Kanazawa Medical Center

Bronchoscopy frequently precipitates intraprocedural hypoxemia. Although several recent randomized controlled trials suggest that high-flow nasal cannula oxygen (HFNO) reduces intraprocedural hypoxemia during bronchoscopy, the overall certainty of this evidence remains insufficient. Hence, we performed a systematic review and meta-analysis to compare the efficacy of HFNO with that of conventional low-flow oxygen therapy (COT) during adult bronchoscopy. MEDLINE, Embase, and trial registries were searched for randomized controlled trials (RCTs) involving adults (18y or older) undergoing bronchoscopy that compared HFNO with COT. The primary outcome was the incidence of hypoxemia during the procedure. The key secondary outcomes were total procedure time, bronchoscopy interruption, and lowest intraprocedural peripheral oxygen saturation. The pooled risk ratios (RRs) or mean differences (MDs) were calculated, and the certainty of evidence was assessed. The protocol was registered with PROSPERO (CRD420251071548). Eleven RCTs (12 study arms) comprising 1714 participants met the inclusion criteria. HFNO was found to significantly reduce the incidence of hypoxemic events compared with COT (RR: 0.39, 95% CI: 0.26-0.59) and lowered the likelihood of procedure interruption (RR: 0.39, 95% CI: 0.27-0.55). HFNO also maintained a higher nadir SpO2 (MD=4.5%, 95% CI: 3.02-5.99). No statistically significant difference was observed in the total procedure time (MD: -0.87min, 95% CI: -1.99 to 0.25). This meta-analysis showed HFNO reduces the incidence of intraprocedural hypoxemia and interruptions during bronchoscopy. Our findings support a selective approach, suggesting the benefits of HFNO are greater in high-risk patients.

Abstract Background: Tumor-infiltrating lymphocytes (TILs) reflect host immune response and are associated with prognosis and treatment response in HER2-positive and triple-negative breast cancer (TNBC). While the International Immuno-Oncology Biomarker Working Group recommends evaluating stromal TILs in tumor areas, intratumoral heterogeneity and small sample size in core needle biopsy (CNB) specimens limit consistent assessment. It remains unclear whether central tumor (CT) or invasive margin (IM) regions should be prioritized and what cut-off values are clinically relevant. Ultrasonographic (US) features may also reflect the immune microenvironment. We previously proposed a TILs-US score based on three US features that predicts lymphocyte-predominant breast cancer (LPBC). This study evaluated the clinical utility of TILs assessment from CT and IM regions, appropriate cut-off values for predicting response in HER2-positive and TNBC using CNB, and explored optimal biopsy targeting through pathologic and US comparisons. Methods: In this multicenter retrospective study, we analyzed 239 patients (124 HER2-positive, 115 TNBC) with cT1-3/cN0-2 breast cancer who underwent surgery after neoadjuvant chemotherapy (NAC). TILs were evaluated using CNB specimens obtained before NAC and assessed separately in the central tumor (CT) and invasive margin (IM) regions. The IM was defined as a 1-mm-wide area centered on the interface between the tumor and surrounding stroma, while the CT was defined as the remaining intratumoral area within the IM boundary. TILs were analyzed using binary cut-offs of 30% and 50%, as well as a three-tier classification: low (0-10%), intermediate (11-49%), and high (≥50%). Pre-treatment ultrasound (US) findings included tumor shape (scored 0-2), internal echo (0-2), and posterior echo (0-3), which were used to calculate a composite TILs-US score ranging from 0 to 7. Associations between TIL levels, US features, and pathological complete response (pCR) were analyzed. Results: Overall, 104 patients achieved pCR (HER2-positive: 39; TNBC: 65). Using a 30% cut-off, TILs were evenly distributed both CT and IM, while ≥50% cases were relatively rare especially CT (CT: 10%; IM: 20%). CT TILs ≥30% was significantly associated with pCR (p=0.001), whereas the ≥50% cut-off was not (p=0.128). In contrast, both 30% and 50% cut-offs in the IM region were predictive of pCR (p<0.001 and p=0.009, respectively). Subtype analysis revealed that in TNBC, TILs ≥30% in both CT and IM regions were significantly correlated with pCR. In HER2-positive cases, however, only IM TILs ≥30% was predictive of pCR. Similar trends were observed with the three-tier classification. Among US features, a small lobulated shape was associated with high TILs levels in both CT and IM regions, while an enhanced posterior echo was correlated with high TILs in the IM region. Conclusion: Our findings suggest that TILs assessment should include the IM in addition to the CT, especially in CNB specimens as provide valuable information. Given the limited tissue area available in CNB specimen, using a 30% cut-off for TILs may offer a clinically meaningful threshold to predict treatment response. In cases where US findings suggest central fibrosis, targeting only the tumor center may result in sampling fibrotic areas with sparse immune and tumor cells, potentially hindering proper evaluation. Therefore, selecting the biopsy target based on US imaging is essential. Especially in HER2-positive breast cancer, as well as TNBC, it is important for operators to consider the optimal needle insertion angle and sampling site to ensure appropriate sampling of viable tumor tissue and immune microenvironment for accurate pathological and immunological evaluation. Citation Format: Y. Kimura, R. Yamaguchi, K. Fukui, A. Kanou, M. Noma, S. Akashi-Tanaka, K. Arihiro, N. Iwamoto, Y. Ohta, T. Okuno, S. Kashiwagi, Y. Kamei, Y. Tanada, S. Nakano, A. Nagata, A. Murakami, Y. Mochitomi, A. Yamakawa, M. Yamaguchi, H. Shima, A. Emi. Ultrasound-guided biopsy-based tils assessment at tumor margins as a predictive biomarker of neoadjuvant treatment response in early her2-positive and triple-negative breast cancer: a multicenter study [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS3-13-18.

ABSTRACT In this study, we examined clinical and cohort data to explore the potential renoprotective effects of natto (fermented soybeans) consumption and its relationship with D‐amino acids. In a clinical study, ten healthy adults consumed one 40‐g pack of natto three times in a single day, and plasma and urine samples were collected 1 h and 24 h after intake. In a 5‐year cohort of 295 adults, natto intake was categorized as none (0 g/day), low (1–10 g/day), middle (11–25 g/day), or high (> 25 g/day). The plasma and urinary D‐alanine levels increased significantly after natto consumption. In the cohort, the adjusted mean annual changes in estimated glomerular filtration rate (eGFR, mL/min/1.73 m 2 ) were −1.41, −0.78, −1.01, and −1.01 for the none, low, middle, and high groups, respectively. Low natto intake was significantly associated with a slower decline in eGFR, although no dose‐dependent trend was observed. No significant differences in gut microbiota diversity or composition were found across intake groups. Natto consumption was associated with increased plasma D‐alanine levels and a slower decline in renal function. Further studies are warranted to clarify the mechanisms underlying these associations.

PIK3CA mutations play a critical role in tumorigenesis by driving constitutive activation of the phosphoinositide 3-kinase (PI3K) signaling pathway. These mutations have been identified in a small subset of non-small cell lung cancer (NSCLC), but their clinical significance and response to chemoimmunotherapy remain unclear. A 44-year-old man with a 24-pack-year smoking history presented with hoarseness and exertional dyspnea. Imaging demonstrated an irregular left upper-lobe pulmonary nodule consistent with the primary lesion, along with metastatic involvement of the left frontal lobe, cervical-mediastinal lymph nodes, right kidney, and lumbar vertebrae. Endobronchial ultrasound-guided transbronchial needle aspiration of the station 4R lymph node confirmed adenosquamous carcinoma. Molecular analysis revealed a PIK3CA E545K mutation without coexisting oncogenic driver alterations. The programmed cell death ligand 1 tumor proportion score indicated low expression (1-9%). Despite first-line carboplatin, nab-paclitaxel, and pembrolizumab followed by second-line carboplatin, pemetrexed, nivolumab, and ipilimumab, the disease progressed rapidly, and the patient died four months after diagnosis. This case illustrates that isolated PIK3CA-mutant NSCLC can be highly refractory to conventional chemoimmunotherapy, including regimens incorporating a cytotoxic T-lymphocyte-associated antigen 4 inhibitor. Further clinical investigation of PI3K-targeted therapies is warranted to establish effective treatment strategies for PIK3CA-mutant NSCLC.

BackgroundImpaired social functioning is one of the core symptoms of schizophrenia (SCZ). Genetic factors have also been implicated in SCZ. To contribute to the discussion on the involvement of genetic factors in SCZ, we evaluated the social functioning of first-degree relatives (FR) of patients with SCZ.MethodsThis was a non-interventional observational study. We examined social functioning using the Japanese version of the Social Functioning Scale (SFS-J) in three groups: SCZ, SCZ FR, and healthy controls (HC). The effects of the groups (SCZ, FR, and HC) on social functioning were evaluated using analysis of covariance. In addition, the cutoff value for SCZ in the SFS total score was calculated, and the trend in the proportion of individuals below the cutoff value in each group was evaluated.ResultsData from 256 subjects (SCZ (n = 44), FR (n = 26), and HC (n = 186)) were analyzed. Group, years of education, intelligence quotient (IQ), and sex were found to be significant factors affecting SFS total scores. The proportion of SFS scores < 140 (the cutoff value for SCZ) was 9.1% in HC, 57.7% in FR, and 95.4% in SCZ, showing a continuous increase in the proportion of SFS scores < 140 across the three groups (P < 0.0001).ConclusionsIn social functioning assessed by SFS, the score for FR was intermediate between those of SCZ and HC. The results of this study suggest that genetic factors may influence social functioning scores in SCZ and FR.

Hyperammonemia typically results from hepatic dysfunction, but obstructive urinary tract infection (UTI) caused by urease-producing bacteria can rarely induce severe hyperammonemia and encephalopathy. We describe a 76-year-old woman with chronic voiding dysfunction who presented with fever and coma, with a markedly elevated serum ammonia level of 380 μg/dL despite normal liver function. Urinalysis revealed markedly alkaline urine and pyuria. Head computed tomography (CT) and magnetic resonance imaging showed no acute abnormalities. Abdominal CT demonstrated marked bladder distention and no findings suggestive of chronic liver disease. Bladder decompression and piperacillin/tazobactam therapy led to rapid improvement, with ammonia falling to 70 μg/dL and full recovery of consciousness within 48 hours. Urine culture later yielded Corynebacterium species, prompting the addition of vancomycin; the organism was subsequently identified as urease-positive Corynebacteriumriegelii. Blood cultures remained negative, and a later plasma amino acid analysis showed no evidence of urea-cycle disorders. The patient had no recurrence of hyperammonemia or UTI during the four-year follow-up. Obstructive UTI due to urease-producing bacteria should be recognized as a reversible cause of acute encephalopathy in elderly patients with urinary retention.

Drug-induced interstitial lung disease (DI-ILD) encompasses a wide spectrum of imaging and histopathologic patterns, sometimes resembling hypersensitivity pneumonitis (HP). Pegylated liposomal doxorubicin (PLD, Doxil®) is a nanoparticulate formulation of doxorubicin designed to reduce systemic toxicity, and pulmonary toxicity is rarely documented. We report a 62-year-old woman with recurrent ovarian carcinoma who developed fever and erythema after the third cycle of PLD, followed by diffuse pulmonary infiltrates. She had no history of allergy, lung disease, or environmental antigen exposure. On admission, chest radiography revealed bilateral fine granular opacities, and high-resolution computed tomography demonstrated diffuse centrilobular ground-glass nodules predominantly in the upper lobes. Bronchoalveolar lavage showed marked lymphocytosis with elevated total cell counts, and transbronchial lung biopsy revealed noncaseating epithelioid granulomas with lymphocytic infiltration, consistent with an HP-like pattern. Microbiologic and autoimmune evaluations were negative. Based on the temporal association with PLD administration, compatible imaging and histopathologic findings, and exclusion of other etiologies, a diagnosis of HP-like DI-ILD induced by PLD was made. Prednisolone 50 mg daily led to rapid defervescence and remarkable radiologic improvement within two weeks, followed by complete remission after tapering and no recurrence during 4.5 months of follow-up until death from progressive ovarian cancer. This case highlights that PLD, though considered relatively safe, can induce HP-like DI-ILD, and prompt recognition with appropriate corticosteroid therapy may achieve favorable outcomes. Clinicians should remain vigilant for this rare but potentially severe pulmonary toxicity.

Late recurrence of breast cancer occurring more than two decades after curative surgery is rare, but in the era of prolonged survival, clinicians may increasingly encounter such cases. Mediastinal or hilar recurrence may radiologically mimic primary lung cancer; however, histological confirmation using endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) enables accurate diagnosis with minimal invasiveness. We report the cases of two patients who developed mediastinal and hilar lymph node metastases nearly 30 years after breast cancer surgery, for whom EBUS-TBNA played a crucial diagnostic role. A 68-year-old woman with a history of right mastectomy for stage I (T1aN0M0) breast cancer 30 years earlier presented with cough and hemoptysis. Chest computed tomography revealed multiple pulmonary nodules, right hilar lymphadenopathy, and sclerotic bone lesions. Fluorodeoxyglucose positron emission tomography/computed tomography showed intense uptake in the right hilar lymph nodes and bones, whereas pulmonary nodules demonstrated only mild uptake. EBUS-TBNA of station 12R revealed adenocarcinoma positive for estrogen and progesterone receptors and negative for human epidermal growth factor receptor 2, confirming metastatic breast carcinoma. The patient was treated with abemaciclib plus fulvestrant, achieving durable disease control for 2.5 years. A 70-year-old woman who had undergone left mastectomy 27 years earlier presented with a dry cough. EBUS-TBNA of stations 4R and 7 confirmed metastatic breast carcinoma. She received nab-paclitaxel followed by trastuzumab deruxtecan, achieving disease control for 20 months. These cases demonstrate that even very late recurrences nearly three decades after surgery can achieve prolonged survival when appropriately diagnosed and optimally treated. EBUS-TBNA is a valuable and minimally invasive diagnostic tool for confirming such a late recurrence.

<bold>Background and Aim:</bold> The role of airway mucus plugging in asthma pathophysiology is well-established. However, its relationship with infectious episodes and type 2 inflammation remains unclear in refractory asthma with bronchiectasis. As part of the BEXAS study (Nomura N, et al. <italic>Respir Res</italic> 2022; 23: 365), this study aimed to clarify the association between mucus plugging, infectious episodes, and type 2 inflammation, with a specific focus on plug location. <bold>Methods:</bold> Patients with refractory asthma complicated by bronchiectasis, but not with allergic bronchopulmonary aspergillosis, were included, if they had high-resolution CT images suitable for mucus score evaluation. Mucus plugging was scored separately for bilateral upper and lower lobes, as well as for the total lung. Cluster analysis was performed using mucus scores in the upper and lower lobes and the number of lobes affected by bronchiolitis. <bold>Results:</bold> Forty-two patients were included, and three distinct clusters were identified. CL 1 (n = 14) was characterized by lower-lobe-dominant mucus plugs, the highest number of bronchiolitis-affected lobes, frequent detection of Pseudomonas, systemic corticosteroid-requiring exacerbations, and bronchopneumonia. This cluster also exhibited the lowest FeNO and %FEV1. CL 2 (n = 6) showed high mucus scores in both lower and upper lobes, along with the highest FeNO levels. CL 3 (n = 22) had the lowest mucus scores overall. The degree of bronchiectasis was comparable among the three clusters. <bold>Conclusions:</bold> Lower-lobe-dominant mucus plugs may reflect the severest phenotype, characterized by frequent bronchiolitis involvement and infectious episodes. The location of mucus plugs may be clinically important.

Gastrosplenic fistula (GSF) is a rare condition associated with gastric or splenic lymphomas. Surgical resection is the most commonly reported treatment, as has been documented in previous studies. We herein report a case of GSF in a 59-year-old man with diffuse large B-cell lymphoma (DLBCL). The patient was successfully treated with chemotherapy alone without the need for surgical resection. Given the patient's advanced stage and the absence of gastrointestinal bleeding or perforation, chemotherapy was selected as the first-line treatment to avoid the risks associated with surgery. The patient received the R-CHOP regimen (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone) along with high-dose methotrexate and intrathecal chemotherapy. No complications related to the fistula were observed during treatment, and the patient achieved complete metabolic remission.