From January 2015 to January 2017, we encountered five terminal cancer patients with implantable cardioverter defibrillators (ICDs) in the palliative care unit of our hospital. Due to delirium or dementia, four of these five patients did not have the decision-making capacity to stop their ICD. Although one patient was capable of making his own decisions, his family did not agree with the medical professional considering the patient’s decision. The families of all five patients made decisions on behalf of the patients. The procedure for stopping the ICD was first discussed with the families at 2–21 days prior to the patients’ deaths. The ICDs were stopped between 3 h and 11 days prior to the patients’ deaths, following the consent of the families, which was obtained after 1–5 consultations. Through these experiences, we became aware of the following problems with regard to stopping ICDs: (1) the lack of experience of medical professionals in decision-making, (2) the lack of recognition of medical professionals to the distress caused to patients by ICDs, (3) the psychological burden and time constraint of discussions, and (4) the lack of knowledge of ICDs among patients and their families. These problems need to be addresses as part of advance care planning for cancer patients. 

Introduction: We report a case of intractable nausea due to zoledronic acid-refractory hypercalcemia for which the nausea was alleviated with denosumab, thereby improving quality of life. Case: A 54-year-old woman presented with metastatic renal pelvis cancer. Elevation of serum calcium level and nausea were noted. After multiple antiemetics were administered with no appreciable symptomatic improvement, treatment with zoledronic acid resulted in a decrease in the calcium level and an improvement of nausea from Japanese version Support Team Assessment Schedule （STAS-J） 3 to 1. After the third dose of zoledronic acid, the corrected calcium level was 11.8 mg/dl, indicating refractory. Because no improvement in nausea was noted, treatment with denosumab was initiated. After the treatment, the calcium level decreased to 9.4 mg/dl, and nausea improved from STAS-J 4 to 0. The patient could spend good time with her family, albeit for a short time, and no progression of the symptoms or adverse events due to denosumab occurred until her death. Discussion: Denosumab appears to be useful for improvement of intractable nausea in zoledronic acid-refractory hypercalcemia.

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.

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.

Objective: This study aimed to reveal the prevalence and characteristics of anguish among delirious patients with advanced cancer receiving specialized palliative care services. Methods: We conducted a subanalysis of a multicenter, prospective, observational study at 14 inpatient palliative care units and 10 general wards that offered psycho-oncology consultation service in Japan. We consecutively enrolled the patients with advanced cancer who were diagnosed with delirium and prescribed antipsychotics. Palliative care specialists decided whether patients suffered from anguish or not. We assessed patients’ background and severity of delirium with the Delirium Rating Scale-Revised (DRS-R-98). Results: Of 818 enrolled patients, 99 (12.1%) suffered from anguish. We observed a significant difference in the mean age (68.9±12.6 vs. 72.1±11.2, p=0.009), prevalence of dementia (2% vs. 10.4%, p=0.005) between patients with anguish and those without anguish. Patients with anguish had lower DRS-R-98 total scores before medication than those without anguish (15.3±8.1 vs. 17.3±7.8, p=0.018), but higher severity score in lability of affect (1.2±0.8 vs 1.0±0.9, p=0.023). Conclusions: The results of this study suggested that patients with anguish tend to be younger, mostly do not have dementia, and have lower delirium severity score but higher score in lability of affect. Nevertheless, further research, investigating appropriate evaluations and medical interventions for patients with anguish is warranted.