Kagoshima Medical Center

As populations age worldwide, breast cancer mortality among older patients continues to rise despite therapeutic advances. This study investigates differences in treatment patterns and outcomes between older and younger patients with metastatic breast cancer. We analyzed clinical data from the Advanced Breast Cancer Database (ABCD) maintained by the Japanese Breast Cancer Research Group. The dataset included patients registered between June 1, 2020, and October 31, 2023, encompassing clinicopathologic information, treatment details, breast cancer specific survival (BCSS), and overall survival (OS). A total of 1629 patients were included. The frequency of chemotherapy and genomic testing decreased with age, yet patients in their 70s demonstrated treatment durations and survival outcomes comparable to those of younger patients. In contrast, patients aged ≥ 80years exhibited shorter duration of second-line therapy (adjusted HR:0.65, 95% CI: 0.43-1.04) and poorer OS (adjusted HR:0.62, 95% CI: 0.37-1.04) and BCSS (adjusted HR:0.66, 95% CI: 0.38-1.14), despite most deaths being attributable to breast cancer rather than non-cancer-related causes. This multicenter retrospective study demonstrates that patients in their 70s can achieve comparable benefits from systemic therapy to younger individuals, emphasizing the importance of not withholding treatment based solely on chronological age. Conversely, the limited effectiveness of later-line therapies in patients aged ≥ 80 highlights the need for individualized treatment strategies that balance efficacy, quality of life, and comorbidities through comprehensive geriatric assessment and shared decision-making.

This study systematically examines the robustness of the Akaike Information Criterion (AIC) in determining the optimal order (p) of an autoregressive (AR) model applied to the RR interval time series of the PhysioNet healthy subject database. The AR approach is widely used to estimate the power spectral density (PSD) of heart rate variability (HRV), and accurate order selection is essential for model stability and reliable spectral estimation. Although the AIC is designed to balance model fit and complexity, it suffers from the problem of arbitrary model selection. This study provides a quantitative robustness analysis of information-criterion-based AR order selection under controlled expansion of the search space. Specifically, we investigated the behavior of the AIC using the PhysioNet database (N = 1257) under conditions where the maximum search order was set to an excessively high value (p = 50), far exceeding the commonly recommended range. Our analysis suggested that the AR model began to capture subtle noise and nonstationary components rather than the intrinsic HRV structure, leading to overfitting and excessive order selection, resulting in false peaks in the PSD and reduced robustness. In conclusion, order decisions based solely on information criteria such as the AIC become unstable when the search range is too large. To ensure robustness, it is recommended to complement the AIC with more stringent criteria such as the Bayesian Information Criterion (BIC) or Final Prediction Error (FPE), in addition to the traditional maximum order restriction.

Hidradenoma can exhibit several cell types, including clear cells, polyhedral eosinophilic cells, squamoid cells, mucinous cells, oxyphilic (oncocytic) cells, and transitional (intermediate) cells. However, sebocytes have not yet been described in hidradenoma. Here, we present a case of CRTC1::MAML2-positive hidradenoma with sebaceous differentiation. In addition, this tumor had two cell-type layers that were morphologically similar to apocrine glandular cells and myoepithelial cells throughout the lesion. A 66-year-old male presented with a 20 mm nodule on his upper lip with a 3-year history. Histopathological examination revealed a multinodular tumor adherent to the overlying epidermis. No surrounding salivary glands were seen. The tumor consisted of eosinophilic ductoglandular cells surrounded by basaloid cells at the outer periphery. Numerous sebocytes were scattered throughout the tumor. Severe nuclear atypia or mitotic figures were not observed. Immunohistochemical examination showed no expression of α-smooth muscle actin, calponin, and S100 protein in the tumor cells. Adipophilin highlighted scattered sebocytic tumor cells. Immunoexpression of MLH1, PMS2, MSH2, and MSH6 was preserved. MAML2 break-apart fluorescence insitu hybridization revealed frequent split signals. Sanger sequencing revealed a CRTC1(e1)::MAML2(e2) fusion. Based on this report, hidradenoma should be included in the differential diagnosis of cutaneous adnexal tumors with sebaceous differentiation other than sebaceous adnexal tumors. In addition, sebocytes should be added to the list of tumor cell types in hidradenoma.

Chemotherapy-induced neutropenia has been identified as a potential prognostic marker for multiple cancers. However, only one retrospective study, NN-2301, has investigated the relationship between neutropenia and treatment effects of nanoliposomal irinotecan/5-fluorouracil/folinic acid (NFF) in pancreatic cancer. In this prospective study, we aimed to clarify whether NFF-induced neutropenia could serve as a prognostic marker in pancreatic cancer. Data were analyzed from the prospective cohort of the NAPOLEON-2 trial, an observational study involving patients with unresectable pancreatic cancer treated with NFF. Neutropenia severity was categorized into three cutoffs: Cutoff A (Grade [Gr] 0 vs. Gr 1-4), cutoff B (Gr 0-1 vs. Gr 2-4), and Cutoff C (Gr 0-2 vs. Gr 3-4), using the Common Terminology Criteria for Adverse Events version 5.0, owing to conformity with previous studies and simplicity. The primary endpoint was overall survival (OS); progression-free survival (PFS) was the secondary endpoint. The neutropenic groups included Gr 1, 2, 3, and 4, with 79, 23, 34, and 7 patients, respectively. At each cutoff, OS and PFS were significantly better in the severe neutropenia groups. Higher neutropenia grades correlated with improved OS (log-rank trend test: χ2 = 8.62, p < .01). Multivariate Cox regression analysis revealed significant differences for all cutoffs: adjusted hazard ratios were 0.57 (95% confidence interval [CI] 0.40-0.83) (Cutoff A), 0.53 (95% CI 0.36-0.78) (Cutoff B), and 0.52 (95% CI 0.34-0.80) (Cutoff C). NFF-induced neutropenia is a valuable prognostic marker in pancreatic cancer and may guide treatment selection.

ABSTRACT Objectives Participating in religious activities benefits older adults’ mental health; however, the effects of grave visitation, a significant religious practice in Japan, on older adults’ mental health remain unclear. Therefore, this study examined the relationship between grave visitation frequency and depressive symptoms. Methods A prospective cohort study of 273 community-dwelling older adults in Japan was conducted with baseline (2018) and follow-up (2022) assessments. Participants were categorized by visitation frequency: more or less than once a week. Changes in visitation frequency were classified as continued high, decreased, continued low, or increased. Depressive symptoms were assessed using the Geriatric Depression Scale (GDS-15). Multivariable linear regressions were used to examine the association between visitation and depressive symptoms. Results Lower visitation at baseline was associated with worse GDS-15 scores in the follow-up. Those with decreased or continued low visitation had significantly worse depressive symptoms. After adjusting for baseline GDS-15 scores and covariates, the decreased group had significantly worse depressive symptoms than the continued high group. Conclusions The findings indicate that changes in grave visitation frequency are significantly associated with depressive symptoms. Clinical Implications Supporting older adults’ access to grave visitation through transportation or community programs may help maintain their well-being and emotional health.

Extramammary Paget disease (EMPD) is a rare malignancy that primarily arises in apocrine gland-bearing areas such as the genital, perianal, and axillary regions. The clinical and biological heterogeneity of EMPD, together with a lack of evidence from large-scale studies, has made it difficult to establish standardized approaches to diagnosis and treatment. To address these issues, the 2025 Japanese Guidelines for the Management of EMPD were developed, providing evidence-based recommendations tailored to the healthcare context in Japan. These guidelines were constructed using the Minds Guideline Development Manual 2020 (ver. 3.0), adhering to systematic review principles and incorporating both Japan and international research findings. A multidisciplinary panel of dermatologists, oncologists, surgeons, and other specialists developed the guidelines through a consensus-based process, which included structured discussions and grading of evidence. The primary focus of this condensed version is on six critical clinical questions, which address key aspects of EMPD management, including the role of mapping biopsy in diagnosis, the use of sentinel lymph node biopsy in cases of suspected dermal invasion, the efficacy of nonsurgical therapies when surgery is not an option, the efficacy of lymph node dissection for multiple regional lymph node metastases, the efficacy of radiation therapy after regional lymph node dissection, and systemic treatment options for advanced disease. The recommendations aim to improve diagnostic accuracy, optimize therapeutic approaches, and support clinical decision-making by providing a clear framework for the management of EMPD. By focusing on these critical areas, the guidelines strive to enhance patient outcomes and contribute to the advancement of evidence-based care for this rare and challenging malignancy.

To investigate patients with prolonged (≥9 months) super-refractory anti-NMDAR encephalitis (NMDARe).

Adjuvant anti-PD-1 (adj PD-1) antibodies are extensively used to improve survival in patients with resected melanoma. Clinical trials on adj PD-1 antibodies have revealed significant improvements in recurrence-free survival (RFS); however, few of these trials have included patients with acral melanoma (AM). Clinical data were retrospectively collected from Japanese patients who underwent resection of stage III sole AM between 2014 and 2021. Survival outcomes, including RFS, distant metastasis-free survival (DMFS), and overall survival (OS), were compared between patients without adjuvant therapy (OBS group) and those receiving adj PD-1 group. This study included 139 patients (OBS: 79; adj PD-1: 60), with a median follow-up of 2.6 years. The baseline characteristics were comparable, except for age and nodal metastasis. No significant differences in survival were observed between the OBS and adj PD-1 groups (3-year RFS: 36.7% v 27.5%, P = .13; 3-year DMFS: 51.0% v 45.3%, P = .51; 3-year OS: 65.3% v 67.4%, P = .45). Multivariate analysis showed no survival benefit of adj PD-1 (RFS: hazard ratio [HR], 1.25, P = .29; DMFS: HR, 1.03, P = .89; and OS: HR, 0.69, P = .23). Each survival outcome after propensity score matching confirmed no significant difference between the matched OBS group (n = 52) and adj PD-1 group (n = 52; 3-year RFS: 34.3% v 25.9%, P = .22; 3-year DMFS: 45.6% v 46.5%, P = .85; 3-year OS: 60.7% v 68.9%, P = .29). Adj PD-1 did not improve the prognosis in sole AM. However, further studies are essential to evaluate the efficacy of the adj anti-PD-1 antibody in AM.

Left main (LM) percutaneous coronary intervention (PCI) with routine intracoronary imaging guidance is recommended; however, its real-world effectiveness remains unclear. A total of 743 consecutive patients undergoing drug-eluting stent implantation for de novo unprotected LM lesions across 19 Japanese National Hospital Organization hospitals where routine imaging guidance was adopted were analyzed. The primary endpoint was 1-year major adverse cardiovascular and cerebrovascular events (MACCE), comprising all-cause death, cerebrovascular disorder, clinical-driven revascularization, and myocardial infarction. In this cohort, acute coronary syndrome was present in 31.2%, with 39.3% classified as Canadian Cardiovascular Society functional angina (CCS) class ≥ III. LM bifurcation lesions were observed in 78.0%, with two-stent implantation in 8.8%. MACCE occurred in 17.5%, with target lesion revascularization and cardiac death rates of 2.0% and 3.4%, respectively. Independent risk factors for MACCE included two-stent implantation (hazard ratio [HR], 2.49), mechanical cardiac support device use (HR, 2.17), CCS class ≥ III (HR, 2.07), 10% increase in left ventricular ejection fraction (HR, 0.72), and radial access (HR, 0.62). Routine imaging-guided LM-PCI is associated with favorable low rate of target lesion revascularization and cardiac death. However, severe left ventricular dysfunction and LM bifurcation treated with two-stent implantation increase risks, requiring more comprehensive management.