, Meguid MM et al (1994) Synergistic effect of rhTNF-a and rhIL-la in inducing anorexia in rats. Am J Physiol 267:R1056–R1064PubMedGoogle Scholar
  48. 48.
    Tisdale MJ (1997) Biology of cachexia. J Natl Cancer Inst 89:1763–1773PubMedCrossRefGoogle Scholar
  49. 49.
    Turrin NP, Ilyin SE, Gayle DA et al (2004) Interleukin-lbeta system in anorectic catabolic tumor-bearing rats. Curr Opin Clin Nutr Metab Care 7:419–426PubMedCrossRefGoogle Scholar
  50. 50.
    Yang ZJ, Blaha V, Meguid MM et al (1999) Interleukin-la injection into ventromedial hypothalamic nucleus of normal rats depresses food intake and increases release of dopamine and serotonin. Pharmacol Biochem Behav 62:61–65PubMedCrossRefGoogle Scholar
  51. 51.
    Debonis D, Meguid MM, Laviano A et al (1995) Temporal changes in meal number and meal size relationship in response to rHu IL-la. Neuroreport 6:1752–1756PubMedCrossRefGoogle Scholar
  52. 52.
    Muscaritoli M, Meguid MM, Beverly JL et al (1996) Mechanism of early tumor anorexia. J Surg Res 60:389–397PubMedCrossRefGoogle Scholar
  53. 53.
    Meguid MM, Sato T, Torelli GF et al (2000) An analysis of temporal changes in meal number and meal size at onset of anorexia in male tumor-bearing rats. Nutrition 16:305–306PubMedCrossRefGoogle Scholar
  54. 54.
    Laviano A, Gleason JR, Meguid MM et al (2000) Effects of intra-VMN mianserin and ILIra on meal number in anorectic tumor-bearing rats. J Investig Med 48:40–48PubMedGoogle Scholar
  55. 55.
    Strassmann G, Masui Y, Chizzonite R, Fong M (1993) Mechanisms of experimental cancer cachexia. Local involvement of IL-1 in colon-26 tumor. J Immunol 150:2341–2345PubMedGoogle Scholar
  56. 56.
    Laviano A, Renvyle T, Meguid MM et al (1995) Relationship between interleukin-1 and cancer anorexia. Nutrition 11:680–683PubMedGoogle Scholar
  57. 57.
    Turrin NP, Gayle D, Ilyin SE et al (2001) Pro-inflammatory and anti-inflammatory cytokine mRNA induction in the periphery and brain following intraperitoneal administration of bacterial lipopolysaccharide. Brain Res Bull 54:443–453PubMedCrossRefGoogle Scholar
  58. 58.
    Robert A, Olafsson AS, Lancaster C, Zhang WR (1991) Interleukin-1 is cytoprotective, antisecretory, stimulates PGE2 synthesis by the stomach, and retards gastric emptying. Life Sci 48:123–134PubMedCrossRefGoogle Scholar
  59. 59.
    McCarthy DO, Daun JM (1992) The role of prostaglandins in interleukin-1 induced gastroparesis. Physiol Behav 52:351–353PubMedCrossRefGoogle Scholar
  60. 60.
    Suto G, Kiraly A, Tache Y (1994)Interleukin 1 beta inhibits gastric emptying in rats: mediation through prostaglandin and corticotropin-releasing factor. Gastroenterology 106:1568–1575PubMedGoogle Scholar
  61. 61.
    Suto G, Kiraly A, Plourde V, Tache Y (1996) Intravenous interleukin-1-beta-induced inhibition of gastric emptying: involvement of central corticotropin-releasing factor and prostaglandin pathways in rats. Digestion 57:135–140PubMedCrossRefGoogle Scholar
  62. 62.
    Tache Y, Monnikes H, Bonaz B, Rivier J (1993) Role of CRF in stress-related alterations of gastric and colonic motor function. Ann N Y Acad Sci 697:233–243PubMedCrossRefGoogle Scholar
  63. 63.
    Daun JM, McCarthy DO (1993) The role of cholecystokinin in interleukin-1-induced anorexia. Physiol Behav 54:237–241PubMedCrossRefGoogle Scholar
  64. 64.
    Kreydiyyeh SI, Haddad JJ, Garabedian BS (1998) Interleukin-1 beta inhibits the intestinal transport of [14C] 3-O-methylglucose in the rat. Life Sci 63:1913–1919PubMedCrossRefGoogle Scholar
  65. 65.
    Cerami A, Tracey KJ, Lowry SF, Beutler B (1987) Cachectin: a pluripotent hormone released during the host response to invasion. Recent Prog Horm Res 43:99–112PubMedGoogle Scholar
  66. 66.
    Lonnroth C, Moldawer LL, Gelin J et al (1990) Tumor necrosis factor-alpha and interleukin-1 alpha production in cachectic, tumor-bearing mice. Int J Cancer 46:889–896PubMedCrossRefGoogle Scholar
  67. 67.
    Gutierrez EG, Banks WA, Kastin AJ (1993) Murine tumor necrosis factor alpha is transported from blood to brain in the mouse. J Neuroimmunol 47:169–176PubMedCrossRefGoogle Scholar
  68. 68.
    Katafuchi T, Motomura K, Baba S et al (1997) Differential effects of tumor necrosis factor-α andβ on rat ventromedial hypothalamic neurons in vitro. Am J Physiol 272:1966–1971Google Scholar
  69. 69.
    Arbos J, Lopez-Soriano FJ, Carbo N, Argiles JM (1992) Effects of tumour necrosis factor-alpha (cachectin) on glucose metabolism in the rat. Intestinal absorption and isolated enterocyte metabolism. Mol Cell Biochem 112:53–59PubMedCrossRefGoogle Scholar
  70. 70.
    Hermann GE, Tovar CA, Rogers RC (1999) Induction of endogenous tumor necrosis factor-alpha: suppression of centrally stimulated gastric motility. Am J Physiol 276:R59–R68PubMedGoogle Scholar
  71. 71.
    Pendleton RG, Bendesky RJ, Schaffer L et al (1987) Roles of endogenous cholecystokinin in biliary, pancreatic and gastric function: studies with L-364,718, a specific cholecystokinin receptor antagonist. J Pharmacol Exp Ther 241:110–116PubMedGoogle Scholar
  72. 72.
    Ljung T, Hellstrom PM (1999) Vasoactive intestinal peptide suppresses migrating myoelectric complex of rat small intestine independent of nitric oxide. Acta Physiol Scand 165:225–231PubMedCrossRefGoogle Scholar
  73. 73.
    Forster ER, Green T, Elliot M et al (1990) Gastric emptying in rats: role of afferent neurons and cholecystokinin. Am J Physiol 258:G552–G556PubMedGoogle Scholar
  74. 74.
    Raybould HE (1991) Capsaicin-sensitive vagal afférents and CCK in inhibition of gastric motor function induced by intestinal nutrients. Peptides 12:1279–1283PubMedCrossRefGoogle Scholar
  75. 75.
    Zarbin MA, Wamsley JK, Innis RB, Kuhar MJ (1981) Cholecystokinin receptors: presence and axonal flow in the rat vagus nerve. Life Sci 29:697–705PubMedCrossRefGoogle Scholar
  76. 76.
    Blackshaw LA, Grundy D (1990) Effects of cholecystokinin (CCK-8) on two classes of gastroduodenal vagal afferent fibre. J Auton Nerv Syst 31:191–201PubMedCrossRefGoogle Scholar
  77. 77.
    Bucinskaite V, Kurosawa M, Miyasaka K et al (1997) Interleukin-lbeta sensitizes the response of the gastric vagal afferent to cholecystokinin in rat. Neurosci Lett 229:33–36PubMedCrossRefGoogle Scholar
  78. 78.
    Smith GP, Jerome C, Cushin BJ et al (1981) Abdominal vagotomy blocks the satiety effect of cholecystokinin in the rat. Science 213:1036–1037PubMedCrossRefGoogle Scholar
  79. 79.
    Raybould HE, Lloyd KC (1994) Integration of postprandial function in the proximal gastrointestinal tract. Role of CCK and sensory pathways. Ann N Y Acad Sci 713:143–156PubMedCrossRefGoogle Scholar
  80. 80.
    Smagin GN, Dunn AJ (2000) The role of CRF receptor subtypes in stress-induced behavioural responses. Eur J Pharmacol 405:199–206PubMedCrossRefGoogle Scholar
  81. 81.
    McCarthy HD, McKibbin PE, Perkins AV et al (1993) Alterations in hypothalamic NPY and CRF in anorexic tumor-bearing rats. Am J Physiol 264:E638–E643PubMedGoogle Scholar
  82. 82.
    Tache Y, Garrick T, Raybould H (1990) Central nervous system action of peptides to influence gastrointestinal motor function. Gastroenterology 98:517–528PubMedGoogle Scholar
  83. 83.
    Martinez V, Rivier J, Wang L, Tache Y (1997) Central injection of a new corticotropin-releasing factor (CRF) antagonist, astressin, blocks CRFand stressrelated alterations of gastric and colonic motor function. J Pharmacol Exp Ther 280:754–760PubMedGoogle Scholar
  84. 84.
    Moldawer LL, Rogy MA, Lowry SF (1992) The role of cytokines in cancer cachexia. JPEN J Parenter Enterai Nutr 16:43–49Google Scholar
  85. 85.
    Noguchi Y, Yoshikawa T, Matsumoto A et al (1996) Are cytokines possible mediators of cancer cachexia? Surg Today 26:467–475PubMedCrossRefGoogle Scholar
  86. 86.
    Matthys P, Billiau A (1997) Cytokines and cachexia. Nutrition 13:763–770PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Italia 2006

Authors and Affiliations

  • Susumu Suzuki
    • 1
  • Carolina G. Goncalves
    • 1
  • Eduardo J. B. Ramos
    • 1
  • Akihiro Asakawa
    • 2
  • Akio Inui
    • 3
  • Michael M. Meguid
    • 1
  1. 1.Department of SurgerySurgical Metabolism and Nutrition Laboratory, Neuroscience Programs, University Hospital, Upstate Medical UniversitySyracuseUSA
  2. 2.Department of Clinical Molecular Medicine, Division of Diabetes, Digestive and kidney DiseasesKobe University Graduate School of MedicineKobeJapan
  3. 3.Department of Behavioral MedicineKagoshima University Graduate School of Medical and Dental SciencesKagoshimaJapan

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