Efficacy of metyrapone for symptoms of adrenocortical carcinoma.

Elevated cortisol by adrenocortical carcinoma leads to a variety of symptoms. We report on the efficacy of metyrapone in treatment of a variety of distressing symptoms caused by elevated cortisol in a patient who refused advanced treatment for adrenocortical carcinoma.

Comparison of plasma concentrations of levobupivacaine with and without epinephrine for thoracic paravertebral block: A randomised trial.

BACKGROUND: Thoracic paravertebral block (TPVB) is effective for analgesia for unilateral thoracic surgery. However, since the paravertebral space is highly vascular, injection of local anaesthetics into the paravertebral space may induce systemic local anaesthetic toxicity. We examined the effect of addition of epinephrine to paravertebral levobupivacaine on its plasma concentration. METHODS: In a randomised single blind trial, twenty-four male patients who were scheduled to undergo elective unilateral pulmonary lobectomy or segmentectomy under general anaesthesia combined with TPVB were enrolled in this study. They were randomly divided into two groups: one group received a single bolus thoracic paravertebral injection of 1 mg/kg of 0.25% levobupivacaine with 5 µg/mL epinephrine and the other group received a single bolus thoracic paravertebral injection of 1 mg/kg of 0.25% levobupivacaine alone. Arterial blood samples were obtained for plasma levobupivacaine assay after injection. The peak plasma concentration (Cmax) and the time to peak plasma concentration (Tmax), for levobupivacaine were calculated. RESULTS: There were no significant differences in patients' characteristics between the two groups. The mean arterial Cmax values of levobupivacaine were 0.48 ± 0.11 µg/mL with epinephrine and 0.71 ± 0.31 µg/mL without epinephrine (P = 0.041). The mean arterial Tmax values of levobupivacaine were 46.0 ± 35.6 min with epinephrine and 12.0 ± 7.2 min without epinephrine (P = 0.005). CONCLUSION: The addition of 5-µg/mL epinephrine to a single bolus thoracic paravertebral injection of 1-mg/kg levobupivacaine significantly decreased Cmax and delayed Tmax of levobupivacaine. The addition of epinephrine to levobupivacaine may be a useful strategy to reduce systemic levobupivacaine toxicity. CLINICAL TRIAL REGISTRATION NUMBER: UMIN 000021942.

A case report of the efficacy and usefulness of asenapine in the treatment of a cancer patient with delirium and aphagia.

OBJECTIVE: Controlling hyperactive and mixed delirium is extremely important for the continuation of cancer treatment in palliative care. In general, oral antipsychotics are the first-line drug therapy for delirium; however, oral administration is problematic in patients presenting dysphagia. In this case report, we describe an end-stage cancer patient with aphagia who developed delirium and responded to sublingual antipsychotic asenapine for treating delirium. We also discuss the effectiveness of asenapine in hyperactive delirium as well as its usefulness for treating delirium in palliative care. METHOD: A cancer patient with delirium was treated with several oral antipsychotics commonly used to treat delirium but did not respond to any of them. The patient subsequently developed aphagia with progression of the disease. Sublingual asenapine was therefore given to treat delirium. RESULT: Asenapine was effective in treating delirium without causing any obvious side effects. SIGNIFICANCE OF RESULTS: In the present case, asenapine was effective in treating hyperactive delirium that did not respond to commonly used antipsychotics. Because asenapine is a sublingual tablet, it can be used in patients with dysphagia and aphagia. In addition, this drug is anticipated to diminish the burden of end-stage patients from taking oral medications. Furthermore, its management is easier compared with injections, and can therefore also be easily used in homecare patients. Based on these perspectives, asenapine may become an important option for treating delirium in palliative care.

Optimal Timing of Removal of Epidural and Urethral Catheters to Avoid Postoperative Urinary Retention Undergoing Abdominal Surgery.

BACKGROUND/AIMS: Postoperative urinary retention (POUR) is one of the most frequent complications of epidural anesthesia. This study aims to clarify risk factors of POUR and to estimate the appropriate timing of urethral catheter removal. METHODS: Between September and December 2014, a retrospective cohort study was conducted on 120 patients who underwent epidural anesthesia and major abdominal surgery. To observe trends in incidence of POUR, we analyzed the order and interval of removal of epidural and urethral catheters using Cochran-Armitage trend test. RESULTS: In this study, 40 patients were diagnosed with POUR (33.3%). Median removal of epidural catheters was 4 postoperative days in the POUR group and 3.5 postoperative days in the non-POUR group (p = 0.04). When the urethral catheter was removed before epidural catheter, incidence of POUR was comparatively greater (p < 0.001). There were no statistical differences in surgical fields, operation approach, epidural catheter levels, or epidural opioid use. No patients had urinary tract infections. CONCLUSION: We demonstrated that removal of urethral catheter before epidural catheter contributed to increasing trends in incidence of POUR. The optimal order and interval of removal of epidural and urethral catheters should be considered to avoid POUR after abdominal surgery.

Low Transthyretin Levels Predict Poor Prognosis in Cancer Patients in Palliative Care Settings.

OBJECTIVES: Although transthyretin (TTR) is a nutritional indicator and is influenced by systemic inflammation, it may be a good prognostic indicator for cancer patients in palliative care settings. This study investigates the correlation between low TTR levels and survival among cancer patients in palliative care settings. METHODS: This was a sub-analysis of a prospective, multicenter cohort study. Patients who had advanced-stage cancer and who were newly referred to palliative care services were eligible to participate; however, those receiving anti-tumor therapy were excluded. Survival analyses were performed to clarify predictors of poor prognosis. RESULTS: A total of 144 patients were enrolled (45.1% female; median age, 72 years). Cox regression analysis revealed that low TTR levels (<10.9 mg/l) (hazard ratio 1.74, P = 0.025), poor muscle power (1.71, P = 0.045), and fatigue (1.89, P = 0.024) were predictors of poor prognosis. Median survival in patients with low TTR levels (<10.9 mg/l) was 26 days, which was significantly shorter than those with high TTR levels (≥10.9 mg/l) (50 days; P < 0.001). CONCLUSION: Low TTR levels may be indicators for poor prognosis among cancer patients in palliative care settings.

Adding items that assess changes in activities of daily living does not improve the predictive accuracy of the Palliative Prognostic Index.

BACKGROUND: Changes in activities of daily living in cancer patients may predict their survival. The Palliative Prognostic Index is a useful tool to evaluate cancer patients, and adding an item about activities of daily living changes might improve its predictive value. AIM: To clarify whether adding an item about activities of daily living changes improves the accuracy of Palliative Prognostic Index. DESIGN: Multicenter prospective cohort study. SETTING: A total of 58 palliative care services in Japan. PARTICIPANTS: Patients aged >20 years diagnosed with locally extensive or metastatic cancer (including hematological neoplasms) who had been admitted to palliative care units, were receiving care by hospital-based palliative care teams, or were receiving home-based palliative care. Palliative care physicians recorded clinical variables at the first assessment and followed up patients 6 months later. RESULTS: A total of 2425 subjects were recruited and 2343 of these had analyzable data. The C-statistic of the original Palliative Prognostic Index was 0.801, and those of modified Palliative Prognostic Indices ranged from 0.793 to 0.805 at 3 weeks. For 6-week survival predictions, the C-statistic of the original Palliative Prognostic Index was 0.802, and those of modified Palliative Prognostic Indices ranged from 0.791 to 0.799. The weighted kappa of the original Palliative Prognostic Index was 0.510, and those of modified Palliative Prognostic Indices ranged from 0.484 to 0.508. CONCLUSION: Adding items about activities of daily living changes to the Palliative Prognostic Index did not improve prognostic value in advanced cancer patients.

Multicenter cohort study on the survival time of cancer patients dying at home or in a hospital: Does place matter?

BACKGROUND: Although the place of death has a great influence on the quality of death and dying for cancer patients, whether the survival time differs according to the place of death is unclear. The primary aim of this study was to explore potential differences in the survival time of cancer patients dying at home or in a hospital. METHODS: This multicenter, prospective cohort study was conducted in Japan from September 2012 through April 2014 and involved 58 specialist palliative care services. RESULTS: Among the 2426 patients recruited, 2069 patients were analyzed for this study: 1582 receiving hospital-based palliative care and 487 receiving home-based palliative care. A total of 1607 patients actually died in a hospital, and 462 patients died at home. The survival of patients who died at home was significantly longer than the survival of patients who died in a hospital in the days' prognosis group (estimated median survival time, 13 days [95% confidence interval (CI), 10.3-15.7 days] vs 9 days [95% CI, 8.0-10.0 days]; P = .006) and in the weeks' prognosis group (36 days [95% CI, 29.9-42.1 days] vs 29 days [95% CI, 26.5-31.5 days]; P = .007) as defined by Prognosis in Palliative Care Study predictor model A. No significant difference was identified in the months' prognosis group. Cox proportional hazards analysis revealed that the place of death had a significant influence on the survival time in both unadjusted (hazard ratio [HR], 0.86; 95% CI, 0.78-0.96; P < .01) and adjusted models (HR, 0.87; 95% CI, 0.77-0.97; P = .01). CONCLUSIONS: In comparison with cancer patients who died in a hospital, cancer patients who died at home had similar or longer survival. Cancer 2016;122:1453-1460. © 2016 American Cancer Society.

[Adverse Effects of Antidepressants and their Treatment].

Antidepressants are used for treatment of not only major depression but also for treatment of neuropathic pain. In guidelines for pharmacological treatment of neuropathic pain, tricyclic antidepressants and sero- tonin noradrenaline reuptake inhibitors are listed as the first line choice and second line choice, respectively. However, antidepressants act on several kinds of neu- ronal receptors, resulting in various adverse effects. In this article, we review common adverse effects of anti- depressant drugs and the prevention and treatments of these adverse effects.

Glasgow prognostic score predicts prognosis for cancer patients in palliative settings: a subanalysis of the Japan-prognostic assessment tools validation (J-ProVal) study.

PURPOSE: The Glasgow prognostic score (GPS), which uses C-reactive protein and albumin levels, is a good predictor of prognosis in cancer patients undergoing anti-tumor therapy. The objective of this study was to investigate the correlation between GPS and survival among cancer patients in palliative settings, as findings in such populations have not been well described. METHODS: This was a subanalysis of a multicenter, prospective, cohort study in patients who were adults, diagnosed with advanced cancer, and first referred to palliative care service in Japan. Patients who were not receiving anti-tumor therapy and who had undergone laboratory examinations were eligible. Clinical features were analyzed to investigate prognostic factors. RESULTS: A total of 1160 patients were enrolled (41.6 % female; median age, 72 years). The independent predictors were Eastern Cooperative Oncology Group performance status (ECOG PS) score of 4 (hazard ratio (HR), 1.54), liver metastasis (HR, 1.21), dyspnea (HR, 1.35), edema (HR, 1.25), prognostic performance index (HR, 1.56), neutrophil-lymphocyte ratio (HR, 1.43), and GPS of 2 (HR, 1.36). The sensitivity and specificity for 3-week prognosis of a GPS of 2 were 0.879 and 0.410. Median survival time with GPS of 0, 1, and 2 was 58 days (95 % confidence interval, 48-81), 43 days (37-50), and 21 days (19-24), respectively (log-rank test, p < 0.001). CONCLUSION: The GPS was a good prognostic indicator for cancer patients in palliative settings.

Independent validation of the modified prognosis palliative care study predictor models in three palliative care settings.

CONTEXT: Accurate prognostic information in palliative care settings is needed for patients to make decisions and set goals and priorities. The Prognosis Palliative Care Study (PiPS) predictor models were presented in 2011, but have not yet been fully validated by other research teams. OBJECTIVES: The primary aim of this study is to examine the accuracy and to validate the modified PiPS (using physician-proxy ratings of mental status instead of patient interviews) in three palliative care settings, namely palliative care units, hospital-based palliative care teams, and home-based palliative care services. METHODS: This multicenter prospective cohort study was conducted in 58 palliative care services including 16 palliative care units, 19 hospital-based palliative care teams, and 23 home-based palliative care services in Japan from September 2012 through April 2014. RESULTS: A total of 2426 subjects were recruited. For reasons including lack of followup and missing variables (primarily blood examination data), we obtained analyzable data from 2212 and 1257 patients for the modified PiPS-A and PiPS-B, respectively. In all palliative care settings, both the modified PiPS-A and PiPS-B identified three risk groups with different survival rates (P<0.001). The absolute agreement ranged from 56% to 60% in the PiPS-A model and 60% to 62% in the PiPS-B model. CONCLUSION: The modified PiPS was successfully validated and can be useful in palliative care units, hospital-based palliative care teams, and home-based palliative care services.

Propofol attenuates angiotensin II-induced vasoconstriction by inhibiting Ca2+-dependent and PKC-mediated Ca 2+ sensitization mechanisms.

PURPOSE: Angiotensin II (Ang II)-induced vascular contraction is mediated by Ca(2+)-dependent mechanisms and Ca(2+) sensitization mechanisms. The phosphorylation of protein kinase C (PKC) regulates myofilament Ca(2+) sensitivity. We have previously demonstrated that sevoflurane inhibits Ang II-induced vasoconstriction by inhibiting PKC phosphorylation, whereas isoflurane inhibits Ang II-induced vasoconstriction by decreasing intracellular Ca(2+) concentration ([Ca(2+)](i)) in vascular smooth muscle. Propofol also induces vasodilation; however, the effect of propofol on PKC-mediated myofilament Ca(2+) sensitivity is poorly understood. The aim of this study is to determine the mechanisms by which propofol inhibits Ang II-induced vascular contraction in rat aortic smooth muscle. METHODS: An isometric force transducer was used to investigate the effect of propofol on vasoconstriction, a fluorometer was used to investigate the change in [Ca(2+)](i), and Western blot testing was used to analyze Ang II-induced PKC phosphorylation. RESULTS: Ang II (10(-7) M) elicited a transient contraction of rat aortic smooth muscle, which was associated with an elevation of [Ca(2+)](i). Propofol (10(-6 )M) inhibited Ang II-induced vascular contraction (P < 0.01) and increase in [Ca(2+)](i) (P < 0.05) in rat aortic smooth muscle. Ang II also induced a rapid increase in [Ca(2+)](i) in cultured vascular smooth muscle cells, which was suppressed by propofol (P < 0.05). Propofol (10(-6) M) attenuated Ang II-stimulated PKC phosphorylation (P < 0.05). CONCLUSION: These results suggest that the inhibitory effect of propofol on Ang II-induced vascular contraction is mediated by the attenuation of a Ca(2+)-dependent pathway and Ca(2+) sensitivity through the PKC signaling pathway.

Involvement of Ca2+ sensitization in ropivacaine-induced contraction of rat aortic smooth muscle.

BACKGROUND: The mechanisms of amino-amide local anesthetic agent-induced vasoconstriction remain unclear. The current study was designed to examine the roles of the protein kinase C (PKC), Rho kinase, and p44/42 mitogen-activated protein kinase (p44/42 MAPK) signaling pathways in calcium (Ca2+)-sensitization mechanisms in ropivacaine-induced vascular contraction. METHODS: Endothelium-denuded rat aortic rings, segments, and strips were prepared. The cumulative dose-response relations of contraction and intracellular Ca2+ concentration to ropivacaine were tested, using isometric force transducers and a fluorometer, respectively. The dose-dependent ropivacaine-induced phosphorylation of PKC and p44/42 MAPK and the membrane translocation of Rho kinase were also detected using Western blotting. RESULTS: Ropivacaine induced a dose-dependent biphasic contractile response and an increase in intracellular Ca2+ concentration of rat aortic rings, increasing at concentrations of 3 x 10 m to 3 x 10 m and decreasing from 10 m to 3 x 10 m, with a greater tension/intracellular Ca2+ concentration ratio than that induced with potassium chloride. The contraction was attenuated in a dose-dependent manner, by the PKC inhibitors bisindolylmaleimide I and calphostin C, the Rho-kinase inhibitor Y 27632, and the p44/42 MAPK inhibitor PD 098059. Ropivacaine also induced an increase in phosphorylation of PKC and p44/42 MAPK, and membrane translocation of Rho kinase in accordance with the contractile responses, which were also significantly inhibited by bisindolylmaleimide I and calphostin C, Y 27632, and PD 098059, correspondingly. CONCLUSION: These findings demonstrated that PKC-, Rho kinase-, and p44/42 MAPK-mediated Ca2+-sensitization mechanisms are involved in the ropivacaine-induced biphasic contraction of rat aortic smooth muscle.