[The Fusion of Cancer Treatment and Cancer Pain Management].

Cancer treatment and cancer pain management constitute a dual approach aimed at improving the quality of life for patients. Their relationship must be complementary. Advances in cancer treatment have been remarkable, leading to increased survival rates in most types of cancer. However, there is a concern about the growing number of patients living with pain. Compared to the advancements in cancer treatment, progress in cancer pain management has been slow. As a basis for this observation, the available opioid analgesics and adjuvant pain-relieving medications have not increased significantly when compared to several years ago, and breakthrough treatments have yet to emerge. Even upon surveying guidelines both domestically and internationally, recommendations for cancer pain treatment are notably ambiguous. In recent years, however, opioid analgesics have proven to be a"double-edged sword". While they play a central role in cancer pain management, they also have cellular effects on tumor proliferation or suppression. This effect varies depending on the type of cancer, and it may be influenced differently by the content of cancer treatment, such as cytotoxic anticancer drugs, molecular targeted drugs, immune checkpoint inhibitors, and more. It may be time to recognize that cancer pain management has an impact on cancer treatment itself. Therefore, a crucial attitude is needed for closer collaboration between experts in cancer treatment and cancer pain management, fostering a co-creative approach in clinical and research settings. Professions such as pharmacists and nurses are essential for bridging this gap. To achieve the fusion beyond the integration of cancer treatment and cancer pain management, a transdisciplinary team, surpassing the boundaries of an interdisciplinary team, is necessary.

Safety and efficacy of naldemedine in cancer patients with opioid-induced constipation: a pooled, subgroup analysis of two randomised controlled studies.

OBJECTIVE: This post hoc, pooled, subgroup analysis of two randomised studies evaluated baseline characteristics that may influence the efficacy and safety of naldemedine in patients with opioid-induced constipation (OIC) and cancer. METHODS: Data for patients who received 0.2 mg naldemedine or placebo were pooled from randomised, placebo-controlled, phase IIb and phase III studies. Proportions of spontaneous bowel movement (SBM) responders and patients with diarrhoea were assessed for each treatment group. For the patient subgroups with or without possible blood-brain barrier (BBB) disruptions, changes in Numerical Rating Scale (NRS) and Clinical Opioid Withdrawal Scale (COWS) scores were assessed. RESULTS: A total of 307 patients were included in this analysis (naldemedine: n=155; placebo: n=152). The pooled proportion of SBM responders was 73.5% with naldemedine versus 35.5% with placebo. There was a significant increase in the proportion of SBM responders with naldemedine versus placebo (38.0% (95% CI 27.6% to 48.4%); p<0.0001). Greater proportions of SBM responders and patients who experienced diarrhoea were observed with naldemedine versus placebo in all subgroups. Changes from baseline in NRS and COWS scores were similar with naldemedine or placebo in patients with or without brain metastases. CONCLUSIONS: Although not powered to detect statistically significant differences in treatment effect among subgroups, this study demonstrated that naldemedine appeared to benefit patients with OIC and cancer, irrespective of baseline characteristics, and did not seem to affect analgesia or withdrawal-even in patients with potential BBB disruptions. Baseline characteristics did not appear to affect the incidence of diarrhoea in patients who received naldemedine. TRIAL REGISTRATION NUMBERS: JapicCTI-111510 and JapicCTI-132340.

Clinical Guidelines for Management of Gastrointestinal Symptoms in Cancer Patients: The Japanese Society of Palliative Medicine Recommendations.

Background: Gastrointestinal symptoms, including nausea, vomiting, bowel obstruction, ascites, constipation, and anorexia, are common and often refractory in advanced cancer patients. The palliation of gastrointestinal symptoms is important in improving the quality of life of cancer patients, as well as that of their families and caregivers. Currently published clinical guidelines for the management of gastrointestinal symptoms in cancer patients do not comprehensively cover the topics or are not based on a formal process for the development of clinical guidelines. Methods: The Japanese Society for Palliative Medicine (JSPM) developed comprehensive clinical guidelines for the management of gastrointestinal symptoms in cancer patients after a formal guideline development process. Results: This article summarizes the recommendations along with their rationale and a short summary of the development process of the JSPM gastrointestinal symptom management guidelines. We established 31 recommendations, all of which are based on the best available evidence and agreement of expert taskforce members. Discussion: Future clinical studies and continuous guideline updates are required to improve gastrointestinal symptom management in cancer patients.

Safety profile of prophylactic rescue dosing of immediate-release oral opioids in cancer patients.

BACKGROUND: Appropriate prophylactic rescue dosing of opioids is considered effective for cancer pain relief, but no study has reported the safety of such prophylactic rescue. We compared the safety of prophylactic rescue dosing of immediate-release oral opioids with that of regular rescue dosing. METHODS: The study included 103 cancer patients who used either immediate-release morphine syrup or immediate-release oxycodone powder at Shizuoka Cancer Center between January and December 2016. Patients were divided into those who mostly used (prophylactic group) and those who never used (regular group) prophylactic rescue doses of opioids and compared the incidence of adverse events (AEs). We also investigated whether the prophylactic rescue dose negatively interfered with its objective activity, such as meals. RESULTS: Incidence of each AE in the prophylactic versus regular groups was as follows: somnolence, 20.6% versus 14.3%; nausea, 22.1% versus 17.1%; constipation, 19.1% versus 20.0%; urinary retention, 1.5% versus 2.9%; delirium, 4.4% versus 8.6%; and pruritus, 0% versus 2.9%. No serious AE associated with prophylactic rescue dosing was observed. No significant difference was observed in the incidence of any AE between the two groups (p > 0.05, Fisher's exact test). No AE interfered with the objective activity of the prophylactic rescue dose. CONCLUSION: Incidence of AEs associated with prophylactic rescue dosing is not different from that associated with regular rescue dosing. In addition, the prophylactic rescue dose did not adversely affect its objective activity, suggesting the safety of appropriate prophylactic rescue dosing was similar to that of regular rescue dosing. TRIAL REGISTRATION: The study approval number in the institution; H29-J30-29-1-3. Registered June 5, 2017.

Efficacy of immediate-release oxycodone for dyspnoea in cancer patient: cancer dyspnoea relief (CDR) trial.

BACKGROUND: Guidelines recommend morphine as the first-line pharmacological treatment for cancer dyspnoea. However, trials with other opioids have not been performed. Our aim was to demonstrate the non-inferiority of oxycodone to morphine for relieving dyspnoea in cancer patients. METHODS: We conducted a multicentre, open-label, parallel-group, randomized control trial. We randomly and equally assigned cancer patients on regular oxycodone who developed dyspnoea to get a single dose of oral immediate-release oxycodone or morphine. We evaluated the change in dyspnoea intensity (numeric rating scale: 0-10) and adverse events after the medication administration. RESULTS: This study was preconfidence interval -maturely terminated. All 17 enroled patients (8 using oxycodone, 9 using morphine) completed evaluations. In the oxycodone group, dyspnoea intensity decreased 1.75 points [95% confidence interval, 0.72-2.78] at 60 min and 1.50 points (95% confidence interval, -0.11 to 3.11) at 120 min. In the morphine group, dyspnoea decreased 1.33 points (95% confidence interval, 0.41-2.25) at 60 min and 1.00 point (95% confidence interval, -0.08 to 2.08) at 120 min. The differences did not fulfil the non-inferiority requirement. Although two and four patients in morphine group developed drowsiness at 60 and 120 min, no patient in oxycodone group developed significant adverse events. CONCLUSIONS: Although we did not show the non-inferiority of oxycodone, oxycodone may have some effectiveness for cancer dyspnoea without significant safety concern. CLINICAL TRIAL REGISTRATION: UMIN-CTR: UMIN 000005760.

Incidence of Delirium Among Patients Having Cancer Injected With Different Opioids for the First Time.

BACKGROUND: Despite the risk of drug-induced delirium, it is difficult to avoid the use of opioids in palliative care. However, no previous study has carefully investigated how the development of delirium varies among patients injected with different opioids for the first time. OBJECTIVES: To reveal the difference in the incidence of delirium between different opioids. DESIGN: The incidence of delirium was compared among 114 patients who had started morphine, oxycodone, or fentanyl injection at Shizuoka Cancer Center between June 2012 and September 2014. RESULTS: The incidence of delirium was 28.9% in the morphine group (n = 38), 19.5% in the oxycodone group (n = 41), and 8.6% in the fentanyl group (n = 35). There was a significant difference between the morphine and fentanyl groups (Fisher's exact test, P = 0.04) but not between the morphine and oxycodone groups (P = 0.43) nor between the oxycodone and fentanyl groups (P = 0.21). CONCLUSIONS: The incidence of delirium after the commencement of fentanyl injection was significantly lower, suggesting that fentanyl is a useful opioid injection drug from the perspective of delirium risk.

Implementation status and explanatory analysis of early advance care planning for Stage IV non-small cell lung cancer patients.

OBJECTIVE: The American Society of Clinical Oncology published the goals of individualized care including advance care planning for advanced cancer patients in 2011. However, no data are available on the implementation status of advance care planning. METHODS: We retrospectively reviewed the electronic medical records and informed consent forms of consecutive Stage IV non-small cell lung cancer patients treated with chemotherapy between January 2010 and December 2012 at our institution. Two outcomes were defined to investigate the advance care planning implementation status: C-D, the duration from the last day of chemotherapy to death and D-D, that from the day of confirmed do-not-attempt-resuscitation order to death. RESULTS: The study included 136 eligible patients. The advance care planning implementation status in participating patients was as follows: 96 (70%) patients received information on 'incurable disease before first-line chemotherapy', 69 (50%) were informed about 'supportive care before first-line chemotherapy', whereas 43 (32%) learned about their prognosis. The do-not-attempt-resuscitation decision was reflected in 29 patients' will (21%). The median C-D was 64 days. Receipt of ≤2 chemotherapy regimens and provision of prognosis information to patients were significantly associated with long C-D in multivariate analysis. The median D-D was 25 days. Provision of information on supportive care before first-line chemotherapy and provision of prognosis information to patients were significantly associated with long D-D in multivariate analysis. CONCLUSIONS: Our results suggest that there is possible benefit from providing information on supportive care before first-line chemotherapy and informing patients about their prognosis in prolonging the duration of supportive care.

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 patient's physical symptoms (49%), and support for patient's decision making (38%). The major activities performed by the PCTs were comprehensive assessment (90%), care for the patient's 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.

[Multiprofessional team working in palliative medicine].

Now, more than ever, palliative medicine has been gaining recognition for its essential role in cancer treatment. Since its beginning, it has emphasized the importance of collaboration among multidisciplinary professionals, valuing a comprehensive and holistic philosophy, addressing a wide range of hopes and suffering that patients and families experience. There are three models (approaches) for the medical teams: multidisciplinary, interdisciplinary, and transdisciplinary. Palliative care teams often choose the interdisciplinary team model, and the teams in the palliative care units may often choose the transdisciplinary team model. Recently, accumulating research has shown the clinical benefits of the interdisciplinary/transdisciplinary approach in palliative care settings. Clarifying appropriate functions and ideal features of physicians in the health care team, and enforcing the suitable team approach will contribute to improve the quality of whole medical practice beyond the framework of "palliative medicine".

Effect of parenteral hydration therapy based on the Japanese national clinical guideline on quality of life, discomfort, and symptom intensity in patients with advanced cancer.

CONTEXT: Although an evidence-based clinical guideline for parenteral hydration therapy was established in Japan, the efficacy of the guideline has not been assessed. OBJECTIVES: Our purpose was to explore the effect of parenteral hydration therapy based on this clinical guideline on quality of life (QoL), discomfort, symptoms, and fluid retention signs in patients with advanced cancer. METHODS: This multicenter, prospective, observational study included 161 patients with advanced abdominal cancer who received guideline-based hydration therapy. We evaluated the longitudinal changes of the global QoL (Item 30 of European Organization for Research and Treatment of Cancer Quality-of-Life Questionnaire-C30); the Discomfort Scale; the intensity of seven physical symptoms; and the severity of fluid retention signs. We also evaluated patient satisfaction and the feeling of benefit from hydration one week after the study commenced, and bronchial secretions, hyperactive delirium, communication capacity, and agitation 48 hours before a patient's death. RESULTS: The global QoL, the Discomfort Scale, and the intensities of all physical symptoms, except for vomiting and drowsiness, were stable throughout the study period. More than 80% of patients maintained all fluid retention signs. Patient global satisfaction was 76.4 (0-100) and feeling of benefit was 5.43 (range 0-7). CONCLUSION: Guideline-based parenteral hydration therapy contributed to maintaining global QoL and provided satisfaction and a feeling of benefit without increasing discomfort and worsening symptoms and fluid retention signs in patients with advanced cancer.

Endocrinological evaluations of brief hand massages in palliative care.

BACKGROUND AND OBJECTIVES: Some patients with advanced cancer make use of complementary therapies for the reduction of anxiety and stress. These patients can suffer distressing end-of-life symptoms, which conventional treatments might not relieve satisfactorily. Although previous studies have suggested that complementary therapies could be useful for reducing distress in patients with cancer, it has remained unclear whether these benefits are applicable at the end-of-life stage. The current study examined to validate salivary chromogranin A (CgA) as a biomarker for relieving stress by hand massage in terminally ill patients. METHODS: The study group comprised 34 inpatients in palliative care units. Each of these patients received a 5-minute massage to the upper extremity. Before and after the massage, saliva samples were collected in order to measure the CgA levels. RESULTS: The brief hand massage appears to reduce levels of stress according to the salivary CgA (p < 0.05). In addition, we found statistically significant changes in patient satisfaction with hand massage. CONCLUSIONS: Salivary CgA could potentially be used as a biomarker to measure relieving stress by hand massage in a palliative-care setting.

Attitudes toward and current practice of complementary and alternative medicine in Japanese palliative care units.

Complementary and alternative medicine (CAM) might enhance the quality of life of patients with cancer. The aim of this study was to investigate the current practice of CAM in Japanese palliative care units. A 17-item questionnaire was mailed to all 150 certified palliative care units in Japan, 80% of which responded. In total, 75 institutions (64%) provided at least one modality of CAM. Only 33% of the palliative care units surveyed had any regulations about patient usage of CAM, and 42% rejected some types of CAM because they caused difficulties for other patients (34%), required medical procedures (26%), used fire (5%), or required outside practitioners (4%). In total, 92% of surveyed palliative care units had no regulation and actually provided CAM. The obstacles to the use of CAM included the availability of certified practitioners, costs, added responsibilities for staff members, and insufficient evidence of efficacy. We concluded that Japanese palliative care units generally had a positive attitude toward CAM, and were willing to provide this type of therapy to patients.

Chondrosarcoma of the nasal septum.

The nasal septum is a particularly rare site of origin of chondrosarcoma. Cranial base invasion may be at hand, with such lesions making complete tumor removal difficult. MRI techniques allow precise definition of tumor extent. In the described case, CT and Dynamic MR imaging were performed in a case of chondrosarcoma of the nasal septum. Imaging clearly illustrated size and extent of the mass with central regions of internal calcification. Dynamic MRI was additionally performed, which helped to define the presumed origin of the lesion from the nasal septum.