Aizawa Hospital

Metastatic colorectal cancer (mCRC) differs clinically based on RAS and BRAF mutations or DNA methylation. However, in mCRC, the prognostic value and biological characteristics of genome-wide DNA methylation status (GWMS) in each RAS/BRAF genotype is unknown. To clarify this, primary tumor samples from patients with informed consent in the phase III TRICOLORE study were collected, and RAS and BRAF mutations, immunohistochemical staining of mismatch repair-related proteins, comprehensive gene expression, and genome-wide DNA methylation were analyzed. The tumor samples were classified into high-methylated colorectal cancer (HMCC) and low-methylated colorectal cancer (LMCC). Gene set enrichment analysis (GSEA) was conducted using microarray data. A total of 226 patients were included and classified into the RAS/BRAF wild-type (wt) (n = 125), RAS mutant (mt) (n = 87), and BRAF mt (n = 14), of whom 22 (17.6%), 30 (34.5%), and 14 (100%) had HMCC. HMCC exhibited significantly worse overall survival (OS) than that of LMCC in the RAS/BRAF wt group but not in the RAS mt group. In GSEA, RAS/BRAF wt HMCC was associated with microsatellite instability and BRAF V600E mutation. The poor prognosis of RAS/BRAF wt HMCC may be attributed to gene expression patterns associated with microsatellite instability and BRAF V600E mutation.

Pharmaceutical access remains a major challenge in Japan’s remote and underserved areas, driven by aging, pharmacist shortages, and inadequate infrastructure. To forge a practical solution, we conducted a pilot study deploying a disaster-response mobile pharmacy vehicle (MPV) for routine, non-disaster use within a pharmacy-less community in Gifu Prefecture. The MPV was operational twice per week for 6 months (October 2022–March 2023), receiving outpatient prescriptions, dispensing medications, and providing essential counseling and adherence support. Over 49 days of operation, 96 patients were served with 97 prescriptions. Pharmacists conducted 13 prescriber clarifications (13.4％), which included leftover-medication adjustments, regimen simplification, and a re-examination referral. One-dose packaging was provided to 15 patients (15.6％). Generic drug use increased from 60.8％ during prepilot in-clinic dispensing to an average of 79.2％ during the pilot. Furthermore, medication notebook presentation increased to 93.8％. The patient reported an enhanced understanding of drug effects and adverse reactions despite a decrease in satisfaction regarding the waiting time. The clinic staff reported substantial benefits, including reduced dispensing workload, relief from inventory management, and increased prescribing flexibility. Even with existing legal and operational limitations, routine MPV deployment was deemed feasible, successfully enhancing pharmaceutical access, improving medication safety, and boosting the quality of care. The findings indicate that MPV is valuable beyond disaster response, establishing it as a sustainable model for enhancing health system resilience and promoting the separation of prescribing and dispensing in remote and medically underserved areas. Additional multisite, controlled studies are required to validate its effectiveness and long-term sustainability.

Life Whisperer Viability (LW) is a software that evaluates embryos from a single image of blastocyst using artificial intelligence and is expected to improve the objectivity of embryo evaluation. In the present study, we retrospectively analyzed the clinical utility of LW. This study included 198 cycles in 135 patients who underwent frozen single embryo transfer. LW scores of transferred embryos were obtained from images taken approximately 116 h after fertilization. Based on LW scores, patients were divided into four groups (poor: 0-2.4; fair: 2.5-7.4; good: 7.5-8.9; excellent: 9.0-10), and rates of positive fetal heartbeat were compared among the groups. In addition, logistic regression analysis was performed to evaluate the association between LW score and the presence or absence of fetal heartbeat. The rate of positive fetal heartbeat was significantly higher in the excellent group (64.3%, 36/56) than in the poor group (27.6%, 8/29) (P<0.05). Logistic regression analysis showed that the odds ratio for LW score was 1.150 (95% confidence interval: 1.040-1.280; P<0.05), indicating a significant association between LW score and presence or absence of fetal heartbeat. LW enables selection of embryos with a high potential for clinical pregnancy, demonstrating its clinical utility.

Background Adaptive deep brain stimulation (aDBS) modulates stimulation based on real-time biomarkers, potentially offering advantages over conventional DBS (cDBS). Clinical evidence under chronic stimulation remains limited. Objectives To compare aDBS versus cDBS efficacy in patients with Parkinson’s disease (PD) under chronic stimulation and examine baseline-dependent patterns of treatment response. Methods This was a pilot, double-blind, randomized crossover trial in nine PD patients with bilateral subthalamic nucleus DBS. Patients underwent consecutive one-month periods of cDBS and aDBS after a four-month postoperative interval. aDBS used a dual-threshold algorithm adjusting amplitude based on sub-thalamic beta-band LFP power. Primary outcomes were daily ON/OFF durations and dyskinesia duration under optimized medication. Mixed-effects ANCOVA estimated treatment effects. Bayesian analyses integrated prior evidence to assess probabilities of clinically meaningful differences. Exploratory analyses examined treatment-by-modifier interactions. Results No statistically significant differences emerged between treatments. Directional effects varied: ON duration favored cDBS, while troublesome dyskinesia and UPDRS scores favored aDBS. Bayesian analyses indicated low probabilities that these differences reached clinical importance (29.4% probability for cDBS advantage on ON time, 7.5% for aDBS advantage on UPDRS Part III). Substantial between-patient heterogeneity was observed. Exploratory analyses suggested higher baseline disease burden enhanced cDBS advantages for motor fluctuations and aDBS advantages for motor severity, though modification effects varied across outcome–baseline combinations. Conclusions aDBS and cDBS showed comparable population-level efficacy. Patient-specific baseline characteristics may influence treatment advantages for specific outcomes. These findings warrant larger trials to identify patient subgroups who may benefit from each stimulation approach under the current form of adaptive stimulation.

BACKGROUND Strabismus and diplopia are well-documented complications following various ophthalmic surgeries; however, no prior reports have linked these complications to orbital fat herniation surgery. Here, we report a case of secondary esotropia resulting from lateral rectus muscle injury following orbital fat herniation surgery. CASE REPORT A man in his 60s presented to our hospital with diplopia during distance fixation, which he noticed a few days after undergoing orbital fat herniation surgery on his right eye. His visual acuity was 24/20 in both eyes. Alternate prism cover testing revealed esotropia of 30 prism diopters for both distance- and near-vision. Mild limitation of abduction in the right eye and conjunctival scarring near the lateral rectus muscle were noted. Injury to the lateral rectus muscle during the previous surgery was suspected. However, due to the mild degree of abduction limitation, transient diplopia was also considered, and the patient was initially observed. However, no improvement in abduction limitation or esotropia was noted over the following months. Consequently, strabismus surgery was performed 8 months after the initial procedure. Intraoperatively, a slipped lateral rectus muscle was identified, and the muscle was advanced to a position 7 mm posterior to the limbus on the sclera. The patient's abduction improved, and satisfactory ocular alignment was achieved postoperatively. CONCLUSIONS When strabismus with ocular motility limitation is observed after orbital fat herniation surgery, the possibility of lateral rectus muscle injury should be considered. If observation does not show improvement, strabismus surgery may be necessary.

Background/AimThe combination of capecitabine and bevacizumab is a standard first-line chemotherapy regimen for vulnerable patients with unresectable colorectal cancer. However, the safety and efficacy of this regimen in Japanese patients have not been sufficiently investigated.Patients and MethodsThis phase II study included patients aged ≥76 years or those aged 65-75 years who were unsuitable for intensive chemotherapy. Capecitabine at 2000 mg/m2/day (days 1-14) plus bevacizumab at 7.5 mg/kg (day 1) were administered every 3 weeks. The primary endpoint was progression-free survival. Secondary endpoints included overall survival, response rate, disease control rate, and toxicities.ResultsThirty-six patients were enrolled between July 2011 and July 2014, of whom 33 were included in the analysis. The median patient age was 78 years (range=67-86 years). A total of 28 patients had a performance status of 0 or 1, and five of 2. The median progression-free and overall survival were 10.3 (95% confidence interval=9.2-15.4) and 27.9 (95% confidence interval=24.2-50.1) months, respectively. The response and disease control rates were 30.3% and 91.0%, respectively. The major grade 3 or 4 toxicities were hypertension (n=12, 36%) and hand-foot syndrome (n=4, 12%). One patient experienced a grade 4 gastrointestinal perforation.ConclusionThe combination of capecitabine and bevacizumab demonstrated favorable efficacy and tolerability in Japanese patients with metastatic colorectal cancer who were unsuitable for intensive chemotherapy.

This study evaluates various radiotherapy techniques for treating metastatic brain tumor (BT), focusing on non‐coplanar volumetric modulated arc radiotherapy (NC‐VMAT), coplanar VMAT (C‐VMAT), Helical TomoTherapy (HT), CyberKnife (CK), Gamma Knife (GK), and ZAP‐X. CT images and structures of 12 patients who underwent CK for a single BT were utilized. Twelve treatment plans were created for each planning device. All plans adopted the approach of prescription doses to planning target volume D99.5%. They were divided into stereotactic radiosurgery (SRS) (prescription dose; 21–23 Gy) and stereotactic radiotherapy (SRT) (prescription dose; 30–36.5 Gy) groups and the same parameters evaluated included Gradient Index (GI), Paddick Conformity Index (CI), and treatment time (t‐time). In the SRS group, mean values of GI and CI values were: NC‐VMAT (4.28, 0.60), C‐VMAT (5.61, 0.44), HT (4.68, 0.42), CK (4.31, 0.61), GK (2.81, 0.82), and ZAP‐X (2.99, 0.80). In the SRT group: NC‐VMAT (3.27, 0.84), C‐VMAT (3.81, 0.82), HT (3.76, 0.65), CK (2.98, 0.77), GK (2.61, 0.90), and ZAP‐X (2.80, 0.84). There were no significant differences in the mean values of CI and GI between ZAP‐X and GK in both groups (p > 0.05). NC‐VMAT and C‐VMAT had shorter t‐time than other techniques in both groups. ZAP‐X is relatively superior in CI and GI for small tumors, similar to GK, while differences with NC‐VMAT and CK diminish as tumor volume increases. ZAP‐X, CK, and GK have longer t‐time than other treatment techniques, regardless of volume.

Aspiration is a critical complication of dysphagia in Parkinson's disease (PD). Current methods for predicting aspiration are unsuitable for routine implementation owing to time constraints, cost, or insufficient predictive accuracy. We assessed the predictive performance of clinical measures, including dopamine transporter (DaT) imaging, for aspiration risk in patients with PD. We retrospectively analyzed data from patients with PD who underwent videofluoroscopic swallowing examinations (VF) and DaT imaging within 12 months. Patients were divided into aspiration and non-aspiration groups based on VF findings. Logistic regression and receiver operating characteristic (ROC) analyses evaluated the predictive performance of DaT imaging parameters including striatal specific binding ratio (SBR) and subregional SBRs, calculated using DaT View and DaTQUANT software. Among 87 patients (38 females; mean age: 64 years; disease duration: 8.3 years [range: 1-20 years]; modified Hoehn and Yahr stages: 2 [range: 1-4]), 14.9% experienced aspiration. DaT View striatal SBRs consistently showed significantly lower values in the aspiration group and negative associations with aspiration in logistic regression models, whereas DaTQUANT exhibited limited significance in intergroup differences and associations. ROC analysis showed DaT View striatal SBR of the better side (SBRbetter) as the optimal predictor (sensitivity 0.62, specificity 0.93at cutoff: 2.03). DaTQUANT subregional analysis identified the anterior putamen as key in aspiration risk. Reduced SBR in DaT imaging shows potential as an indicator of aspiration risk in patients with PD. These findings can help clinicians identify patients at risk of aspiration, allowing for proactive referral for detailed evaluation.

Glioblastoma multiforme (GBM) is a highly aggressive primary brain tumor with a poor prognosis. It commonly affects the brain and rarely spreads outside the central nervous system owing to barriers like the blood-brain barrier. We present a rare case of GBM with atypical features mimicking autoimmune meningitis, complicating the diagnosis. A 45-year-old previously healthy man presented with persistent headaches, dizziness, vomiting, neck pain, diplopia from bilateral abducens nerve palsy, and cognitive dysfunction. The cerebrospinal fluid analysis did not confirm meningitis, although initial clinical and radiological findings suggested autoimmune meningitis. Head magnetic resonance imaging (MRI) showed postcontrast leptomeningeal enhancement and meningeal thickening. A spinal MRI revealed a contrast-enhancing lesion at the L1 level with leptomeningeal enhancement of the spinal cord. Despite empirical steroid therapy, his condition worsened, resulting in severe neurological deficits and impaired consciousness. A biopsy confirmed GBM through L1-2 laminectomy. Although adjuvant therapy was scheduled, his health rapidly declined, and he passed away on the 24th day of admission before receiving chemotherapy or radiotherapy. GBM can rarely present with noticeable symptoms and radiological features resembling autoimmune meningitis, posing diagnostic challenges. GBM cases involving spinal dissemination typically have a poorer prognosis, emphasizing the necessity of thorough diagnostic strategies. These should encompass histopathological biopsy and advanced imaging for optimal management, as delayed intervention significantly impacts survival. This report highlights the importance of maintaining a high level of suspicion for GBM and prompt intervention, including biopsy, in the presence of atypical clinical, radiological, and laboratory signs suggestive of meningitis.