Safety and Effectiveness of Perospirone in Comparison to Risperidone for Treatment of Delirium in Patients with Advanced Cancer: A Multicenter Prospective Observational Study in Real-World Psycho-Oncology Settings

The clinical benefit of perospirone for treatment of delirium in patients with advanced cancer is not sufficiently clear. The objective of this study was to compare the safety and effectiveness of perospirone to those of risperidone for the treatment of delirium in patients with advanced cancer. This is a secondary analysis of a multicenter prospective observational study in nine psycho-oncology consultation services in Japan. The study used the Delirium Rating Scale (DRS) Revised-98 to measure effectiveness and the CTCAE (Common Terminology Criteria for Adverse Events) version 4 to assess safety. Data from 16 patients who received perospirone and 53 patients who received risperidone were analyzed. The mean age was 70 years in the perospirone group and 73 years in the risperidone group. Both groups showed a significant decrease in the total score of DRS-R-98 after three days of treatment (perospirone: 11.7 (7.9-15.4) to 7.0 (3.3-10.7), difference −4.7, effect size=0.72, p=0.003; risperidone: 15.5 (13.6-17.4) to 12.2 (10.1-14.2), difference −3.3, effect size=0.55, p=0.00). The risperidone group showed significant improvements in sleep-wake cycle disturbance, orientation, attention, and visuospatial ability. In the perospirone group, there was a significant improvement of sleep-wake cycle disturbance. The median daily dose of perospirone was 4 mg/day. There were fewer episodes of somnolence as an adverse event in the perospirone group. Low-dose perospirone was thus found to be effective for the treatment of delirium in patients with advanced cancer and may be associated with fewer episodes of over-sedation as an adverse event

Protective effects of cold spinoplegia with fasudil against ischemic spinal cord injury in rabbits

ObjectiveParaplegia remains a serious complication after surgical repair of thoracoabdominal aortic aneurysms. The aim of this study was to evaluate the neuroprotective efficacy of fasudil, a Rho kinase (ROCK) inhibitor, by reducing the number of infiltrating cells in the ventral horn and increasing the induction of eNOS against ischemic spinal cord injury in rabbits.MethodsEighteen Japanese white rabbits were divided into three groups: saline (group 1, n = 7, 4°C) and fasudil (group 2, n = 6, 4°C) were immediately infused into the isolated segmental lumbar arteries over 30 seconds after aortic clamping. Group 3 (n = 5) was the sham-operated group. Hind limb function was evaluated 4 and 8 hours, and 1 and 2 days after 15 minutes of transient ischemia. Cell damage was analyzed by hematoxylin and eosin staining and temporal profiles of endothelial nitric oxide synthase immunoreactivity were performed. The number of intact motor neuron cells and infiltrating cells in the ventral horn were compared.ResultsTwo days after reperfusion, group 2 and group 3 showed better neurologic function, a greater number of intact motor neuron cells, and a smaller number of infiltrating cells in the ventral horn than group 1. The induction of endothelial nitric oxide synthase (eNOS) was prolonged up to 2 days after reperfusion in group 2.ConclusionThese results indicate that fasudil has neuroprotective effects against ischemic spinal cord injury in rabbits by reducing the number of infiltrating cells in the ventral horn and prolonging the expression of eNOS.Clinical RelevanceParaplegia or paralysis caused by spinal cord ischemia remains a devastating and unpredictable complication after descending and thoracoabdominal aortic surgery. This study has revealed that fasudil has a neuroprotective effect against ischemic spinal cord injury in rabbits. Inhibition of the Rho/Rho kinase pathway by fasudil reduces the number of infiltrating cells in the ventral horn and prolongs the expression of eNOS. In the near future, Rho kinase may be an important therapeutic target for paraplegia induced by spinal cord ischemia

食餌操作によるモデルラットにおける骨シーキング物質の骨格摂取の増大(英語)

富山医科薬科大学 医 放射線原著論

Effect of intracarotid infusion of etoposide: modification of the permeability of the blood-brain barrier and the blood-tumor barrier in rat brain tumor model

The effect of intracarotid infusion of etoposide on the permeability of the blood-brain barrier (BBB) and brain-tumor barrier (BTB) was investigated using a model of rats injected with C6 glioma cells. Fifty four glioma-bearing rats were divided into 3 groups and treated with 0, 3, or 15 mg/kg of etoposide infused into the internal carotid artery. BBB or BTB permeability was evaluated qualitatively by the leakage of Evans blue (6 animals in each group) or quantitatively by the diffusion of carboplatin [cis-diammine (1,1-cyclobutane-dicarboxylato) platinum(II); CBDCA] (12 animals in each group) into the normal brain or the tumor tissue. BBB and BTB disruption augmented significantly in proportion to the dose of etoposide. The degree of disruption of BTB was greater than that of BBB, but the rate of disruption of BBB in proportion to increasing the dose of etoposide was higher than that in the BTB. Histopathologically, no obvious changes were observed in the animals of either the control group or the 3 mg/kg group but degenerative changes in the neurons of the hippocampus of the infused hemisphere were seen in the 15 mg/kg group. This change is thought to be caused by apoptosis because of the positive reaction with TdT-mediated dUTP-biotin nick-end labeling (TUNEL) method. Our results suggest that intracarotid infusion of etoposide can increase drug delivery of concurrent antitumor agents into tumor tissue, but cerebral parenchymal cell damage is expected with a higher dosage of etoposide. Therefore, the dosage of etoposide for intracarotid infusion should be lower than 15 mg/kg in order to reduce neurotoxicity of both etoposide and concurrent anticancer drugs.</p

Sphingosine 1-Phosphate (S1P) in the Peritoneal Fluid Skews M2 Macrophage and Contributes to the Development of Endometriosis

Sphingosine 1-phosphate (S1P), an inflammatory mediator, is abundantly contained in red blood cells and platelets. We hypothesized that the S1P concentration in the peritoneal cavity would increase especially during the menstrual phase due to the reflux of menstrual blood, and investigated the S1P concentration in the human peritoneal fluid (PF) from 14 non-endometriosis and 19 endometriosis patients. Although the relatively small number of samples requires caution in interpreting the results, S1P concentration in the PF during the menstrual phase was predominantly increased compared to the non-menstrual phase, regardless of the presence or absence of endometriosis. During the non-menstrual phase, patients with endometriosis showed a significant increase in S1P concentration compared to controls. In vitro experiments using human intra-peritoneal macrophages (MΦ) showed that S1P stimulation biased them toward an M2MΦ-dominant condition and increased the expression of IL-6 and COX-2. An in vivo study showed that administration of S1P increased the size of the endometriotic-like lesion in a mouse model of endometriosis

Results of laparoscopic subtotal cholecystectomy by laparoscopic linear stapler in difficult cases with severe cholecystitis

Laparoscopic subtotal cholecystectomy (LSC) has been recognized as a safe and feasible alternative surgical procedure for a difficult laparoscopic cholecystectomy (LC) with severe inflammation in Calot’s triangle. We compared the surgical outcomesof cholecystectomy for acute cholecystitis between standard LC and LSC using laparoscopic linear stapler. 172 patients were diagnosed as acute cholecystitis, among them, 16 patients who underwent LSC and other 156 patients who underwent standardLC were enrolled in this study. The severity grading of acute cholecystitis in LSC group was significantly higher than LC group. Operation time was longer in the LSC group than LC group. LSC had significantly more intraoperative blood loss compared to LC. However, there was no significant difference in the postoperative complications between two groups. LSC using laparoscopic linear stapler contributes surgeons avoid common bile duct injury in difficult LC

A case of surgical resection for well-differentiated squamous cell carcinoma arising in a ciliated hepatic foregut cyst

Ciliated hepatic foregut cysts (CHFC) are extremely rare, and most are benign cysts of the liver arising from remnants of the embryonic foregut. CHFC is usually found incidentally and as mostly asymptomatic cysts. We report squamous cell carcinoma (SCC) arising in a CHFC in a 50-year-old Japanese woman. She consulted our hospital for upper abdominal pain.A computed tomography and an ultrasound showed a cystic region including calcification and a solid mass in segment 4 of the liver. Left hepatectomy, B6 bile duct resection, and biliary-jejunal anastomosis were performed. Microscopic examination revealed that part of the cyst was lined by a characteristic ciliated pseudostratified columnar epithelium surrounding a connective tissue, a slightly thick fibrotic smooth muscle stromal layer, and an outer fibrous capsule. The cyst wall contained a low-papillary mural nodule showing atypical squamous hyperplasia with high-grade dysplasia. Stromal invasion was identified at the base of the nodule, leading to the diagnosis of well-differentiated SCC arising from a CHFC. We recommend careful clinical follow-up for patients with relatively large CHFCs as potentially malignant lesions and excision if they show any clinical manifestation