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Z Gastroenterol 2002; 40(11): 929-936
DOI: 10.1055/s-2002-35411
Übersicht
© Karl Demeter Verlag im Georg Thieme Verlag Stuttgart · New York

Tumoranorexie - Tumorkachexie bei ­gastrointestinalen Tumoren: Standards und Visionen

Tumour Anorexia - Tumour Cachexia in Case of Gastrointestinal Tumours: ­Standards and VisionsJ. Ockenga1 , M. Pirlich1 , S. Gastell1 , H. Lochs1
  • 1Medizinische Klinik mit Schwerpunkt Gastroenterologie, Hepatologie und Endokrinologie, Humboldt Universität, Charité, Berlin
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Publication History

Publication Date:
18 November 2002 (online)

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Zusammenfassung

Patienten mit Tumoren des Gastrointestinaltrakts - insbesondere mit einem Pankreaskarzinom - entwickeln regelhaft eine Fehl­ernährung, die wesentlich zur Morbidität und Mortalität beiträgt. Die gegenwärtigen Therapiemöglichkeiten geben dem behandelnden Arzt nur begrenzt die Möglichkeit zu einer erfolgreichen Behandlung und münden oftmals in einem therapeutischen Nihilismus. Prinzipiell ist zwischen einer Tumoranorexie und einer Tumorkachexie zu unterscheiden, oftmals liegt jedoch eine Kombination beider vor. In den letzten Jahren gelang es, die Pathophysiologie dieser Veränderungen weiter aufzuklären. Die vorliegende Übersicht möchte zum einen die momentanen Behandlungsmöglichkeiten aufzeigen, aber auch den aktuellen Kenntnisstand und mögliche neue Ansätze reflektieren.

Abstract

The development of progressive malnutrition or cachexia is frequent in patients with gastrointestinal cancer - especially in patients with a carcinoma of the pancreas. The cachexia syndrome which is characterised by loss of body weight, negative nitrogen balance and fatigue significantly affects patients’ quality of life, morbidity and survival. Because the currently established therapeutical strategies are often disappointing many physicians tended to develop a therapeutical nihilism. Cancer anorexia and cachexia are two distinct syndromes which may have synergistic effects in a patient. This review highlights the growing understanding of the multidimensional pathophysiological background. An algorithm of the current treatment strategies is given. In addition, we discuss new anabolic and anticatabolic agents (e. g. eicosapentanoic acid) and the results from first clinical trials.

Schlüsselwörter

Kachezeie - Karzinom - Pankreas - Ernährung - Ubiquitin - Fehl­ernährung

Key words

Cachexia - anorexia - cancer - pancreatic neoplasms - nutrition - nutrition disorders - gastrointestinal disease - ubiquitin

Literatur

  • 1 Chamberlain R S, Fong Y. Nutritional and metabolic aspects of gastrointestinal cancer.  Curr Opin Clin Nutr Metab Care. 1999;  2 381-385
    Google Scholar
  • 2 Cooperman A M, Chivati J, Chamberlain R S. Nutritional and metabolic aspects of pancreatic cancer.  Curr Opin Clin Nutr Metab Care. 2000;  3 17-21
    Google Scholar
  • 3 Cooperman A M. Pancreatic cancer: the bigger picture.  Surg Clin North Am. 2001;  81 557-574
    Google Scholar
  • 4 Grosvenor M, Bulcavage L, Chlebowski R T. Symptoms potentially influencing weight loss in a cancer population. Correlations with primary site, nutritional status, and chemotherapy administration.  Cancer. 1989;  63 330-334
    Google Scholar
  • 5 Kotler D P. Cachexia.  Ann Intern Med. 2000;  133 622-634
    Google Scholar
  • 6 Bischoff S C, Ockenga J, Manns M P. Artificial nutrition in intensive internal medicine. Chances and problems.  Internist (Berl). 2000;  41 1041-1061
    Google Scholar
  • 7 Bozzetti F. Nutrition and gastrointestinal cancer.  Curr Opin Clin Nutr Metab Care. 2001;  4 541-546
    Google Scholar
  • 8 Suttmann U, Ockenga J, Selberg O. et al . Incidence and prognostic value of malnutrition and wasting in human immunodeficiency virus-infected outpatients.  J Acquir Immune Defic Syndr Hum Retrovirol. 1995;  8 239-246
    Google Scholar
  • 9 Tisdale M J. Wasting in cancer.  J Nutr. 1999;  129 243-246
    Google Scholar
  • 10 Nixon D W, Lawson D H, Kutner M. et al . Hyperalimentation of the cancer patient with protein-calorie undernutrition.  Cancer Res. 1981;  41 2038-2045
    Google Scholar
  • 11 Evans W K, Nixon D W, Daly J M. et al . A randomized study of oral nutritional support versus ad lib nutritional intake during chemotherapy for advanced colorectal and non-small-cell lung cancer.  J Clin Oncol. 1987;  5 113-124
    Google Scholar
  • 12 Potter J M, Roberts M A, McColl J H. et al . Protein energy supplements in unwell elderly patients - a randomized controlled trial.  JPEN J Parenter Enteral Nutr. 2001;  25 323-239
    Google Scholar
  • 13 Boieng H. Kalzium und Antioxidantien als Supplemente in der Krebsprophylaxe - Statusbericht zu den Interventionsstudien.  Aktuelle Ernährungs Medizin. 2002;  26 130-136
    Google Scholar
  • 14 Inui A. Cancer anorexia-cachexia syndrome: are neuropeptides the key?.  Cancer Res. 1999;  59 4493-4501
    Google Scholar
  • 15 Plata-Salaman C R, Oomura Y, Kai Y. Tumor necrosis factor and interleukin-1 beta: suppression of food intake by direct action in the central nervous system.  Brain Res. 1988;  448 106-114
    Google Scholar
  • 16 Yang Z J, Blaha V, Meguid M M. et al . Interleukin-1alpha injection into ventromedial hypothalamic nucleus of normal rats depresses food intake and increases release of dopamine and serotonin.  Pharmacol Biochem Behav. 1999;  62 61-65
    Google Scholar
  • 17 Mantovani G, Maccio A, Mura L. et al . Serum levels of leptin and proinflammatory cytokines in patients with advanced-stage cancer at different sites.  J Mol Med. 2000;  78 554-561
    Google Scholar
  • 18 Ockenga J, Bischoff S C, Tillmann H L. et al . Elevated bound leptin correlates with energy expenditure in cirrhotics.  Gastroenterology. 2000;  119 1656-1662
    Google Scholar
  • 19 Mantovani G, Maccio A, Massa E, Madeddu C. Managing cancer-related anorexia/cachexia.  Drugs. 2001;  61 499-514
    Google Scholar
  • 20 Loprinzi C L, Schaid D J, Dose A M. et al . Body-composition changes in patients who gain weight while receiving megestrol acetate.  J Clin Oncol. 1993;  11 152-154
    Google Scholar
  • 21 Bruera E, Neumann C M, Pituskin E. et al . Thalidomide in patients with cachexia due to terminal cancer: preliminary report.  Ann Oncol. 1999;  10 857-859
    Google Scholar
  • 22 Goldberg R M, Loprinzi C L, Mailliard J A. et al . Pentoxifylline for treatment of cancer anorexia and cachexia? A randomized, double-blind, placebo-controlled trial.  J Clin Oncol. 1995;  13 2856-2859
    Google Scholar
  • 23 Wigmore S J, Plester C E, Ross J A, Fearon K C. Contribution of anorexia and hypermetabolism to weight loss in anicteric patients with pancreatic cancer.  Br J Surg. 1997;  84 196-197
    Google Scholar
  • 24 Mulligan H D, Beck S A, Tisdale M J. Lipid metabolism in cancer cachexia.  Br J Cancer. 1992;  66 57-61
    Google Scholar
  • 25 Drott C, Persson H, Lundholm K. Cardiovascular and metabolic response to adrenaline infusion in weight-losing patients with and without cancer.  Clin Physiol. 1989;  9 427-439
    Google Scholar
  • 26 McDevitt T M, Todorov P T, Beck S A. et al . Purification and characterization of a lipid-mobilizing factor associated with cachexia-inducing tumors in mice and humans.  Cancer Res. 1995;  55 1458-1463
    Google Scholar
  • 27 Groundwater P, Beck S A, Barton C. et al . Alteration of serum and urinary lipolytic activity with weight loss in cachectic cancer patients.  Br J Cancer. 1990;  62 816-821
    Google Scholar
  • 28 Hirai K, Hussey H J, Barber M D. et al . Biological evaluation of a lipid-mobilizing factor isolated from the urine of cancer patients.  Cancer Res. 1998;  58 2359-2365
    Google Scholar
  • 29 Tisdale M J. Biomedicine. Protein loss in cancer cachexia.  Science. 2000;  289 2293-2294
    Google Scholar
  • 30 Tisdale M J. Cancer anorexia and cachexia.  Nutrition. 2001;  17 438-442
    Google Scholar
  • 31 Mitch W E, Goldberg A L. Mechanisms of muscle wasting. The role of the ubiquitin-proteasome pathway.  N Engl J Med. 1996;  335 1897-1905
    Google Scholar
  • 32 Guttridge D C, Mayo M W, Madrid L V. et al . NF-kappaB-induced loss of MyoD messenger RNA: possible role in muscle decay and cachexia.  Science. 2000;  289 2363-2366
    Google Scholar
  • 33 Todorov P, Cariuk P, McDevitt T. et al . Characterization of a cancer cachectic factor.  Nature. 1996;  379 739-742
    Google Scholar
  • 34 Smith H J, Lorite M J, Tisdale M J. Effect of a cancer cachectic factor on protein synthesis/degradation in murine C2C12 myoblasts: modula­tion by eicosapentaenoic acid.  Cancer Res. 1999;  59 5507-5513
    Google Scholar
  • 35 Kawamura I, Morishita R, Tomita N. et al . Intratumoral injection of oligonucleotides to the NF kappa B binding site inhibits cachexia in a mouse tumor model.  Gene Ther. 1999;  6 91-97
    Google Scholar
  • 36 Mitch W E, Price S R. Transcription factors and muscle cachexia: is ­there a therapeutic target?.  Lancet. 2001;  357 734-735
    Google Scholar
  • 37 Combaret L, Ralliere C, Taillandier D. et al . Manipulation of the ubiquitin-proteasome pathway in cachexia: pentoxifylline suppresses the activation of 20S and 26S proteasomes in muscles from tumor-bearing rats.  Mol Biol Rep. 1999;  26 95-101
    Google Scholar
  • 38 Keifer J A, Guttridge D C, Ashburner B P. et al . Inhibition of NF-kappa B activity by thalidomide through suppression of IkappaB kinase activity.  J Biol Chem. 2001;  276 22382-22387
    Google Scholar
  • 39 Ockenga J, Rohde F, Suttmann U. et al . Ketotifen in HIV-infected pa­tients: effects on body weight and release of TNF-alpha.  Eur J Clin Pharmacol. 1996;  50 167-170
    Google Scholar
  • 40 Hussey H J, Tisdale M J. Effect of a cachectic factor on carbohydrate metabolism and attenuation by eicosapentaenoic acid.  Br J Cancer. 1999;  80 1231-1235
    Google Scholar
  • 41 Sauer L A, Dauchy R T, Blask D E. Mechanism for the antitumor and anticachectic effects of n-3 fatty acids.  Cancer Res. 2000;  60 5289-5295
    Google Scholar
  • 42 Pirlich M, Muller C, Sandig G. et al . Increased proteolysis after single-dose exposure with hepatotoxins in HepG2 cells.  Free Radic Biol Med. 2002;  15 283-291 (33)
    Google Scholar
  • 43 Pirlich M, Kiok K, Sandig G. et al . Alpha-lipoic acid prevents ethanol-induced protein oxidation in mouse hippocampal HT22 cells.  Neurosci Lett. 2002 Aug 9;  328 (2) 93-96
    Google Scholar
  • 44 Price S A, Tisdale M J. Mechanism of inhibition of a tumor lipid-mobi­lizing factor by eicosapentaenoic acid.  Cancer Res. 1998;  58 4827-4831
    Google Scholar
  • 45 James M J, Gibson R A, Cleland L G. Dietary polyunsaturated fatty acids and inflammatory mediator production.  Am J Clin Nutr. 2000;  71 343S-348S
    Google Scholar
  • 46 Hussey H J, Tisdale M J. Effect of the specific cyclooxygenase-2 inhibitor meloxicam on tumour growth and cachexia in a murine model.  Int J Cancer. 2000;  87 95-100
    Google Scholar
  • 47 Barber M D, Ross J A, Voss A C. et al . The effect of an oral nutritional supplement enriched with fish oil on weight-loss in patients with pancreatic cancer.  Br J Cancer. 1999;  81 80-86
    Google Scholar
  • 48 Barber M D, McMillan D C, Preston T. et al . Metabolic response to feed­ing in weight-losing pancreatic cancer patients and its modulation by a fish-oil-enriched nutritional supplement.  Clin Sci (Colch). 2000;  98 389-399
    Google Scholar
  • 49 Gogos C A, Ginopoulos P, Salsa B. et al . Dietary omega-3 polyunsaturated fatty acids plus vitamin E restore immunodeficiency and prolong survival for severely ill patients with generalized malignancy: a randomized control trial.  Cancer. 1998;  82 395-402
    Google Scholar
  • 50 McMillan D C, Wigmore S J, Fearon K C. et al . A prospective randomized study of megestrol acetate and ibuprofen in gastrointestinal cancer patients with weight loss.  Br J Cancer. 1999;  79 495-500
    Google Scholar

Dr. med. Johann Ockenga

Medizinische Klinik mit Schwerpunkt Gastroenterologie, Hepatologie und Endokrinologie, Humboldt Universität, Charité

Schumannstraße 20/21

10117 Berlin

Email: johann.ockenga@charite.de

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