Objective: Almost half of all patients with cancer experience dyspnea, which can have various causes. Although systemic corticosteroids are administered to relieve symptoms, their efficacy has not been established. This systematic review aims to determine the efficacy of systemic corticosteroids for dyspnea in patients with cancer. Methods: CENTRAL, MEDLINE, EMBASE, and Ichushi-Web databases were searched for articles published from their inception to September 23, 2019, on studies of systemic corticosteroid administration for dyspnea in patients with cancer. The primary outcome measure was dyspnea intensity, as assessed by patient-reported outcomes. Secondary outcome measures were quality of life, delirium, and severe adverse events. Results: Two RCTs were included in the meta-analysis. With regard to alleviating dyspnea, the systematic corticosteroid group was associated with significantly greater dyspnea relief than the placebo group (mean difference: −0.71 [95% CI: −1.4 to −0.03]). However, a meta-analysis of quality of life and delirium could not be performed due to insufficient data. Analysis of severe adverse events showed no significant difference in their incidence between the corticosteroid and control groups (relative rate: 0.96 [95% CI: 0.19-4.93]). Conclusions: Systemic corticosteroids may be effective in treating dyspnea in patients with cancer, particularly those with lung involvement. Limiting the conditions for which corticosteroids are approved is expected to promote their appropriate use and minimize their adverse effects. However, further investigation is needed to determine the appropriate dosage, and the conditions in which corticosteroids are effective.

Objective: To evaluate the efficacy of high-flow nasal cannula oxygen (HFNC) for dyspnea in patients with advanced disease. Methods: A literature search was conducted using MEDLINE, Cochrane Library, EMBASE, and Ichu-shi Web. Inclusion criteria were: 1) randomized controlled trials evaluating the effect of HFNC on dyspnea; 2) aged 18 years or older with advanced disease with hypoxemia; 3) control group was conventional oxygen therapy or noninvasive positive pressure ventilation. Exclusion criteria were: 1) patients in intensive care unit, 2) weaning from ventilator. Results: Six studies (4 from database searches, and 2 from hand searches) were included. In the 2 studies evaluating short-term intervention, one showed HFNC was more efficacious, and the other conventional oxygen was more efficacious. In the 2 studies evaluating long-term interventions: one showed HFNC was more efficacious, and the other showed no significant difference. In the 2 studies evaluating the intervention during exercise, one showed HFNC was more efficacious, and the other showed no significant difference. Conclusion: HFNC may be effective for dyspnea in patients with advanced disease associated with hypoxemia.

Background: Factors requiring midazolam in addition to systemic opioids to control dyspnea in cancer patients have yet to be evaluated. Methods: We retrospectively analyzed data for cancer patients who received systemic opioids to relieve dyspnea from April 2019 to July 2021 in Wakayama Medical University Hospital, Japan. Patients were divided into an opioid-alone group and an opioid plus midazolam group, according to the treatment of dyspnea. Results: The total of 107 patients included 85 patients (79.4%) in the opioid alone group and 22 patients (20.6%) in the opioid plus midazolam group. Age<60 years (p=0.004) and male sex (p=0.034) was significantly associated with the addition of midazolam. Multivariate analysis found age <60 years (OR=5.34, 95%CI: 1.66–17.21; p=0.005) was associated with the addition of midazolam. Conclusion: Age <60 years is factor requiring midazolam in addition to systemic opioids to control dyspnea in cancer patients.

Objective: To evaluate the efficacy of fan therapy for the relief of dyspnea in patients with chronic progressive disease. Methods: A systematic electronic database search of all available articles published before October 23, 2019 was conducted using Ichushi-Web of the Japan Medical Abstract Society databases, CENTRAL, EMBASE, and MEDLINE. In addition, a hand-search for updates was performed using PubMed on June 30, 2020 and December 7, 2021. The inclusion criteria were: 1) any RCTs comparing the effect of fan therapy with any other intervention, and 2) patients aged ≥18 years. Exclusion criteria were: 1) duplicate references, and 2) conference presentations. Results: We identified 110 studies, of which 10 met our criteria for inclusion. Finally, five studies were used in the meta-analysis. Fan therapy significantly improved dyspnea in patients with chronic progressive disease compared to control groups with a standardized mean difference of −1.43 (95% confidence interval: −2.70 to −0.17, I2=94%, p<0.0001). Conclusion: Fan therapy was found to be effective in reducing dyspnea in chronic progressive disease.

Objectives: Spiritual pain is not formally defined. The aim of this study was to clarify the beliefs about spiritual pain among Japanese palliative care physicians and liaison psychiatrists and to compare their beliefs. Methods: A nationwide questionnaire survey was conducted by mail August, 2019 on certified palliative care physicians and liaison psychiatrists. We asked 9 questions about spiritual pain (i.e. current status, definition, and the delivery of care) using a 5-Likert scale. Result: 387 palliative care physicians (response rate, 53%) and 374 psychiatrists (45%) responded. 72% (76% of the palliative care physicians/69% of the psychiatrists) reported that spiritual pain was distinct from depression, but 69% (66/71) reported that it was not defined adequately; and 59% (59/60) perceived the risks of using the words ambiguously. Only 43% (40/47) recommended the universal definition of spiritual pain, and opinions about how spiritual pain should be defined (i.e, higher being, meaning/value, or specific terms) differed among physicians. Perception about spiritual pain of the physicians were significantly associated with their religion, while beliefs about spiritual pain were essentially similar between palliative care physicians and psychiatrists. Conclusion: Although physicians regarded the definition of spiritual pain as being inadequate, the opinions about preferable definition differed among physicians. Discussion about the value of developing a consensus of spiritual pain is needed.

Introduction: We encountered a patient in whom pruritus was induced by obstructive jaundice associated with metastatic liver cancer. Nalfurafine hydrochloride, a selective κ receptor agonist, improved the patient’s pruritus. Case Presentation: The patient was a 70-year-old woman who developed metastatic liver tumor-associated jaundice after surgery for colorectal cancer. She developed pruritus, which was not improved by an antihistamine or a selective serotonin reuptake inhibitor treatment. Nalfurafine was administered for suspected central pruritus. The numerical rating scale for pruritus improved from 9 to 3. Discussion: Compared to other skin diseases such as urticaria and atopic dermatitis, pruritus that accompanies a systemic disease such as chronic renal failure and liver disease does not respond to existing therapeutic drugs in many patients. Chronic liver disease-associated pruritus is intractable and central. Pruritus through central and peripheral mechanisms was mixed in this patient; however, central pruritus may have been dominant. The antipruritic effect of nalfurafine has been confirmed. It may be an effective therapeutic drug for obstructive jaundice-associated pruritus.

Introduction: Paroxysmal atrial fibrillation (Paf) occurred in an inpatient who has been prescribed methadone for cancer pain in our palliative care unit, but oral administration of aprindine (antiarrhythmic agent) succeeded in defibrillation and methadone administration could be continued. Case: A 75-year-old man had developed multiple bone metastases after resection of thyroid cancer. Due to refractory cancer pain, switching from oxycodone to methadone was performed. Pain relief was achieved with methadone 40 mg/day and without QT interval prolongation. After methadone administration about 9 months, there suddenly became loss of appetite in the morning of one day. ECG examination revealed Paf onset. Aprindine 20 mg was orally administered for the purpose of defibrillation. After about 2 hours sinus rhythm was gained and later without recurrence. Conclusion: This case was considered to have the coincidental complication of paroxysmal atrial fibrillation in the course of methadone administration. If administration of antiarrhythmic agents is performed in a patient whom has been prescribed methadone, it is feared to lead to result in QT interval prolongation due to drug interactions. It is important to carefully select an agent that rarely leads to QT prolongation.

Purpose：Methadone is an opioid used in Japan for the treatment of cancer pain. A thorough consideration of complex pharmacokinetics with individual differences and of serious adverse effects is necessary before switching to methadone; therefore, methadone is not yet widely used. We examined the analgesic and adverse effects of methadone through clinical cases and considered the clinical significance of methadone as an opioid analgesic for the treatment of cancer pain. Methods：The clinical course of 44 patients with cancer pain who were switched to methadone from other opioids was analyzed. Results：Out of the 44 cases investigated, 37 cases （84.1％） were successful. In the successful cases, pain intensity before and after methadone administration was reduced from an average of 7.5 to 2.8, respectively, on the numerical rating scale. Strong drowsiness （six cases） and nausea （three cases） were observed as adverse effects. However, no serious effects, such as QT prolongation and respiratory depression, were recognized. Conclusion：For patients with refractory cancer pain who require a high opioid dose, methadone is considered to be one of the alternatives in pain therapeutics.

Background: Methadone can only be administered orally in Japan. However, it is unclear how to treat pain when patients become unable to take methadone orally because of the progression of the disease. Aims: To assess retrospectively end-of-life pain control management after patients become unable to take methadone orally. Methods: Twenty-eight patients with cancer pain undergoing treatment with oral methadone died at a palliative care unit between April 2013 and September 2014. All patients died of cancer and were unable to swallow before death. We assessed pain control approaches after the patients became unable to take methadone orally. Results: Twenty-one patients survived 1 day or longer after becoming unable to swallow. Methadone was switched to another opioid because of pain. Of these 21 patients, 10 patients survived for 1 week or longer after being switched to another opioid. At this point, methadone would be mostly eliminated from the blood circulation. Among these 10 patients, seven patients were treated with subcutaneous morphine, and three patients were excluded because their pain could not be evaluated. The conversion ratio from final oral methadone dosage to oral morphine equivalent dose of opioids used on the seventh day was 6.1. Conclusion: Even when patients become unable to ingest methadone, switching to other opioids may not always be necessary because of the long half-life of methadone when pain is absent at the end of life. If necessary, pain could be managed by switching to other opioids with a conversion ratio of 6.1.

Introduction: This is the first report about an outpatient who was successfully switched from oxycodone to methadone without any serious problems in Japan. Case report: A man in his 60s who was diagnosed as advanced pancreatic cancer with multiple bone and liver metastases. Since he complained severe cancer pain in spite of taking oxycodone 40mg/day, he was referred to the palliative care team. After discussion about switching from oxycodone to methadone in the palliative care team and obtaining informed consent from him, it was decided to prescribe methadone in the outpatient setting. During induction of methadone, a palliative care certified nurse (CN) played important roles about explanation of futures, pharmacodynamics, pharmacokinetics and side effects, education how to take, monitoring of analgesic and side effects and supports to patient anxieties about methadone. His dose titration of methadone was completed for 15 days, and his adequate dose was decided as 20 mg/day finally. After titration of methadone, pain relief could be achieved. Conclusion: Although methadone has a possibility to improve management of cancer pain, it has some serious problems, such as respiratory depression, QT interval prolongation and others due to unsuitable use. Therefore, patients with prescription of methadone must be educated, monitored and supported by special medical staff with much experiences and knowledge about cancer pain, opioid therapy and methadone. CNs may play important role to keep safety and resolve patients and families’ anxieties for prescription of methadone.