Akita University Hospital

Hydrogel spacers are commonly used to reduce rectal toxicity during radiation therapy for prostate cancer. Although generally safe, rare, serious complications may occur. We report the case of a man with diabetes and renal failure who developed a refractory rectal ulcer and fistula five months after spacer placement, followed by Fournier's gangrene. The patient recovered following surgical drainage and antibiotic therapy. This is the first reported case of Fournier's gangrene following hydrogel spacer insertion. Spacer-related rectal wall infiltration might have contributed to this finding. Clinicians should recognize such adverse events and consider early intervention in high-risk patients presenting with hematochezia or perineal symptoms.

Adipocytes play a central role in energy balance by integrating lipid storage, thermogenesis, and endocrine regulation. Their diversity—comprising white, brown, and beige adipocytes—emerges through tightly coordinated transcriptional and epigenetic programs. In addition to transcription factors, epigenetic mechanisms such as DNA methylation and histone modifications mediated by acetyltransferases, methyltransferases, and demethylases shape the chromatin states that govern adipocyte differentiation and function. The concept of metabolic memory refers to the long-lasting imprint that environmental and nutritional cues make on cells and tissues; it can facilitate rapid adaptation to subsequent challenges but also predispose organisms to metabolic dysfunction and related complications. Recent technological advances have revealed that cold exposure and obesity leave epigenomic marks on adipocytes, providing mechanistic insights into how metabolic memory is encoded. This review highlights the fundamental principles of the adipose tissue epigenome, the regulation of adipocyte identity, and how epigenomic memory links environmental history to long-term metabolic health.

Background This study aimed to identify tumor lesion-related factors associated with possible missed gastric cancer (PMGC) during screening endoscopy, with particular focus on cases following Helicobacter pylori (HP) eradication. Methods We analyzed consecutive gastric cancer (GC) cases detected at 11 health check-up institutions in Akita prefecture, Japan. The study focused on 171 GC cases with at least one negative endoscopy within the preceding 2 years. Based on histological assessment, GCs with pT1b or deeper invasion were classified as PMGCs. Their clinical characteristics were compared with those of the remaining pT1a GCs. A backward stepwise logistic regression analysis was performed to identify tumor lesion-related factors associated with PMGC. Results Among 171 GC cases, 39 (22.8%) were classified as PMGC, while the remaining 132 served as controls. Overall, 108 cases (63.2%) occurred in individuals with prior HP eradication, and eradication status was not statistically associated with PMGC. Multivariable regression analysis limited to post-eradication cases revealed that upper third location and undifferentiated histology were significantly associated with PMGC, with odds ratios (95% confidence intervals) of 5.65 (1.88–16.90) and 8.35 (2.22–31.40), respectively. Conclusions Undifferentiated histology and upper third location were associated with missed diagnoses of GC during screening endoscopy in individuals with prior HP eradication. These findings are clinically relevant for improving the quality of endoscopic examinations in health check-up settings, especially given the increasing prevalence of post-eradication GC.

Reports of traumatic coccygeal dislocations or fracture-dislocations are rare, and there is no established consensus regarding their treatment. We report a case of traumatic anterior dislocating coccygeal fracture in a young female patient who initially underwent closed reduction, which was not feasible. A 17-year-old girl sustained an injury after falling backward down the stairs. Radiographs revealed anterior dislocation of the second coccygeal vertebra and distal segments, accompanied by small bone fragments, leading to the diagnosis of a traumatic coccygeal fracture-dislocation. An attempt at closed perianal reduction was made, but the dislocated second coccygeal vertebra was displaced proximally and overlapped with the first coccygeal vertebra. Furthermore, its distance from the anus was too large to prevent reduction. The approach was switched to open surgery. Reduction was achieved via a small incision using a technique similar to intrafocal pinning, and stability was achieved by applying axial compression. The pain resolved rapidly postoperatively. Although a mild alignment abnormality remained, the patient returned to sports activities eight weeks postoperatively without symptoms. Although correction of coccygeal alignment abnormalities is preferred, favorable reports exist regarding conservative treatment. Treatment selection should consider factors such as sex, age, and activity level.

To summarize descriptively health-related quality of life (HRQOL) and physical activity (PA) evaluated with a mobile application and wearable device among patients with hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR + /HER2 -) advanced breast cancer (ABC) treated with first- or second-line palbociclib plus endocrine therapy (ET) or ET alone. HRQOL was assessed with the EORTC QLQ-C30 at baseline and Day 15 of 6 treatment cycles (~ 24weeks). PA metrics were averaged on a weekly basis for 24weeks. Co-primary endpoints were mean change from baseline in Global Health Status (GHS) and sedentary time. Ninety-nine patients were enrolled; 78 received palbociclib plus ET (mean age: 57.2years; 75.6% initiated first-line treatment) and 21 received ET alone (mean age: 56.3years; 90.5% initiated first-line treatment). Baseline mean GHS score was 60.9 in the palbociclib plus ET group and 64.3 in the ET alone group; mean changes from baseline to Day 15 of Cycle 6 were +4.8 and +2.9, respectively, and not deteriorated beyond the 10-point clinically significant threshold in either treatment group. Baseline mean sedentary time was 581min/day in the palbociclib plus ET group and 513min/day in the ET alone group; mean changes from baseline to Week 24 were -22 and -102min/day, respectively. In this real-world study of women with HR+/HER2- ABC in Japan, neither palbociclib plus ET nor ET alone had any substantial detrimental impacts on HRQOL, according to patients' assessments recorded in a smartphone-based mobile application, and PA, as measured by a wearable device. ClinicalTrials.gov NCT04736576; registered, February 3, 2021.

e13050 Background: Treatment of hormone receptor (HR)-positive HER2-negative advanced breast cancer (ABC) with CDK4/6 inhibitors (CDK4/6i) significantly extends progression-free survival (PFS) compared to endocrine monotherapy. While reports on chemotherapy-free survival (CFS) exist in Europe and the U.S., few studies have been published in Asia. This study aims to assess the non-inferiority of CFS in HR-positive HER2-negative ABC by comparing the CDK4/6i and endocrine monotherapy groups as first-line treatments. Methods: This multi-center, retrospective observational study included patients with HR-positive HER2-negative ABC who received first-line endocrine therapy between 2015 and 2020. The characteristics of patients who chose CDK4/6i or monotherapy were examined. Additionally, CFS, PFS, and PFS2 (combined PFS for patients on first- and second-line endocrine therapy) were assessed. Patient characteristics were adjusted using inverse probability of treatment weighting (IPTW). A non-inferiority margin for CFS of 1.2 was set. Results: Of 443 cases, 125 were in the CDK4/6i group and 318 in the monotherapy group. The CDK4/6i group had a higher proportion of patients with PS 0 and organ metastasis (lung, liver), while the monotherapy group had more bone-only metastasis. After adjusting for patient background using IPTW, differences between the groups remained only based on the time of diagnosis (CDK4/6 inhibitors were approved in Japan in 2017). During a median follow-up of 36 months for the CDK4/6i group and 46 months for the monotherapy group, 298 CFS events (67%) occurred. The median CFS was 30 months for the CDK4/6i group and 35 months for the monotherapy group (HR: 0.93, 95% CI: 0.70–1.24). In patients with PS 0, no liver metastasis, de novo stage IV, or DFI ≥60 months, the median CFS for the monotherapy group was 48 months. The median PFS was 12 months for both groups, with no significant difference (HR: 1.11, 95% CI: 0.88–1.40). However, PFS2, which included patients continuing first-line treatment or received endocrine therapy in second-line treatment was 33 months for the CDK4/6i group and 28 months for the monotherapy group, with the CDK4/6i group showing a significant extension (HR: 1.41, 95% CI: 1.01–1.97). Discussion: In this limited sample study, the monotherapy group showed a slightly better trend in CFS. The CDK4/6i had more adverse events compared to the monotherapy. In Japan, where universal health insurance system exists, the out-of-pocket costs for CDK4/6i are significantly higher. In subgroups with a good prognosis, starting monotherapy as first-line treatment may result in a long CFS, making the selection of CDK4/6i as second-line treatment a viable treatment strategy. Conclusions: In HR-positive HER2-negative ABC, the monotherapy group did not show non-inferiority in CFS compared to the CDK4/6i group, with a small difference in this real-world cohort.

A strong association exists between sleep duration and glycemic control in patients with type 2 diabetes (T2D), yet convincing evidence of a causal link remains lacking. Improving sleep is increasingly emphasized in clinical T2D treatment guidance, highlighting the need for effective, scalable sleep interventions that can affordably serve large populations through mobile health (mHealth). This study aims to pilot an intervention that extends sleep duration by modifying bedtime behavior, assessing its efficacy among short-sleeping (≤6 hours per night) patients with T2D, and establishing robust evidence that extending sleep improves glycemic control. This randomized, single-blinded, multicenter study targets 70 patients with T2D from 9 institutions in Japan over a 12-week intervention period. The sleep extension intervention, BedTime, is developed using the Theory of Planned Behavior (TPB) and focuses on TPB's constructs of perceived and actual behavioral control (ABC). The pilot intervention combines wearable actigraphy devices with SMS text messaging managed by human operators. Both the intervention and control groups will use an actigraphy device to record bedtime, sleep duration, and step count, while time in bed (TIB) will be assessed via sleep diaries. In addition, the intervention group will receive weekly bedtime goals, daily feedback on their bedtime performance relative to those goals, identify personal barriers to an earlier bedtime, and select strategies to overcome these barriers. The 12-week intervention period will be followed by a 12-week observational period to assess the sustainability of the intervention's effects. The primary outcome is the between-group difference in the change in hemoglobin A1c (HbA1c) at 12 weeks. Secondary outcomes include other health measures, sleep metrics (bedtime, TIB, sleep duration, total sleep time, and sleep quality), behavioral changes, and assessments of the intervention's usability. The trial commenced on February 8, 2024, and is expected to conclude in February 2025. Patient recruitment ended on August 29, 2024, with 70 participants enrolled. The intervention period concluded on December 6, 2024, and the observation period ended on February 26, 2025, with 70 participants completing the observation period. The data analysis is currently underway, and results are expected to be published in July 2025. This trial will provide important evidence on the causal link between increased sleep duration and improved glycemic control in short-sleeping patients with T2D. It will also evaluate the efficacy of our bedtime behavior change intervention in extending sleep duration, initially piloted with human operators, with the goal of future implementation via an mHealth smartphone app. If proven effective, this intervention could be a key step toward integrating sleep-focused mHealth into the standard treatment for patients with T2D in Japan. Japan Registry of Clinical Trials jRCT1030230650; https://jrct.niph.go.jp/latest-detail/jRCT1030230650. DERR1-10.2196/64023.

Many immunoassay methods have been developed for quantifying vancomycin levels in biological fluids. Recently, the LM1010, a high-performance liquid chromatography-based medical diagnostic device was approved. This study compared the results obtained with LM1010 with those obtained using ARCHITECT plus chemiluminescent immunoassay (CLIA) to measure vancomycin levels in patient serum samples. The retention times measured with LM1010 for vancomycin and its major and minor crystalline degradation products (CDP-1) were 2.50, 2.38, and 1.91 min, respectively, and the separation was satisfactory. When five CLIA calibrator samples (5.0 – 100 μg/mL) were analyzed using LM1010, the concentrations were lower than expected, with an average of −12.96％ (range: −7.07％ to −17.53％). In addition, in a Japanese external quality control survey examination, LM1010 demonstrated high accuracy (0.33％ to −6.68％). A strong correlation was observed between the results obtained using LM1010 (calculated by peak height) and CLIA (r = 0.9682). The slope of the Deming regression comparing LM1010 to CLIA was 0.831, and a Bland–Altman plot for LM1010 relative to CLIA showed a mean negative bias (±1.96 standard deviation) of −2.356 (−6.108 – 1.396) μg/mL. Thus, the results obtained with CLIA were higher than those obtained with LM1010. If the calibrators for CLIA are adjusted by considering cross-reactivities with CDP-1 or other metabolites, the vancomycin concentrations in patient samples determined using CLIA may be higher than those determined using LM1010. Overall, vancomycin concentrations should be analyzed using an assay with higher accuracy, such as LM1010.

Immunohistochemistry (IHC) is crucial for determining cancer treatments. We previously developed a rapid IHC method and have now developed a fully automated rapid IHC stainer (R-Auto). This study aimed to evaluate the clinical reliability of the R-Auto protocol for staining estrogen receptors (ERs) in breast cancer specimens and evaluate the staining performance. Between January 2015 and June 2020, 188 surgical specimens collected from breast cancer patients treated at our hospital were evaluated via ER staining using R-Auto, conventional manual IHC, and a commercial autostainer. The specimens were scored using Allred scores, after which the staining results were compared between R-Auto and conventional IHC or the commercial autostainer. Weighted kappa coefficients and AC1 statistics were used to assess the agreement between the methods. The AC1 statistic for comparison between R-Auto and conventional IHC was 0.9490 (0.9139-0.9841), with a 95.7% agreement rate, and that for comparison between R-Auto and the commercial autostainer was 0.9095 (0.8620-0.9570), with a 92.6% agreement. There was, thus, substantial agreement between R-Auto and both conventional IHC and the commercial autostainer. However, R-Auto shortened the time required for IHC from 209 min with conventional IHC to 121 min. R-Auto enables a good staining performance in a shorter time with less effort.

ABSTRACTINTRODUCTIONPulmonary cavernous hemangioma (PCH) is extremely rare and, due to the lack of specific radiological characteristics, is often misdiagnosed as other pulmonary diseases, including metastatic tumors. Here, we report a case of multiple PCH lesions with concomitant hepatic cavernous hemangioma (HCH), emphasizing the diagnostic implications of imaging findings.CASE PRESENTATIONA 57-year-old man presented with fever. CT revealed numerous well-circumscribed pulmonary nodules and multiple low-density hepatic lesions. Dynamic contrast-enhanced CT demonstrated mild, nonspecific enhancement of the pulmonary nodules, whereas the hepatic lesions showed enhancement from the center to the periphery. Serum tumor markers were within normal limits, and PET-CT revealed no abnormal fluorodeoxyglucose uptake in any of the lesions. Although the hepatic lesions appeared suggestive of hemangioma on imaging, the possibility of malignancy, such as hepatic angiosarcoma and its pulmonary metastases, could not be completely ruled out. Therefore, both hepatic and pulmonary biopsies were performed, and histopathological examination confirmed cavernous hemangioma in both organs.CONCLUSIONSPCH is a rare benign tumor lacking distinctive imaging characteristics; therefore, differentiation from metastatic pulmonary tumors is often challenging and represents a key diagnostic issue. Although definitive diagnosis currently relies on surgical biopsy, combining suggestive imaging findings—such as the presence of microcalcifications within nodules and the absence of fluorodeoxyglucose uptake on PET-CT—may help avoid unnecessary invasive procedures.