A Survey of Near-Miss Dispensing Errors in Hospital Pharmacies in Japan: DEPP-J Study-Multi-Center Prospective Observational Study-

The aim of this study was to determine the proportion of near-miss dispensing errors in hospital pharmacies in Japan. A prospective multi-center observational study was conducted between December 2018 and March 2019. The primary objective was to determine the proportion of near-miss dispensing errors in hospital pharmacy departments. The secondary objective was to determine the predictive factors for near-miss dispensing errors using multiple logistic regression analysis. The study was approved by the ethical committee at The Institute of Medical Sciences, University of Tokyo, Japan. A multi-center prospective observational study was conducted in 20 hospitals comprising 8862 beds. Across the 20 hospitals, we assessed data from 553 pharmacists and 53039 prescriptions. A near-miss dispensing error proportion of 0.87% (n = 461) was observed in the study. We found predictive factors for dispensing errors in day-time shifts: a higher number of drugs in a prescription, higher number of quantified drugs, such as liquid or powder formula, in a prescription, and higher number of topical agents in a prescription; but we did not observe for career experience level for clinical pharmacists. For night-time and weekend shifts, we observed a negative correlation of near-miss dispensing errors with clinical pharmacist experience level. We found an overall incidence of near-miss dispensing errors of 0.87%. Predictive factors for errors in night-time and weekend shifts was inexperienced pharmacists. We recommended that pharmacy managers should consider education or improved work flow to avoid near-miss dispensing errors by younger pharmacists, especially those working night or weekend shifts.

[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.

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.

Human nonsense-mediated mRNA decay factor UPF2 interacts directly with eRF3 and the SURF complex.

Nonsense-mediated mRNA decay (NMD) is an mRNA degradation pathway that regulates gene expression and mRNA quality. A complex network of macromolecular interactions regulates NMD initiation, which is only partially understood. According to prevailing models, NMD begins by the assembly of the SURF (SMG1-UPF1-eRF1-eRF3) complex at the ribosome, followed by UPF1 activation by additional factors such as UPF2 and UPF3. Elucidating the interactions between NMD factors is essential to comprehend NMD, and here we demonstrate biochemically and structurally the interaction between human UPF2 and eukaryotic release factor 3 (eRF3). In addition, we find that UPF2 associates with SURF and ribosomes in cells, in an UPF3-independent manner. Binding assays using a collection of UPF2 truncated variants reveal that eRF3 binds to the C-terminal part of UPF2. This region of UPF2 is partially coincident with the UPF3-binding site as revealed by electron microscopy of the UPF2-eRF3 complex. Accordingly, we find that the interaction of UPF2 with UPF3b interferes with the assembly of the UPF2-eRF3 complex, and that UPF2 binds UPF3b more strongly than eRF3. Together, our results highlight the role of UPF2 as a platform for the transient interactions of several NMD factors, including several components of SURF.

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.

Language Lateralization by Passive Auditory fMRI in Presurgical Assessment for Temporal Lobe Epilepsy: A Single-Center Retrospective Study.

Background: In temporal lobe epilepsy (TLE), estimating the potential risk of language dysfunction before surgery is a necessary procedure. Functional MRI (fMRI) is considered the most useful to determine language lateralization noninvasively. However, there are no standardized language fMRI protocols, and several issues remain unresolved. In particular, the language tasks normally used are predominantly active paradigms that require the overt participation of patients, making assessment difficult for pediatric patients or patients with intellectual disabilities. In this study, task-based fMRI with passive narrative listening was applied to evaluate speech comprehension to estimate language function in Japanese-speaking patients with drug-resistant TLE. Methods: Twenty-one patients (six with intellectual disabilities) participated. Patients listened to passive auditory stimuli with combinations of forward and silent playback, and forward and backward playback. The activation results were extracted using a block design, and lateralization indices were calculated. The obtained fMRI results were compared to the results of the Wada test. Results: The concordance rate between fMRI and the Wada test was 95.2%. Meaningful responses were successfully obtained even from participants with intellectual disabilities. Conclusions: This passive fMRI paradigm can provide safe and easy presurgical language evaluation, particularly for individuals who may not readily engage in active paradigms.

Subthalamic deep brain stimulation can improve gastric emptying in Parkinson's disease.

It is established that deep brain stimulation of the subthalamic nucleus improves motor function in advanced Parkinson's disease, but its effects on autonomic function remain to be elucidated. The present study was undertaken to investigate the effects of subthalamic deep brain stimulation on gastric emptying. A total of 16 patients with Parkinson's disease who underwent bilateral subthalamic deep brain stimulation were enrolled. Gastric emptying was expressed as the peak time of (13)CO(2) excretion (T(max)) in the (13)C-acetate breath test and was assessed in patients with and without administration of 100-150 mg levodopa/decarboxylase inhibitor before surgery, and with and without subthalamic deep brain stimulation at 3 months post-surgery. The pattern of (13)CO(2) excretion curve was analysed. To evaluate potential factors related to the effect of subthalamic deep brain stimulation on gastric emptying, we also examined the association between gastric emptying, clinical characteristics, the equivalent dose of levodopa and serum ghrelin levels. The peak time of (13)CO(2) excretion (T(max)) values for gastric emptying in patients without and with levodopa/decarboxylase inhibitor treatment were 45.6 ± 22.7 min and 42.5 ± 13.6 min, respectively (P = not significant), thus demonstrating levodopa resistance. The peak time of (13)CO(2) excretion (T(max)) values without and with subthalamic deep brain stimulation after surgery were 44.0 ± 17.5 min and 30.0 ± 12.5 min (P < 0.001), respectively, which showed that subthalamic deep brain stimulation was effective. Simultaneously, the pattern of the (13)CO(2) excretion curve was also significantly improved relative to surgery with no stimulation (P = 0.002), although the difference with and without levodopa/decarboxylase inhibitor was not significant. The difference in peak time of (13)CO(2) excretion (T(max)) values without levodopa/decarboxylase inhibitor before surgery and without levodopa/decarboxylase inhibitor and subthalamic deep brain stimulation after surgery was not significant, although motor dysfunction improved and the levodopa equivalent dose decreased after surgery. There was little association between changes in ghrelin levels (Δghrelin) and changes in T(max) values (ΔT(max)) in the subthalamic deep brain stimulation trial after surgery (r = -0.20), and no association between changes in other characteristics and ΔT(max) post-surgery in the subthalamic deep brain stimulation trial. These results showed that levodopa/decarboxylase inhibitor did not influence gastric emptying and that subthalamic deep brain stimulation can improve the dysfunction in patients with Parkinson's disease possibly by altering the neural system that controls gastrointestinal function after subthalamic deep brain stimulation. This is the first report to show the effectiveness of subthalamic deep brain stimulation on gastrointestinal dysfunction as a non-motor symptom in Parkinson's disease.

Gamma Knife Radiosurgery for Metastatic Brain Tumors from Uterine Cervical and Endometrial Carcinomas: Histopathological Analysis of Survival and Local Control. A Japanese Multi-Institutional Cooperative and Retrospective Cohort Study.

OBJECTIVE: A retrospective comparative analysis of the outcomes of gamma knife radiosurgery (GKRS) for brain metastases from uterine cervical carcinoma (CC) and endometrial carcinoma (EC), investigated the efficacy and prognostic factors for survival and local tumor control. Histopathological analysis was also performed. METHODS: The authors retrospectively reviewed 61 patients with 260 tumors of CC and 73 patients with 302 tumors of EC who had undergone GKRS. RESULTS: The survival times after GKRS had no difference between CC and EC. Uncontrolled primary cancer was significant unfavorable factor. CC resulted in significantly higher neurological death and post-GKRS neurological deterioration. New lesions appeared intracranially after GKRS, with no significant difference between CC and EC. Local tumor control rates at 6, 12, and 24 months after GKRS were 90.0%, 86.6%, and 78.0% for CC and 92.2%, 87.9%, and 86.4% for EC. Primary cancer of CC, more than 7 cm3 volume, and prescription dose less than 20 Gy were significantly correlated in control failure. Local tumor control rates were significantly lower for squamous cell carcinoma in CC. No significant differences were found between histopathological subtypes of EC. CONCLUSIONS: This study established a relationship between the efficacy of GKRS for CC and EC brain metastases and the histopathological. Though, survival time after GKRS has no difference between CC and EC, CC was significantly higher neurogenic death and neurological deterioration after GKRS. Squamous cell carcinoma had a significantly lower rate of local tumor control among all CC, thereby resulting in CC having lower local tumor control than EC.

Comparison of first-line radiosurgery for small-cell and non-small cell lung cancer brain metastases (CROSS-FIRE).

INTRODUCTION: Historical reservations regarding stereotactic radiosurgery (SRS) for small-cell lung cancer (SCLC) brain metastases include concerns for short-interval and diffuse central nervous system (CNS) progression, poor prognoses, and increased neurological mortality specific to SCLC histology. We compared SRS outcomes for SCLC and non-small cell lung cancer (NSCLC) where SRS is well established. METHODS: Multicenter first-line SRS outcomes for SCLC and NSCLC from 2000 to 2022 were retrospectively collected (n = 892 SCLC, n = 4785 NSCLC). Data from the prospective Japanese Leksell Gamma Knife Society (JLGK0901) clinical trial of first-line SRS were analyzed as a comparison cohort (n = 98 SCLC, n = 814 NSCLC). Overall survival (OS) and CNS progression were analyzed using Cox proportional hazard and Fine-Gray models, respectively, with multivariable adjustment for cofactors including age, sex, performance status, year, extracranial disease status, and brain metastasis number and volume. Mutation-stratified analyses were performed in propensity score-matched retrospective cohorts of epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) positive NSCLC, mutation-negative NSCLC, and SCLC. RESULTS: OS was superior for patients with NSCLC compared to SCLC in the retrospective dataset (median OS = 10.5 vs 8.6 months; P < .001) and in the JLGK0901 dataset. Hazard estimates for first CNS progression favoring NSCLC were similar in both datasets but reached statistical significance in the retrospective dataset only (multivariable hazard ratio = 0.82, 95% confidence interval = 0.73 to 0.92, P = .001). In the propensity score-matched cohorts, there were continued OS advantages for NSCLC patients (median OS = 23.7 [EGFR and ALK positive NSCLC] vs 13.6 [mutation-negative NSCLC] vs 10.4 months [SCLC], pairwise P values < 0.001), but no statistically significant differences in CNS progression were observed in the matched cohorts. Neurological mortality and number of lesions at CNS progression were similar for NSCLC and SCLC patients. Leptomeningeal progression was increased in patients with NSCLC compared to SCLC in the retrospective dataset only (multivariable hazard ratio = 1.61, 95% confidence interval = 1.14 to 2.26, P = .007). CONCLUSIONS: After SRS, SCLC histology was associated with shorter OS compared to NSCLC. CNS progression occurred earlier in SCLC patients overall but was similar in patients matched on baseline factors. SCLC was not associated with increased neurological mortality, number of lesions at CNS progression, or leptomeningeal progression compared to NSCLC. These findings may better inform clinical expectations and individualized decision making regarding SRS for SCLC patients.

Comparison of subjective symptoms of temporomandibular disorders in young patients by age and gender.

The authors assessed the subjective symptoms of temporomandibular disorders (TMDs) in 167 young patients using self-reported forms, with five ratings for pain intensity and six ratings for difficulty in activities of daily living (ADL), to compare TMD symptoms according to gender and three age groups: group 1: 6- to 12-year-olds (juvenile); group 2: 13- to 15-year-olds (early adolescent); group 3: 16- to 18-year-olds (late adolescent). No significant gender differences were found in the symptoms among the groups, except for headache and neck pain in group 3. Pain intensity and tightness in the jaw/face, headache, and neck pain, as well as the ADL-related difficulty in prolonged jaw opening, eating soft/hard foods, and sleeping significantly differed among the groups (p < 0.01, Kruskal-Wallis test). Therefore, late adolescent patients with TMDs have higher pain intensity in the orofacial region and greater difficulty in ADL than do early adolescent and juvenile patients with TMDs.

Growth potential of small residual tumors after vestibular schwannoma surgery: comparison between remnants and the natural history of small tumors.

OBJECTIVE: Due to the heterogeneous definitions of tumor regrowth and various tumor volume distributions, the nature of small remnants after vestibular schwannoma (VS) surgery and the appropriate timing of adjuvant stereotactic radiosurgery for these remnants remain unclear. In this study, the growth potential of small remnants (< 1 cm3) after VS surgery was compared with that of treatment-naïve (TN) small VSs. METHODS: This retrospective single-center study included 44 patients with VS remnants following subtotal resection (STR) of a large VS (remnant group) and 75 patients with TN VS (< 1 cm3; TN group). A 20% change in tumor volume over the imaging interval indicated radiographic progression or regression. Tumor progression-free survival (TPFS) rates were estimated using the Kaplan-Meier method. RESULTS: In the remnant group, the mean preoperative tumor volume was 13.8 ± 9.0 cm3 and the mean tumor resection rate was 95% ± 5%. The mean tumor volume at the start of the observation period did not differ significantly between the two groups (remnant vs TN: 0.41 ± 0.29 vs 0.34 ± 0.28 cm3, p = 0.171). The median periods until tumor progression was detected were 15.1 (range 4.9-76.2) months and 44.7 (range 12.6-93.2) months in the TN and remnant groups, respectively. In the remnant group, the TPFS rates were 74% and 70% at 3 and 5 years after the surgery, respectively, compared with 59% and 47% in the TN group. The log-rank test demonstrated a significant difference (p = 0.008) in the TPFS rates between the two groups. Furthermore, 42 patients each from the remnant and TN groups were matched based on tumor volume. TPFS was significantly longer in the remnant group than in the TN group (3-year rates, 77% vs 62%; 5-year rates, 73% vs 51%; p = 0.02). In the remnant group, 18% of the tumor remnants demonstrated regression during follow-up, compared with 9% in the TN group, but this intergroup difference was not significant (p = 0.25). CONCLUSIONS: This study demonstrated that the growth potential of small VS remnants was lower than that of TN tumors. Observing for small remnants may be appropriate after STR of a large VS. Given the risk of tumor regrowth, careful observation using MRI should be mandatory during follow-up.

Gamma Knife radiosurgery for metastatic brain tumors from ovarian cancer: histopathological analysis of survival and local control. A Japanese multi-institutional cooperative and retrospective cohort study.

OBJECTIVE: Brain metastasis is rare in ovarian cancer patients. The results of Gamma Knife radiosurgery (GKRS) for the treatment of patients with brain metastases from ovarian cancer were retrospectively analyzed to derive the efficacy and prognostic factors for survival and local tumor control. Further histopathological analysis was also performed. METHODS: The authors retrospectively reviewed the medical records of 118 patients with 566 tumors who had undergone GKRS at the 10 GKRS institutions in Japan. RESULTS: After the initial GKRS, the median overall survival time was 18.1 months. Multivariate analysis showed that uncontrolled primary cancer (p = 0.003) and multiple intracranial metastases (p = 0.034) were significant unfavorable factors. Ten patients died of uncontrolled brain metastases at a median of 17.1 months. The 6-, 12-, and 24-month neurological death rates were 3.2%, 4.6%, and 11.9%, respectively. The 6-, 12-, and 24-month neurological deterioration rates were 7.2%, 13.5%, and 31.4%, respectively. The 6-, 12-, and 24-month distant brain control failure rates were 20.6%, 40.2%, and 42.3%, respectively. Median tumor volume was 1.6 cm3 and marginal dose was 20 Gy. The 6-, 12-, and 24-month local tumor control rates were 97.6%, 95.2%, and 88.0%, respectively. Peritumoral edema (p = 0.043), more than 7-cm3 volume (p = 0.021), and prescription dose less than 18 Gy (p = 0.014) were factors that were significantly correlated in local tumor control failure. Eight patients had symptomatic radiation injury. The 6-, 12-, and 24-month GKRS-related complication rates were 3.3%, 7.8%, and 12.2%, respectively. Primary ovarian cancer was histopathologically diagnosed for 313 tumors in 69 patients. Serous adenocarcinoma was found in 37 patients and other types in 32 patients. Median survival times were 32.3 months for the serous type and 17.4 months for other types after initial GKRS. Patients with serous-type tumors survived significantly longer than patients with other types (p = 0.039). The 6-, 12-, and 24-month local tumor control rates were 100%, 98.8%, and 98.8%, respectively. Serous-type tumors were a significantly good prognosis factor for local tumor control after GKRS (p = 0.005). CONCLUSIONS: This study established a relationship between the efficacy of GKRS treatment for brain metastases and the histological type of primary ovarian cancer. GKRS for ovarian cancer brain metastasis can provide satisfactory survival and local control, especially in cases of serous adenocarcinoma.

Stereotactic radiosurgery results for brain metastasis patients with renal cancer: A validity study of Renal Graded Prognostic Assessment and proposal of a new grading index (JLGK2101 Study).

BACKGROUND AND PURPOSE: The Renal Graded Prognostic Assessment (GPA) is relatively new and has not been sufficiently validated using a different dataset. We thus developed a new grading index, the Renal Brain Metastasis Score (Renal-BMS). MATERIALS AND METHODS: Using our dataset including 262 renal cancer patients with brain metastases (BMs) undergoing stereotactic radiosurgery (SRS) (test series), we validity tested the Renal-GPA. Next, we applied clinical factor-survival analysis to the test series and thereby developed the Renal-BMS. This system was then validated using another series of 352 patients independently undergoing SRS at nine gamma knife facilities in Japan (verification series). RESULTS: Using the test series, with the Renal-GPA, 95% confidence intervals (CIs) of the post-SRS median survival times (MSTs) overlapped between pairs of neighboring subgroups. Among various pre-SRS clinical factors of the test series, six were highly associated with overall survival. Therefore, we assigned scores for six factors, i.e., "KPS ≥ 80%/<80% (0/3)", "tumor numbers 1-4/≥5 (score; 0/2)", "controlled primary cancer/not (0/2)", "existing extra-cerebral metastases/not (0/3)", "blood hemoglobin ≥ 11.0/<11.0 g/dl (0/1)" and "interval from primary cancer to SRS ≥ 5/<5 years (0/1)". Patients were categorized into three subgroups according to the sum of scores, i.e., 0-4, 5-8 and 9-12. In the test and verification series, post-SRS MSTs differed significantly (p < 0.0001) with no overlaps of 95% CIs among the three subgroups. CONCLUSIONS: The Renal BMS has the potential to be very useful to physicians selecting among aggressive treatment modalities for renal cancer patients with BMs.

A Practical Grading Scale for Predicting Outcomes of Radiosurgery for Dural Arteriovenous Fistulas: JLGK 1802 Study.

BACKGROUND AND PURPOSE: To assess the long-term outcomes of intracranial dural arteriovenous fistula (DAVF) treated with stereotactic radiosurgery (SRS) alone or embolization and SRS (Emb-SRS) and to develop a grading system for predicting DAVF obliteration. METHODS: This multi-institutional retrospective study included 200 patients with DAVF treated with SRS or Emb-SRS. We investigated the long-term obliteration rate and obliteration-associated factors. We developed a new grading system to estimate the obliteration rate. Additionally, we compared the outcomes of SRS and Emb-SRS by using propensity score matching. RESULTS: The 3- and 4-year obliteration rates were 66.3% and 78.8%, respectively. The post-SRS hemorrhage rate was 2%. In the matched cohort, the SRS and Emb-SRS groups did not differ in the rates of obliteration (P=0.54) or post-SRS hemorrhage (P=0.50). In multivariable analysis, DAVF location and cortical venous reflux (CVR) were independently associated with obliteration. The new grading system assigned 2, 1, and 0 points to DAVFs in the anterior skull base or middle fossa, DAVFs with CVR or DAVFs in the superior sagittal sinus or tentorium, and DAVFs without these factors, respectively. Using the total points, patients were stratified into the highest (0 points), intermediate (1 point), or lowest (≥2 points) obliteration rate groups that exhibited 4-year obliteration rates of 94.4%, 71.3%, and 60.4%, respectively (P<0.01). CONCLUSIONS: SRS-based therapy achieved DAVF obliteration in more than three-quarters of the patients at 4 years of age. Our grading system can stratify the obliteration rate and may guide physicians in treatment selection.

Inter- and intraobserver reliability of the hand-held monitor for measuring salivary alpha-amylase level.

BACKGROUND: Alpha-amylase levels can be used to quantify the psychological stress. A hand-held salivary alpha-amylase (sAA) monitor was recently developed for measuring sAA levels. This study investigated the inter- and intraobserver reliability of this novel instrument. METHODS: Saliva was collected from 32 healthy volunteers. To determine the interobserver reliability, three observers measured the sAA levels in 10 samples. To determine the intraobserver reliability, one observer performed consecutive sAA measurements in 32 samples. The sAA levels in these 32 samples were also measured by a conventional laboratory enzymatic analysis, and these measurements were compared with those obtained using the hand-held monitor. RESULTS: Intraclass correlation coefficients indicated excellent inter- and intraobserver reliability (0.99 and 0.92, respectively). The results from the monitor and the lab assay showed a significant positive correlation (r = 0.96, p < 0.001). CONCLUSIONS: These results suggest that the hand-held monitor is highly reliable for measuring the sAA level.

An aberrant venous channel mimicking the perilabyrinthine cells in the petrous bone of a patient with vestibular schwannoma: illustrative case.

BACKGROUND: Anatomical variations, such as high jugular bulbs and air cell development in the petrosal bone, should be evaluated before surgery. Most bone defects in the internal auditory canal (IAC) posterior wall are observed in the perilabyrinthine cells. An aberrant vascular structure passing through the petrous bone is rare. OBSERVATIONS: A 48-year-old man presented with a right ear hearing disturbance. Magnetic resonance imaging revealed a 23-mm contrast-enhancing mass in the right cerebellopontine angle extending into the IAC, consistent with a right vestibular schwannoma. Preoperative bone window computed tomographic scans showed bone defects in the IAC posterior wall, which ran farther posteroinferiorly in the petrous bone, reaching the medial part of the jugular bulb. The tumor was accessed via a lateral suboccipital approach. There was no other major vein in the cerebellomedullary cistern, except for the vein running from the brain stem to the IAC posterior wall. To avoid complications due to venous congestion, the authors did not drill out the IAC posterior wall or remove the tumor in the IAC. LESSONS: Several aberrant veins in the petrous bone are primitive head sinus remnants. Although rare, their surgical implication is critical in patients with vestibular schwannomas.

Predicting Potential of Rapid Tumor Growth in Small to Medium Vestibular Schwannomas on the Basis of Sway Assessed Using Posturography.

OBJECTIVE: The relationship between quantitative posturography results and growth of vestibular schwannomas (VSs) during conservative management has not been studied. We aimed to clarify the relationship between the presence of disequilibrium based on posturographic measurement and VS growth. METHODS: This retrospective, single-center study included 53 patients with VSs (Koos stage I or II) managed conservatively after initial diagnosis. Radiographic progression was considered present if 20% volumetric growth was observed over the imaging interval. Posturography was performed at initial diagnosis, and sway velocity (SV) and sway area were calculated. Tumor growth-free survival was estimated using the Kaplan-Meier method. RESULTS: Mean follow-up period was 2.87 ± 2.58 years, up to tumor growth detection or last follow-up magnetic resonance imaging. Tumor growth incidence was 40.8% and 61.2% at 2 and 5 years, respectively. Cerebellopontine angle extension and SV with eyes open were related to tumor growth. Tumor growth-free survival of patients with cerebellopontine angle extension and patients with intracanalicular tumor at 2 years was 37.3% and 76.4%, respectively. Tumor growth-free survival of patients with SV >2.06 cm/second and patients with SV ≤2.06 cm/second at 2 years was 30.8% and 68.9%, respectively. The Cox hazard model demonstrated a significant risk for future tumor growth with SV >2.06 cm/second (relative risk, 2.475; 95% confidence interval, 1.11-5.37, P = 0.027). CONCLUSIONS: We demonstrated a positive correlation between SV with eyes open and future tumor growth. Posturographic data are objective and quantitative; thus, SV may be a potential predictor of future growth of VSs.