Hiromichi Matsuoka

Early palliative intervention for patients with advanced cancer.

BACKGROUND Early palliative intervention in advanced cancer patients with metastatic non-small-cell-lung cancer has been shown to improve survival time. Possibly, palliative intervention at the time of outpatient care further improves patient survival time. OBJECTIVE We performed a comparative study of late and early referrals of patients with advanced cancer to clarify the appropriate time for palliative intervention and the improvement in survival time. METHODS Two hundred and one cancer patients, all since deceased, who were treated in our department over a period of 4 years were divided into two groups: patients who experienced outpatient services for <7 days (late referral group, 64 patients) and those who experienced outpatient services for ≥7 days (early referral group, 137 patients). Survival time, duration of chemotherapy and post-progression survival were retrospectively analyzed through examination of medical records. RESULTS Survival time of the early referral group was longer than that of the late referral group in all the cases (19.0 vs. 6.5 months, P < 0.001). Survival time in advanced non-small-cell lung cancer was 3.5 and 14.0 months (P = 0.010) and 16.5 and 20.9 months (P = 0.039) in advanced colorectal cancer, respectively. There was no significant difference in gastric cancer (P = 0.310). Post-progression survival in each group was 0.7 and 2.7 months (P = 0.018) in non-small-cell lung cancer. CONCLUSIONS The results of this study suggested that early outpatient referral and palliative intervention leads to improvement of the outcome in patients with advanced non-small-cell lung cancer and colorectal cancer. A prospective comparative study is warranted.

Gender differences in cancer-related distress in Japan: a retrospective observation study

BackgroundCancer care is currently the most important medical issue in Japan. Total pain of cancer patients consists of a combination of four factors: physical, psychological, social distress, and spiritual pain. Previous studies showed female cancer patients ask for more psychological support and seem to suffer different types of distress compared with male patients, for example, appearance-related symptoms. However, other factors of cancer distress related to gender have not been defined comprehensively. The aim of this study is to clarify the gender differences in cancer distress types in order to elucidate the measures that should be taken in Japan to improve the quality of whole cancer care based on gender-based medicine.MethodsThe data of new patients who had visited the psycho-oncology outpatient service of Kinki University Hospital during the period of May 2013 to October 2015 were collected. Demographic factors and all assessed items were extracted from the patients’ medical charts retrospectively. Based on an inquiry of cancer patients in 2010, each item representing the four factors of “total pain” of cancer patients was chosen, i.e., physical distress (pain, changes in appearance), psychological distress (anxiety, depression), social distress (family problems, job-related problems), and spiritual pain; together with sexuality issues, and answers were analyzed. Hospital Anxiety Depression Scale (HADS) was used for the assessment of psychological distress. Chi-square test and Fisher’s exact test were performed for gender differences in the cancer distress types. Pearson’s analysis and multiple logistic regression analysis were performed for the association of gender with each item.ResultsThe data of 101 cancer patients were analyzed and there were more female patients than male patients (female: male ratio = 71:30). Female cancer patients were more likely to suffer from psycho-social issues such as changes in appearance, family problems and sexuality issues than male patients, and male patients were more likely to have spiritual pain.ConclusionsThere were gender differences in the distress types of cancer patients. In order to improve the quality of whole cancer care, more intensive intervention by medical professionals and social support is needed from the viewpoint of gender-based medicine and psycho-oncology.

Chemotherapeutic drugs that penetrate the blood-brain barrier affect the development of hyperactive delirium in cancer patients.

OBJECTIVE Delirium is a frequently encountered psychiatric disease in terminal cancer patients. However, the mechanism of delirium is unclear. The aim of our study was to investigate the relationship between administration of chemotherapy drugs that penetrate the blood-brain barrier (BBB) and the development of delirium in cancer patients. METHOD We retrospectively analyzed 166 cancer patients (97 males, 69 females) continuously who died between September of 2007 and January of 2010 using a review of medical charts. Multiple logistic regression analysis was employed to investigate the effects of antineoplastic drugs penetrating the BBB on development of delirium in cancer patients with control for other risk factors. RESULTS In multivariate analysis, antineoplastic drugs that penetrated the BBB were significantly associated with development of delirium (OR = 18.92, CI 95 = 1.08-333.04, p < 0.001). SIGNIFICANCE OF RESULTS The use of chemotherapy drugs that penetrate the BBB may be a risk factor for delirium. This information may allow palliative care doctors and medical oncologists to predict which patients are at increased risk for delirium.

Psychological Problems for Non-Japanese Speaking Patients in Japan

The psychological problems of non-Japanese people are becoming more outstanding, in accordance with the increase of foreign nationals in Japan. Five illustrative cases of English-speaking patients were analyzed, from the viewpoint of psychosomatic medicine. The most common psychiatric disorders were adjustment disorders, because of the cultural differences and language barriers.

Prospective replication study implicates the catechol-O-methyltransferase Val158Met polymorphism as a biomarker for the response to morphine in patients with cancer

Genetic differences in humans cause clinical difficulties in opioid treatment. Previous studies indicate that a single nucleotide polymorphism in the catechol-O-methyltransferase (COMT) gene (rs4680; p.Val158Met) may present as a predictive biomarker for the response to morphine treatment. In our previous pilot exploratory study, patients with a G/G genotype were demonstrated to require a higher dose of morphine, compared with patients with A/A and A/G genotypes. In the present study, the aim was to replicate the findings in an independent cohort of opioid-treatment-naïve patients exhibiting various types of cancer. This prospective study was conducted from 2011 to 2012 at the Kindai University Faculty of Medicine. A total of 50 patients with opioid-treatment naïve and histologically confirmed malignant neoplasms who were scheduled to undergo opioid treatment were evaluated in the present study. Assessments were conducted pre-treatment (day 1), post-treatment (day 1), and one week after treatment (day 8). The required dose of morphine on day 1 was significantly higher for patients with the G/G genotype of COMT, compared with those with the A/A and A/G genotypes (P=0.013). The results of the present study provide additional evidence that the COMT genotype may be a predictive biomarker for the response to morphine treatment.

Side effects of corticosteroids in patients with advanced cancer: a systematic review

PurposeCorticosteroids are commonly used in palliative care settings, but are associated with several side effects. Although adverse events (AEs) are highly distressing for patients, few data are available from prospective studies to look at incidence or predictors of such harms. The aim of this study is to identify AE reporting among studies of patients with advanced cancer receiving corticosteroids for any reason.MethodsA systematic review was conducted using the following data sources: PubMed, Medline, SCOPUS, Cochrane reviews, and CINAHL. Randomized controlled trials (RCTs) with patients with advanced cancer assessing the effect of corticosteroids were included. Consecutive cohort observational studies of corticosteroid toxicities in cancer patients were also included.ResultsTwenty-seven RCTs and 12 consecutive cohort observational studies were identified. The most frequently reported primary outcome of RCTs was nausea and vomiting (8/27). Dexamethasone was prescribed in almost half of RCTs (13/27). In consecutive cohort studies, the primary outcomes were a wide variety of symptoms. Dexamethasone was also the most common glucocorticoid used (7/12). In terms of quality of AE reporting, two RCTs and one consecutive cohort study used a validated AE assessment tool in their studies.ConclusionsSide effects of corticosteroids in advanced cancer patients were poorly reported with few data using validated tools. Researchers should be aware of the guideline of AE reporting to provide the best evidence of risk-benefit balance. Developing specific consensus guidelines about AE reporting in studies of glucocorticoids in studies of people with advanced cancer would be useful.

Expectation of a Decrease in Pain Affects the Prognosis of Pain in Cancer Patients: a Prospective Cohort Study of Response to Morphine

PurposeCancer pain is a multidimensional experience that includes physiological, sensory, affective, cognitive, behavioral, and sociocultural dimensions. Few prospective studies have examined the relationship between a patient’s expectation of pain improvement and the pain prognosis. The aim of this prospective study was to investigate whether patients’ expectation to pain reduction was associated with pain intensity after morphine treatment in opioid treatment-naïve patients with various types of cancer.MethodsThe subjects were patients scheduled for cancer pain treatment with morphine who were taking nonsteroidal anti-inflammatory drugs daily. Morphine treatment was performed according to the standard method, including titration (NCCN Guidelines™, Adult Cancer Pain). Simple regression analysis was performed between pain intensity numerical rating scale (NRS) (day 8) as the dependent variable, expectation of pain decrease NRS (day 1), tumor types, and the following covariates as independent variables: patients’ characteristics such as age, gender, PS (day 1), genotype of catechol-O-methyltransferase, total scores of Hospital Anxiety and Depression Scale (day 1), and pain intensity NRS (day 1). Multiple regression analysis was performed using forced entry methods with pain intensity NRS (day 8) as the dependent variable, and expectation of pain decrease NRS (day 1) and the covariates as independent variables that had a p value <0.05 in the simple regression models.ResultsA total of 100 patients with baseline data were included, and 97 patients (51% female) met the inclusion criteria. Patients with a high expectation of pain decrease NRS had a significantly lower pain intensity NRS (day 8) (p = 0.001).ConclusionNon-pharmacological factors such as expectations for pain treatment could also be important factors to treat cancer pain, which might be associated with communication skills in physicians.

Clinical Response to Everolimus of EGFR–Mutation-Positive NSCLC With Primary Resistance to EGFR TKIs

We describe an effect of everolimus in a patient with epidermal growth factor receptor (EGFR)emutationpositive nonesmall-cell lung cancer. Targeted resequencing showed mutations in tuberous sclerosis protein-complex 1 and 2. These mutations in tuberous sclerosis proteincomplex 1 and 2 could confer marked primary resistance to EGFR tyrosine kinase inhibitors (TKIs). Mammalian target of rapamycin inhibitor could be able to overcome primary resistance to EGFR TKIs. Mammalian target of rapamycin is a valuable target for the treatment of nonesmall-cell lung cancer resistant to EGFR TKIs.

Study protocol for a multi-institutional, randomised, double-blinded, placebo-controlled phase III trial investigating additive efficacy of duloxetine for neuropathic cancer pain refractory to opioids and gabapentinoids: the DIRECT study

Introduction Management of patients with cancer suffering from neuropathic pain refractory to opioids and gabapentinoids remains an important challenge. Duloxetine is one of the choices after first-line treatment fails. The efficacy of duloxetine has been reported in patients with non-cancer disease and in chemotherapy-induced peripheral neuropathy, but no randomised clinical trials have examined its effects on neuropathic cancer pain refractory to first-line treatment. The objective of this study is to assess the analgesic efficacy of duloxetine in patients suffering from neuropathic cancer pain refractory to opioids and gabapentinoids. Methods and analysis A multi-institutional, prospective, randomised, double-blind, placebo-controlled, two-parallel trial is planned. The inclusion criteria are adult patients with cancer suffering from neuropathic cancer pain refractory to opioids and gabapentinoids, patients with a Numerical Rating Scale (NRS) pain score of 4 or higher and patients with a total Hospital Anxiety and Depression Scale score of less than 20. Patients with chemotherapy-induced peripheral neuropathy are excluded. The study will take place at 14 sites across Japan. Participants will be randomised (1:1 allocation ratio) to a duloxetine intervention group or a placebo control group. Evaluations will be made at baseline (T0 randomisation), day 0 (T1), day 3 (T2) and day 10 (T3). The primary endpoint is defined as the difference in NRS score for pain intensity (average over the previous 24 hours) at T3 between the duloxetine and placebo groups. A sample size of 70 patients will be examined between July 2015 and March 2018. Ethics and dissemination Ethics approval was obtained at all participating sites. The results of this study will be submitted for publication in international peer-reviewed journals and the key findings presented at international scientific conferences. Trial registration number UMIN000017647; Pre-results. Protocol version 2.2, 26 April 2017.

The physical and psychological problems of immigrants to Japan who require psychosomatic care: a retrospective observation study

BackgroundAs the number of immigrants to Japan increases, the health problems of foreign nationals also have an increasing impact on Japanese medical institutions. The aim of this study was to clarify the Japan–specific health problems related to both the physical and psychological symptoms of foreign nationals from the viewpoint of psychosomatic medicine. The second aim was to clarify the measures that should be taken in Japan and similar countries where immigration may still be considered less than common.Case PresentationThe study period was from June 2004 to May 2015. The data of non-Japanese patients who had visited the Department of Psychosomatic Medicine, Kinki University Hospital and its branches, Sakai Hospital and Nihonbashi Clinic, were collected. All patients were aged 16 years or over. Multiple factors, such as age, sex, nationality, length of stay, marital status, employment status, level of Japanese proficiency, clinical symptoms, physical and psychiatric diagnosis, psycho-social factors and therapy were retrospectively analyzed from the medical charts of 20 non-Japanese patients. Cases were divided into two groups; early onset and late onset cases. This study showed that multiple factors related to the health problems of non-Japanese patients were combined and had a mutual influence, however, they can be summarized into two important clinical observations. These are 1) cultural differences, and 2) language barriers related to both the physical and psychological symptoms of non-Japanese patients from the viewpoint of psychosomatic medicine.ConclusionsFuture efforts should focus on sensitizing health care professionals in Japan to the psychosomatic problems of non-Japanese patients as well as on facilitating medical systems with services such as medical professional interpreters and liaison-consultation models. It is essential to take measures against language barriers and to promote the field of transcultural psychiatry and psychosomatic medicine in Japan. In addition, the Japanese government should introduce a more comprehensive social support system for non-Japanese people.