Eisho Yoshikawa

Smaller regional volumes of brain gray and white matter demonstrated in breast cancer survivors exposed to adjuvant chemotherapy.

Previous studies have shown cognitive impairment in breast cancer survivors who were exposed to adjuvant chemotherapy. Neural damage by chemotherapy might have played some part in these findings. The current study explored the regional brain volume difference between breast cancer survivors exposed to adjuvant chemotherapy (C+) and those unexposed (C−).

Development of a brief screening interview for adjustment disorders and major depression in patients with cancer.

Adjustment disorders and major depression are common psychiatric disorders in patients with cancer and have a serious impact on quality of life. The problem in clinical oncology settings is underrecognition of these disorders; as a result, screening is recommended to detect them. The goal of the current study was to develop a new, brief screening tool for adjustment disorders and major depression and to compare its performance with that of existing screening methods.

No adverse effects of adjuvant chemotherapy on hippocampal volume in Japanese breast cancer survivors.

SummaryWe investigated the adverse effects of adjuvant chemotherapy on the hippocampus in Japanese breast cancer survivors with (n=44) and without (n=31) adjuvant chemotherapy. There were no significant differences in hippocampal volume (magnetic resonance imaging) or additionally in memory function (Wechsler Memory Scale-Revised) between the two groups.

Depression and survival in patients with non-small cell lung cancer after curative resection : a preliminary study

Psychological depression is thought to be a predictor of poor survival among cancer patients. The objective of the present study was to investigate the association between depression and survival in surgically treated Japanese patients with non‐small cell lung cancer (NSCLC). From June 1996 through April 1999, a total of 229 patients with postoperative lung cancer were enrolled. Three months after the patients’ surgery, the Structured Clinical Interview for DSM‐III‐R (SCID) and the Profile of Mood States (POMS) were used to assess the patient for depression, based on the interviewers’ rating and a self‐report, respectively. The follow‐up period consisted of a total of 14 342 person‐months (median = 69 months). As of January 2004, 55 deaths had occurred within the follow‐up period. A Cox regression was used to estimate the hazard ratio (HR) of mortality adjusting for age, sex, smoking status, occasion of diagnosis, pathological stage and preoperative percentage forced expiratory volume in 1 s. The depression‐dejection subscale on the POMS was divided into three score levels. The multivariate HR of survival for individuals with depression, as diagnosed by the SCID, was 2.2 (95% confidence interval 0.8–6.0) (P‐value = 0.14), compared with individuals without depression. The multivariate HR of survival for subjects in the highest level of the POMS Depression–Dejection subscale was 1.4 (0.7–2.6), compared with in the lowest level (trend P‐value = 0.0502). This prospective cohort study in Japan does not support the hypothesis that depression is associated with survival among NSCLC patients after curative resection, but further analysis involving a long‐term follow‐up period is needed. (Cancer Sci 2006; 97: 199–205)

Prefrontal cortex and amygdala volume in first minor or major depressive episode after cancer diagnosis.

BACKGROUND Major and minor depressive episodes in cancer patients are frequent and are frequently seen as the first depressive episode in a patients life. However, the neurological basis of these depressive episodes remains largely unknown. METHODS Subjects were 51 breast cancer survivors (BCS) who had no history of any depressive episode before the cancer diagnosis (11 BCS with a history of a first minor depressive episode after cancer diagnosis, 11 BCS with a history of a first major depressive episode after cancer diagnosis, and 29 BCS with no history of any depressive episode after cancer diagnosis). We analyzed the prefrontal cortex (PFC) and amygdala volumes in a 1.5-Tesla Magnetic Resonance Imaging scanner. We characterized the structural correlates of depression using two complementary approaches. The first was voxel-based morphometry (VBM) that allowed us to scan the entire brain for reactive gray matter deficit. The second was classical volumetry focusing on the amygdala. RESULTS Voxel-based morphometry revealed no brain region, including PFC, for which volume was significantly different among the three groups. There were trend-level differences in the left amygdala volume in the manual tracing method among the three groups. The left amygdala volumes in the subjects with a first minor and/or major depressive episode were significantly smaller than in those with no history of any depressive episode. CONCLUSIONS It might be suggested that amygdala volume was associated with a first minor and/or major depressive episode after cancer diagnosis.

Marital status, social support and survival after curative resection in non-small-cell lung cancer.

It has been suggested that marital status and social support are associated with survival in cases of lung cancer, and that such an association may be mediated by several factors. In this prospective cohort study, we investigated the effect of marital status and social support on survival after curative resection for non‐small cell lung carcinoma (NSCLC) in Japan. From June 1996 to April 1999, a total of 238 patients with resectable NSCLC were enrolled. Marital status and social support were assessed. The presence and absence of confidants and the satisfaction level with the confidants were used as factors reflecting social support. During the follow‐up period, 57 deaths from all causes were identified through January 2004. For the statistical analysis, Cox proportional hazards regression analyses were used. With regard to marital status, the multivariable adjusted hazard ratio (HR) of unmarried patients versus married patients was 0.8 (95% confidence interval, 0.3–1.8) (P‐value = 0.53) after controlling for potential confounding factors, including age, sex, occasion of cancer diagnosis, pathological stage, smoking status, smoking status after surgery and serum albumin level. Similarly, the multivariable adjusted HR of patients without confidants versus those with confidants was 1.0 (0.5–2.2) (P‐value = 0.90), whereas the multivariable adjusted HR of the dissatisfied‐with‐confidants group versus the satisfied‐with‐confidants group was 0.7 (0.4–1.3) (P‐value = 0.28). The present data do not support the hypothesis that marital status and social support are associated with survival in NSCLC. (Cancer Sci 2006; 97: 206–213)

Personality and cancer survival: the Miyagi cohort study.

We tested the hypothesis that personality plays a role in cancer outcome in a population-based prospective cohort study in Japan. In July 1990, 41 442 residents of Japan completed a short form of the Eysenck Personality Questionnaire-Revised and a questionnaire on various health habits, and between January 1993 and December 1997, 890 incident cases of cancer were identified among them. These 890 cases were followed up until March 2001, and a total of 356 deaths from all causes was identified among them. Cox proportional-hazards regression was used to estimate the hazard ratio (HR) of death according to four score levels on each of four personality subscales (extraversion, neuroticism, psychoticism, and lie), with adjustment for potential confounding factors. Multivariable HRs of deaths from all causes for individuals in the highest score level on each personality subscale compared with those at the lowest level were 1.0 for extraversion (95% CI=0.8–1.4; Trend P=0.73), 1.1 for neuroticism (0.8–1.6; Trend P=0.24), 1.2 for psychoticism (0.9–1.6; Trend P=0.29), and 1.0 for lie (0.7–1.5; Trend P=0.90). The data obtained in this population-based prospective cohort study in Japan do not support the hypothesis that personality is associated with cancer survival.

Association between adjuvant regional radiotherapy and cognitive function in breast cancer patients treated with conservation therapy

Although protracted cognitive impairment has been reported to occur after radiotherapy even when such therapy is not directed to brain areas, the mechanism remains unclear. This study investigated whether breast cancer patients exposed to local radiotherapy showed lower cognitive function mediated by higher plasma interleukin (IL)‐6 levels than those unexposed. We performed the Wechsler Memory Scale‐Revised (WMS‐R) and measured plasma IL‐6 levels for 105 breast cancer surgical patients within 1 year after the initial therapy. The group differences in each of the indices of WMS‐R were investigated between cancer patients exposed to adjuvant regional radiotherapy (n = 51) and those unexposed (n = 54) using analysis of covariance. We further investigated a mediation effect by plasma IL‐6 levels on the relationship between radiotherapy and the indices of WMS‐R using the bootstrapping method. The radiotherapy group showed significantly lower Immediate Verbal Memory Index and Delayed Recall Index (P = 0.001, P = 0.008, respectively). Radiotherapy exerted an indirect effect on the lower Delayed Recall Index of WMS‐R through elevation of plasma IL‐6 levels (bootstrap 95% confidence interval = −2.6626 to −0.0402). This study showed that breast cancer patients exposed to adjuvant regional radiotherapy in conservation therapy might have cognitive impairment even several months after their treatment. The relationship between the therapy and the cognitive impairment could be partially mediated by elevation of plasma IL‐6 levels.

Twenty-four-hour urinary cortisol levels before complete resection of non-small cell lung cancer and survival

Cortisol has been speculated to play a role in survival from cancer. The objective of this study was to investigate the association between 24-h urinary cortisol levels and survival from non-small cell lung cancer. From June 1996 to April 1999, a total of 226 patients with resectable non-small cell lung cancer were enrolled. Urine samples were collected over a 24-h period before the curative resections. A total of 14 650 person-months (median = 71 months, range = 1–97 months) were accrued. Over the follow-up period, 56 deaths from all causes were identified through January 2004. Cox proportional hazards regression analyses were used to estimate the relative risk (RR) of death from all causes according to three categories of 24-h urinary cortisol levels. Multivariable RRs of death from all causes for individuals in the highest and intermediate categories, compared with the lowest category, were 1.09 (95% confidence interval = 0.54–2.21) and 1.17 (0.55–2.46), respectively (p for trend = 0.17). The present data do not support the hypothesis that 24-h urinary cortisol levels are associated with survival from non-small cell lung cancer.

Clinical experience of the pharmacological treatment algorithm for major depression in advanced cancer patients: preliminary study

INTRODUCTION : Treatment of major depression in advanced cancer patients is often difficult because of their special characteristics. METHOD : The authors developed a treatment algorithm for major depression in advanced cancer patients and report on their clinical experience using it. The applicability, tolerability, and clinical efficacy of the algorithm were evaluated in 95 advanced cancer patients with major depression. RESULTS : The algorithm was not suitable for seven patients and was not used correctly in 14 cases. It was correctly applied to 74 patients (77%), 23 of whom dropped out for cancer-related reasons (deterioration of physical condition, transfer to other hospitals, cancer death). As for tolerability, 22 patients (43%) of the 51 dropped out of the antidepressant treatment regimen because of delirium due to deterioration of their physical condition, adverse effects of the antidepressant, etc. In the 29 cases that could be followed up, clinical efficacy was evaluated for 4 weeks, and improvement was observed in 22 cases (76%). CONCLUSION : These preliminary findings suggest that use of the algorithm may be feasible, but that it requires some alterations to manage major depression in advanced cancer patients. (Int J Psych Clin Pract 2002; 6: 83-89)