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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

	ABSTRACT

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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 (F_1,21 = 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.

	INTRODUCTION

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Increasing evidence is accumulating regarding the association between depressive symptoms and increased morbidity and mortality in the general population as well as across several chronic diseases,^1-12 including cancer.^13-18 Reviews of the literature conclude that the prevalence of depressive symptoms in people diagnosed with cancer ranges between 22% and 29%.^19,20 Because of the high prevalence of depressive symptoms in people with cancer and the association with decrements in survival, the underlying biologic mechanisms associated with this link warrant further research.

Although several studies have now confirmed an association between depressive symptoms and increased cancer-related mortality,^13-19 many of the studies suffer from methodologic flaws including lack of standardized instruments to assess depressive symptoms^13-16 and the inclusion of other psychiatric diagnoses or psychiatric symptoms under the diagnosis of depression.^17,18

At this time, the predominant theory explaining the link between depressive symptoms and survival is modulation of the immune system. Ample evidence exists regarding the relationship between depressive symptoms and immune system modulation both in the general population^22,23 and in people diagnosed with cancer.^24,25 Excellent reviews are available that describe in detail the link between depression and immune system modulation²⁶; however, many unanswered questions still remain regarding the relationship between depressive symptoms and immune system functioning, including the temporal relationship between depressive symptoms and immune system modulation, differentiation between the effects of stress and depressive symptoms on immune system modulation,^27,28 dissociation regarding the independent effects of depression on inflammatory and natural killer (NK) immune responses,^29-31 and understanding the biologic mechanisms underlying subtypes of depressive symptoms.

Understanding the prevalence and physiologic consequences of depressive symptoms in hepatobiliary carcinoma (HBC) is critical because of the expected increase in prevalence of HBC in the next decade³² and the high rates of distress reported by people diagnosed with this cancer type.³³ The aims of the present study were to assess the prevalence of depressive symptoms in patients with HBC at diagnosis, examine the relationship between depressive symptoms and survival while controlling for sociodemographic and disease-specific variables as well as somatic symptoms of depression, and preliminarily test a mediational model of depression and survival, with immune system modulation as a possible mediator. The study will address limitations of previous research such as studying the association between depressive symptoms, immunity, and survival in a relatively homogenous sample of cancer patients; eliminating possible confounding effects of somatic symptoms in the evaluation of depression; adjusting for the influence of other psychosocial variables that have had an influence on immune system functioning^34-66; and testing the link among depressive symptoms, immune system parameters, and survival in a virally related cancer^67-73 in which immune system modulation has been demonstrated to be associated with disease progression.^74-93

	PATIENTS AND METHODS

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Design
The design of the study was prospective in that patients were followed from diagnosis to death. Patients were recruited from April 2003 to April 2006.

Participants
Participants were consecutive patients who were referred to a large tertiary center for the evaluation and treatment of one or more liver masses.⁹⁴ Sample 1 was part of an ongoing assessment of quality of life of patients with HBC (n = 78), and sample 2 was recruited specifically to study the relationship between psychosocial factors and immune functioning (n = 23). Eligibility criteria for the first study included biopsy proven diagnosis of HBC (hepatocellular, cholangiocarcinoma, neuroendocrine carcinoma of the liver, or colorectal cancer with metastases to the liver), age 18 years or older, fluency in English, and no active treatment for hepatitis B and/or C. Exclusion criteria included symptoms of psychosis and illness too severe to complete battery of questionnaires. The inclusion and exclusion criteria for the second study were the same with the exception that the diagnosis could only include hepatitis B–or C–related hepatocellular carcinoma.

Instruments
Sociodemographic questionnaire. The sociodemographic questionnaire queried participants regarding their age, sex, race, education, religious affiliation, marital status, residence, employment status, income, English proficiency, health insurance status, and religious affiliation. For the purposes of this study, age,⁹⁵ sex,³² and race⁹⁶ were included in the analyses because these variables have been demonstrated to be related to depressive symptoms and/or survival in people diagnosed with HBC in prior research.

Depressive symptoms. The Center for Epidemiological Studies Depression Scale (CES-D)⁹⁷ was used to assess depressive symptoms. The CES-D provides a narrow-band index for the presence of depression and is a 20-item self-report questionnaire that queries patients regarding depressive symptoms in the last 7 days. Participants responded to the items on a four-point Likert scale (0 = rarely or none of the time; 1 = some or a little of the time; 2 = occasionally or a moderate amount of time; and 3 = most or all of the time). The clinical cutoff has been established with a score of 16. The CES-D has been found to be reliable in studies of patients with breast cancer⁹⁸ and has demonstrated adequate content validity.⁹⁹ Two somatic symptoms (I did not feel like eating; my appetite was poor and my sleep was restless) were eliminated in a subset of the analyses (clinical cutoff score 14) to decrease the influence of somatic symptoms on immune system functioning and survival.

Immune System Parameters
Immune assays were performed at the University of Pittsburgh Cancer Institute's Immunologic Monitoring and Cellular Products Laboratory.

NK cell number and cytotoxicity. NK cells are large granular lymphocytes that constitute a major component of the innate immune system and attack cells that have been infected by foreign bodies.¹⁰⁰ NK cell number and cytotoxicity were measured using peripheral-blood mononuclear cells isolated on Ficoll-Hypaque gradients. A chromium-release assay was performed at the Immunologic Monitoring and Cellular Products Laboratory. Peripheral-blood mononuclear cells were plated in 96 wells at four different effector to target ratios and coincubated with chromium-labeled K562 targets for 4 hours at 37°C. The cells were harvested, and the percentage of specific lysis was determined using the following formula: 100 x (mean experimental counts per minute [cpm] –mean spontaneous release cpm)/(mean maximum release cpm –mean spontaneous release cpm). The results were expressed in lytic units (LU)/10⁷ cell plated. The absolute number and the percentage of NK cells (CD3^–CD56⁺CD16⁺) was determined by a single-platform flow cytometry–based method. Whole blood was used for staining of NK cells with fluorochrome-labeled monoclonal antibodies. Following lysis of the crythrocytes and the addition of sizing beads, NK cells were enumerated in a Coulter flow cytometer (Beckman Coulter, Fullerton, CA). Isotype controls were included. NK cell activity was expressed in LU/10⁶ NK cells present in the participants' peripheral circulation and provides an estimate of NK cell activity on a per-cell basis.

Cytokines. Cytokines, including interleukin (IL) -4, IL-5, interferon gamma (IFN-), and tumor necrosis factor alpha (TNF-), were assessed as a part of the present study.^101-106 Plasma cytokine levels of IL4, IL-5, IFN-, and TNF- were measured using commercially available enzyme-linked immunosorbent assays (R&D Systems, Minneapolis, MN). Plasma samples collected on the day of testing were frozen at –70°C and assayed in batches. Ninety-six–well plates were coated with monoclonal antibodies to IL-4, IL-5, IFN-, or TNF-. Standards, controls, and thawed samples were added, followed by biotinylated antibody against the appropriate cytokine, and terminated with H₂SO₄. The colorimetric reaction was analyzed with a plate spectrophotometer at 450 nm. Cytokine concentrations were extrapolated using standard curve with linear regression from a log-linear curve.

Survival
Survival was measured from the date of diagnosis at the University of Pittsburgh Medical Center's Liver Cancer Center until death of the patient. Survival data were gathered from the patient's family or the Social Security Death Index.

Confounding Variables
The following variables were measured and analyzed secondary to the effect on immune system function. Acute stress was measured using the Impact of Events Scale–Revised,¹⁰⁷ the Perceived Stress Scale,¹⁰⁸ and the Hassles and Uplifts Scale.¹⁰⁹ Chronic stress was measured using the Recent Life Changes Questionnaire,¹¹⁰ and traumatic stress was assessed using the Life Events Questionnaire.¹¹¹ Tobacco use was measured using the Fagerstrom Tolerance Questionnaire.¹¹² Alcohol use was measured using the Alcohol Use Disorders Identification Test.¹¹³ Physical activity was assessed using the International Physical Activity Questionnaire.^114,115 Sleep quality was assessed using the Pittsburgh Sleep Quality Index.¹¹⁶ Social support was measured using the Interpersonal Support Evaluation List.¹¹⁷

Disease-Specific Characteristics
Disease-specific information was gathered from the patients' medical records. On the basis of previous research, the following variables were included because they have been found to be associated with survival: cancer type by biopsy,¹¹⁸ presence of hepatitis B and C,¹¹⁹ cirrhosis,¹²⁰ tumor size,¹²¹ number of lesions,¹²² vascularity of lesion, and vascular invasion by computed tomography scan.¹²³

Procedure
Both studies were approved by the University of Pittsburgh's Institutional Review Board. Patients in both samples were referred to the principal investigator by their treating oncologist at the first appointment in which the patient was evaluated. The principal investigator explained the risks and benefits of the study to the patient, and the patient's written informed consent was obtained. Each patient completed the battery of questionnaires at the time of diagnosis. In addition, patients in the second study (n = 23) had blood drawn at the time of their routine blood draws to assess immune system parameters.

Data Analysis
All of the data were entered, verified, and analyzed using SPSS version 14 (SPSS Inc, Chicago, IL). Descriptive statistics were performed to obtain measures of central tendency, distribution, and percentages for each variable and internal consistency of the questionnaires, where appropriate, using Cronbach's coefficient. ² analysis or analysis of variance was used to test differences between the two samples on sociodemographic or disease-specific variables.

The variables were categorized for analyses according to the following clinically meaningful groups: sex, age ( 50 or > 50 years), race (white or nonwhite), cancer type (by diagnosis), presence or absence of hepatitis B and/or C, presence or absence of cirrhosis, size of lesion (< 5 or 5 cm), number of lesions ( two or > two lesions), vascularity of lesion (hypervascular/mixed vascularity or hypovascular), and the presence of vascular invasion. The CES-D was dichotomized according to the clinical criteria with (score 16) and without somatic symptoms (score 14).

Using analysis of variance, sociodemographic, disease-specific factors, stress, health-related behaviors, social support, and immune system functioning were tested to determine the association with depressive symptoms. Cox regression analyses were used to test the relationship between psychosocial factors, immunity, and survival. Power was tested using NCSS and PASS software (NCSS, Kaysville, UT).¹²⁴ The statistical approach outlined by Baron and Kenny¹²⁵ was used to test the mediation of depressive symptoms and survival, with immune system parameters serving as the mediator.

	RESULTS

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Sociodemographic and Disease-Specific Factors for the Entire Sample
One hundred thirty-one patients were approached to participate in the study. Figure 1 outlines the recruitment process.

View larger version (21K): [in this window] [in a new window] [PowerPoint Slide for Teaching]   Fig 1. Recruitment process of study participants. The figure depicts the number of patients who were eligible to participate, number of patients who agreed or refused to participate, and number of participants who reported a Center for Epidemiological Studies Depression Scale (CES-D) score of less than or 16 and their status at the end of the study.

Table 2 lists information regarding substance use including alcohol, tobacco, illicit drug, and antidepressant medication use. Of the entire sample, 49% of patients reported drinking two or more drinks per day before their diagnosis. Thirty-seven percent of patients reported a history of tobacco use, and 12% reported a history of drug use. Nineteen percent of patients reported being prescribed an antidepressant before their diagnosis of cancer.

Psychosocial Factors and Survival in HBC
Median survival time was 10.3 months for the entire sample, and 28% of patients had censored data (72% of patients had died at the time of analysis). Using Cox regression analysis with sociodemographic and disease-specific variables entered into the model, the variables of acute, chronic, and traumatic stress (n = 23); sleep (n = 23); alcohol, tobacco, and drug use (n = 101); and social support (n = 23) were not found to be related to survival. Using Cox regression analysis adjusting for sociodemographic and disease-specific variables, we found that depressive symptoms significantly predicted survival (Breslow ² = 32.4, P = .006). Only vascular invasion (P = .001) and CES-D score 16 (P = .03) significantly predicted decreased survival (Table 5).

View larger version (9K): [in this window] [in a new window] [PowerPoint Slide for Teaching]   Fig 2. Cumulative survival of patients diagnosed with hepatobiliary carcinoma with vascular invasion and a Center for Epidemiological Studies Depression Scale (CES-D) score of 16 (clinical range) versus a CES-D score of less than 16.

View larger version (10K): [in this window] [in a new window] [PowerPoint Slide for Teaching]   Fig 3. Cumulative survival of patients diagnosed with hepatobiliary carcinoma without vascular invasion and a Center for Epidemiological Studies Depression Scale (CES-D) score of 16 (clinical range) versus a CES-D score of less than 16.

Psychosocial Factors and Immunity
In a subsample of patients (n = 23), the associations between psychosocial factors and immunity were tested using analysis of covariance. Current alcohol consumption was found be associated with NK cell activity (F_1,20 = 4.8, P = .04). Patients with depressive symptoms in the clinical range of the CES-D (score 16) had significantly higher levels of CD8 (F_1,39 = 5.8, P = .02) and lower NK cell numbers (F_1,21 = 9.39, P = .003) compared with patients who reported CES-D scores of less than 16 (Fig 4). Only a subsample of patients (n = 10) had detectable ranges of IL-4 and IFN-. The associations between CES-D scores and IL-4 (F_1,10 = 2.2, P = .17), IL-5 (F_1,19 = 1.1, P = .30), IFN- (F_1,8 = 0.009, P = .93), and TNF- (F_1,20 = 0.70, P = .41) were not significant.

View larger version (11K): [in this window] [in a new window] [PowerPoint Slide for Teaching]   Fig 4. Difference in natural killer (NK) cell number in patients (n = 23) diagnosed with hepatobiliary carcinoma who reported a Center for Epidemiological Studies Depression Scale (CES-D) score of less than 16 versus 16.

Depressive Symptoms, Immunity, and Survival
In the test of the mediation model concerning the link between depressive symptoms and survival, with NK cell number as a mediator, depressive symptoms were no longer found to be significantly related to survival (Table 6).

	DISCUSSION

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The higher prevalence of depressive symptoms in people diagnosed may be explained by several factors. Simon et al²¹ have pointed out that a poor prognosis poses a greater psychological threat and, as a result, may be related to worse emotional functioning. Although there has been inconsistent results regarding the relationship between stage of cancer and psychological distress, the majority of studies have reported that more advanced disease, as with HBC, is associated with greater distress.^135-141 Additional factors, such as higher rates of substance abuse or dependence in this population^142,143 and/or the disruption of neuroendocrine and immune markers, which has been observed in colorectal and pancreatic cancer,^144,145 may also contribute to the higher rates of depressive symptoms found in this population.

Consistent with previous research in breast¹⁴⁶ and colon cancer,¹⁴⁷ depressive symptoms and decreased survival were found to be associated with decreased NK cell numbers in patients diagnosed with HBC. Although the sample size was limited in the present study and included only hepatitis B–and C–related hepatocellular carcinoma, the model testing the mediation between depressive symptoms and survival, with NK cell number as the mediator, was preliminarily supported, which suggests that further research is justified with a larger sample.

The results of this study suggest that, at a minimum, screening for depressive symptoms and referral for treatment of depression should be performed in clinical settings where patients with HBC or other immune-mediated cancers may present for diagnosis and/or treatment. Although previous research has found that psychosocial interventions improve quality of life, immune system functioning, and even survival,^148,149 randomized controlled trials testing the efficacy of psychosocial and pharmacologic interventions to reduce depression and improve health-related quality of life are warranted. If the tenets of this research are correct, then reduction of depressive symptoms through psychotherapy and/or pharmacologic intervention in patients diagnosed with HBC may enhance immune system functioning and possibly survival.

	AUTHORS' DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST

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The author(s) indicated no potential conflicts of interest.

	AUTHOR CONTRIBUTIONS

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Conception and design: Jennifer L. Steel, T. Clark Gamblin, Marion C. Olek, Brian I. Carr

Administrative support: Jennifer L. Steel, David A. Geller, T. Clark Gamblin, Brian I. Carr

Provision of study materials or patients: David A. Geller, T. Clark Gamblin, Marion C. Olek, Brian I. Carr

Collection and assembly of data: Jennifer L. Steel, Marion C. Olek, Brian I. Carr

Data analysis and interpretation: Jennifer L. Steel, T. Clark Gamblin, Marion C. Olek

Manuscript writing: Jennifer L. Steel, David A. Geller, T. Clark Gamblin, Marion C. Olek, Brian I. Carr

Final approval of manuscript: Jennifer L. Steel, David A. Geller, T. Clark Gamblin, Marion C. Olek, Brian I. Carr

	NOTES

 
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.

	REFERENCES

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1. Narkush RE, Schwab JJ, Farris P, et al: Mortality and community mental health: The Alachua Country, Florida Mortality Study. Arch Gen Psychiatry 34:1393-1401, 1977[Abstract/Free Full Text]

2. Murphy JM, Olivier DC, Sobol AM, et al: Diagnosis and outcome: Depression and anxiety in the general population. Psychol Med 16:117-126, 1986[Medline]

3. Kaplan GA, Reynolds P: Depression and cancer mortality and morbidity: Prospective evidence from the Alameda County Study. J Behav Med 11:1-13, 1988[CrossRef][Medline]

4. Bruce ML, Leaf PJ: Psychiatric disorders and 15-month mortality in a community sample of older adults. Am J Public Health 79:727-730, 1989[Abstract/Free Full Text]

5. Somervell PD, Kaplan BH, Heiss G, et al: Psychologic distress as a predictor of mortality. Am J Epidemiol 130:1013-1023, 1989[Abstract/Free Full Text]

6. Bruce ML, Leaf PJ, Rozal GP, et al: Psychiatric status and 9-year mortality data in the New Haven Epidemiological Catchments Area Study. Am J Psychiatry 151:716-721, 1994[Abstract/Free Full Text]

7. Huppert FA, Whittington JE: Symptoms of psychological distress predict 7-year mortality. Psychol Med 25:1073-1078, 1995[Medline]

8. Simonsick EM, Wallace RB, Blazer DG, et al: Depressive symptomatology and hypertension-associated morbidity and mortality in older adults. Psychosom Med 57:427-435, 1995[Abstract/Free Full Text]

9. Peveler R, Carson A, Rodin G: Depression in medical patients. BMJ 325:149-152, 2002[Free Full Text]

10. Carney RM, Blumenthal JA, Freedland KE, et al: Depression and late mortality after myocardial infarction in the Enhancing Recovery in Coronary Heart Disease (ENRICHD) study. Psychosom Med 66:466-474, 2004[Abstract/Free Full Text]

11. Yaffe K, Edwards ER, Covinsky KE, et al: Depressive symptoms and risk of mortality in frail, community-living elderly persons. Am J Geriatr Psychiatry 11:561-567, 2003[CrossRef][Medline]

12. Harris EC, Barraclogh B: Excess mortality of mental disorder. Br J Psychiatry 173:11-53, 1998[Abstract/Free Full Text]

13. Shekelle RB, Raynor WJ, Ostfeld AM, et al: Psychological depression and 17-year risk of death from cancer. Psychosom Med 43:117-125, 1981[Abstract/Free Full Text]

14. Loberiza FR, Rizzo JD, Bredeson CN, et al: Association of depressive syndrome and early death among patients after stem-cell transplantation for malignant diseases. J Clin Oncol 20:2118-2126, 2002[Abstract/Free Full Text]

15. Hoodin F, Kalbfleisch KR, Thornton J, et al: Psychosocial influences on 305 adults' survival after bone marrow transplantation: Depression, smoking, and behavioral self-regulation. J Psychosom Res 57:145-154, 2004[CrossRef][Medline]

16. Faller H, Schmidt M: Prognostic value of depressive coping and depression in survival of lung cancer patients. Psychooncology 13:359-363, 2004[CrossRef][Medline]

17. Hjerl K, Andersen EW, Keiding N, et al: Depression as a prognostic for breast cancer mortality. Psychosomatics 44:24-30, 2003[Abstract/Free Full Text]

18. Goodwin JS, Zhang DD, Ostir GV: Effect of depression on diagnosis, treatment, and survival of older women with breast cancer. J Am Geriatr Soc 52:106-111, 2004[CrossRef][Medline]

19. Hotopf M, Chidgey J, Addington-Hall J, et al: Depression in advanced disease: A systematic review—Part I: Prevalence and case finding. Palliat Med 16:81-97, 2002[Abstract/Free Full Text]

20. Raison CL, Miller AH: Depression in cancer: New Developments regarding diagnosis and treatment. Biol Psychiatry 54:283-294, 2003[CrossRef][Medline]

21. Simon A, Pamer SC, Coyne JC: Cancer and depression, in Steptoe A (ed): Depression and Physical Illness. Cambridge, United Kingdom, Cambridge University Press, 2006

22. Miller G, Cohen S, Herbert TB: Pathways linking major depression and immunity in ambulatory female patients. Psychosom Med 61:850-860, 1999[Abstract/Free Full Text]

23. Irwin M: Psychoneuroimmunology of depression: Clinical implications. Brain Behav Immun 16:1-16, 2002[CrossRef][Medline]

24. Musselman DL, Miller AH, Porter MR, et al: Higher than normal plasma interleukin-6 concentrations in cancer patients with depression: Preliminary findings. Am J Psychiatry 158:1252-1257, 2001[Abstract/Free Full Text]

25. Cohen S, Herbert TB: Health psychology: Psychological factors and physical disease from the perspective of human psychoneuroimmunology. Annu Rev Psychol 47:113-142, 1996[CrossRef][Medline]

26. Reiche EMV, Nunes SOV, Morimoto HK: Stress, depression, and the immune system and cancer. Lancet 5:617-625, 2004[CrossRef]

27. Holden RJ, Pakula IS, Mooney PA: An immunological model connecting the pathogenesis of stress, depression and carcinoma. Med Hypotheses 51:309-314, 1998[CrossRef][Medline]

28. Pike J, Irwin MR: Dissociation of inflammatory markers and natural killer cell activity in major depressive disorder. Brain Behav Immun 20:169-174, 2005[CrossRef][Medline]

29. Zorrilla L, Luborsky JR, McKay R, et al: The relationship of depression and stressors to immunological assays: A meta-analytic review. Brain Behav Immunol 15:199-226, 2001[CrossRef][Medline]

30. Maunsell E, Brisson J, Mondor M, et al: Stressful life events and survival after breast cancer. Psychosom Med 63:301-315, 2001

31. Appelberg B, Katila H, Rimon R: Plasma interleukin-1 beta and sleep architecture in schizophrenia and other nonaffective psychoses. Psychosom Med 59:529-532, 1998

32. Harrison TJ: Viral hepatitis and primary liver cancer, in Arrand JR, Harper DR (eds): Viruses and Human Cancer. Oxford, United Kingdom, BIOS Scientific Publishers Limited, 1998

33. Zabora J, Brintzenhofeszoc K, Curbow B, et al: The prevalence of psychological distress by cancer site. Psychooncology 10:19-28, 2001[CrossRef][Medline]

34. Irwin M, Smith TL, Christian G: Electroencephalographic sleep and natural killer activity in depressed patients and control subjects. Psychosom Med 54:10-21, 1992[Abstract/Free Full Text]

35. Savard J, Miller SM, Mills M, et al: Association between subjective sleep quality and depression on immunocompetence in low-income women at risk for cervical cancer. Psychosom Med 61:496-507, 1999[Abstract/Free Full Text]

36. Palmblad J, Petrini B, Wasserman J, et al: Lymphocyte and granulocyte reactions during sleep deprivation. Psychosom Med 41:273-278, 1979[Abstract/Free Full Text]

37. Moldofsky H, Lue FA, Eisen J, et al: The relationship of interleukin-1 and immune functions to sleep in humans. Psychosom Med 48:309-318, 1986[Abstract/Free Full Text]

38. Uthgenannt D, Schoolmann D, Pietrowsky R, et al: Effects of sleep on the production of cytokines in humans. Psychosom Med 57:97-104, 1995[Abstract/Free Full Text]

39. Irwin M, Mascovich A, Gillin JC, et al: Partial sleep deprivation reduces natural killer cell activity in humans. Psychosom Med 56:493-498, 1994[Abstract/Free Full Text]

40. Kronfol Z, Nair M, Zhang Q, et al: Circadian immune measures in healthy volunteers: Relationship to hypothalamic-pituitary-adrenal axis hormones and sympathetic neurotransmitters. Psychosom Med 59:42-50, 1997[Abstract/Free Full Text]

41. Hall M, Baum A, Buysse DJ, et al: Sleep as a mediator of the stress-immune relationship. Psychosom Med 60:48-51, 1998[Abstract/Free Full Text]

42. Lacks P, Morin CM: Recent advances in the assessment and treatment of insomnia. J Consult Clin Psychol 60:586-594, 1992[CrossRef][Medline]

43. MacGregor RR: Alcohol and immune defense. JAMA 256:1474-1479, 1986[Abstract/Free Full Text]

44. Grunberg NE, Baum A: Biological commonalties of stress and substance abuse, in Shiffman IS, Willis TA (eds): Coping and Substance Use. San Diego, CA, Academic Press, 1985, pp 25-62

45. Laso FJ, Madruga JI, San Miguel JF, et al: Long lasting immunological effects of ethanol after withdrawal. Cytometry 26:275-280, 1996[CrossRef][Medline]

46. Geissler M, Gesien A, Wanda JR: Chronic ethanol effects on cellular immune responses to hepatitis B virus envelope protein: An immunologic mechanism for reduction of persistent viral infection in alcoholics. Hepatology 26:764-770, 1997[CrossRef][Medline]

47. Holt PG: Immune and inflammatory function in cigarette smokers. Thorax 42:241-249, 1987[Free Full Text]

48. Friedman H, Klein T, Specter S: Immunosuppression by marijuana and components, in Ader R, Felten DL, Cohen N (eds): Psychoneuro-Immunology. San Diego, CA, Academic Press, 1991, pp 66-85

49. Dews PB (ed): Caffeine. New York, NY, Springer-Verlag, 1987

50. Butrum RP, Clifford CK, Lanza E: NCI dietary guidelines: Rationale. Am J Clin Nutr 48:888-895, 1988 (suppl 3)[Abstract/Free Full Text]

51. Klaish LA: Relationship of body size with breast cancer. J Clin Oncol 2:287-293, 1984[Abstract]

52. Garland M, Willett WC, Manson JE, et al: Antioxidant micronutrients and breast cancer. J Am Coll Nutr 12:400-411, 1993[Abstract]

53. Venkatraman JT, Pendergast D: Effects of the level of dietary fat intake and endurance exercise on plasma cytokines in runners. Med Sci Sports Exerc 30:1198-1204, 1998

54. Sarin SK, Dhingra N, Bansal A, et al: Dietary and nutritional abnormalities in alcoholic liver disease: A comparison with chronic alcoholics without liver disease. Am J Gasteroenterol 92:777-783, 1997[Medline]

55. Kusaka Y, Kondou H, Morimoto K: Healthy lifestyles are associated with higher natural killer cell activity. Prev Med 21:602-615, 1992[CrossRef][Medline]

56. Nair MP, Krofol ZA, Schwartz SA: Effects of alcohol and nicotine on cytotoxic function of human lymphocytes. Clin Immunol Immunopathol 54:395-409, 1990[CrossRef][Medline]

57. Windle M, Mondul T, Whitney RB, et al: A discriminant function analysis of various interferon parameters among alcoholic and heavy smokers. Drug Alcohol Depend 31:139-147, 1993[CrossRef][Medline]

58. Starkenburg S, Munroe ME, Waltenbaugh C: Early alteration in leukocyte populations and Th1/Th2 function in ethanol-consuming mice. Alcohol Clin Exp Res 25:1221-1230, 2001[CrossRef][Medline]

59. Irwin M, Miller C: Decreased natural killer cell responses and altered interleukin-7 and interleukin-10 production in alcoholism: An interaction between alcohol dependence and African American ethnicity. Alcohol Clin Exp Res 24:560-569, 2000[CrossRef][Medline]

60. Laso FJ, Lapena P, Madruga JI, et al: Alterations in tumor necrosis factor-alpha, interferon-gamma, and interleukin-6 production by natural killer cell-enriched peripheral blood mononuclear cells in chronic alcoholism: Relationship with liver disease and ethanol intake. Alcohol Clin Exp Res 21:1226-1231, 1997[Medline]

61. Ben-Eliyahu S, Page GG, Yirmiya R, et al: Acute alcohol intoxication suppresses natural killer cell activity and promotes tumor metastasis. Nat Med 2:457-460, 1996[CrossRef][Medline]

62. Schantz SP, Campbell BH, Guillamondegui OM: Pharyngeal carcinoma and natural killer cell activity. Am J Surg 152:467-474, 1986[CrossRef][Medline]

63. Miyazaki T, Ishikawa T, Nakata A, et al: Association between perceived social support and Th1 dominance. Biol Psychol 70:30-37, 2005[CrossRef][Medline]

64. Dixon D, Cruess S, Kilbourn K, et al: Social support mediates loneliness and human herpesvirus type 6 (HHV-6) antibody titers. J Appl Soc Psychol 31:1111-1132, 2001[CrossRef]

65. Uchino B, Cacioppo JT, Kiecolt-Glaser JK: The relationship between social support and physiological processes: A review with emphasis on underlying mechanisms and implications for health. Psychol Bull 119:488-531, 1996[CrossRef][Medline]

66. Kiecolt-Glaser JK, McGuire L, Robles TF, et al: Psychoneuroimmunology: Psychological influences on immune function and health. J Consult Clin Psychol 70:537-547, 2002[CrossRef][Medline]

67. Antoni MH: Psychoneuroendocrinology and psychoneuroimmunology of cancer: Plausible mechanisms worth pursuing? Brain Behav Immun 17:S84-S91, 2003 (suppl)[CrossRef][Medline]

68. Han SL, Zhu B, Yao JG, et al: Diagnosis and surgical treatment of primary hepatic cholangiocarcinoma. Hepatogastroenterology 52:348-351, 2005[Medline]

69. Kanazawa A, Kubo S, Hirohashi K, et al: Two cases of intrahepatic cholangiocarcinoma detected after interferon therapy for chronic hepatitis C. Hepatogastroenterology 52:1869-1973, 2005[Medline]

70. Wiwanitkit V: Seroprevalence of hepatitis virus B seropositive in patients with cholangiocarcinoma: A summary. Asian Pac J Cancer Prev 6:27-28, 2005[Medline]

71. Grayson W, Rhemtula HA, Taylor LF, et al: Detection of human papillomavirus in large cell neuroendocrine carcinoma of the uterine cervix: A study of 12 cases. J Clin Pathol 55:108-114, 2002[Abstract/Free Full Text]

72. Harkins L, Volk AL, Samanta M, et al: Specific localization of human cytomegalovirus nucleic acids and proteins in human colorectal cancer. Lancet 360:1557-1563, 2002[CrossRef][Medline]

73. Liu HX, Ding YQ, Yao KT: Investigation of Epstein-Barr virus in Chinese colorectal tumors. World J Gastroenterol 9:2464-2468, 2003[Medline]

74. Nakajima T, Mizushima N, Kanai K: Relationship between natural killer activity and development of hepatocellular carcinoma in patient with cirrhosis of the liver. Jpn J Clin Oncol 17:327-332, 1998

75. Okanoue T, Itoh Y, Minami M, et al: Interferon therapy lowers the rate of progression to hepatocellular carcinoma in chronic hepatitis C but not significantly in an advanced stage: A retrospective study in 1148 patients. J Hepatol 30:653-659, 1999[CrossRef][Medline]

76. Fang Y, Wang L, Jin J, et al: Focal adhesion kinase affects the sensitivity of human hepatocellular carcinoma cell line SMMC-7721 to tumor necrosis factor-alpha/cycloheximide-induced apoptosis by regulating protein kinase B levels. Eur J Biochem 268:4513-4519, 2001[Medline]

77. Taketomi A, Shimada M, Shirabe K, et al: Natural killer cell activity in patients with hepatocellular carcinoma. Cancer 83:58-63, 1998[CrossRef][Medline]

78. Actis GC, Ponzetto A, D'Urso N, et al: Chronic active hepatitis: Interferon-activated natural killer like cells against a hepatoma cell line transfected with the hepatitis B virus nucleic acid. Liver 11:106-113, 1991[Medline]

79. Kawarabayashi N, Seki S, Hatsuse K, et al: Decrease of CD56+ cell and natural killer cells in cirrhotic livers with hepatitis C may be involved in their susceptibility to hepatocellular carcinoma. Hepatology 32:962-969, 2000[CrossRef][Medline]

80. Nakajima T, Mizushima N, Kanai K: Relationship between natural killer activity and development of hepatocellular carcinoma in patient with cirrhosis of the liver. Jpn J Clin Oncol 17:327-332, 1998

81. Oshikiri T, Miyamoto M, Morita T, et al: Tumor-associated antigen recognized by the 22-1-1 monoclonal antibody encourages colorectal cancer progression under the scanty CD8+ T cells. Clin Cancer Res 12:411-416, 2006[Abstract/Free Full Text]

82. McMillan DC, Fyffe GD, Wotherspoon HA, et al: Prospective study of circulating T-lymphocyte subpopulations and disease progression in colorectal cancer. Dis Colon Rectum 40:1068-1077, 1997[CrossRef][Medline]

83. Durrant LG, Buckley DJ, Spendlove I, et al: Low doses of 105AD7 cancer vaccine preferentially stimulate anti-tumor T-cell immunity. Hybridoma 16:23-26, 1997[Medline]

84. Norris S, Doherty DG, Curry M, et al: Selective reduction of natural killer cells and T cells expressing inhibitory receptors for MHC class I in the livers of patients with hepatic malignancy. Cancer Immunol Immunother 52:53-58, 2003[Medline]

85. Takagi S, Miyagawa S, Ichikawa E, et al: Dendritic cells, T-cell infiltration, and Grp94 expression in cholangiocellular carcinoma. Human Pathol 35:881-886, 2004[CrossRef][Medline]

86. Fogar P, Sperti C, Basso D, et al: Decreased total lymphocyte counts in pancreatic cancer: An index of adverse outcome. Pancreas 32:22-28, 2006[CrossRef][Medline]

87. Uchida M, Ichida T, Sato K, et al: Detection of intracellular interleukin-2 production in peripheral T lymphocytes by flow cytometry in patients with pancreatobiliary malignancies. J Gastroenterol Hepatol 15:1212-1218, 2000[CrossRef][Medline]

88. Cubillos L, Gonzalez S, Sepulveda C, et al: Immunological evaluation of patients with invasive carcinoma of the gallbladder. J Cancer Res Clin Oncol 119:497-500, 1993[CrossRef][Medline]

89. Tsujimoto T, Kuriyama S, Yamazaki M, et al: Augmented hepatocellular carcinoma progression and depressed Kupffer cell activity in rat cirrhotic livers. Int J Oncol 18:41-47, 2001[Medline]

90. Wang D, Yang E, Cheng LY: Effects of IFN-gamma, TNF-alpha and EGF on expression of HLA class I antigen and the proliferation of human hepatocellular carcinoma HepG2 cells. Anticancer Res 17:181-188, 1997[Medline]

91. Feng X, Tang X, Zheng Z: Preliminary studies on the effects of tumor necrosis factor gene transfer on the growth of human hepatocellular carcinoma cells in nude mice. Zhonghua Zhong Liu Za Zhi 17:167-169, 1995[Medline]

92. Osawa Y, Nagaki M, Banno Y, et al: Possible involvement of reactive oxygen species in D-galactosamine-induced sensitization against tumor necrosis factor-alpha induced hepatocyte apoptosis. J Cell Physiol 187:374-385, 2001[CrossRef][Medline]

93. Atarashi Y, Yasumura S, Nambu S, et al: A novel human tumor necrosis factor alpha mutein, F4614, inhibits in vitro and in vivo growth of murine and human hepatoma: Implications for immunotherapy of hepatocellular carcinoma. Hepatology 28:57-67, 1998[CrossRef][Medline]

94. Geller DA, Tsung A, Marsh JW, et al: Outcome of 1,000 liver cancer patients evaluated at the UPMC liver cancer center. J Gastrointest Surg 10:63-68, 2006[CrossRef][Medline]

95. Shimada K, Sano T, Sakamoto Y, et al: A long-term follow-up and management study of hepatocellular carcinoma patients reviving for 10 years or longer after curative hepatectomy. Cancer 104:1939-1947, 2005[CrossRef][Medline]

96. Chin OL, Chu DZ, Clarke KG, et al: Ethnic differences in behavior or hepatocellular carcinoma. Cancer 85:1931-1936, 1999[Medline]

97. Radloff LS: The CES-D scale: A self-report depression scale for research in the general population. Appl Psychol Measure 1:385-401, 1977[CrossRef]

98. Hann D, Winter K, Jacobsen P: Measurement of depressive symptoms in cancer patients: Evaluation of the Center for Epidemiological Studies Depression Scale (CES-D). J Psychosom Res 46:437-443, 1999[CrossRef][Medline]

99. Okun A, Stein R, Bauman L, et al: Content validity of the Psychiatric Symptom Index, CES-Depression Scale, and State-Trait Anxiety Inventory from the perspective of DSM-IV. Psychol Rep 79:1059-1069, 1996[Medline]

100. Herberman RB: Natural killer (NK) cells and their possible roles in resistance against disease. Clin Immunol Rev 1:1-65, 1981[Medline]

101. Howard M, Harada N: Guidebook to Cytokines and Their Receptors. New York, NY, Oxford Press, 1994

102. Banchereau J, Ryback ME: The Cytokine Handbook (ed 2). New York, NY, Academic Press, 1994

103. Yokota T: Peptide Growth Factors and Their Receptors. New York, NY, Springer-Verlag, 1990

104. Sideras P, Noma T, Honjo T: Structure and function of interleukin 4 and 5. Immunol Rev 102:189-212, 1988[CrossRef][Medline]

105. Wheelock EF, Schenker S, Combes B: Absence of circulating interferon in patients with infectious and serum hepatitis. Proc Soc Exp Biol Med 128:251-253, 1968[CrossRef][Medline]

106. Beutler B, Cerami A: Cachectin: More than a tumor necrosis factor. N Engl J Med 316:379-385, 1987[Medline]

107. Joseph SA, Williams R, Yule W, et al: Factor analysis of the Impact of events scale with survivors of two disasters at sea. Personality and Individual Differences 13:693-697, 1992[CrossRef]

108. Kohn PM, Macdonald JE: The Survey of Recent Life Experiences: A decontaminated Hassles Scale for adults. J Behav Med 15:221-236, 1992[CrossRef][Medline]

109. Dohrenwend BP, Link BG, Kern R, et al: Measuring life events: The problem of variability within event categories. Stress Medicine 6:179-187, 1990[CrossRef]

110. Pearson JE, Long T: Life change measurement, scoring, reliability, and subjective estimate of adjustment. Measure Evaluation Counseling Development 18:72-80, 1985

111. DeLongis A, Folkman S, Lazarus RS: The impact of daily stress on health and mood: Psychological and social resources as mediators. J Pers Soc Psychol 54:486-495, 1986

112. Fagerstrom K-O, Schneider NG: Measuring nicotine dependence: A review of the Fagerstrom Tolerance Questionnaire. J Behav Med 12:159-182, 1989[CrossRef][Medline]

113. Selzer ML: NIAA Treatment Handbook Series 2: Alcoholism Treatment Assessment Research Instruments. Rockville, MD, National Institute on Alcohol Abuse and Alcoholism, 1985

114. Booth M: Assessment of physical activity: An international perspective. Res Q Exerc Sport 71:S114-S120, 2000 (suppl 2)[Medline]

115. Craig CL, Marshall AL, Sjöström M, et al: International Physical Activity Questionnaire (IPAQ): 12-country reliability and validity. Med Sci Sports Exerc 35:1381-1395, 2003

116. Buysse DJ, Reynolds CF, Monk TH, et al: Pittsburgh Sleep Quality Index: Temporal profiles of the course of depression during treatment. Arch Gen Psychiatry 54:1016-1024, 1997[Abstract/Free Full Text]

117. Cohen S, Hoberman HM: Positive events and social supports as buffers of life change stress. J App Soc Psych 13:99-125, 1983[CrossRef]

118. Ueno S, Tanabe G, Yoshida A, et al: Postoperative prediction of and strategy for metastatic recurrent hepatocellular carcinoma according to histologic activity in hepatitis. Cancer 86:248-254, 1999[CrossRef][Medline]

119. Capussott L, Muratore A, Amisano M, et al: Liver resection for hepatocellular carcinoma on cirrhosis: Analysis of mortality, morbidity, and survival—A European single center experience. Eur J Surg Oncol 31:986-993, 2005[CrossRef][Medline]

120. Dupont-Bierre E, Compagnon P, Raoul JL, et al: Resection of hepatocellular carcinoma in noncirrhotic liver: Analysis of risk factors for survival. J Am Coll Surg 201:663-670, 2005[CrossRef][Medline]

121. Katyal S, Oliver JH, Peterson MS, et al: Prognostic significance of arterial phase CT for prediction of response to transcatheter arterial chemoembolization in unresectable hepatocellular carcinoma: A retrospective analysis. Am J Gerontol 175:1665-1672, 2000

122. Hayashi M, Matsui O, Ueda K, et al: Progression to hypervascular hepatocellular carcinoma: Correlation with intranodular blood supply evaluated with CT during intraarterial injection of contrast material. Radiology 225:143-149, 2002[Abstract/Free Full Text]

123. Bruix J, Sala M, Llovet JM: Chemoembolization for hepatocellular carcinoma. Gastroenterology 127:179-188, 2004 (supp 1)[CrossRef][Medline]

124. Hintze J: NCSS and PASS Number Cruncher Statistics Systems. www.ncss.com

125. Baron RM, Kenny DA: The moderator-mediator variable distinction in social psychological research: Conceptual, strategic and statistical considerations. J Pers Soc Psychol 51:1173-1182, 1986[CrossRef][Medline]

126. Jiang W, Babyak MA, Rozanski A, et al: Depression and increased myocardial ischemic activity in patients with ischemic heart disease. American Heart J 146:55-61, 2003[CrossRef][Medline]

127. Ransom S, Jacobsen PB, Booth-Jones M: Validation of the distress thermometer with bone marrow transplant patients. Psycho-Oncology 15:604-612, 2006[CrossRef][Medline]

128. Black SA: Increased health burden associated with comorbid depression in older diabetic Mexican Americans: Results from the Hispanic Estabished Population for the Epidemiologic Study of the Elderly survey, Diabetes Care 22:56-64, 1999[Abstract/Free Full Text]

129. Patten SB, Lavorato DH, Metz LM: Clinical correlates of CES-D depressive symptom ratings in an MS population. General Hospital Psychiatry 27:439-445, 2005[CrossRef][Medline]

130. Fowler JM, Carpenter KM, Gupta P, et al: The gynecologic oncology consult: Symptom presentation and concurrent symptoms of depression and anxiety. Obstetrics & Gynecology 103:1211-1217, 2004[CrossRef][Medline]

131. Haringsma R, Engels GI, Beekman ATF, et al: The criterion validity of the Center for Epidemiological Studies Depression Scale (CES-D) in a sample of self-referred elders with depressive symptomatology. International Journal of Geriatric Psychiatry 19:558-563, 2004[CrossRef][Medline]

132. American Psychiatric Association.Diagnostic and Statistical Manual of Mental Disorders (ed 4). Washington, DC, American Psychiatric Association, 1994

133. Newport JD, Nemeroff CB: Assessment and treatment of depression in the cancer patient. J Psychosom Res 45:215-237, 1998[CrossRef][Medline]

134. Harringsma R, Engels GI, Beekman ATF, et al: The criterion validity of the Center for Epidemiological Studies Depression Scale (CES-D) in a sample of self-referred elders with depressive symptomatology. Int J Geriatr Psychiatry 19:558-563, 2004[CrossRef][Medline]

135. Lloyd-Williams M, Friedman T: Depression in palliative care patients-a prospective study. Eur J Cancer Care 10:270-274, 2001[CrossRef]

136. Osborne RH, Elsworth GR, Hopper JL: Age specific norms and determinants of anxiety and depression in 731 women with breast cancer recruited through a population-based cancer registry. Eur J Cancer 39:755-776, 2003[CrossRef][Medline]

137. Gallagher J, Parle M, Cairns D: Appraisal and psychological distress six months after diagnosis of breast cancer. Br J Health Psychol 7:365-376, 2002[CrossRef][Medline]

138. Shimozuma K, Ganz PA, Petersen L, et al: Quality of life in the fist year after breast cancer surgery: Rehabilitation needs and patterns of recovery. Breast Cancer Res Treat 56:45-57, 1999[CrossRef][Medline]

139. Kissane DW, Grabsch B, Love A, et al: Psychiatric disorder in women with early stage and advanced breast cancer: A comparative analysis. Aust N Z J Psychiatry 38:320-326, 2004[CrossRef][Medline]

140. Bleiker EM, Pouwer F, van der Ploeg HM, et al: Psychological distress two years after diagnosis of breast cancer: Frequency and prediction. Patient Educ Couns 40:209-217, 2000[CrossRef][Medline]

141. Norum J: Adjuvant chemotherapy in Duke's B and C colorectal cancer has only a minor influence on psychological distress. Support Cancer Care 5:318-321, 1997[CrossRef]

142. Haavisto A, Sourander A, Multimaki P, et al: Factors associated with depressive symptoms among 18-year-old boys: A prospective 10-year follow-up study. J Affect Disord 83:143-154, 2004[CrossRef][Medline]

143. Dodge R, Sindelar J, Sinha R: The role of depression symptoms in predicting drug abstinence in outpatient substance abuse treatment. J Subst Abuse Treat 28:189-196, 2005[CrossRef][Medline]

144. Passik SD, Breitbart WS: Depression in patients with pancreatic carcinoma: Diagnostic and treatment issues. Cancer Suppl 78:615-626, 1996

145. Allen-Mersh TG, Glover C, Fordy C, et al: Relation between depression and circulating immune products in patients with advanced colorectal cancer. J R Soc Med 91:408-413, 1998[Abstract]

146. Sachs G, Rasoul-Rockenschaub S, Aschauer H, et al: Lytic effector cell activity and major depressive disorder in patients with breast cancer: A prospective study. J Neuroimmunol 59:83-89, 1995[CrossRef][Medline]

147. Orsi AJ, McCorkle R, Tax A, et al: The relationship between depressive symptoms and immune status phenotypes in patients undergoing surgery for colorectal cancer. Psychooncology 5:311-319, 1996[CrossRef]

148. Miller G, Cohen S: Psychological interventions and the immune system: A meta-analytic review and critique. Health Psychol 20:47-63, 2001[CrossRef][Medline]

149. Spiegel D: Cancer and depression. Br J Psychiatry Suppl 30:109-116, 1996

Submitted March 6, 2006; accepted January 8, 2007.

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