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Lacrimal glands are the main exocrine glands of the eyes. Situated within the orbit, behind the upper eyelid and towards the temporal side of each eye, they secrete lacrimal fluid as a major component of the tear film. Here we identify cells with characteristics of lacrimal gland primordia that emerge in two-dimensional eye-like organoids cultured from human pluripotent stem cells1. When isolated by cell sorting and grown under defined conditions, the cells form a three-dimensional lacrimal-gland-like tissue organoid with ducts and acini, enabled by budding and branching. Clonal colony analyses indicate that the organoids originate from multipotent ocular surface epithelial stem cells. The organoids exhibit notable similarities to native lacrimal glands on the basis of their morphology, immunolabelling characteristics and gene expression patterns, and undergo functional maturation when transplanted adjacent to the eyes of recipient rats, developing lumina and producing tear-film proteins.
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Aparelho Lacrimal , Células-Tronco Pluripotentes , Animais , Humanos , Aparelho Lacrimal/metabolismo , Organoides , Ratos , Lágrimas/metabolismoRESUMO
Although the development of prosocial behavior has been widely studied from the behavioral aspect, the neural mechanisms underlying prosocial behavior in the early stages of development remain unclear. Therefore, this study investigated the neural mechanisms underlying the emergence of prosocial behavior in 3-year-old children. Brain activity in the medial pFC and right TPJ (rTPJ) and facial expression activity, which are related to the ability to infer others' mental states (mentalizing), during the observation of prosocial and antisocial scenes were measured using functional near-infrared spectroscopy and electromyography, respectively. Subsequently, the children's helping and comforting behaviors toward an experimenter were assessed to examine prosocial behavioral tendencies. A correlation analysis revealed that the children who showed stronger activity levels in the rTPJ while observing prosocial scenes had more immediate helping behaviors toward others than those who did not show stronger response levels. Moreover, the amount of facial expression activity correlated with prosocial behavior, including both helping and comforting behaviors. These results suggest that the development of mentalizing ability and the social evaluation of others' actions, mediated by the rTPJ, contribute to the emergence of prosocial behavior.
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Lobo Parietal , Comportamento Social , Espectroscopia de Luz Próxima ao Infravermelho , Lobo Temporal , Humanos , Pré-Escolar , Masculino , Feminino , Lobo Temporal/fisiologia , Lobo Parietal/fisiologia , Expressão Facial , Eletromiografia , Mapeamento Encefálico , Comportamento Infantil/fisiologia , Teoria da Mente/fisiologiaRESUMO
BACKGROUND: The mechanism underlying a poor prognosis in patients with lower-extremity artery disease (LEAD) with heart failure is unknown. We examined the prognostic impact of the left ventricular ejection fraction (LVEF) in patients with LEAD who underwent endovascular therapy (EVT).MethodsâandâResults: From August 2014 to August 2016, 2,180 patients with LEAD (mean age, 73.2 years; male, 71.9%) underwent EVT and were stratified into low-LVEF (LVEF <40%; n=234, 10.7%) and not-low LVEF groups. In the low- vs. not-low LVEF groups, there was a higher prevalence of heart failure (i.e., history of heart failure hospitalization or New York Heart Association functional class III or IV symptoms) (44.0% vs. 8.3%, respectively), diabetes mellitus, chronic kidney disease, below-the-knee lesion, critical limb ischemia, and incidence of major cardiovascular and cerebrovascular events (MACCEs) and major adverse limb events (MALEs) (P<0.001, all). Low LVEF independently predicted MACCEs (hazard ratio: 2.23, 95% confidence interval: 1.63-3.03; P<0.001) and MALEs (hazard ratio: 1.85, 95% confidence interval: 1.15-2.96; P=0.011), regardless of heart failure (P value for interaction: MACCEs: 0.27; MALEs: 0.52). CONCLUSIONS: Low LVEF, but not symptomatic heart failure, increased the incidence of MACCEs and MALEs. Intensive cardiac dysfunction management may improve LEAD prognosis after EVT.
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Procedimentos Endovasculares , Insuficiência Cardíaca , Disfunção Ventricular Esquerda , Humanos , Masculino , Idoso , Prognóstico , Volume Sistólico , Função Ventricular Esquerda , Insuficiência Cardíaca/diagnóstico , Extremidade Inferior , Procedimentos Endovasculares/efeitos adversosRESUMO
BACKGROUND AND OBJECTIVE: Lymphangioleiomyomatosis (LAM) is a rare neoplastic disease associated with the functional tumour suppressor genes TSC1 and TSC2 and causes structural destruction in the lungs, which could potentially increase the risk of lung cancer. However, this relationship remains unclear because of the rarity of the disease. METHODS: We investigated the relative risk of developing lung cancer among patients diagnosed with LAM between 2001 and 2022 at a single high-volume centre in Japan, using data from the Japanese Cancer Registry as the reference population. Next-generation sequencing (NGS) was performed in cases where tumour samples were available. RESULTS: Among 642 patients diagnosed with LAM (sporadic LAM, n = 557; tuberous sclerosis complex-LAM, n = 80; unclassified, n = 5), 13 (2.2%) were diagnosed with lung cancer during a median follow-up period of 5.13 years. All patients were female, 61.5% were never smokers, and the median age at lung cancer diagnosis was 53 years. Eight patients developed lung cancer after LAM diagnosis. The estimated incidence of lung cancer was 301.4 cases per 100,000 person-years, and the standardized incidence ratio was 13.6 (95% confidence interval, 6.2-21.0; p = 0.0008). Actionable genetic alterations were identified in 38.5% of the patients (EGFR: 3, ALK: 1 and ERBB2: 1). No findings suggested loss of TSC gene function in the two patients analysed by NGS. CONCLUSION: Our study revealed that patients diagnosed with LAM had a significantly increased risk of lung cancer. Further research is warranted to clarify the carcinogenesis of lung cancer in patients with LAM.
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Neoplasias Pulmonares , Linfangioleiomiomatose , Humanos , Linfangioleiomiomatose/genética , Linfangioleiomiomatose/epidemiologia , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/epidemiologia , Feminino , Japão/epidemiologia , Pessoa de Meia-Idade , Fatores de Risco , Adulto , Incidência , Idoso , Estudos de Coortes , Masculino , Sistema de Registros , População do Leste AsiáticoRESUMO
BACKGROUND: Rapid identification of causative bacteria in treatment of acute otitis media (AOM) is of paramount importance for appropriate antibiotic use. MATERIALS AND METHODS: This prospective observational study was conducted in 15 hospitals and clinics in Japan between 2018 and 2020. A new rapid antigen test kit (AOS-116), which simultaneously detects antigens for Streptococcus pneumoniae (Sp) and Haemophilus influenzae (Hi), was applied for middle ear fluids (MEFs) and nasopharyngeal secretions (NPSs) in patients with moderate to severe AOM. We investigated relationship between the results of rapid test, severity at initial visit, and clinical course. RESULTS: Regarding performance accuracy based on culture results, AOS-116 showed 1) high (>80%) sensitivity, specificity, and negative predictive value (NPV) in MEFs for both antigens, 2) high sensitivity, specificity, and positive predictive value (PPV) in NPSs for Hi antigen, and 3) high specificity, and PPV in NPSs for Sp antigen. Regarding predictive value of nasopharyngeal culture and antigen detection for causative middle ear pathogens, similar results were observed between AOS-116 and culture, which was characterized with high sensitivity and NPV for both pathogens. MEFs/NPSs positive for Hi antigen were significantly associated with eardrum findings, and severity. MEFs/NPSs positive for pneumococcal antigen were significantly associated with severity of otalgia, fever, and otorrhea. Among patients with prior antimicrobial treatment, improvement tended to be slower in cases positive for Hi than in cases negative. CONCLUSION: The rapid antigen detection test is useful as a decision-making tool for prescribing antimicrobial agents and may play an important role in promoting appropriate antimicrobial use.
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BACKGROUND: Recent advancements in and the proliferation of autonomous mobility technology, such as intelligent wheelchairs, have made it possible to provide mobility services for patients with reduced mobility due to musculoskeletal disorders. In the present study, we conducted a preliminary clinical study to assess the safety and feasibility of in-hospital autonomous transportation using a driverless mobility (wheelchair) for patients with musculoskeletal disorders. METHODS: From January to February 2022, 51 patients with musculoskeletal disorders exhibiting gait disturbance who presented to our institution were included in the present study. Driverless mobility rides were conducted over a straight-line distance of 100 m from the orthopaedic outpatient reception to the payment counter after the outpatient consultation. We assessed the quality of life using an EQ-5D-5 L index and pain using a VAS score before riding the mobility to investigate the patient's condition. After the ride, a questionnaire survey was conducted to assess patient satisfaction on a 5-point scale. In addition, adverse events during the mobility ride were investigated. RESULTS: Overall satisfaction levels showed that 44 out of 51 (86%) patients rated the level as 3 or higher. There were no significant differences in the level of satisfaction based on the cause of disorders or EQ-5D-5 L Index. Among 19 patients who rated the level of satisfaction as 2-3, the ratio of postoperative patients and those with pain tended to be higher (p < 0.05). While 26 of 51 (51%) patients reported moments of feeling unsafe during the mobility ride, no actual adverse events, such as collisions, were observed. CONCLUSIONS: An in-hospital autonomous transportation service using a driverless mobility for patients with musculoskeletal disorders demonstrated high satisfaction levels and was safe with no severe adverse events observed. The expansion of autonomous mobility deployment is expected to achieve mobility as a service in medical care.
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Estudos de Viabilidade , Doenças Musculoesqueléticas , Satisfação do Paciente , Humanos , Masculino , Doenças Musculoesqueléticas/terapia , Doenças Musculoesqueléticas/fisiopatologia , Doenças Musculoesqueléticas/diagnóstico , Feminino , Pessoa de Meia-Idade , Adulto , Idoso , Qualidade de Vida , Cadeiras de Rodas , Transporte de Pacientes/métodos , Limitação da Mobilidade , Inquéritos e Questionários , Idoso de 80 Anos ou maisRESUMO
PURPOSE: To elucidate clinical outcomes using a digital drainage system (DDS) for massive air leakage (MAL) after pulmonary resection. METHODS: A total of 135 consecutive patients with pulmonary resection air leakage of > 100 ml/min on the DDS were evaluated retrospectively. In this study, MAL was defined as ≥ 1000 ml/min on the DDS. We analyzed the clinical characteristics and surgical outcomes of patients with MAL compared with non-MAL (101-999 ml/min). Using the DDS data, the duration of the air leak was plotted with the KaplanâMeier method and compared using the log-rank test. RESULTS: MAL was detected in 19 (14%) patients. The proportions of heavy smokers (P = 0.04) and patients with emphysematous lung (P = 0.03) and interstitial lung disease (P < 0.01) were higher in the MAL group than in the non-MAL group. The MAL group had a higher persistence rate of air leakage at 120 h after surgery than the non-MAL group (P < 0.01) and required significantly more frequent pleurodesis (P < 0.01). Drainage failure occurred in 2 (11%) and 5 (4%) patients from the MAL and non-MAL groups, respectively. Neither reoperation nor 30-day surgical mortality was observed in patients with MAL. CONCLUSIONS: MAL was able to be treated conservatively without surgery using the DDS.
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Pneumopatias , Complicações Pós-Operatórias , Humanos , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/cirurgia , Estudos Retrospectivos , Pneumonectomia/métodos , Drenagem , Pulmão , Pneumopatias/etiologiaRESUMO
PURPOSE: We evaluated the surgical outcomes of salvage extended surgery after definitive medical treatment with an immune-checkpoint inhibitor (ICI) for locally advanced or unresectable non-small-cell lung cancer (NSCLC). METHODS: The subjects of this single-center retrospective analysis were 14 patients who underwent salvage surgery after ICI treatment between May, 2017 and April, 2023 at our institute. We reviewed the comprehensive surgical outcomes, including operative procedures, intraoperative findings, and postoperative morbidities. Overall survival (OS) was calculated using a Kaplan-Meier estimation. RESULTS: The initial clinical stage before medical treatment (c-stage) was stage III in eight patients, stage IV in five patients, and one patient had postoperative lung cancer recurrence. The indications for surgery were as follows: local control for relapse or residual tumor in ten patients and discontinuation of systemic therapy because of treatment-related complications in four patients. The surgical modes were segmentectomy (n = 1), lobectomy (n = 4), bilobectomy (n = 3), pneumonectomy (n = 6), and bronchoplasty (n = 7). Grade 3 or higher postoperative morbidities were observed in six patients, including only one case of 90-day mortality. CONCLUSIONS: Our series demonstrated that the surgical outcome of salvage extended surgery after ICI therapy may be positive with careful selection of the procedure and indication.
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Carcinoma Pulmonar de Células não Pequenas , Inibidores de Checkpoint Imunológico , Neoplasias Pulmonares , Estadiamento de Neoplasias , Pneumonectomia , Terapia de Salvação , Humanos , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/patologia , Terapia de Salvação/métodos , Neoplasias Pulmonares/cirurgia , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Inibidores de Checkpoint Imunológico/uso terapêutico , Masculino , Idoso , Feminino , Pessoa de Meia-Idade , Estudos Retrospectivos , Pneumonectomia/métodos , Resultado do Tratamento , Idoso de 80 Anos ou mais , Recidiva Local de Neoplasia , Taxa de SobrevidaRESUMO
PURPOSE: Among non-small cell lung cancers (NSCLC), 5 years is a benchmark in cancer control and treatment, but a certain percentage of cases recur after 5 years. The long-term post-recurrence outcomes remain controversial. To examine the accurate prognostic factors associated with survival and cancer recurrence among 5-year survivors, a landmark analysis that considered competing risks was performed. METHODS: Complete resection of NSCLC was performed in 2482 patients between January 2003 and December 2015. A total of 1431 patients were 5-year survivors without recurrence. A landmark time analysis was applied to the overall survival (OS) and recurrence-free survival (RFS) from 5 years after surgery, and the findings were calculated using the Kaplan-Meier method. The cumulative incidence of cause-specific death and recurrence was estimated using the cumulative incidence function, while carefully considering the competing risks. RESULTS: Postoperative recurrence was detected in 732 patients, of whom 68 (9.3%) had recurrence after 5 years. The median follow-up period was 8.2 years. In the competing risk analysis, the independent poor prognostic factors associated with cause-specific death were age ≥ 75 years, lymph node metastasis and pleural invasion. CONCLUSIONS: Patients requiring a follow-up for > 5 years were aged ≥ 75 years and had either lymph node metastasis or pleural invasion.
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We propose a hands-free control system for a human-guided smart stroller. The proposed method uses real-time peer-to-peer localization technology of the human and stroller to realize an intuitive hands-free control system based on the relative position between the human and the stroller. The control method is also based on functional and mechanical safety to ensure the safety of the stroller's occupant (child) and the pilot (parent) during locomotion. In this paper, first, we present a preliminary investigation of the humans' preference for the relative position in the context of hands-free guided strollers. Then, we present the control method and a prototype implemented with an electric wheelchair and UWB sensors for localization. We present an experimental evaluation of the proposed method with 14 persons walking with the developed prototype to investigate the usability and soundness of the proposed method compared to a remote joystick and manual operation. The evaluation experiments were conducted in an indoor environment and revealed that the proposed method matches the performance of joystick control but does not perform as well as manual operation. Notably, for female participants, the proposed method significantly surpasses joystick performance and achieves parity with manual operation, which shows its efficacy and potential for a smart stroller. Also, the results revealed that the proposed method significantly decreased the user's physical load compared to the manual operation. We present discussions on the controllability, usability, task load, and safety features of the proposed method, and conclude this work with a summary assessment.
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Cadeiras de Rodas , Humanos , Feminino , Masculino , Caminhada/fisiologia , Adulto , Desenho de Equipamento , Interface Usuário-ComputadorRESUMO
Vascular endothelial cells form a monolayer in the vascular lumen and act as a selective barrier to control the permeability between blood and tissues. To maintain homeostasis, the endothelial barrier function must be strictly integrated. During acute inflammation, vascular permeability temporarily increases, allowing intravascular fluid, cells, and other components to permeate tissues. Moreover, it has been suggested that the dysregulation of endothelial cell permeability may cause several diseases, including edema, cancer, and atherosclerosis. Here, we reviewed the molecular mechanisms by which endothelial cells regulate the barrier function and physiological permeability.
Assuntos
Permeabilidade Capilar , Células Endoteliais , Endotélio Vascular , Humanos , Animais , Endotélio Vascular/metabolismo , Células Endoteliais/metabolismo , Transdução de SinaisRESUMO
This study aimed to compare lower limb events associated with preplanned and finally selected treatment strategies-the validity and usefulness of the physician-chosen strategy were verified.We examined the data of 1003 patients in the registry of multicenter endovascular treatment for superficial femoral and popliteal artery disease study and prospectively enrolled patients who underwent endovascular treatment (EVT) of the femoropopliteal (FP) artery between February 2017 and June 2018 from 67 Japanese institutes. The outcome measures were major adverse limb events (MALE) and target vessel revascularization.The EVT strategies were classified into balloon angioplasty-alone (37.3%), primary stenting (26.7%), and provisional stenting (36.0%) groups. In the initial strategy analysis for the balloon angioplasty-alone, primary stenting, and provisional stenting groups, two-year rates of freedom from MALE (95% confidence interval) were 0.680 (0.620-0.732), 0.754 (0.688-0.808), and 0.798 (0.746-0.840), respectively. Additionally, the rate of MALE was significantly higher among patients in the balloon angioplasty-alone group than among those in the primary or provisional stenting groups in the initial strategy analysis (P = 0.007). Changes in treatment strategy were more frequent in the primary stenting group than in the other groups. Furthermore, the rate of MALE did not significantly differ among the three groups in the final strategy analysis (P = 0.56).Limb outcomes for the final applied strategy did not differ among the three strategies. Additionally, the physician's selection bias was mostly appropriate in the EVT of the FP artery.
Assuntos
Angioplastia com Balão , Doença Arterial Periférica , Humanos , Artéria Femoral/cirurgia , Doença Arterial Periférica/cirurgia , Doença Arterial Periférica/etiologia , Artéria Poplítea/cirurgia , Artéria Poplítea/patologia , Stents , Resultado do Tratamento , Grau de Desobstrução Vascular , Estudos Multicêntricos como AssuntoRESUMO
Dirty necrosis (DN) is a form of tumor necrosis (TN) with prominent neutrophil infiltration and cell detritus in the necrotic foci. This study aimed to characterize the clinicopathological features of DN in metastatic lung cancers of the colon and rectum (MLCRs). A total of 227 patients who underwent pulmonary metastasectomy and complete resection for MLCR were included in this study. TN was evaluated using digitally scanned resection specimens. These slides were immunostained for biomarkers of NETosis (citrullinated histone H3 [citH3] and myeloperoxidase [MPO]), and the area positive for citH3 and MPO was further quantified. TN was observed in 216 cases (95.2%), and 54 (25.0%) of these cases had DN. The presence of TN was not associated with a worse prognosis; however, patients with DN had a significantly shorter overall survival than those without DN (p < 0.01). Furthermore, the presence of DN was a poor prognostic factor in both the univariate and multivariate analyses. Immunohistochemical analysis revealed that the percentage of citH3-positive and MPO-positive areas in the DN-positive cases was significantly higher than that in the DN-negative cases (p < 0.01 and p < 0.01, respectively). In surgically resected MLCR, DN is the characteristic TN subtype associated with poor prognosis and neutrophil extracellular traps (NETs).
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Neoplasias Pulmonares , Reto , Humanos , Prognóstico , Reto/patologia , Histonas , Neoplasias Pulmonares/cirurgia , Neoplasias Pulmonares/patologia , Colo/patologia , Necrose , Neutrófilos/patologiaRESUMO
BACKGROUND: Lobectomy is the standard of care for early-stage non-small-cell lung cancer (NSCLC). The survival and clinical benefits of segmentectomy have not been investigated in a randomised trial setting. We aimed to investigate if segmentectomy was non-inferior to lobectomy in patients with small-sized peripheral NSCLC. METHODS: We conducted this randomised, controlled, non-inferiority trial at 70 institutions in Japan. Patients with clinical stage IA NSCLC (tumour diameter ≤2 cm; consolidation-to-tumour ratio >0·5) were randomly assigned 1:1 to receive either lobectomy or segmentectomy. Randomisation was done via the minimisation method, with balancing for the institution, histological type, sex, age, and thin-section CT findings. Treatment allocation was not concealed from investigators and patients. The primary endpoint was overall survival for all randomly assigned patients. The secondary endpoints were postoperative respiratory function (6 months and 12 months), relapse-free survival, proportion of local relapse, adverse events, proportion of segmentectomy completion, duration of hospital stay, duration of chest tube placement, duration of surgery, amount of blood loss, and the number of automatic surgical staples used. Overall survival was analysed on an intention-to-treat basis with a non-inferiority margin of 1·54 for the upper limit of the 95% CI of the hazard ratio (HR) and estimated using a stratified Cox regression model. This study is registered with UMIN Clinical Trials Registry, UMIN000002317. FINDINGS: Between Aug, 10, 2009, and Oct 21, 2014, 1106 patients (intention-to-treat population) were enrolled to receive lobectomy (n=554) or segmentectomy (n=552). Patient baseline clinicopathological factors were well balanced between the groups. In the segmentectomy group, 22 patients were switched to lobectomies and one patient received wide wedge resection. At a median follow-up of 7·3 years (range 0·0-10·9), the 5-year overall survival was 94·3% (92·1-96·0) for segmentectomy and 91·1% for lobectomy (95% CI 88·4-93·2); superiority and non-inferiority in overall survival were confirmed using a stratified Cox regression model (HR 0·663; 95% CI 0·474-0·927; one-sided p<0·0001 for non-inferiority; p=0·0082 for superiority). Improved overall survival was observed consistently across all predefined subgroups in the segmentectomy group. At 1 year follow-up, the significant difference in the reduction of median forced expiratory volume in 1 sec between the two groups was 3·5% (p<0·0001), which did not reach the predefined threshold for clinical significance of 10%. The 5-year relapse-free survival was 88·0% (95% CI 85·0-90·4) for segmentectomy and 87·9% (84·8-90·3) for lobectomy (HR 0·998; 95% CI 0·753-1·323; p=0·9889). The proportions of patients with local relapse were 10·5% for segmentectomy and 5·4% for lobectomy (p=0·0018). 52 (63%) of 83 patients and 27 (47%) of 58 patients died of other diseases after lobectomy and segmentectomy, respectively. No 30-day or 90-day mortality was observed. One or more postoperative complications of grade 2 or worse occurred at similar frequencies in both groups (142 [26%] patients who received lobectomy, 148 [27%] who received segmentectomy). INTERPRETATION: To our knowledge, this study was the first phase 3 trial to show the benefits of segmentectomy versus lobectomy in overall survival of patients with small-peripheral NSCLC. The findings suggest that segmentectomy should be the standard surgical procedure for this population of patients. FUNDING: National Cancer Center Research and the Ministry of Health, Labour, and Welfare of Japan.
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Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Mastectomia Segmentar , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , PneumonectomiaRESUMO
AIMS: Bronchiolar adenoma (BA) is a novel entity in the 2021 WHO classification of lung tumours. The expression profile of mucin core proteins in BAs is not clear. The aim of this study was to clarify the expression profiles of mucins and to validate the clinicopathologic and molecular features of BAs. METHODS AND RESULTS: We examined the clinicopathological, immunohistochemical, and molecular features of 20 BAs. Our cohort comprised 10 proximal and 10 distal BAs. Only seven of 18 patients (39%) were accurately diagnosed with BA at the time of intraoperative consultation. The frequent genetic alterations were BRAF V600E (35%) and KRAS (30%) mutations, which were mutually exclusive. The expression of MUC1, MUC4, and MUC5B was observed in all cases and that of MUC5AC and MUC6 was observed in nine (45%) and five (25%) cases, respectively. MUC4 was diffusely expressed in 18 cases. In contrast, MUC1, MUC5AC, MUC5B, and MUC6 displayed a patchy expression pattern. These expression patterns were similar to that of bronchiolar epithelium in normal lung tissue. In addition, overexpression of MUC1 and MUC4 on the entire cell surface was not observed in any of the BAs, suggesting their benign nature. CONCLUSION: BA commonly exhibits diffuse MUC4 and patchy MUC1 and MUC5B expression. Its unique expression pattern is probably attributed to mucin expression specific to the bronchiolar epithelium. These results confirm the clinicopathologic and molecular characteristics of BA, including the difficulty in intraoperative frozen section diagnosis and the broad morphologic spectrum of BA derived from the bronchiolar epithelium.
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Adenoma , Mucinas , HumanosRESUMO
AIMS: A distinct subset of lung adenocarcinomas (LADs), arising from a series of peripheral lung cells defined as the terminal respiratory unit (TRU), is characterised by thyroid transcription factor 1 (TTF-1) expression. The clinical relevance of transcription factors (TFs) other than TTF-1 remains unknown in LAD and was explored in the present study. METHODS AND RESULTS: Seventy-one LAD samples were subjected to high-throughput transcriptome screening of LAD using cap analysis gene expression (CAGE) sequencing data; CAGE provides genome-wide expression levels of the transcription start sites (TSSs). In total, 1083 invasive LAD samples were subjected to immunohistochemical examination for paired box 9 (PAX9) and TTF-1 expression levels. PAX9 is an endoderm development-associated TF that most strongly and inversely correlates with the expression of TTF-1 TSS subsets. Immunohistochemically, PAX9 expression was restricted to the nuclei of ciliated epithelial and basal cells in the bronchi and bronchioles and the nuclei of epithelial cells of the bronchial glands; moreover, PAX9 expression was observed in 304 LADs (28%). PAX9-positive LADs were significantly associated with heavy smoking, non-lepidic subtype, EGFR wild-type tumours and PD-L1 expression (all P < 0.0001). All these characteristics were opposite to those of TRU-type LADs with TTF-1 expression. PAX9 expression was an independent prognostic factor for decreased overall survival (P = 0.022). CONCLUSIONS: Our results revealed that PAX9 expression defines an aggressive subset of LADs preferentially occurring in smokers that may arise from bronchial or bronchiolar cells.
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Adenocarcinoma de Pulmão , Adenocarcinoma , Neoplasias Pulmonares , Humanos , Neoplasias Pulmonares/patologia , Fumantes , Adenocarcinoma/patologia , Proteínas Nucleares/metabolismo , Fator Nuclear 1 de TireoideRESUMO
Subtypes of small cell lung carcinoma (SCLC) are defined by the expression of ASCL1, NEUROD1, and POU2F3 markers. The aim of our study was to explore the extent to which the intratumoral heterogeneity of ASCL1, NEUROD1, and POU2F3 may lead to discrepancies in expression of these markers in surgical samples and their matched tissue microarray (TMA) and lymph node (LN) metastatic sites. METHODS AND RESULTS: The cohort included 77 patients with SCLC. Immunohistochemical examinations were performed on whole slides of the primary tumour, paired TMAs, and metastatic LN sites. Samples with H-scores >50 were considered positive. Based on the ASCL1, NEUROD1, and POU2F3 staining pattern, we grouped the tumours as follows: ASCL1-dominant (SCLC-A), NEUROD1-dominant (SCLC-N), ASCL1/NEUROD1 double-negative with POU2F3 expression (SCLC-P), and negative for all three markers (SCLC-I). In whole slides, 40 SCLC-A (52%), 20 SCLC-N (26%), 15 SCLC-P (20%), and two SCLC-I (3%) tumours were identified. Comparisons of TMAs or LN metastatic sites and corresponding surgical specimens showed that positivity for ASCL1, NEUROD1, and POU2F3 in TMAs (all P < 0.0001) or LN metastatic sites (ASCL1, P = 0.0047; NEUROD1, P = 0.0069; POU2F3, P < 0.0001) correlated significantly with that of corresponding surgical specimens. CONCLUSION: The positivity for these markers in TMAs and LN metastatic sites was significantly correlated with that of corresponding surgical specimens, indicating that biopsy specimens could be used to identify molecular subtypes of SCLC in patients.
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Neoplasias Pulmonares , Carcinoma de Pequenas Células do Pulmão , Humanos , Carcinoma de Pequenas Células do Pulmão/genética , Neoplasias Pulmonares/genética , Metástase Linfática , Regulação Neoplásica da Expressão Gênica , Linhagem Celular Tumoral , Fatores de Transcrição Hélice-Alça-Hélice Básicos , Fatores de Transcrição de Octâmero/metabolismoRESUMO
PURPOSE: To investigate whether the severity of calcification assessed by the peripheral artery calcification scoring system (PACSS) was associated with clinical outcomes of drug-coated balloon (DCB) angioplasty for femoropopliteal lesions. MATERIALS AND METHODS: We retrospectively analyzed 733 limbs with intermittent claudication of 626 patients, who underwent DCB angioplasty for de novo femoropopliteal lesions between January 2017 and February 2021 at seven cardiovascular centers in Japan. The patients were categorized using the PACSS classification (grades 0-4: no visible calcification of the target lesion, unilateral wall calcification < 5 cm, unilateral calcification ≥ 5 cm, bilateral wall calcification < 5 cm, and bilateral calcification ≥ 5 cm, respectively). The main outcome was primary patency at 1 year. The Cox proportional hazards analysis was used to explore whether the PACSS classification was an independent predictor of clinical outcomes. RESULTS: The distribution of PACSS was grade 0 in 38%, grade 1 in 17%, grade 2 in 7%, grade 3 in 16%, and grade 4 in 23%. The 1-year primary patency rates in these grades, respectively, were 88.2%, 89.3%, 71.9%, 96.5%, and 82.6%, respectively (p < 0.001). Multivariate analysis disclosed that PACSS grade 4 (hazard ratio: 1.82, 95% confidence interval 1.15-2.87, p = 0.010) was associated with restenosis. CONCLUSION: The PACSS grade 4 calcification was independently associated with poor clinical outcomes after DCB angioplasty for de novo femoropopliteal lesions.
Assuntos
Angioplastia com Balão , Doença Arterial Periférica , Calcificação Vascular , Humanos , Artéria Femoral/diagnóstico por imagem , Artéria Poplítea/diagnóstico por imagem , Estudos Retrospectivos , Doença Arterial Periférica/diagnóstico por imagem , Doença Arterial Periférica/terapia , Resultado do Tratamento , Fatores de Risco , Angioplastia com Balão/efeitos adversos , Calcificação Vascular/diagnóstico por imagem , Calcificação Vascular/terapia , Materiais Revestidos Biocompatíveis , Grau de Desobstrução VascularRESUMO
PURPOSE: To compare the outcomes of thromboendarterectomy (TEA) and endovascular therapy (EVT) with stenting for patients with atherosclerotic common femoral artery (CFA) occlusive disease. MATERIALS AND METHODS: From a retrospective registry of 1193 consecutive patients with CFA treatment performed between 2018 and 2020 at 66 institutions in Japan, we identified patients who underwent TEA (n=432) or stent implantation (n=157). The primary outcome measures were the 1-year primary patency of TEA versus stenting with propensity score matching. The secondary outcome measures were perioperative complications, length of hospital stay, any reintervention, limb salvage, and overall survival. Interaction analysis for primary patency was performed with propensity score stratification to determine the appropriate target population for CFA stenting. RESULTS: Propensity score matching extracted 101 pairs (101 patients in the EVT group and 253 patients in the TEA group). The 1-year primary patency rate was significantly higher in the TEA cohort (92.8% vs 84.6%, p=0.006). The freedom from reintervention rate was also significantly higher in the TEA cohort (94.0% vs 89.9%, p=0.030). However, the 1-year limb salvage (98.7% vs 100.0%, p=0.32), 1-year overall survival (90.8% vs 85.0%, p=0.14), and frequency of perioperative complications were not significantly different between the cohorts (6.9% vs 14.2%, p=0.10). Based on interaction analysis, the superiority of TEA over EVT in terms of patency was less apparent in patients with advanced age and chronic heart failure. CONCLUSIONS: Thromboendarterectomy was superior to stenting in terms of primary patency and freedom from revascularization at 1 year. There was no significant difference in the incidence of perioperative complications between both groups. Thromboendarterectomy may be recommended as the standard treatment strategy for patients with atherosclerotic CFA disease, whereas stenting may be considered for patients with advanced age and chronic heart failure. CLINICAL IMPACT: Thromboendarterectomy compared to stenting was the preferred revascularization strategy for patients with CFA disease in terms of primary patency and freedom from target lesion revascularization during the 1st year. The difference was attenuated in subgroups with advanced age (85 years or older) or chronic heart failure, thus stenting may be considered in patients with these backgrounds.
RESUMO
PURPOSE: To compare the 3-year clinical outcomes of endoluminal bypass with those of surgical bypass for complex femoropopliteal (FP) arterial lesions. MATERIALS AND METHODS: In this retrospective multicenter study, 530 patients with symptomatic peripheral artery disease (Rutherford classification 1-3, 66.0%; 4-6, 34.0%) who underwent either endoluminal bypass with Viabahn stent grafts (n = 276) or surgical bypass (n = 254) (with saphenous vein grafts, 74.4%; prosthetic grafts, 25.6%) for FP arterial lesions between 2010 and 2018 were analyzed. The propensity score-matched analysis was performed to compare the 3-year clinical outcomes of endoluminal bypass with those of surgical bypass. The primary end point was primary patency (freedom from restenosis). The secondary end points were secondary patency, freedom from target lesion revascularization (TLR), limb salvage, and overall survival. The interaction effect of baseline characteristics on the association of the revascularization strategy with the risk of restenosis was analyzed using the Poisson mixed-effect model. RESULTS: The propensity score-matched analysis extracted 107 pairs. After propensity score matching, the primary patency rate at 1, 2, and 3 years was 84.5%, 75.1%, and 70.9%, respectively, for the endoluminal bypass group versus 78.6%, 73.3%, and 72.0%, respectively, for the surgical bypass group (P = .65). There was no significant difference in secondary patency, freedom from TLR, limb salvage, and overall survival (all P > .05). The subsequent interaction analysis revealed that the involvement of popliteal lesions, small distal reference vessel diameters, and long lesions favored surgical bypass over endoluminal bypass because of improved primary patency (all P for interaction < .05). CONCLUSIONS: The 3-year clinical outcomes after endoluminal bypass or surgical bypass for FP arterial lesions were similar.