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J Pain Symptom Manage. 2010 May;39(5):859-71. doi: 10.1016/j.jpainsymman.2009.09.019.

Cancer-related symptom clusters, eosinophils, and survival in hepatobiliary cancer: an exploratory study.

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Department of Surgery, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15213, USA.



The study of symptom clusters is gaining increased attention in the field of oncology in an attempt to improve the quality of life of patients diagnosed with cancer.


The aims of the present study were to 1) determine the prevalence and distribution of pain, fatigue, and symptoms of depression and their covariation as a cluster in people with hepatobiliary carcinoma (HBC), 2) characterize how variation in each individual symptom and/or their covariation as a cluster are associated with changes in immunity, and 3) determine if the symptom clusters, and associated biomarkers, are related to survival in people diagnosed with HBC.


Two hundred six participants diagnosed with HBC completed a battery of standardized questionnaires measuring cancer-related symptoms. Peripheral blood leukocytes were measured at diagnosis and at three- and six-month follow-ups. Survival was measured from the date of diagnosis to death.


Cancer-related symptoms were prevalent and two-step hierarchical cluster analyses yielded three symptom clusters. High levels of pain, fatigue, and depression were found to be associated with elevated eosinophil percentages (F[1,78]=3.1, P=0.05) at three- and six-month follow-up using repeated-measures analysis of variance. Using multivariate latent growth curve modeling, pain was the primary symptom associated with elevated eosinophil percentages between diagnosis and six months (z=2.24, P=0.05). Using Cox regression, vascular invasion and age were negatively associated with survival (Chi-square=21.6, P=0.03). While stratifying for vascular invasion, Kaplan-Meier survival analysis was performed, and eosinophil levels above the median for the sample were found to be related to increased survival in patients with and without vascular invasion (Breslow Chi-square=4.9, P=0.03). Symptom clusters did not mediate the relationship between eosinophils and survival.


Cancer-related symptoms, particularly pain and depression, were associated with increased percentages of eosinophils. The presence of symptoms may reflect tumor cell death and be indicative of response to treatment, or other processes, in patients with HBC.

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