The Role of Pineal Hormone Melatonin in Cancer Cachexia

  • Paolo Lissoni
  • Luca A. Fumagalli
  • Fernando Brivio
  • Gianstefano Gardani
  • Angelo Nespoli


Melatonin (N-acetyl-5-methoxytriptamine) is the best-known among the indoles produced by the pineal gland (also called the epiphysis) according to a circadian rhythm. The pineal gland is the regulator of photic and nonphotic effects of the sun; indeed, it is the anatomical structure that coordinates the body’s functions with the most important environmental rhythm, that is the light/dark rhythm. This fact may help us in understanding the history of the pineal gland: ancient myths and philosophic systems all over the world assigned a significant role to this gland, with respect to the health of the body and the spirit. Indeed, Cartesius (Reneé Descartes) described the pineal gland as the site of the soul. The Greek name given by Vesalius to the pineal gland, epiphysis (επι = above; φυσισ = nature), implies that it is the counterpart of the hypophysis (υπο = below φυσισ = nature), whereas effectively the physiological activity of the pineal gland counterbalances that of the hypothalamic-pituitary-adrenal (HPA) axis.


Pineal Gland Natl Cancer Inst Cancer Cachexia Advanced Cancer Patient Melatonin Administration 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Garcia-Maurino S, Pozo D, Calvo JR, Guerrero JM(2000) Correlation between nuclear melatoninreceptor expression and enhanced cytokine produc-tion in human lymphocytic and monocytic celllines. J Pineal Res 29:129–137PubMedCrossRefGoogle Scholar
  2. 2.
    Karasek M, Gruszka A, Lawnicka H et al (2003)Melatonin inhibits growth of diethylstilbestrol-induced prolactin-secreting pituitary tumor invitro: possible involvement of nuclear RZR/RORreceptors. J Pineal Res 34:294–296PubMedGoogle Scholar
  3. 3.
    Carrillo-Vico A, Garcia-Maurino S, Calvo JR, Guerrero JM (2003) Melatonin counteracts the inhi-bitory effect of PGE2 on IL-2 production in humanlymphocytes via its mtl membrane receptor. FASEBJ 17:755–757Google Scholar
  4. 4.
    Bartsch C, Bartsch H, Fuchs U et al (1989) Stage-dependent depression of melatonin in patients withprimary breast cancer. Correlation with prolactin,thyroid stimulating hormone, and steroid receptors. Cancer 64:426–433PubMedCrossRefGoogle Scholar
  5. 5.
    Tamarkin L, Danforth D, Lichter A et al (1982)Decreased nocturnal plasma melatonin peak inpatients with estrogen receptor positive breast can-cer. Science 216:1003–1005PubMedCrossRefGoogle Scholar
  6. 6.
    Lissoni P, Viviani S, Bajetta E (1986) A clinical studyof the pineal gland activity in oncologic patients. Cancer 57:837–842PubMedCrossRefGoogle Scholar
  7. 7.
    Falkson G, Falkson HC, Steyn ME et al (1990)Plasma melatonin in patients with breast cancer. Oncology 47:401–405PubMedCrossRefGoogle Scholar
  8. 8.
    Lissoni P, Crispino S, Barni S et al (1990) Pinealgland and tumor cell kinetics: serum levels of mela-tonin in relation to Ki-67 labeling rate in breast can-cer. Oncology 47:275–277PubMedCrossRefGoogle Scholar
  9. 9.
    Hill SM, Blask DE (1988) Effects of the pineal hor-mone melatonin on the proliferation and morpholo-gical characteristics of human breast cancer cells(MCF-7) in culture. Cancer Res 48:6121–6126PubMedGoogle Scholar
  10. 10.
    Cos S, Blask DE, Lemus-Wilson A, Hill AB (1991)Effects of melatonin on the cell cycle kinetics and‘estrogen-rescue’ of MCF-7 human breast cancercells in culture. J Pineal Res 10:36–42PubMedCrossRefGoogle Scholar
  11. 11.
    Marelli MM, Limonta P, Maggi R et al (2000)Growth-inhibitory activity of melatonin on humanandrogen-independent DU 145 prostate cancer cells. Prostate 45:238–244PubMedCrossRefGoogle Scholar
  12. 12.
    Bizzarri M, Cucina A, Valente MG et al (2003)Melatonin and vitamin D3 increase TGF-betalrelease and induce growth inhibition in breast can-cer cell cultures. J Surg Res 110:332–337PubMedCrossRefGoogle Scholar
  13. 13.
    Dauchy RT, Blask DE, Sauer LA et al (1999) Dimlight during darkness stimulates tumor progressionby enhancing tumor fatty acid uptake and metabo-lism. Cancer Lett 144:131–136PubMedCrossRefGoogle Scholar
  14. 14.
    Blask DE, Dauchy RT, Sauer LA et al (2002) Lightduring darkness, melatonin suppression and cancerprogression. Neuroendocrinol 23:52–56Google Scholar
  15. 15.
    Blask DE, Dauchy RT, Sauer LA et al (2003) Growthand fatty acid metabolism of human breast cancer(MCF-7) xenografts in nude rats: impact of constantlight-induced nocturnal melatonin suppression. Breast Cancer Res Treat 79:313–320PubMedCrossRefGoogle Scholar
  16. 16.
    Travis R, Allen D, Fentiman I, Key T (2004)Melatonin and breast cancer: a prospective study. JNatl Cancer Inst 96:475–482Google Scholar
  17. 17.
    Hansen J (2001) Increased breast cancer risk amongwomen who work predominantly at night. Epidemiology 12:74–77PubMedCrossRefGoogle Scholar
  18. 18.
    Davis S, Mirick DK, Stevens RG (2001) Night shiftwork, light at night, and risk of breast cancer. J NatlCancer Inst 93:1557–1562Google Scholar
  19. 19.
    Shernhammer ES, Laden F, Speizer FE et al (2003)Night-shift work and risk of colorectal cancer in thenurses’health study. J Natl Cancer Inst 95:825–828CrossRefGoogle Scholar
  20. 20.
    Hrushesky WJM, Blask DE (2004) Melatonin andbreast cancer: a prospective study. J Natl Cancer96:888–889Google Scholar
  21. 21.
    Esposti D, Lissoni P, Tancini G et al (1988) A studyon the relationship between the pineal gland andthe opioid system in patients with cancer.Preliminary considerations. Cancer 62:494–499PubMedCrossRefGoogle Scholar
  22. 22.
    Lissoni P, Barni S, Tancini G (1994) Pineal-opioidsystem interactions in the control of immunoin-flammatory responses. Ann N Y Acad Sci741:191–196PubMedCrossRefGoogle Scholar
  23. 23.
    Guerrero JM, Reiter RJ (2002) Melatonin-immunesystem relationships. Curr Top Med Chem 2:167–179PubMedCrossRefGoogle Scholar
  24. 24.
    Lissoni P (1999) The pineal gland as a central regu-lator of cytokine network. Neuroendocrinol Lett20:343–349PubMedGoogle Scholar
  25. 25.
    Esposti D, Lissoni P, Mauri R et al (1988) The pinealgland-opioid system relation: melatonin-naloxoneinteractions in regulating GH and LH releases inman J Endocrinol Invest 11:103–106PubMedGoogle Scholar
  26. 26.
    Stanley KE (1980) Prognostic factors for survival inpatients with inoperable lung cancer. J Natl CancerInst 65:25–32Google Scholar
  27. 27.
    Lavin PT, Bruckner HW, Plaxe SC (1982) Studies inprognostic factors relating to chemotherapy foradvanced gastric cancer. Cancer 50:2016–2023PubMedCrossRefGoogle Scholar
  28. 28.
    Lissoni P, Barni S, Rovelli F, Tancini G (1991) Lowersurvival in metastatic cancer patients with reducedinterleukin-2 blood concentrations. Oncology48:125–127PubMedCrossRefGoogle Scholar
  29. 29.
    Fischer JR, Schindel M, Stein N (1995) Selective sup-pression of cytokine secretion in patients with smallcell lung cancer. Ann Oncol 6:921–926PubMedGoogle Scholar
  30. 30.
    Monson JRT, Ramsden C, Guillou PJ (1986)Decreased IL-2 production in patients withgastrointestinal cancer. Br J Surg 73:483–486PubMedCrossRefGoogle Scholar
  31. 31.
    Rayman P, Uzzo RG, Kolenko V et al (2000) Tumor-induced dysfunction in Interleukin-2 productionand Interleukin-2 receptor signaling: a mechanismof immune escape. Cancer J Sci Am 6(S1):S81–S87PubMedGoogle Scholar
  32. 32.
    Dolan MJ, Clerici M, Blatt S et al (1995) In vitro Tcell function, delayed-type hypersensitivity skintesting, and CD4+ T cell subset phenotyping inde-pendently predict survival time in patients infectedwith human immunodeficiency virus. J Infect Dis172:79–87PubMedGoogle Scholar
  33. 33.
    Lissoni P, Tancini G, Barni S et al (1989) Alterationsof pineal gland and of T lymphocyte subsets inmetastatic cancer patients: preliminary results. JBiol Regul Homeost Agents 3:181–183Google Scholar
  34. 34.
    Lissoni P, Barni S, Ardizzoia A et al (1992)Immunological effects of a single evening subcuta-neous injection of low-dose interleukin-2 in asso-ciation with the pineal hormone melatonin inadvanced cancer patients. J Biol Regul HomeostAgents 6:132–136Google Scholar
  35. 35.
    Lissoni P, Ardizzoia A, Tisi E et al (1993)Amplification of eosinophilia by melatonin duringthe immunotherapy of cancer with interleukin-2. JBiol Regul Homeost Agents 7:34–36Google Scholar
  36. 36.
    Lissoni P, Barni S, Tancini G et al (1993) A study ofthe mechanisms involved in the immunostimulatoryaction of the pineal hormone in cancer patients. Oncology 50:399–402PubMedCrossRefGoogle Scholar
  37. 37.
    Lissoni P, Barni S, Brivio F et al (1995) Treatment ofcancer-related thrombocytopenia by low-dose sub-cutaneous interleukin-2 plus the pineal hormonemelatonin: a biological phase II study. J Biol RegulHomeost Agents 9:52–54Google Scholar
  38. 38.
    Lissoni P, Barni S, Brivio F et al (1995) A biologicalstudy on the efficacy of low-dose subcutaneousinterleukin-2 plus melatonin in the treatment ofcancer-related thrombocytopenia. Oncology52:360–362PubMedCrossRefGoogle Scholar
  39. 39.
    Carrillo-Vico A, Calvo JR, Abreu P et al (2004)Evidence of melatonin synthesis by humanlymphocytes and its physiological significance: pos-sible role as intracrine, autocrine, and/or paracrinesubstance. FASEB J 18:537–539PubMedGoogle Scholar
  40. 40.
    El-Sokkary GH, Reiter RJ, Abdel-Ghaffar Skh (2003)Melatonin supplementation restores cellular prolife-ration and DNA synthesis in the splenic and thymiclymphocytes of old rats. Neuroendocrinol Lett24:215–223PubMedGoogle Scholar
  41. 41.
    Huang YS, Jiang JW, Cao XD, Wu GC (2003)Melatonin enhances lymphocyte proliferation anddecreases the release of pituitary pro-opiomelano-cortin-derived peptides in surgically traumatizedrats. Neurosci Lett 343:109–112PubMedCrossRefGoogle Scholar
  42. 42.
    Kuhlwein E, Irwin M (2001) Melatonin modulationof lymphocyte proliferation and Thl/Th2 cytokineexpression. J Neuroimmunol 117:51–57PubMedCrossRefGoogle Scholar
  43. 43.
    Lissoni P, Rovelli F, Meregalli S et al (1997)Melatonin as a new possible anti-inflammatoryagent. J Biol Regul Homeost Agents 11:157–159PubMedGoogle Scholar
  44. 44.
    Cuzzocrea S, Reiter RJ (2002) Pharmacologicalactions of melatonin in acute and chronic inflam-mation. Curr Top Med Chem 2:153–165PubMedCrossRefGoogle Scholar
  45. 45.
    Beutler B, Cerami A (1986) Cachectin and tumor-necrosis factor as two sides of the same biologicalcoin. Nature 320:584–588PubMedCrossRefGoogle Scholar
  46. 46.
    Sacco S, Aquilini L, Ghezzi P et al (1998)Mechanisms of the inhibitory effects of melatoninon tumor-necrosis factor production in vivo and invitro. Eur J Pharmacol 343:249–255PubMedCrossRefGoogle Scholar
  47. 47.
    Lissoni P, Barni S, Tancini G (1994) Role of thepineal gland in the control of the macrophage func-tions and its possible implication in cancer: a studyof interactions between tumor-necrosis factor alphaand the pineal hormone melatonin. J Biol RegulHomeost Agents 8:126–129Google Scholar
  48. 48.
    Lissoni P, Barni S, Crispin S et al (1989) Endocrineand immune effects of melatonin therapy in meta-static cancer patients. Eur J Cancer Clin Oncol25:789–795PubMedCrossRefGoogle Scholar
  49. 49.
    Reiter RJ, Tan DX (2003) What constitutes a physio-logical concentration of melatonin? J Pineal Res34:79–80PubMedCrossRefGoogle Scholar
  50. 50.
    Akagi T, Ushinohama K, Ikesue S et al (2004)Chronopharmacology of melatonin in mice to maxi-mize the antitumor effect and minimize the rhythmdisturbance effect. J Pharmacol Exp Ther308:378–384PubMedCrossRefGoogle Scholar
  51. 51.
    Serfaty M, Kennell-Webb S, Warner J et al (2002)Double blind randomised placebo controlled trial oflow dose melatonin for sleep disorders in dementia. Int J Geriatr Psychiatry 17:1120–1127PubMedCrossRefGoogle Scholar
  52. 52.
    Naguib M, Hammond DL, Schmid PG 3rd et al(2003) Pharmacological effects of intravenous mela-tonin: comparative studies with thiopental and pro-pofol. Br J Anaesth 90:504–507PubMedCrossRefGoogle Scholar
  53. 53.
    Lissoni P, Paolorossi F, Tancini G et al (1996) Is therea role for melatonin in the treatment of neoplasticcachexia? Eur J Cancer 32A:1340–1343PubMedCrossRefGoogle Scholar
  54. 54.
    Vijayalaxmi, Thomas CR Jr, Reiter RJ, Herman TS(2002) Melatonin: from basic research to cancertreatment clinics. J Clin Oncol 20:2575–2601PubMedCrossRefGoogle Scholar
  55. 55.
    Lissoni P, Malugani F, Manganini V et al (2003)Psychooncology and cancer progression-relatedalterations of pleasure-associated neurochemicalsystem: abnormal neuroendocrine response to apo-morphine in advanced cancer patients. Neuroendocrinol Lett 24:50–53PubMedGoogle Scholar
  56. 56.
    Sephton SE, Sapolsky RM, Kraemer HC, Spiegel D(2000) Diurnal cortisol rhythm as a predictor ofbreast cancer survival. J Natl Cancer Inst 9:994–1000CrossRefGoogle Scholar
  57. 57.
    Lissoni P, Chilelli M, Villa S et al (2003) Five yearssurvival in metastatic non-small cell lung cancerpatients treated with chemotherapy alone or che-motherapy and melatonin: a randomized trial. JPineal Res 35:12–15CrossRefGoogle Scholar
  58. 58.
    Cerea G, Vaghi M, Ardizzoia A et al (2003)Biomodulation of cancer chemotherapy for meta-static colorectal cancer: a randomized study ofweekly low-dose irinotecan alone versus irinotecanplus the oncostatic pineal hormone melatonin inmetastatic colorectal cancer patients progressing on5-fluorouracil-containing combinations. AnticancerRes 23:1951–1954Google Scholar
  59. 59.
    Lissoni P, Barni S, Meregalli S et al (1995)Modulation of cancer endocrine therapy by melato-nin: a phase II study of tamoxifen plus melatonin inmetastatic breast cancer patients progressing undertamoxifen alone. Br J Cancer 71:854–856PubMedGoogle Scholar
  60. 60.
    Lissoni P, Cazzaniga M, Tancini G et al (1997)Reversal of clinical resistance to LHRH analogue inmetastatic prostate cancer by the pineal hormonemelatonin: efficacy of LHRH analogue plus melato-nin in patients progressing on LHRH analoguealone. Eur Urol 31:178–181PubMedGoogle Scholar
  61. 61.
    Lissoni P, Barni S, Tancini G et al (1994) A randomi-sed study with subcutaneous low-dose interleukin 2alone vs interleukin 2 plus the pineal neurohormonemelatonin in advanced solid neoplasms other thanrenal cancer and melanoma. Br J Cancer 69:196–199PubMedGoogle Scholar
  62. 62.
    Lissoni P, Barni S, Cazzaniga M et al (1994) Efficacyof the concomitant administration of the pineal hor-mone melatonin in cancer immunotherapy withlow-dose IL-2 in patients with advanced solidtumors who had progressed on IL-2 alone. Oncology51:344–347PubMedCrossRefGoogle Scholar
  63. 63.
    Lissoni P, Barni S, Mandata M et al (1999) Decreasedtoxicity and increased efficacy of cancer chemothe-rapy using the pineal hormone melatonin in meta-static solid tumour patients with poor clinical sta-tus. Eur J Cancer 35:1688–1692PubMedCrossRefGoogle Scholar
  64. 64.
    Lissoni P (2002) Is there a role for melatonin in sup-portive care? Support Care Cancer 10:110–116PubMedCrossRefGoogle Scholar
  65. 65.
    Reiter RJ, Tan DX, Sainz RM et al (2002) Melatonin:reducing the toxicity and increasing the efficacy ofdrugs. J Pharm Pharmacol 54:1299–1321PubMedCrossRefGoogle Scholar
  66. 66.
    Maestroni GJ (2000) Neurohormones and catechola-mines as functional components of the bone mar-row microenvironment. Ann N Y Acad Sci 917:29–37PubMedCrossRefGoogle Scholar
  67. 67.
    Rodriguez C, Mayo JC, Sainz RM et al (2004)Regulation of antioxidant enzymes: a significantrole for melatonin. J Pineal Res 36:1–9PubMedCrossRefGoogle Scholar
  68. 68.
    Karasek M, Reiter RJ, Cardinali DP, Pawlikowski M(2002) Future of melatonin as a therapeutic agent. Neuro Endocrinol Lett23(Suppl 1):118–121PubMedGoogle Scholar
  69. 69.
    Lissoni P, Mandala M, Rossini F et al (1999) GrowthFactors: Thrombopoietic Property of the PinealHormone Melatonin. Hematology 4:335–343PubMedGoogle Scholar
  70. 70.
    Lissoni P, Bucovec R, Bonfanti A et al (2001)Thrombopoietic properties of 5-methoxytryptami-ne plus melatonin versus melatonin alone in thetreatment of cancer-related thrombocytopenia. JPineal Res 30:123–126CrossRefGoogle Scholar
  71. 71.
    Steindl PE, Finn B, Bendok B et al (1995) Disruptionof the diurnal rhythm of plasma melatonin in cir-rhosis. Ann Intern Med 123:274–277PubMedGoogle Scholar
  72. 72.
    Reynolds FD, Dauchy R, Blask D et al (2003) Thepineal gland hormone melatonin improves survivalin a rat model of sepsis/shock induced by zymosanA. Surgery 134:474–479PubMedCrossRefGoogle Scholar
  73. 73.
    Yerer MB, Aydogan S, Yapislar H et al (2003)Melatonin increases glutathione peroxidase activityand deformability of erythrocytes in septic rats. JPineal Res 35:138–139CrossRefGoogle Scholar
  74. 74.
    Mundigler G, Delle-Karth G, Koreny M et al (2002)Impaired circadian rhythm of melatonin secretionin sedated critically ill patients with severe sepsis. Crit Care Med 30:536–540PubMedCrossRefGoogle Scholar
  75. 75.
    Wichmann MW, Haisken JM, Ayala A, Chaudry IH(1996) Melatonin administration following hemor-rhagic shock decreases mortality from subsequentseptic challenge. J Surg Res 65:109–114PubMedCrossRefGoogle Scholar
  76. 76.
    Wurtman RJ, Larin F, Axelrod J et al (1968)Formation of melatonin and 5-hydroxyindole aceticacid from 14C-tryptophan by rat pineal glands inorgan culture. Nature 217:953–954PubMedCrossRefGoogle Scholar
  77. 77.
    Reiter RJ, Fraschini F (1969) Endocrine aspects ofthe mammalian pineal gland: a review. Neuroendocrinology 5:219–255PubMedCrossRefGoogle Scholar
  78. 78.
    Axelrod J (1970) The pineal gland. Endeavour29:144–148PubMedGoogle Scholar
  79. 79.
    Miller FP, Maickel RP (1970) Fluorometric determi-nation of indole derivatives. Life Sci I 9:747–752PubMedCrossRefGoogle Scholar
  80. 80.
    Ebels I, Balemans MG, Tommel DK (1972)Separation of pineal extracts on Sephadex G-10. 3.Isolation and comparison of extracted and synethe-tic melatonin. Anal Biochem 50:234–244PubMedCrossRefGoogle Scholar
  81. 81.
    Koslow SH, Green AR (1973) Analysis of pineal andbrain indole alkylamines by gas chromatography-mass spectrometry. Adv Biochem Psychopharmacol7:33–43PubMedGoogle Scholar
  82. 82.
    Zurburg W, Ebels I (1975) Separation of pinealextracts by gelfiltration. II. Identification and isola-tion of two indoles from sheep pineal glands. JNeural Transm 36:59–69CrossRefGoogle Scholar
  83. 83.
    Axelrod J (1974) The pineal gland: a neurochemicaltransducer. Science 184:1341–1348PubMedCrossRefGoogle Scholar
  84. 84.
    Ebels I (1975) Pineal factors other than melatonin. Gen Comp Endocrinol 25:189–198PubMedCrossRefGoogle Scholar
  85. 85.
    Ebels I, Horwitz-Bresser AE (1976) Separation ofpineal extracts by gelfiltration. IV. Isolation, locationand identification from sheep pineals of three indo-les, identical with 5-hydroxytryptophol, 5-methoxytryptophol and melatonin. J Neural Transm38:31–41PubMedCrossRefGoogle Scholar
  86. 86.
    Reiter RJ, Vaughan MK (1977) Pineal antigonadotro-phic substances: polypeptides and indoles. Life Sci21:159–171PubMedCrossRefGoogle Scholar
  87. 87.
    Pavel S (1978) Arginine vasotocin as a pineal hor-mone. J Neural Transm Suppl(13):135–155Google Scholar
  88. 88.
    Lissoni P, Fumagalli L, Paolorossi F et al (1997)Anticancer neuroimmunomodulation by pineal hor-mones other than melatonin:preliminary phase IIstudy of the pineal indole 5-methoxytryptophol inassociation with low-dose IL-2 and melatonin. J BiolRegul Horneost Agents 11:119–122Google Scholar
  89. 89.
    Lissoni P (2000) Modulation of anticancer cytokinesIL-2 and IL-12 by melatonin and the other pinealindoles 5-methoxytryptamine and 5-methoxytryp-tophol in the treatment of human neoplasms. Ann NY Acad Sci 917:560–567PubMedCrossRefGoogle Scholar
  90. 90.
    Lissoni P, Bucovec R, Bonfanti A et al (2001)Thrombopoietic properties of 5-methoxytryptami-ne plus melatonin versus melatonin alone in thetreatment of cancer-related thrombocytopenia. JPineal Res 30:123–126CrossRefGoogle Scholar
  91. 91.
    Viviani S, Bidoli P, Spinazze S et al (1992)Normalization of the light/dark rhythm of melato-nin after prolonged subcutaneous administration ofinterleukin-2 in advanced small cell lung cancerpatients. J Pineal Res 12:114–117PubMedCrossRefGoogle Scholar
  92. 92.
    Lissoni P, Mandala M, Brivio F (2000) Abrogation ofthe negative influence of opioids on IL-2 immuno-therapy of renal cell cancer by melatonin. Eur Urol38:115–118PubMedCrossRefGoogle Scholar
  93. 93.
    Lissoni P, Malugani F, Malysheva O et al (2002)Neuroimmunotherapy of untreatable metastaticsolid tumors with subcutaneous low-dose interleu-kin-2, melatonin and naltrexone: modulation ofinterleukin-2-induced antitumor immunity by bloc-king the opioid system. Neuro Endocrinol Lett23:341–344PubMedGoogle Scholar

Copyright information

© Springer-Verlag Italia 2006

Authors and Affiliations

  • Paolo Lissoni
    • 1
  • Luca A. Fumagalli
    • 2
  • Fernando Brivio
    • 2
  • Gianstefano Gardani
    • 1
  • Angelo Nespoli
    • 2
  1. 1.Department of General Surgery, Division of Oncology and RadiotherapyUniversity of Milano-Bicocca at San Gerardo HospitalMonzaItaly
  2. 2.Department of Surgical Sciences and Intensive Therapy, Department of General SurgeryUniversity of Milano-Bicocca at San Gerardo HospitalMonzaItaly

Personalised recommendations