Journal of Clinical Oncology, Vol 25, No 17 (June 10), 2007: pp. 2397-2405
© 2007 American Society of Clinical Oncology.
DOI: 10.1200/JCO.2006.06.4592
Depression, Immunity, and Survival in Patients With Hepatobiliary Carcinoma
Jennifer L. Steel,
David A. Geller,
T. Clark Gamblin,
Marion C. Olek,
Brian I. Carr
From the University of Pittsburgh School of Medicine, Liver Cancer Center, Pittsburgh, PA
Address reprint requests to Jennifer L. Steel, PhD, University of Pittsburgh School of Medicine, Department of Surgery, Starzl Transplantation Institute, 3459 Fifth Ave, Montefiore 7 South, Pittsburgh, PA 15213; e-mail: steeljl{at}msx.upmc.edu
Purpose: The aims of the present study were to assess the prevalence of depressive symptoms at diagnosis, test the association between depressive symptoms and survival, and preliminarily test a mediational model of depression, immunity, and survival in patients with hepatobiliary carcinoma (HBC).
Patients and Methods: One hundred one patients diagnosed with HBC were prospectively studied. Depressive symptoms were measured at diagnosis using the Center for Epidemiological Studies Depression Scale (CES-D). Sociodemographic and disease-specific data were gathered from the patients' charts. In a subsample of patients, stress; alcohol, tobacco, and drug use; sleep quality; physical activity; social support; natural killer (NK) cell number and cytotoxicity; and plasma levels of interleukin (IL) -4, IL-5, tumor necrosis factor alpha, and interferon gamma were measured. Survival was measured from date of diagnosis to death.
Results: At diagnosis, 37% of patients reported a CES-D score of  16 (clinical range). Using Cox regression analysis, sociodemographic and disease-specific variables and CES-D score significantly predicted survival (Breslow  2 = 32.4, P = .006). Only vascular invasion (P = .001) and CES-D score 16 (P = .03) were significant predictors. In a subsample of 23 patients, patients who reported a CES-D score of 16 were found to have significantly lower NK cell numbers than patients who reported a CES-D score of less than 16 (F1,21 = 9.39, P = .003). A robust trend was found in which NK cell number was associated with survival. A mediational model linking depressive symptoms and survival, with NK cell number as a mediator, was preliminarily supported.
Conclusion: Secondary to the high prevalence of depressive symptoms and impact on survival, psychological and pharmacologic interventions should be designed and implemented in patients diagnosed with HBC.
Supported in part by the American Cancer Society and grants to the Pittsburgh Mind Body Center (National Institutes of Health Grants No. HL065111, HL065112, HL076852, and HL076858).
Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.
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