Makoto Kobayakawa

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.

Levels of omega-3 fatty acid in serum phospholipids and depression in patients with lung cancer.

Previous studies suggested that omega-3 fatty acids (FAs) have therapeutic effects against depression, but there is no evidence in the oncological setting. Our preliminary study reported the association between lower omega-3 FA intake and occurrence of depression in lung cancer patients. To explore the association further, the present study examined whether depression was associated with lower levels of omega-3 FAs in serum phospholipids. A total of 717 subjects in the Lung Cancer Database Project were divided into three groups by two cutoff points of the Hospital Anxiety and Depression Scale depression subscale (HADS-D). In all, 81 subjects of the nondepression and minor depression groups (HADS-D<5 and 5⩽HADS-D⩽10, respectively) were selected to match with 81 subjects of the major depression group (HADS-D>10) for age, gender, clinical stage, and performance status. Fatty acids were assayed by gas chromatography and compared among the three matched groups. There were no differences between the major depression group and nondepression group in any FAs. The minor depression group had higher mean levels of docosahexaenoic acid (mean±s.d. (%), nondepression: 7.40±1.54; minor depression: 7.90±1.40; major depression: 7.25±1.52, P=0.017). These results suggested that serum FAs are associated with minor, but not major, depression in lung cancer patients.

Behavioral activation can normalize neural hypoactivation in subthreshold depression during a monetary incentive delay task.

BACKGROUND Late adolescents are under increased risk of developing depressive symptoms. Behavioral activation is an effective treatment for subthreshold depression, which can prevent the development of subthreshold depression into a major depressive disorder. However, the neural mechanisms underlying the efficacy of behavioral activation have not been clearly understood. We investigated neural responses during reward processing by individuals with subthreshold depression to clarify the neural mechanisms of behavioral activation. METHODS Late adolescent university students with subthreshold depression (n=15, age 18-19 years) as indicated by a high score on the Becks Depression Inventory-ll (BDI-ll) and 15 age-matched controls with a low BDI-ll score participated in functional magnetic resonance imaging scanning conducted during a monetary incentive delay task on two occasions. The Individuals in the subthreshold depression group received five, weekly behavioral activation sessions between the two scanning sessions. Moreover, they did not receive any medication until the study was completed. RESULTS Behavioral activation significantly reduced depressive symptoms. Moreover, compared to the changes in brain functions in the control group, the behavioral activation group showed functional changes during loss anticipation in brain structures that mediates cognitive and emotional regulation, including the left ventrolateral prefrontal cortex and angular gyrus. LIMITATIONS Replication of the study with a larger sample size is required to increase the generalizability of these results. CONCLUSIONS Behavioral activation results in improved functioning of the fronto-parietal region during loss anticipation. These results increase our understanding of the mechanisms underlying specific psychotherapies.

Hippocampal activation during associative encoding of word pairs and its relation to symptomatic improvement in depression: A functional and volumetric MRI study

BACKGROUND Altered emotional memory is one of the core cognitive functions that causes and maintains depression. Although many studies have investigated the relationship between hippocampal volume, depression and treatment response, no studies have investigated the relationship for hippocampal activity. Additionally, few studies have examined the relationship between functional and structural abnormalities in depression. METHODS We conducted a functional and volumetric MRI study investigating associative encoding of positive, negative and neutral word pairs in 13 healthy controls, and 14 untreated depressives. We carried out fMRI during a memory-encoding task at baseline. Treatment response was clinically assessed six weeks after pharmacotherapy began. Then, we explored the relation between brain activation during encoding of each word pair and symptomatic improvement. RESULTS Relative to controls, depressives exhibited decreased activity in the left hippocampus during encoding positive word pairs and, in contrast, increased activity in the right hippocampus during encoding negative or neutral word pairs. Poor response to treatment was associated with smaller activation within the left hippocampus during the memory encoding of positive word pairs. Overall results were not confounded by hippocampal volume. LIMITATIONS We could not appreciate any disease alteration during the retrieving phase. CONCLUSION We found qualitative differences in hippocampus functioning between depressives and healthy controls. In addition, the left hippocampus could have an effect on treatment response in depression by contributing to the dysfunctional encoding of positive information.

Assessment of Reasons for Referral and Activities of Hospital Palliative Care Teams Using a Standard Format: A Multicenter 1000 Case Description

CONTEXT The many benefits of hospital palliative care teams (PCTs) are well known. However, their specific activities have not been fully clarified, and no standardized methods for reporting PCT activities are available. OBJECTIVES The aim of this study was to investigate, through the use of a standard format, the activities performed by hospital PCTs in Japan. METHODS This was a prospective observational study. A total of 21 hospital PCTs were included in this study, and each recruited approximately 50 consecutively referred patients. Participating PCTs filled in a standard form for reporting activities. RESULTS We obtained data from 1055 patients who were referred to PCTs. Of the 1055 patients, 1005 patients (95%) had cancer. The median number of reasons for referral and problems identified by PCTs was two (0-22) and four (0-18), respectively. The two major reasons for referral were pain (63%) and anxiety/depression/grief/emotional burden (22%). The major recommendations were pharmacological treatment (74%), care for the patients physical symptoms (49%), and support for patients decision making (38%). The major activities performed by the PCTs were comprehensive assessment (90%), care for the patients physical symptoms (77%), and pharmacological treatment (74%). CONCLUSION The components of hospital PCT activities were successfully measured using the Standard Format for Reporting Hospital PCT Activity. The results of this study and the format for reporting hospital PCT activity could be effective in improving hospital PCT practice and for the education of new hospital PCT members.

Continuous Intravenous Infusion of Ketamine and Lidocaine as Adjuvant Analgesics in a 5-Year-Old Patient with Neuropathic Cancer Pain

For difficult to treat neuropathic pain from cancer, adjuvant analgesics are often used with opioids. We present the case of a 5-year-old girl who was diagnosed with meningitis caused by malignant T-cell lymphoma. She had severe neuropathic pain not relieved by increasing doses of a fentanyl infusion. Intravenous administration of ketamine and lidocaine in combination with fentanyl provided excellent analgesia without significant side effects. Ketamine and lidocaine can be safely infused together with concomitant opioids for the treatment of refractory neuropathic pain caused by cancer.