Hiroyuki Nishie

Nonimmersive Virtual Reality Mirror Visual Feedback Therapy and Its Application for the Treatment of Complex Regional Pain Syndrome: An Open‐Label Pilot Study

OBJECTIVE Chronic pain conditions such as phantom limb pain and complex regional pain syndrome are difficult to treat, and traditional pharmacological treatment and invasive neural block are not always effective. Plasticity in the central nervous system occurs in these conditions and may be associated with pain. Mirror visual feedback therapy aims to restore normal cortical organization and is applied in the treatment of chronic pain conditions. However, not all patients benefit from this treatment. Virtual reality technology is increasingly attracting attention for medical application, including as an analgesic modality. An advanced mirror visual feedback system with virtual reality technology may have increased analgesic efficacy and benefit a wider patient population. In this preliminary work, we developed a virtual reality mirror visual feedback system and applied it to the treatment of complex regional pain syndrome. DESIGN A small open-label case series. Five patients with complex regional pain syndrome received virtual reality mirror visual feedback therapy once a week for five to eight sessions on an outpatient basis. Patients were monitored for continued medication use and pain intensity. RESULTS Four of the five patients showed >50% reduction in pain intensity. Two of these patients ended their visits to our pain clinic after five sessions. CONCLUSION Our results indicate that virtual reality mirror visual feedback therapy is a promising alternative treatment for complex regional pain syndrome. Further studies are necessary before concluding that analgesia provided from virtual reality mirror visual feedback therapy is the result of reversing maladaptive changes in pain perception.

Refractory cachexia is associated with increased plasma concentrations of fentanyl in cancer patients

Background An appropriate plasma concentration of fentanyl is the key to achieving good pain control in cancer patients. Cachexia, a multifactorial syndrome, is known to affect drug-metabolizing enzymes. However, the fentanyl concentrations in the blood of patients with cachexia have not been analyzed. The aim of this study was to evaluate the influence of cancer cachexia on dose-adjusted plasma fentanyl concentrations in cancer patients. Methods Blood was collected from 21 Japanese cancer patients treated with a 24-hour trans-dermal fentanyl patch during the steady state of fentanyl plasma concentration. Plasma fentanyl concentrations were analyzed using liquid chromatography with tandem mass spectrometry (LC-MS/MS), and the levels were adjusted with the dose of fentanyl. Laboratory data were collected, and the cachexia stage was determined, based on study by Fearon et al. Multiple regression analysis was performed to identify the factors that affected fentanyl plasma concentrations. Results Eight patients were classified as precachexia, nine as cachexia, and four as refractory cachexia, and the median dose-adjusted fentanyl concentrations (ng/mL per mg/kg/day) were 27.5, 34.4, and 44.5, respectively. The dose-adjusted fentanyl concentration in patients with refractory cachexia was higher than that in patients with precachexia (Kruskal–Wallis test and post hoc Mann–Whitney U-test, P<0.01). The factors that were found to possibly affect the dose-adjusted concentration of fentanyl included aspartate aminotransferase, C-reactive protein, and estimated glomerular filtration rate, when analyzed as six independent variables (multiple regression analysis, P<0.05). Conclusion The dose-adjusted plasma concentrations of fentanyl increased with progression of cancer cachexia. Such an increase is associated with a multifactorial and systemic syndrome in cancer cachexia patients, including lower albumin, higher C-reactive protein, and impaired kidney function. In patients with cancer cachexia, we suggest that evaluation of cancer cachexia might help pain management when using a transdermal fentanyl patch in palliative care.

Establishing Cutoff Points for Defining Symptom Severity Using the Edmonton Symptom Assessment System-Revised Japanese Version

CONTEXT Symptom screening is important for appropriate symptom management. It remains uncertain as to which scores on the Edmonton Symptom Assessment System-Revised (ESAS-r) comprise the optimal cutoff points to determine symptom severity for Japanese cancer patients. OBJECTIVES To investigate optimal cutoff points for individual ESAS-r items for detecting symptom severity and to evaluate the screening performance of the ESAS-r depression item in Japanese cancer patients. METHODS We recruited cancer patients receiving palliative care from five tertiary acute hospitals in Japan. We asked participants to complete the ESAS-r Japanese version, Verbal Rating Symptom Severity Scale, and Quick Inventory of Depressive Symptomatology-Self-Report Japanese version. We calculated sensitivity and specificity for detecting severe and moderate/severe symptoms evaluated by the Verbal Rating Symptom Severity Scale at different cutoff points of the ESAS-r. We also calculated sensitivity and specificity for detecting both the presence of depression and moderate/severe depression evaluated by the Quick Inventory of Depressive Symptomatology-Self-Report at various cutoff points for the depression item of the ESAS-r Japanese version. RESULTS A total of 292 participants completed the questionnaire. For most of the ESAS-r symptoms, cutoff points to achieve the best balance between sensitivity and specificity were 5-7 for determining severe intensity and 3-4 for determining moderate/severe intensity. For the ESAS-r depression item, a cutoff point of 2 achieved the best balance between sensitivity and specificity for detecting both the presence of depression and moderate/severe depression. CONCLUSION The ESAS-r Japanese version can accurately represent the severity of many symptoms. The cutoff points established for determining the level of symptom severity using ESAS-r provides a guide for symptom management in Japanese cancer patients.

The Effect of Guidance regarding Home Exercise and ADL on Adolescent Females Suffering from Adverse Effects after HPV Vaccination in Japanese Multidisciplinary Pain Centers

Background. Two prophylactic papillomavirus (HPV) vaccines have been available for primary prevention of cervical cancer. Although serious adverse effects (AE) were rare, more than 230 women have been suffering from severe AEs such as persistent pain and headache in Japan. Our research group started to treat adolescent females suffering from the AEs. Objective. To survey the characteristics of and the effects of cognitive behavioral therapy on adolescent female suffering from the AEs in Japanese multidisciplinary pain centers. Methods. One hundred and forty-five patients suffering from the AEs were reviewed retrospectively and 105 patients of them were provided guidance on home exercise and activities of daily living based partially on a cognitive-behavioral approach. The intensity of pain was rated by the patients using a numerical rating scale (NRS). Furthermore, the Hospital Anxiety and Depression Scale (HADS) and the Pain Catastrophizing Scale (PCS) were used. Results. Eighty out of the 105 patients who received the guidance were followed up, 10 displayed a marked improvement, and 43 showed some improvement. Conclusions. Guidance on home exercise and activities of daily living based on a cognitive-behavioral approach alleviated the AEs that women suffered from after HPV vaccination in Japan.

“Engagement ring” image conveys regrettable outcome for aged patients with non-small cell lung cancer: Impressive feature of skull bone tumor

A 92-year-old woman was referred to our hospital from a local nursing home because of a tonic-clonic seizure. Esophagogastroduodenoscopy had been performed at another clinic two months earlier after the patient had complained of appetite loss and a small bump on her forehead. No abnormal findings were observed and the cause of her bump was concluded as an accident. Thus, further examination was not planned. Head computed tomography (CT) imaging on admission revealed an irregular-shaped tumor on the frontal bone invading into cranial dura mater (Fig 1). A hilar mass with pulmonary atelectasis in the left upper division bronchus was also observed on chest CT (Fig 2). The cause of the seizure was immediately proven to be symptomatic epilepsy as a result of brain invasion from skull bone metastasis of non-small cell lung cancer, which is considered a rare condition. Daily administration of levetiracetam (1000 mg) was initiated to control symptoms and the epilepsy was relieved. Unfortunately only digestive tract disease was excluded after further examination when the patient complained of appetite loss. It is regrettable that a protruding bump on her forehead was misdiagnosed as mere swelling caused by an accident without further radiological examination using magnetic resonance imaging or CT. As evidenced by our case in which the patient’s diagnosis was overlooked, current Japanese public health administration

Site-specific induction of intestinal hypoxia-inducible factor-1α after hemorrhagic shock.

The intestine is a major target organ in hemorrhagic shock (HS)-induced tissue injury. Hypoxia-inducible factor (HIF)-1α is the primary transcription factor responsible for regulating cellular response to changes in oxygen tension. Since HS is an acute hypoxic insult, the present study examined changes in the gene expression of HIF-1α in various regions of the intestine, as well as the distribution of HIF-1α protein in the intestinal cells of a rat model of HS. Levels of HIF-1α mRNA were marginally detectable in the intestine of sham-operated control animals, but obviously induced following HS. Duodenal, jejunal and colonic levels of HIF-1α mRNA robustly increased and reached a maximum during the ischemic phase of HS, followed by a rapid decrease almost to control levels during the early phase of resuscitation. The induction of HIF-1α mRNA was maximal in the duodenum. In contrast to the duodenum, jejunum and colon, in the ileum the HIF-1α mRNA level did not increase after HS. Consistent with enhanced HIF-1α gene expression, HIF-1α protein was expressed in the mucosal cells of the duodenum, jejunum and colon, but not in the ileum following HS. These findings indicate that intestinal HIF-1α expression was up-regulated at both the transcriptional and protein level in a site-specific manner in this rat model of HS. Differential regulation of HIF-1α expression along the longitudinal axes of the intestine might be a determinant of the adaptive response to HS-induced intestinal damage.