Subthalamic nucleus local field potential stability in patients with Parkinson's disease.

BACKGROUND: Despite the large body of work on local field potentials (LFPs), a measure of oscillatory activity in patients with Parkinson's disease (PD), the longitudinal evolution of LFPs is less explored. OBJECTIVE: To determine LFP fluctuations collected in clinical settings in patients with PD and STN deep brain stimulation (DBS). METHODS: Twenty-two STN-DBS patients (age: 67.6 ± 8.3 years; 9 females; disease duration: 10.3 ± 4.5 years) completed bilateral LFP recordings over three visits in the OFF-stimulation setting. Peak and band power measures were calculated from each recording. RESULTS: After bilateral LFP recordings, at least one peak was detected in 18 (81.8%), 20 (90.9%), and 22 (100%) patients at visit 1, 2, and 3, respectively. No significant differences were seen in primary peak amplitude (F = 2.91, p = 0.060) over time. Amplitude of the second largest peak (F = 5.49, p = 0.006) and low-beta (F = 6.89, p = 0.002), high-beta (F = 13.23, p < 0.001), and gamma (F = 12.71, p < 0.001) band power demonstrated a significant effect of time. Post hoc comparisons determined low-beta power (Visit 1-Visit 2: t = 3.59, p = 0.002; Visit 1-Visit 3: t = 2.61, p = 0.031), high-beta (Visit 1-Visit 2: t = 4.64, p < 0.001; Visit 1-Visit 3: t = 4.23, p < 0.001) and gamma band power (Visit 1-Visit 2: t = 4.65, p < 0.001; Visit 1-Visit 3: t = 4.00, p < 0.001) were significantly increased from visit 1 recordings to both follow-up visits. CONCLUSION: Our results provide substantial evidence that LFP can reliably be detected across multiple real-world clinical visits in patients with STN-DBS for PD. Moreover, it provides insights on the evolution of these LFPs.

[Deep Brain Stimulation of Globus Pallidus].

The globus pallidus internus(GPi)has evolved as a potential target for deep brain stimulation(DBS)in patients with advanced Parkinson's disease(PD). GPi stimulation has a significant impact on intractable hyperkinetic movement disorders. Optimal surgical procedures require a combination of image-based targeting and intraoperative microelectrode recording(MER)strategies. Provocation with stimulation through microelectrode or a DBS electrode is also crucial for refining the appropriate electrode position and obtaining a wide therapeutic window of stimulation parameters. In patients with PD, the best target for deep brain stimulation, whether subthalamic nucleus(STN)or the GPi, has been a subject of interest in recent medical literature. STN remains the preferred target for DBS in patients with advanced PD worldwide. In postoperative medication reduction, numerous data support that STN stimulation reduces the total dose of anti-parkinsonian drugs compared to GPi stimulation. However, GPi stimulation has shown a direct anti-dyskinetic effect, without reducing levodopa. Thus, GPi stimulation might be recommended for patients with neurocognitive or neuropsychiatric issues. GPi stimulation has a potential for treating hyperkinetic movement disorders. In patients with PD, STN stimulation is preferred worldwide; however, GPi stimulation has a clinical advantage only for select patients.

Impact of breast cancer subtype on clinical outcomes after Gamma Knife radiosurgery for brain metastases from breast cancer: a multi-institutional retrospective study (JLGK1702).

INTRODUCTION: Brain metastasis (BM) is one of the most important issues in the management of breast cancer (BC), since BMs are associated with neurological deficits. However, the importance of BC subtypes remains unclear for BM treated with Gamma Knife radiosurgery (GKS). Thus, we conducted a multicenter retrospective study to compare clinical outcomes based on BC subtypes, with the aim of developing an optimal treatment strategy. METHODS: We studied 439 patients with breast cancer and 1-10 BM from 16 GKS facilities in Japan. Overall survival (OS) was analyzed by the Kaplan-Meier method, and cumulative incidences of systemic death (SD), neurologic death (ND), and tumor progression were estimated by competing risk analysis. RESULTS: OS differed among subtypes. The median OS time (months) after GKS was 10.4 in triple-negative (TN), 13.7 in Luminal, 31.4 in HER2, and 35.8 in Luminal-HER2 subtype BC (p < 0.0001). On multivariate analysis, poor control of the primary disease (hazard ratio [HR] = 1.84, p < 0.0001), active extracranial disease (HR = 2.76, p < 0.0001), neurological symptoms (HR 1.44, p = 0.01), and HER2 negativity (HR = 2.66, p < 0.0001) were significantly associated with worse OS. HER2 positivity was an independent risk factor for local recurrence (p = 0.03) but associated with lower rates of ND (p = 0.03). TN histology was associated with higher rates of distant brain failure (p = 0.03). CONCLUSIONS: HER2 positivity is related to the longer OS after SRS; however, we should pay attention to preventing recurrence in Luminal-HER2 patients. Also, TN patients require meticulous follow-up observation to detect distant metastases and/or LMD.

Comparison of two-stage Gamma Knife radiosurgery outcomes for large brain metastases among primary cancers.

PURPOSE: Stereotactic radiosurgery (SRS) is typically considered for patients who cannot undergo surgical resection for large (> 10 cm3) brain metastases (BMs). Staged SRS requires adaptive planning during each stage of the irradiation period for improved tumor control and reduced radiation damage. However, there has been no study on the tumor reduction rates of this method. We evaluated the outcomes of two-stage SRS across multiple primary cancer types. METHODS: We analyzed 178 patients with 182 large BMs initially treated with two-stage SRS. The primary cancers included breast (BC), non-small cell lung (NSCLC), and gastrointestinal tract cancers (GIC). We analyzed the overall survival (OS), neurological death, systemic death (SD), tumor progression (TP), tumor recurrence (TR), radiation necrosis (RN), and the tumor reduction rate during both stages. RESULTS: The median survival time after the first Gamma Knife surgery (GKS) procedure was 6.6 months. Compared with patients with BC and NSCLC, patients with GIC had shorter OS and a higher incidence of SD. Compared with patients with NSCLC and GIC, patients with BC had significantly higher tumor reduction rates in both sessions. TP rates were similar among primary cancer types. There was no association of the tumor reduction rate with tumor control. The overall cumulative incidence of RN was 4.2%; further, the RN rates were similar among primary cancer types. CONCLUSIONS: Two-stage SRS should be considered for BC and NSCLC if surgical resection is not indicated. For BMs from GIC, staged SRS should be carefully considered and adapted to each unique case given its lower tumor reduction rate and shorter OS.

Three-institution study on applicability of initial brain metastasis velocity for breast cancer brain metastasis patients undergoing stereotactic radiosurgery.

PURPOSE: This study aimed to validate whether the recently-proposed prognostic grading system, initial brain metastasis velocity (iBMV), is applicable to breast cancer patients receiving stereotactic radiosurgery (SRS). We focused particularly on whether this grading system is useful for patients with all molecular types, i.e., positive versus negative for EsR, PgR and HER2. METHODS AND MATERIALS: This was an institutional review board-approved, retrospective cohort study using our database, prospectively accumulated at three gamma knife institutes, during the 20-year-period since 1998. We excluded patients for whom the day of primary cancer diagnosis was not available, had synchronous presentation, lacked information regarding molecular types, and/or had received pre-SRS radiotherapy and/or surgery. We ultimately studied 511 patients categorized into two classes by iBMV scores, i.e., < 2.00 and ≥ 2.00. RESULTS: The median iBMV score for the entire cohort was 0.97 (IQR 0.39-2.84). Median survival time (MST) in patients with iBMV < 2.00, 15.9 (95% CI 13.0-18.6, IQR 7.5-35.5) months, was significantly longer than that in patients with iBMV ≥ 2.00, 8.2 (95% CI 6.8-9.9, IQR 3.9-19.4) months (HR 1.582, 95% CI: 1.308-1.915, p < 0.0001). The same results were obtained in patients with EsR (-), PgR (-), HER2 (+) and HER2 (-) cancers, while MSTs did not differ significantly between iBMV < 2.00 vs ≥ 2.00 in patients with EsR (+) and PgR (+) cancers. CONCLUSIONS: This system was clearly shown to be applicable to breast cancer patients with SRS-treated BMs. However, this system is not applicable to patients with hormone receptor (+) breast cancer.

Applicability and limitations of a recently-proposed prognostic grading metric, initial brain metastasis velocity, for brain metastasis patients undergoing stereotactic radiosurgery.

PURPOSE: This study, based on our brain metastasis (BM) patients undergoing stereotactic radiosurgery (SRS) procedures, aimed to validate whether the recently-proposed prognostic grading system, initial brain metastasis velocity (iBMV, scoring the cumulative number of BMs at the time of SRS divided by time [years] since the initial primary cancer diagnosis), is generally applicable. METHODS: This was an institutional review board-approved, retrospective cohort study using our prospectively accumulated database including 3498 patients who underwent SRS for BMs during the 19.5-year-period between July, 1998 and December, 2017. We excluded four lost to follow-up, 24 for whom the day of primary cancer diagnosis was not available, 665 with synchronous presentation and 651 with pre-SRS radiotherapy and/or surgery, ultimately studying 2150 patients. Patients were categorized into two classes by iBMV scores, i.e., < 2.00 and ≥ 2.00. RESULTS: In a multivariable model, iBMV was directly associated with a higher risk of death (p < 0.0001). The median survival time of patients with iBMV scores < 2.00, 10.0 (95% CI; 9.2-10.9) months, was longer than that of patients with iBMV scores ≥ 2.00, 6.3 (5.6-6.7) months, showing a significant difference between the two groups (HR 1.599, 95% CI 1.458-1.753, p < 0.0001). The same results were obtained in patients with non-small cell lung, breast, kidney or other cancers. Among 608 patients who underwent repeat SRS for newly-developed BMs, iBMV score categories correlated well with brain metastasis velocity risk groups (p < 0.0001). CONCLUSIONS: Our present results support the validity of iBMV for predicting survival after SRS.

The impact of EGFR-TKI use on clinical outcomes of lung adenocarcinoma patients with brain metastases after Gamma Knife radiosurgery: a propensity score-matched analysis based on extended JLGK0901 dataset (JLGK0901-EGFR-TKI).

PURPOSE: Recent advances in targeted therapy have prolonged overall survival (OS) for patients with lung cancer. The impact of epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKI) on brain metastases (BM) treated with stereotactic radiosurgery (SRS) has not, however, been fully elucidated. We investigated the influence of post-SRS EGFR-TKI use on the efficacy and toxicity of SRS for BM from lung adenocarcinoma. METHODS: We used the updated dataset of the Japanese Leksell Gamma Knife (JLGK) 0901 study, which proved the efficacy of Gamma Knife SRS in patients with BM. Propensity score matching (PSM) analysis was employed to determine the impact of concurrent or post-SRS EGFR-TKI use on OS, neurological death, intracranial disease recurrence and SRS-related adverse events. RESULTS: Among 1194 patients registered in the JLGK0901 study, 608 eligible lung adenocarcinoma patients were identified and 238 (39%) had received EGFR-TKI concurrently or during the post-SRS clinical course. After PSM, there were 200 patient pairs with/without post-SRS EGFR-TKI use. EGFR-TKI use was associated with longer OS (median 25.5 vs. 11.0 months, HR 0.60, 95% CI 0.48-0.75, p < 0.001), although the long-term OS curves eventually crossed. Distant intracranial recurrence was more likely in patients receiving EGFR-TKI (HR 1.45, 95% CI 1.12-1.89, p = 0.005). Neurological death, local recurrence and SRS-related adverse event rates did not differ significantly between the two groups. CONCLUSIONS: Although patients receiving EGFR-TKI concurrently or after SRS had significantly longer OS, the local treatment efficacy and toxicity of SRS did not differ between patients with/without EGFR-TKI use.

Stereotactic radiosurgery in elderly patients with brain metastases: comparison with non-elderly patients using database of a multi-institutional prospective observational study (JLGK0901-Elderly).

PURPOSE: Stereotactic radiosurgery (SRS) has been increasingly used for elderly patients with brain metastases (BMs). However, no studies based on a large sample size have been reported. To compare SRS treatment results between elderly and non-elderly patients, we performed a subset study of elderly patients using our prospectively-accumulated multi-institution study database (JLGK0901 Study, Lancet Oncol 15:387-395, 2014). METHODS: During the 2009-2011 period, 1194 eligible patients undergoing gamma knife SRS alone for newly diagnosed BMs were enrolled in this study from 23 gamma knife facilities in Japan. Observation was discontinued at the end of 2013. The 1194 patients were divided into the two age groups, 693 elderly ( ≥ 65 years) and 501 non-elderly ( < 65 years) patients. Our study protocol neither set an upper age limit nor required dose de-escalation. RESULTS: Median post-SRS survival time was significantly shorter in the elderly than in the non-elderly patient group (10.3 vs 14.3 months, HR 1.380, 95% CI 1.218-1.563, p < 0.0001). However, regarding all secondary endpoints including neurological death, neurological deterioration, SRS-related complications, leukoencephalopathy, local recurrence, newly-developed tumors, meningeal dissemination, salvage SRS, whole brain radiotherapy and surgery and decreased mini-mental state examination scores, the elderly patient group was not inferior to the non-elderly patient group. In the 693 elderly patients, there was no post-SRS median survival time difference between those with 5-10 versus 2-4 tumors (10.8 vs 8.9 months, HR 0.936, 95% CI 0.744-1.167, p = 0.5601). CONCLUSIONS: We conclude that elderly BM patients are not unfavorable candidates for SRS alone treatment.

Eighty percent survival rate at 15 years for 1p/19q co-deleted oligodendroglioma treated with upfront chemotherapy irrespective of tumor grade.

INTRODUCTION: Chromosomes 1p/19q co-deletion is a robust molecular marker for the diagnosis of oligodendroglial tumors, and has been included in the 2016 WHO modified classification. Although treatment for oligodendroglioma is controversial, upfront chemotherapy is regarded as one of the treatment option for low-grade tumor. We have treated all the 1p/19q co-deleted oligodendrogliomas, both grades II and III, with upfront chemotherapy without conventional radiotherapy for 20 years. The clinical experience from this trial may be suggestive for understanding of the biological features of oligodendroglioma with 1p/19q co-deletion toward precision medicine. METHODS: This is a long-term retrospective data of the non-selected patients with 1p/19q co-deleted oligodendrogliomas uniformly treated with up-front chemotherapy. Seventy consecutive patients (48 with grade II and 22 with grade III tumors) were included. RESULTS: The median follow-up period was 13 years. The 5-, 10-, and 15-year progression-free survival (PFS) rates were 85.7%, 54.8%, and 31.5%, respectively, and the median PFS was 146 months. In most cases, tumor recurrence was remained local and could be controlled by salvage surgery and/or chemotherapy. The 5-, 10-, and 15-year overall survival (OS) rates were 96.8%, 88.7%, and 80.0%, respectively, and the median OS was not reached. These survival data compared favorably with previous large clinical studies employing radiotherapy. Tumor grades based on World Health Organization classification, extent of surgery, and age affected neither PFS nor OS. Most patients were able to return to their premorbid social life. CONCLUSIONS: The long-term results drawn from 20-years of single institution experience show that the patients with 1p/19q co-deleted oligodendrogliomas can be successfully treated with up-front chemotherapy alone without compromising OS.

Predictive potential of preoperative electroencephalogram for neuropsychological change following subthalamic nucleus deep brain stimulation in Parkinson's disease.

BACKGROUND: Deep brain stimulation of the bilateral subthalamic nucleus (STN-DBS) improves motor fluctuation and severe dyskinesia in advanced Parkinson's disease (PD). Effects on non-motor symptoms, such as neurocognitive side effects, can also influence the quality of life of both patients with PD and caregivers. Predictive quantitative factors associated with postoperative neurocognitive deterioration therefore warrant further attention. Here, we evaluated preoperative electroencephalogram (EEG) as a predictive marker for changes in neurocognitive functions after surgery. METHODS: Scalp EEG was recorded preoperatively from 17 patients with PD who underwent bilateral STN-DBS. Global relative power in the theta, alpha, and beta bands was calculated. Cognitive function was assessed with neuropsychological batteries preoperatively and 1 year after STN-DBS. RESULTS: Performance on the Symbol Search subtest of the WAIS III declined 1 year after DBS. The theta band was chosen for analysis with a 40% cutoff point for increased (≥ 40%) and decreased (< 40%) power. No significant differences between the two groups in baseline performance on most neuropsychological batteries were found, except for the Digit Symbol Coding subtest of the WAIS III. Changes in visual spatial functions were significantly different between groups. The increased theta band power group demonstrated a significant deterioration in performance on the WAIS III Matrix Reasoning subtest and the copy and immediate recall tasks of the Rey-Osterrieth complex figure test. CONCLUSIONS: These findings suggest that preoperative increases in theta power are related to postoperative deterioration of visuospatial function, which indicates the predictive potential of preoperative quantitative EEG for neurocognitive changes after STN-DBS.

Effects of bilateral pallidal deep brain stimulation on chorea after pulmonary thromboendarterectomy with deep hypothermia and circulatory arrest: a case report.

A 41-year-old man was diagnosed with chronic pulmonary thromboembolism and underwent pulmonary thromboendarterectomy (PTE) with deep hypothermia and circulatory arrest. Five days after the operation, chorea emerged in the lower extremities. The patient was referred to our hospital for disabling chorea 16 years after PTE. Neurological examination revealed choreatic movements in the four extremities. Brain magnetic resonance images indicated atrophy in the bilateral head of the caudate nuclei. The patient underwent deep brain stimulation (DBS) of the bilateral globus pallidus interna (GPi). Continuous GPi-DBS diminished the choreatic movements. GPi-DBS may be a treatment option for sustained choreatic movements after PTE.

Cortical Venous Redness Represents Tissue Circulation Status in Patients With Moyamoya Disease.

BACKGROUND AND PURPOSE: Venous oxygen saturation (SO2) is measured in medical fields to assess tissue circulation insufficiency. This study aimed to elucidate the use of a cortical venous redness measurement to evaluate hemodynamic changes during revascularization surgery for patients with moyamoya disease. METHODS: In this retrospective case-series analysis, we first quantitatively measured and correlated SO2 and R intensity of 24-bit color digital red-green-blue pictures of blood samples from 3 volunteers. Subsequently, based on intraoperative digital pictures of 29 patients with moyamoya disease, we measured the R intensities of a cortical vein near the anastomosis site before and after anastomosis. Cerebral blood flow (CBF) at the site was measured using a single-photon emission computed tomography before and 1 to 3 days after surgery. Venous R intensity and CBF were measured twice by 4 raters, and their correlations were examined using generalized linear mixed effect model and linear regression analysis. RESULTS: A strong linear correlation was found between blood R intensity and its SO2 (coefficients, 0.522; 95% confidence interval, 0.364-0.680, using generalized linear mixed effect model). Venous R intensity before the anastomosis was not correlated with preoperative CBF (coefficients, 0.000352; 95% confidence interval, -0.000369 to 0.00107, by generalized linear mixed effect); however, the increases in venous R intensity after anastomosis were correlated with postoperative increases in CBF (R2, 0.367; 95% confidence interval, 0.116-0.618 to 0.548; 95% confidence interval, 0.331-0.764, by linear regression analysis). CONCLUSIONS: Cortical venous redness represented impaired CBF and could be a useful parameter for assessing hemodynamic changes during revascularization surgery.

Gamma knife radiosurgery in movement disorders: Indications and limitations.

Functional radiosurgery has advanced steadily during the past half century since the development of the gamma knife technique for treating intractable cancer pain. Applications of radiosurgery for intracranial diseases have increased with a focus on understanding radiobiology. Currently, the use of gamma knife radiosurgery to ablate deep brain structures is not widespread because visualization of the functional targets remains difficult despite the increased availability of advanced neuroimaging technology. Moreover, most existing reports have a small sample size or are retrospective. However, increased experience with intraoperative neurophysiological evaluations in radiofrequency thalamotomy and deep brain stimulation supports anatomical and neurophysiological approaches to the ventralis intermedius nucleus. Two recent prospective studies have promoted the clinical application of functional radiosurgery for movement disorders. For example, unilateral gamma knife thalamotomy is a potential alternative to radiofrequency thalamotomy and deep brain stimulation techniques for intractable tremor patients with contraindications for surgery. Despite the promising efficacy of gamma knife thalamotomy, however, these studies did not include sufficient follow-up to confirm long-term effects. Herein, we review the radiobiology literature, various techniques, and the treatment efficacy of gamma knife radiosurgery for patients with movement disorders. Future research should focus on randomized controlled studies and long-term effects. © 2016 International Parkinson and Movement Disorder Society.

A case-matched study of stereotactic radiosurgery for patients with brain metastases: comparing treatment results for those with versus without neurological symptoms.

We aimed to reappraise whether post-stereotactic radiosurgery (SRS) results for brain metastases differ between patients with and without neurological symptoms. This was an institutional review board-approved, retrospective cohort study using our prospectively accumulated database including 2825 consecutive BM patients undergoing gamma knife SRS alone during the 15-year period since July 1998. The 2825 patients were divided into two groups; neurologically asymptomatic [group A, 1374 patients (48.6 %)] and neurologically symptomatic [group B, 1451 (51.4 %)]. Because there was considerable bias in pre-SRS clinical factors between groups A and B, a case-matched study was conducted. Ultimately, 1644 patients (822 in each group) were selected. The standard Kaplan-Meier method was used to determine post-SRS survival. Competing risk analysis was applied to estimate cumulative incidences of neurological death, neurological deterioration, local recurrence, re-SRS for new lesions and SRS-induced complications. Post-SRS median survival times (MSTs) did not differ between the two groups; 7.8 months in group A versus 7.4 months in group B patients (HR 1.064, 95 % CI 0.963-1.177, p = 0.22). However, cumulative incidences of neurological death (HR 1.637, 95 % CI 1.174-2.281, p = 0.0036) and neurological deterioration (HR 1.425, 95 % CI 1.073-1.894, p = 0.014) were significantly lower in the group A than in the group B patients. Neurologically asymptomatic patients undergoing SRS for BM had better results than symptomatic patients in terms of both maintenance of good neurological state and prolonged neurological survival. Thus, we conclude that screening computed tomography/magnetic resonance imaging is highly beneficial for managing cancer patients.

Oral health under use of continuous positive airway pressure and interest in alternative therapy in patients with obstructive sleep apnoea: a questionnaire-based survey.

BACKGROUND: Obstructive sleep apnoea (OSA) is associated with a variety of adverse health outcomes. Continuous positive airway pressure (CPAP) is considered first-line treatment for sleep apnoea patients, but there are few studies on oral health in patients with OSA who are using CPAP. OBJECTIVE: This study aimed to estimate the prevalence of oral symptoms and interest in alternative treatments such as oral appliance (OA) therapy in CPAP users. METHODS: A questionnaire was used to ascertain oral health including denture use, oral symptoms at present and since the start of CPAP, and interest in OA therapy. Relevant demographic and clinical data were collected from medical records. RESULTS: The 744 participants who completed the questionnaire had following characteristics (mean ± standard deviation): age (55.1 ± 12.9 years); apnoea-hypopnoea index (40.9 ± 23.2/h); body mass index (27.9 ± 5.2 kg/m(2) ) and length of CPAP usage (49.1 ± 30.7 months); halitosis (30.4%); and gingival bleeding (27.5%). Nearly half (44.6%) complained of dry mouth since beginning CPAP therapy. Patients with diabetes were older (57.8 ± 11.9 vs. 54.2 ± 12.8 years), had a higher rate of denture use (28.3 vs. 19.0%), more dental clinic visits (71.4 vs. 58.7%) and more oral symptoms (50.0 vs. 38.2%) than non-diabetes patients (p < 0.05). Thirty-eight per cent of subjects were interested in OA therapy. CONCLUSIONS: This study exhibited that almost 40% of CPAP users had oral symptoms. In particular, OSA patients with diabetes may be at high risk of oral disease.

Stereotactic radiosurgery in combination with up-front high-dose methotrexate as a first-line treatment for newly diagnosed primary central nervous system lymphoma.

The efficacy of stereotactic radiosurgery (SRS) instead of whole brain radiotherapy (WBRT) following high-dose methotrexate (HD-MTX) for primary central nervous system lymphoma (PCNSL) is unclear. To clarify whether SRS in combination with up-front HD-MTX supplements the effect of HD-MTX in remaining or refractory lesions after initial HD-MTX treatment. The authors conducted a retrospective review for newly diagnosed PCNSL patients who underwent SRS after HD-MTX as a first-line treatment. The local control (LC), the progression-free survival (PFS), the recurrence patterns, the salvage treatments, the overall survival (OS), the Karnofsky Performance Status (KPS), the activities of daily living (ADL) were analyzed as well as radiosurgical parameters. Twenty patients underwent SRS for 51 lesions with the median volume of 0.45 cm(3). The median age at SRS was 67 (range 37-82). The median KPS at SRS was 90. The LC rate at 2 years was 86.0 %, the median PFS after SRS was 17 months, necessitating additional SRS and chemotherapy. The median OS was 52 months. No significant side effects related to SRS were observed. During follow-up period, the good ADL preservation was achieved for 13 months from SRS. Patients with KPS ≥ 90 at SRS demonstrated longer ADL preservation (32 months from SRS). SRS following up-front HD-MTX without WBRT provided excellent LC, acceptable OS and the long ADL preservation period. These benefits may be more emphasized especially in patients with good KPS, but should be validated in a large patient population.

Noncontact Monitoring of Respiration by Dynamic Air-Pressure Sensor.

We have previously reported that a dynamic air-pressure sensor system allows respiratory status to be visually monitored for patients in minimally clothed condition. The dynamic air-pressure sensor measures vital information using changes in air pressure. To utilize this device in the field, we must clarify the influence of clothing conditions on measurement. The present study evaluated use of the dynamic air-pressure sensor system as a respiratory monitor that can reliably detect change in breathing patterns irrespective of clothing. Twelve healthy volunteers reclined on a dental chair positioned horizontally with the sensor pad for measuring air-pressure signals corresponding to respiration placed on the seat back of the dental chair in the central lumbar region. Respiratory measurements were taken under 2 conditions: (a) thinly clothed (subject lying directly on the sensor pad); and (b) thickly clothed (subject lying on the sensor pad covered with a pressure-reducing sheet). Air-pressure signals were recorded and time integration values for air pressure during each expiration were calculated. This information was compared with expiratory tidal volume measured simultaneously by a respirometer connected to the subject via face mask. The dynamic air-pressure sensor was able to receive the signal corresponding to respiration regardless of clothing conditions. A strong correlation was identified between expiratory tidal volume and time integration values for air pressure during each expiration for all subjects under both clothing conditions (0.840-0.988 for the thinly clothed condition and 0.867-0.992 for the thickly clothed condition). These results show that the dynamic air-pressure sensor is useful for monitoring respiratory physiology irrespective of clothing.

Stereotactic radiosurgery for patients with multiple brain metastases (JLGK0901): a multi-institutional prospective observational study.

BACKGROUND: We aimed to examine whether stereotactic radiosurgery without whole-brain radiotherapy (WBRT) as the initial treatment for patients with five to ten brain metastases is non-inferior to that for patients with two to four brain metastases in terms of overall survival. METHODS: This prospective observational study enrolled patients with one to ten newly diagnosed brain metastases (largest tumour <10 mL in volume and <3 cm in longest diameter; total cumulative volume ≤15 mL) and a Karnofsky performance status score of 70 or higher from 23 facilities in Japan. Standard stereotactic radiosurgery procedures were used in all patients; tumour volumes smaller than 4 mL were irradiated with 22 Gy at the lesion periphery and those that were 4-10 mL with 20 Gy. The primary endpoint was overall survival, for which the non-inferiority margin for the comparison of outcomes in patients with two to four brain metastases with those of patients with five to ten brain metastases was set as the value of the upper 95% CI for a hazard ratio (HR) of 1·30, and all data were analysed by intention to treat. The study was finalised on Dec 31, 2012, for analysis of the primary endpoint; however, monitoring of stereotactic radiosurgery-induced complications and neurocognitive function assessment will continue for the censored subset until the end of 2014. This study is registered with the University Medical Information Network Clinical Trial Registry, number 000001812. FINDINGS: We enrolled 1194 eligible patients between March 1, 2009, and Feb 15, 2012. Median overall survival after stereotactic radiosurgery was 13·9 months [95% CI 12·0-15·6] in the 455 patients with one tumour, 10·8 months [9·4-12·4] in the 531 patients with two to four tumours, and 10·8 months [9·1-12·7] in the 208 patients with five to ten tumours. Overall survival did not differ between the patients with two to four tumours and those with five to ten (HR 0·97, 95% CI 0·81-1·18 [less than non-inferiority margin], p=0·78; pnon-inferiority<0·0001). Stereotactic radiosurgery-induced adverse events occurred in 101 (8%) patients; nine (2%) patients with one tumour had one or more grade 3-4 event compared with 13 (2%) patients with two to four tumours and six (3%) patients with five to ten tumours. The proportion of patients who had one or more treatment-related adverse event of any grade did not differ significantly between the two groups of patients with multiple tumours (50 [9%] patients with two to four tumours vs 18 [9%] with five to ten; p=0·89). Four patients died, mainly of complications relating to stereotactic radiosurgery (two with one tumour and one each in the other two groups). INTERPRETATION: Our results suggest that stereotactic radiosurgery without WBRT in patients with five to ten brain metastases is non-inferior to that in patients with two to four brain metastases. Considering the minimal invasiveness of stereotactic radiosurgery and the fewer side-effects than with WBRT, stereotactic radiosurgery might be a suitable alternative for patients with up to ten brain metastases. FUNDING: Japan Brain Foundation.

Inhibition of JNK in HaCaT cells induced tight junction formation with decreased expression of cytokeratin 5, cytokeratin 17 and desmoglein 3.

Epidermal keratinocytes proliferate in the basal layer, differentiate, migrate through the spinous layer, granular layer and cornified layer, and finally are peeled off from the surface of skin with layer-specific expression of differentiation markers, including cytokeratins and cell-cell junction proteins such as desmogleins. Basal cells express CK5, CK14 and Ki67. In contrast, the suprabasal cells in the spinous and granular layers express CK1 and CK10 without Ki67. Inhibition of c-Jun NH2-terminal protein kinase (JNK) in HaCaT cells, a human epidermal keratinocyte cell line, induced the formation of tight junctions, which occurs in the granular layer in vivo. These cells lost their expression of CK5 and CK17, exhibited decreased expression of desmoglein 3 and had no Ki67 labeling in the nucleus. These results suggest that inhibition of JNK causes HaCaT cells to differentiate from basal- and spinous-like cells to granular-like cells. The inhibition of JNK in HaCaT cells provides a useful in vitro model system to study the differentiation of epidermal keratinocytes.