The purpose of this study was to investigate the effect of attenuation of exercise-induced oxidative stress by antioxidant administration on brain-derived neurotrophic factor (BDNF) expression in the rat hippocampus. Wistar rats were assigned to four groups: non-exercise (Cont), exercise (Ex), or the combination of exercise with antioxidant administration (small dose: SP, large dose: LP) group. Exercise groups were subjected to treadmill running for 10 consecutive days. The exercise load increased gradually by 5 m/min per day for the first 5 days (10 m/min-30 m/min), and maintained at 30 m/min for the last 5 days. In addition, SP and LP were injected with N-tert butyl-a-phenyl nitrone (PBN) 1h prior to exercise. High-intensity exercise resulted in increased hippocampal 4-hydroxy-2-nonenal (4-HNE) contents compared with Cont. But this elevation was completely suppressed by a large dose of PBN. In Ex and SP, serum total antioxidative power were significantly decreased compared with Cont, whereas no changes were observed in LP. There was a significant negative correlation between hippocampal 4-HNE contents and serum total antioxidative power in SP and LP, suggesting the hypothesis that exercise-induced reduction in total antioxidant power might lead hippocampal 4-HNE accumulation. Furthermore, there was a significant increase of hippocampal BDNF level in LP compared with Cont and Ex. These findings indicate that an increase of oxidative stress might not have a beneficial effect on hippocampal BDNF expression. Our results of this study also suggest that attenuation of exercise-induced oxidative stress by some antioxidants contributes to BDNF expression in the hippocampus.

Purpose: Blepharospasm is a condition characterized by abnormal contractions or twitching of the eyelid due to excessive contractions of the orbicular muscle. The purpose of the present study was to clarify the prevalence and severity of blepharospasm in end-term cancer patients and to clarify the correlation between agonal facies and angor animi or blepharospasm. Method: Diagnoses were made using the Wakakura method and the nictitating stress test, and the severity of the condition was evaluated on the basis of a palpebral dystonia grade classification system. In this positive observational study, all patients were hospitalized in our institution between October and December 2010. Result: Of the 51 evaluations, 19 (37.3%) were diagnosed with blepharospasm, and the severity of nine was ≥3 according to a five-point grading scale. Many cases were treated using antipsychotics or benzodiazepine, and an improvement was observed in all the seven cases that had medication adjustments. Diagnostically, there was no correlation between glabellar lines and pain. Agonal facies in end-term cancer patients included elements of blepharospasm in addition to angor animi. Conolusion: Blepharospasm frequently occurred in patients admitted in the palliative care unit, and it decreased their quality of life. It is important to evaluate this condition and to consider medication adjustments.

Introduction: The use of methadone in Japan is limited to cases being switched from the preceding use of strong opioids; the stop-and-go strategy is recommended in which the previously used opioid analgesic is discontinued and methadone is initiated at its full estimated dosage. Case: Refractory cancer pain due to an iliolumbar syndrome was temporarily exacerbated by the stop-and-go switching to methadone from morphine along with ketamine. Pain relief was achieved upon readministration and concomitant use of morphine with methadone after approximately two weeks. Discussion: Through examining this case, we believe that a stepwise switching strategy, rather than the stop-and-go strategy, could be more useful. Considering that overdosage may cause side effects, it is safer to initiate methadone with a small dose. However, more studies need to be conducted to decide whether the establishment of the initial dosage and dosage adjustment should be made more flexible to avoid pain intensification. Further investigation is required on whether the concomitant use of adjuvant analgesics such as ketamine, which similar to methadone is an NMDA receptor antagonist, should be continued when switching to methadone.

Continuous subcutaneous injections of medication are effective in controlling symptoms of the terminal stage of cancer. Chlorpromazine and levomepromazine occasionally cause skin irritation. We examined all patients who underwent continuous subcutaneous administration of psychotropic drugs (chlorpromazine, levomepromazine, midazolam) at the palliative care unit of our hospital from April 2010 to March 2013, the frequency of adverse skin reactions of Common Terminology Criteria for Adverse Events (CTCAE) v4.0 grade 3 or above. Of the 603 hospitalized patients, 389 (64.5%) underwent continuous subcutaneous administration of one of the three drugs. The frequency of grade 3 or above (ulceration or necrosis) adverse skin reactions was 4 out of 345 chlorpromazine cases (1.2%; 95% CI: 0.0-2.3%), 2 out of 90 levomepromazine cases (2.2%; 95% CI: −0.8-5.2%), and 0 out of 210 midazolam cases (0.0%; 95% CI: 0.0-0.0%). The frequency of serious adverse skin reactions caused by continuous subcutaneous administration of psychotropic drugs was low, suggesting that this treatment is relatively safe for the skin.

Rectal irritative symptoms in cancer patients are often refractory to treat and exacerbate their quality of life. We experienced a peadiatric case of rectal irritative symptoms treated by Yokukansan. A 9 year-old boy developed rectal irritative symptoms as itching sensation in rectum caused by relapsed rhabdomyosarcoma in pelvis. Oral Yokukansan, which is common Japanese Kampo medicine for temper tantrum of children, was administered and relieved his symptoms. Yokukansan is known as adjuvant drug for neuropathic pain. It could be one of the adjuvant drugs for refractory symptoms in palliative care setting.

Background: Cancer may have impacts on parents for child rearing. There has been few reports regarding what support is needed for them. The aim of this study is to investigate the needs of support system for cancer patients who have young children. Methods: First, we retrospectively studied records of specialized support for patients who had young children by palliative care team in National Cancer Center Hospital (NCCH) from April 2013 to September 2015. The data was collected from the NCCH electronic medical records. Next, we qualitatively classified the concerns about child-rearing of patients and their family. Results: A total of 131 (Male/Female: 41/90) cases received specialized support for patients who had young children during study period. The average age of patients was 43.3. Top three of primary sites of the patients were gastrointestinal tract, lung and breast. Approximately eighty percent of the patients were in the state of the recurrence and/or progressive cancer. The average age of their young children (n=239) was 9.6 (ages 0-17). The parents’ perceptions of child-related stressors were classified into three subcategories: 1. How to tell children about illness and treatment, 2. How to manage children’s reaction and emotion after having told them about illness, and 3. How to keep the parents’ role of child-rearing. Discussion: We found that patients who have children (age 0-17) have various types of concerns depending on their condition or age of children. Therefore, multi-disciplinary team approach for improving an effective support system was needed.

Food and eating are of great significance to humans, as we are the only creatures that establish relationships and sustain a social network through food and eating. Recent studies revealed that patients with advanced cancer and their family members often experience complicated eating-related distress due to tumors themselves, side effects of cancer treatments, and negative impacts of cancer cachexia. Therefore, we suggested the importance of the integration of palliative, supportive, and nutritional care to alleviate eating-related distress among patients and family members, and the significance of the development of tools to measure their distress in supportive and palliative care settings. No care strategies for eating-related distress experienced by patients and family members have been established, and the development of an interdisciplinary psychosocial approach and integrative care is required. As such, we are planning to start a nutritional support and cancer cachexia clinic in the National Cancer Center, and disseminate a newly developed care program across Japan.

Although palliative sedation therapy (PST) is considered to alleviate intolerable and refractory symptoms in dying patients with advanced cancer, there have been few studies regarding the situation of tertiary cancer center. We conducted a retrospective survey of the medical records of the patients who died between April 2015 and March 2016 at the National Cancer Center Hospital in Japan. PST was conducted in 75 out of 431 patients (17.4%). The patient demographics were as follows: sex (male/female), 48/27; median age, 61 years (range 5-83; 11 patients (14.7%) were aged under 39 years); and primary sites were lung, 18 (24.7%)/ pancreas, 11 (14.7%)/ hematopoietic organs, 11 (14.7%)/ bones and soft tissues, 8 (10.7%)/ and the others, 27 (36.0%). The main target symptoms for PST were dyspnea (38, 50.7%) and delirium (30, 40.0%). The most commonly used sedative agent was midazolam (72, 96.0%). Continuous deep sedation was intended in 61 patients (81.3%) at the death. Median survival from the start of PST were 2 days (range 0-54). The differences between palliative care team (PCT) intervention group and control group were lower age (58 vs. 62.5, P=0.048) and uniformity of initial midazolam dose (5-12 vs. 9.6-25.2 mg/day). Distinctive feature in this study was large proportion of adolescent and young adult patients with rare cancers. PCT might have different approaches to sedation in comparison to non-PCT medical staffs.

Context: Delirium in cancer is often difficult to control and refractory when haloperidol is invalid which is considered standard therapy. We need second and subsequent-line therapy to reduce hyperactivity and not to over-sedation for refractory delirium. Objectives: To investigate the efficacy and safety of continuous subcutaneous infusion chlorpromazine on delirium refractory to first-line antipsychiatric medications in advanced cancer palliative care setting. Method: The study population consisted of patients who received continuous subcutaneous infusion chlorpromazine for delirium at two certified PCU. Primary endpoint was the proportion of patients who showed improvements in delirium severity by Delirium Rating Scale Revised 98 score of less than 13 or decrease from baseline and maintained the ability to communicate coherently by Communication Capacity Scale Item-4 score of 2 or less. Secondary outcome were the Nursing Delirium Screening Scale subscale score, and injection site reactions evaluated according to the Common Terminology Criteria for Adverse Events. These outcome measures were assessed at baseline, 48 hours and 7 days after the start of the study. Result: Among eighty-four patients, sixty were positive responders (71.4%, 95% CI [61–80]). The mean CCS Item-4 scores significantly decreased from the baseline value of 1.48 (range 0–3) to 1.03 (range 0–3) at post-treatment (p<0.001). Grade 2 or higher injection site reactions were observed in 1 patient (1.2%, 95% CI [0–7]). Conclusion: Our study suggested that continuous subcutaneous infusion chlorpromazine could improve refractory delirium symptoms and patients’ communication capabilities. Although most of the skin disorders observed in association with chlorpromazine were mild, their incidence rates were relatively high, suggesting the need for careful monitoring.