Hakodate Central General Hospital

In this nationwide retrospective study, we sought to evaluate the oncologic and functional outcomes and safety of transoral surgery (TOS) for hypopharyngeal and laryngeal squamous cell carcinomas in Japan and to clarify the appropriate indications for various TOS modalities. Data were obtained from the Head and Neck Cancer Registry of Japan. Patients who underwent transoral or endoscopic resection between 2011 and 2016 were selected. Detailed clinical information was collected from 55 institutions using web-based case report forms. Surgical modalities analyzed included endoscopic mucosal resection (EMR), endoscopic submucosal dissection (ESD), endoscopic laryngopharyngeal surgery (ELPS), transoral laser microsurgery (TLM), and transoral videolaryngoscopic surgery (TOVS). In total, 1825 patients were included (hypopharyngeal cancer, 62.5 %; laryngeal cancer, 37.5 %). Most cases (77.5 %) were T1 or lower, and 90.8 % were Stage II or earlier. TLM is predominantly used for glottic cancers, ELPS/ESD for superficial hypopharyngeal lesions, and TOVS for more advanced tumors, reflecting distinct indications for each modality. The 5-year disease-specific survival (DSS), recurrence-free survival (RFS), and overall survival (OS) were 97.1 %, 84.3 %, and 85.4 %, respectively. The laryngeal preservation rate was 98.2 %. Tracheostomy was performed in 5.0 % of cases, mainly for airway protection; major complications, including pneumonia (2.4 %), hemorrhage (1.1 %), fistula formation (0.4 %), and vocal cord fixation (2.6 %), occurred in <3 % of patients. Postoperative functional outcomes were favorable, with persistent dysphagia (Functional Outcome Swallowing Scale stage ≥ 3) in 1.6 % and tube feeding dependence in 1.8 %. Non-robot-assisted TOS demonstrated excellent oncologic control and functional preservation of the larynx with low complication rates in early-stage hypopharyngeal and laryngeal cancers. Each surgical modality has distinct indications depending on the tumor site, depth of invasion, and institutional expertise. These findings support the use of TOS as a safe and effective treatment option for selected patients. Further procedural standardization and data accumulation are required to refine the indications and facilitate their broader adoption in clinical practice.

Human retinas have unique anatomical structures called the macula and an associated characteristic vascular pattern. Despite its clinical importance, the mechanism underlying the human-specific vascular pattern remains unknown because of limitations in experimental approaches using primate samples. This study aimed to elucidate such vascular formation process. We first examined the effects of four hypothetical factors contributing to foveal avascular zone (FAZ) formation: inhibitory molecule secretion, chemoattractant depletion, tissue deformation (towing), and tip cell migration restriction. None reproduced the features of the human retinal vascular structure. Next, we developed a mathematical model of human retinal vascular development by considering endothelial cells and astrocytes. We assumed that retinal vessels form via angiogenesis according to the gradient of vascular endothelial growth factor and that astrocytes dynamically expand while avoiding the fovea, providing scaffolds for angiogenesis. Our astrocyte-coupling model recapitulated various features of the human retinal vascular pattern, including a radially outward vascular pattern from the optic disc, inferior and superior temporal arcades, FAZ formation, a radially inward vascular pattern around FAZ, and a vertically facing pattern toward the horizontal vascular borderline in the temporal region of FAZ. Other models did not support the other four hypotheses. Our model explained human-specific retinal vascular formation as the combination of angiogenesis and vascular growth restriction by retinal astrocytes. These results also suggest the importance of astrocyte dynamics, particularly their timing of spreading. Our modeling framework can be extended to abnormal vascular patterns observed in diseases, including retinopathy of prematurity.

Epithelial-myoepithelial carcinoma (EMC) occurs in the salivary glands, but pulmonary EMC (P-EMC) is an extremely rare histological type. Here, we report a case of effective thoracoscopic lung reduction for P-EMC. A woman in her 80s was referred to our hospital following detection of an abnormal shadow on a chest CT performed during an annual lung cancer screening programme. The mass was 11 mm in the right lower lobe, and 11 mm and 5 mm multiple nodules were identified in the left lower lobe. A thoracoscopic partial right lung resection was performed for diagnosis and treatment, and the patient was diagnosed with P-EMC. After a follow-up of approximately 2 years, a left basal segmentectomy and lymph node dissection by complete video-assisted thoracoscopic surgery were performed. The final pathology revealed a P-EMC.

Abstract Background Transcatheter left atrial appendage closure (LAAC) with the WATCHMAN device has emerged as an alternative treatment option to oral anticoagulants. The WATCHMAN device was introduced in Japan in 2019, followed by the newer WATCHMAN FLX device in 2021. However, few studies have investigated sex differences in the outcomes of the LAAC procedure. Objective This study aimed to evaluate sex differences in LAAC procedures in Japan. To adjust for confounding factors, we employed two innovative matching methods: propensity score (PS) and inverse probability of treatment weighting (IPTW). Methods The TERMINATOR (Transcatheter Modification of Left Atrial Appendage by Obliteration with Device) registry is a multicenter, real-world registry involving 23 institutions in Japan. This study enrolled 1,817 patients with atrial fibrillation who underwent LAAC at these institutions between September 2019 and September 2023. The primary efficacy endpoint was a composite of ischemic stroke, transient ischemic attack, or systemic embolism at 12 months. The primary safety endpoint was a composite of hemorrhagic stroke or anemia requiring transfusion at 12 months. The secondary endpoint was all-cause mortality through 12 months. A retrospective analysis was performed to compare clinical outcomes following LAAC, using propensity score matching (PSM) at a 1:1 ratio and IPTW to minimize potential bias. Results Of the 1,171 patients analyzed, 332 (28.4%) were women. Compared with men, women were older (78.1 ± 7.7 years vs. 74.86 ± 8.1 years; P &amp;lt; 0.001) and more likely to have paroxysmal atrial fibrillation (45.2% vs. 36.6%; P = 0.007). The CHA2DS2-VA and HAS-BLED scores were comparable between the sexes (4.4 ± 1.3 vs. 4.5 ± 1.4; P = 0.751 and 3.3 ± 0.8 vs. 3.3 ± 0.9; P = 1.000, respectively). After PSM, 330 men and 330 women were selected for the final analysis. As shown in the Kaplan–Meier analysis (Figure), no statistical differences were observed between the sexes in the primary efficacy and safety endpoints or the secondary endpoint. The IPTW method produced similar results. Conclusion In patients with atrial fibrillation undergoing LAAC, women demonstrated similar safety and efficacy outcomes compared with men.

要旨 過去5年間に3例のビッカースタッフ型脳幹脳炎（Bickerstaff brainstem encephalitis: BBE）を経験した。症例①は70歳代の女性，ギラン・バレー症候群（Guillain–Barré syndrome: GBS）と抗GQ1b抗体陰性BBEの合併例で標準治療に反応なく死亡退院した。症例②は40歳代の男性，症例③は20歳代の男性，いずれも抗GQ1b抗体陽性BBEの標準治療に反応不良のためシクロホスファミドパルス療法（intravenous cyclophosphamide: IVCY）を行ったところ軽快した。BBEは脳幹を病変の首座とする自己免疫疾患であり，眼球運動障害，運動失調，意識障害を三徴とする希少疾患である。フィッシャー症候群（Fisher syndrome: FS）とは自己抗体が共通しており，FSからの移行例と考えられている。ほとんどの場合寛解するが死亡例も存在し，抗GQ1b抗体陰性例やGBS合併例は後遺症を残す割合が高い。原因不明の意識障害患者やGBS/FSが疑われた患者はBBEを疑うことが肝要であり，MRIで異常を認めなくとも脳幹機能の低下の有無を観察すべきである。IVCYのBBEへの有効性は証明されておらず，症例の集積が必要である。

Sequential therapy with different novel androgen receptor signaling inhibitors (ARSIs) is a possible treatment option for patients who have increased prostate-specific antigen (PSA) levels. The aim of the present study was to investigate cross-resistance among ARSIs and its predictors in non-metastatic castration-resistant prostate cancer (nmCRPC). In this multicenter retrospective study, we evaluated 75 patients with nmCRPC who had progressed after treatment with one ARSI and were subsequently treated with a second ARSI. The primary endpoint was cross-resistance among ARSIs, which was identified by comparing PSA responses to treatment with first and second ARSIs. The secondary endpoints were changes in PSA doubling time (PSADT) from diagnosis of nmCRPC to initiation of treatment with a second ARSI and predictors of PSA non-responsiveness to treatment with that second ARSI. The rates of any PSA response, PSA decline ≥ 50%, and PSA decline ≥ 90% to treatment with a second ARSI were significantly lower than those to the first ARSI administered (45% vs. 88%, P < 0.001; 9.3% vs. 71%, P < 0.001; 2.7% vs. 33%, P < 0.001; respectively). The PSADT shortened to some degree in 31 patients (41%). According to multivariable analysis, only PSADT before initiation of treatment with a second ARSI was significantly associated with no PSA response to treatment with that second ARSI. We identified significant cross-resistance among ARSIs in patients with nmCRPC. The PSADT before initiation of treatment with a second ARSI may be useful for predicting the efficacy of treatment with a second ARSI.

Abstract Background Sequential therapy with different novel androgen receptor signaling inhibitors (ARSIs) is a possible treatment option for patients who have increased prostate-specific antigen (PSA) levels. The aim of the present study was to investigate cross-resistance among ARSIs and its predictors in non-metastatic castration-resistant prostate cancer (nmCRPC). Methods In this multicenter retrospective study, we evaluated 75 patients with nmCRPC who had progressed after treatment with one ARSI and were subsequently treated with a second ARSI. The primary endpoint was cross-resistance among ARSIs, which was identified by comparing PSA responses to treatment with first and second ARSIs. The secondary endpoints were changes in PSA doubling time (PSADT) from diagnosis of nmCRPC to initiation of treatment with a second ARSI and predictors of PSA non-responsiveness to treatment with that second ARSI. Results The rates of any PSA response, PSA decline ≥ 50%, and PSA decline ≥ 90% to treatment with a second ARSI were significantly lower than those to the first ARSI administered (45% vs. 88%, P &lt; 0.001; 9.3% vs. 71%, P &lt; 0.001; 2.7% vs. 33%, P &lt; 0.001; respectively). The PSADT shortened to some degree in 31 patients (41%). According to multivariable analysis, only PSADT before initiation of treatment with a second ARSI was significantly associated with no PSA response to treatment with that second ARSI. Conclusions We identified significant cross-resistance among ARSIs in patients with nmCRPC. The PSADT before initiation of treatment with a second ARSI may be useful for predicting the efficacy of treatment with a second ARSI.