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Pulmonologists in primary care clinics are positioned between those in tertiary hospitals and general practitioners in clinics and are anticipated to promote hospital-clinic collaboration for patients with chronic obstructive pulmonary disease (COPD). However, the clinical features of patients in primary respiratory clinics are unclear. This multicenter study cross-sectionally compared the characteristics of patients with COPD in a respiratory clinic (n = 69) with those in a university hospital (n = 124). More patients visited the clinic for symptom relief without a referral, whereas more visited the hospital for consultation of abnormal spirometry/computed tomography (CT). The patients in the clinic showed female predilection, higher prevalence of current smokers, severe dyspnea, and concomitant heart failure, and higher CT-measured cross-sectional area ratio of pectoralis muscle to adjacent subcutaneous adipose tissue compared to those in the hospital (all p 0.05). The observed differences between the two groups suggest the need to establish the role of primary pulmonologists in hospital-clinic collaboration for better COPD management.

Background: Physiological and prognostic associations of centrilobular emphysema (CLE) and paraseptal emphysema (PSE) in smokers with and without chronic obstructive pulmonary disease (COPD) have been increasingly recognized, but the associations with extrapulmonary abnormalities, such as muscle wasting, osteoporosis, and cardiovascular diseases, remain unestablished. Objectives: The aim of the study was to investigate whether CLE was associated with extrapulmonary abnormalities independent of concomitant PSE in smokers without airflow limitation. Methods: This retrospective study consecutively enrolled current smokers without airflow limitation who underwent lung cancer screening with computed tomography and spirometry. CLE and PSE were visually identified based on the Fleischner Society classification system. Cross-sectional areas of pectoralis muscles (PM) and adjacent subcutaneous adipose tissue (SAT), bone mineral density (BMD), and coronary artery calcification (CAC) were evaluated. Results: Of 310 current smokers without airflow limitation, 83 (26.8%) had CLE. The PSE prevalence was higher (67.5% vs. 23.3%), and PM area, SAT area, and BMD were lower in smokers with CLE than in those without (PM area (mean), 34.5 versus 38.6 cm2; SAT area (mean), 29.3 versus 36.8 cm2; BMD (mean), 158.3 versus 178.4 Hounsfield unit), while CAC presence did not differ. In multivariable models, CLE was associated with lower PM area but not with SAT area or BMD, after adjusting for PSE presence, demographics, and forced expiratory volume in 1 s. Conclusions: The observed association between CLE and lower PM area suggests that susceptibility to skeletal muscle loss could be high in smokers with CLE even without COPD.

Pembrolizumab, an anti-PD-1 monoclonal antibody, revolutionized the treatment for advanced urothelial carcinoma. However, the standard treatment for patients after disease progression with pembrolizumab had not been established until the recent approval of enfortumab vedotin. We analyzed the treatment of these patients in the real world, and the patient background and outcomes.We extracted data from 543 patients who experienced progressive disease after pembrolizumab initiation from a Japanese nation-wide cohort of platinum-refractory, metastatic urothelial carcinoma.The median overall survival of the 543 patients was 3.5 months (95% confidence interval 3.0-4.1). Of these, only 20.6% (n = 112) received chemotherapy as a subsequent systemic treatment after progressive disease. The regimen of chemotherapy was very diverse. The median overall survival was 11.9 months (95% confidence interval 9.2-14.7) for patients who received chemotherapy, compared to 2.4 months for those who did not receive chemotherapy (95% confidence interval 2.1-2.9; P 0.0001). Patients who received subsequent chemotherapy were more likely to have better performance status, neutrophil-to-lymphocyte ratio3, hemoglobin11 mg/dL, and history of a single chemotherapeutic regimen at pembrolizumab initiation.This report highlights the real-world practice of the management after pembrolizumab treatment failure in the pre-enfortumab vedotin era, characterized by infrequent use of subsequent anticancer therapy comprising various regimens, reflecting the lack of a standard treatment. Clinical introduction of enfortumab vedotin is expected to improve treatment outcomes in this setting. The present study will provide important baseline data for evaluating the influence of enfortumab vedotin on clinical practices and outcomes.

Yuki Abe,1 Masaru Suzuki,1 Hiroshi Shima,2 Yusuke Shiraishi,2 Naoya Tanabe,2 Susumu Sato,2 Kaoruko Shimizu,1 Hirokazu Kimura,1 Hironi Makita,1,3 Toyohiro Hirai,2 Satoshi Konno,1 Masaharu Nishimura1,3 1Department of Respiratory Medicine, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Kita-ku, Sapporo, 060-8638, Japan; 2Department of Respiratory Medicine, Graduate School of Medicine, Kyoto University, Kyoto, 606-8507, Japan; 3Hokkaido Medical Research Institute for Respiratory Diseases, Chuo-ku, Sapporo, 060-0063, JapanCorrespondence: Masaru SuzukiDepartment of Respiratory Medicine, Faculty of Medicine, Hokkaido University, Kita 15, Nishi 7, Kita-ku, Sapporo, 060-8638, JapanTel +81-11-706-5911Fax +81-11-706-7899Email suzumasa@med.hokudai.ac.jpPurpose: Low body mass index (BMI) has been reported to be associated with poor prognosis in patients with chronic obstructive pulmonary disease (COPD). In contrast, a detailed analysis of the association between body weight change over time and prognosis is not sufficient, particularly in Japanese patients with COPD who have been reported to be much thinner compared to Westerners. This study aimed to investigate the relationship between annual body weight change and long-term prognosis in Japanese patients with COPD in two independent cohorts.Patients and Methods: We analyzed 279 patients with COPD who participated in the Hokkaido COPD cohort study as a discovery cohort. We divided participants into three groups according to quartiles of annual body weight change calculated by the data from the first 5 years: weight loss group ( 0.20 kg/year). The association between annual body weight change and prognosis was replicated in the Kyoto University cohort (n = 247).Results: In the Hokkaido COPD cohort study, the weight loss group had significantly worse mortality than the other groups, whereas there was no difference in BMI at baseline. In the multivariate analysis, annual body weight change was an independent risk factor for all-cause mortality, which was confirmed in the Kyoto University cohort.Conclusion: Annual body weight loss is associated with poor prognosis in Japanese patients with COPD, independent of baseline BMI. Longitudinal assessment of body weight is important for the management of COPD.Keywords: annual body weight change, body mass index, chronic obstructive pulmonary disease, mortality, prognosis, weight loss

Uncontrolled airway mucus is associated with diverse diseases. We hypothesized that the physical characteristics of infiltrating granulocytes themselves affect the clinical properties of mucus. Surgically obtained nasal mucus from patients with eosinophilic chronic rhinosinusitis (ECRS) and neutrophil-dominant non-eosinophilic chronic rhinosinusitis (non-ECRS) was assessed in terms of computed tomography (CT) density, viscosity, water content, wettability, and granulocyte-specific proteins. In an observational study, we found that nasal mucus from patients with ECRS had significantly higher CT density, viscosity, dry weight, and hydrophobicity than mucus from patients with non-ECRS. The levels of eosinophil-specific proteins in nasal mucus correlated with its physical properties. When isolated human eosinophils and neutrophils were stimulated to induce extracellular traps followed by aggregate formation, we found that cell aggregates showed physical and pathological findings that closely resembled mucus. Co-treatment with heparin (which slenderizes the structure of eosinophil extracellular traps) and DNase efficiently induced a reduction in the viscosity and hydrophobicity of both eosinophil aggregates and eosinophilic mucus. The present study highlights the pathogenesis of mucus stasis in infiltrated granulocyte aggregates from a new perspective. The combination of DNase and heparin might be a novel therapeutic modality against pathologic viscous eosinophilic mucus.One Sentence SummaryIntraluminal accumulation and activation of eosinophils contribute to the clinical properties of airway mucus and may serve as a therapeutic target.

Dysanapsis, a mismatch between airway tree caliber and lung size, contributes to a large variation in lung function on spirometry in healthy subjects. However, it remains unclear whether other morphological features of the airway tree could be associated with the variation in lung function independent of dysanapsis. This study used lung cancer screening chest computed tomography (CT) and spirometry data from asymptomatic never smokers. Dysanapsis and the complexity of airway tree geometry were quantified on CT by measuring airway to lung ratio (ALR) and airway fractal dimension (AFD). Moreover, total airway count (TAC), ratio of airway luminal surface area to volume (SA/V), longitudinal tapering and irregularity of the radius of the internal lumen from the central to peripheral airways (Tapering index and Irregularity index) were quantified. In 431 asymptomatic never smokers without a history of lung diseases, lower ALR was associated with lower forced expiratory volume in 1 s (FEV

Two spirometry criteria have been proposed for early chronic obstructive pulmonary disease (COPD) in young smokers: 1) forced expiratory volume in 1 s (FEVThis retrospective study analysed medical check-up data from 13,010 consecutive subjects aged50 years who underwent current and 3 previous spirometry tests in Japan. Current ≥10 pack-year smokers were the main focus of analysis; those meeting one or more spirometry criteria were diagnosed with early COPD. Early COPD was categorized into three subtypes: FEVOf the 1579 current ≥ 10 pack-year smokers, 488 (30.9%) met the early COPD criteria. Multivariate multinomial logistic models adjusted for age, sex, height, body mass index (BMI) and smoking history indicated that past BMI increase and low exercise were associated with higher type 2 early COPD incidence (odds ratio (OR) [95% confidence interval (CI)] = 4.30 [3.10, 6.04], and 0.80 [0.69, 0.93], respectively) but not with higher type 1 incidence. A history of asthma was associated with higher type 3 incidence (OR [95% CI] = 1.98 [1.18, 3.07]).The 3 types of spirometry-based early COPD have different clinical factors. Their trajectories should be explored in longitudinal studies.

Bladder cancer (BlC) is the fourth most common cancer in males worldwide, but few systemic chemotherapy options for its effective treatment exist. The development of new molecularly-targeted agents against BlC is therefore an urgent issue. The Hippo signaling pathway, with its upstream LATS kinases and downstream transcriptional co-activators YAP1 and TAZ, plays a pivotal role in diverse cell functions, including cell proliferation. Recent studies have shown that overexpression of YAP1 occurs in advanced BlCs and is associated with poor patient prognosis. Accessing data from our previous screening of a chemical library of compounds targeting the Hippo pathway, we identified DMPCA (N-(3,4-dimethoxyphenethyl)-6-methyl-2,3,4,9-tetrahydro-1H-carbazol-1-amine) as an agent able to induce the phosphorylation of LATS1 and YAP1/TAZ in BlC cells, thereby suppressing their viability both in vitro and in mouse xenografts. Our data indicate that DMPCA has a potent anti-tumor effect, and raise the possibility that this agent may represent a new and effective therapeutic option for BlC.

We report the use of combination chemotherapy of gemcitabine (800 mg/m² on day1 and 8) and nedaplatin (60 mg/m² on day 1), including neoadjuvant therapy in four cases of squamous cell carcinoma of the urinary tract. In each case, the dose was reduced after assessing the performance status and renal function of the patient. Among the four cases, the best overall outcome was complete response in one case, partial response in two cases, and stable disease in one case. The main adverse event observed was thrombocytopenia; however, no serious adverse events were observed, and this regimen was safely administered. Therefore, we believe that this regimen could be an effective treatment option for progressive squamous cell carcinoma originating from the urinary tract.

BACKGROUND: Preserved ratio impaired spirometry (PRISm) is a common spirometry finding, but its heterogeneous manifestations and frequent transitions to airflow limitation (AFL), chronic obstructive pulmonary disease, or normal spirometry hinder establishing an appropriate management strategy. This study examined whether transition to AFL and baseline comorbidities are more frequent in subjects with definite PRISm (PRISm confirmed on both current and past two spirometry tests) versus incident PRISm (PRISm confirmed only on a current test with past normal spirometry records) than in normal spirometry. METHODS: Archived medical check-up data of subjects aged ≥40 years (n=10828) with two past spirometry records, in a Japanese hospital, were cross-sectionally analyzed. Among them, data from those with follow-up spirometry after three years (n=6467) were used to evaluate transition to AFL. PRISm was defined as forced volume in 1s (FEV1)/forced vital capacity ≥0.7 and % predicted FEV1

Takamasa Kitajima,1 Satoshi Marumo,1 Hisanori Amimoto,2 Yusuke Shiraishi,3 Haruka Yamaki,3 Masahiro Shirata,3 Daiki Inoue,1 Motonari Fukui1 1Respiratory Disease Center, Kitano Hospital, Tazuke Kofukai Medical Research Institute, Osaka, Japan; 2Department of Respiratory Medicine, Kobe City Medical Center West Hospital, Kobe, Japan; 3Department of Respiratory Medicine, Kyoto University, Graduate School of Medicine, Kyoto, JapanCorrespondence: Takamasa Kitajima, Respiratory Disease Center, Kitano Hospital, Tazuke Kofukai Medical Research Institute, 2-4-20 Ohgimachi, Kita-ku, Osaka, 530-8480, Japan, Tel +81-6-6312-8831, Fax +81-6-6361-8867, Email m-kitajima@kitano-hp.or.jpPurpose: An episodic increase in transcutaneous carbon dioxide pressure (PtcCO2) is often recognized in patients with advanced chronic obstructive pulmonary disease (COPD) by overnight PtcCO2 monitoring. This phenomenon, called episodic nocturnal hypercapnia (eNH), mainly corresponds to rapid eye movement (REM) sleep-related hypoventilation. However, it is unclear whether eNH is associated with the frequency of COPD exacerbation. We aimed to investigate whether a relationship exists between COPD exacerbation and eNH.Patients and Methods: We enrolled consecutive patients with stable, severe, or very severe COPD with a daytime arterial carbon dioxide pressure (PaCO2) < 55.0 mmHg who underwent overnight PtcCO2 monitoring from April 2013 to January 2017. We retrospectively analyzed the prevalence of eNH and sleep-associated hypoventilation (SH) as defined by the American Academy of Sleep Medicine. Moreover, we compared the relationship between the frequency of COPD exacerbations in the previous year and eNH or SH.Results: Twenty-four patients were included in this study. The study patients had a mean daytime PaCO2 and nocturnal PtcCO2 of 43.3 ± 6.8 mmHg and 42.9 ± 9.6 mmHg, respectively. Six (25.0%) and 11 (45.9%) of the 24 patients met the SH and eNH criteria, respectively. The odds ratios of SH and eNH for at least one annual exacerbation were 1.0 [95% confidence interval (CI): 0.16– 6.00] and 11.1 [95% CI: 1.39– 87.7], respectively. The odds ratios of SH and eNH for at least two annual exacerbations were 0.3 [95% CI: 0.04– 2.64] and 6.6 [95% CI: 1.06– 39.4], respectively.Conclusion: In patients with advanced COPD and a daytime PaCO2 < 55.0 mmHg, eNH may be associated with a history of more frequent exacerbations than SH. Further studies are required to validate these findings.Keywords: episodic nocturnal hypercapnia, sleep-associated hypoventilation, exacerbations, arterial carbon dioxide pressure, rapid eye movement

Abe Y, Suzuki M, Shima H, et al. Int J Chron Obstruct Pulmon Dis. 2021;16:3243–3253. The authors have advised there is an error with the ethics approval number of Kyoto University on pages 3245 and 3252. On page 3245, Kyoto University Cohort section, last sentence, the text “(E182 and R03112)” should read “(E182, R0311-2, and R1660-1)”. On page 3252, Ethics Approval and Informed Consent section, the text “(E182 and R0311-2)” should read “(E182, R0311-2, and R1660-1)”. The authors apologize for these errors. Read the original article

Introduction: Current Global initiative for COPD(GOLD) advocates ABCD classification for treatment strategy. Although FEV1 was removed in 2017 GOLD report, it9s not fully understood whether the removal of physiological evaluation would affect the predictivity of future exacerbations. This study focused on COPD patients without frequent exacerbation history(group A and B) to test the hypothesis that impaired FEV1 or respiratory oscillometry index would be associated with a higher risk of exacerbation independent of ABCD classification. Methods: This retrospective analysis of a prospective cohort study included stable patients with COPD who underwent spirometry, respiratory oscillometry and chest CT, completed mMRC dyspnea scale and COPD assessment test and were followed up for 5 years to monitor exacerbations. Results: Of total 134 male patients enrolled, 119(88.8%) were classified into group A and B. In univariable Cox proportional hazard model, hazard ratios of FEV1 and resonant frequency(Fres) for exacerbation risk in group A and B patients were the highest among physiological indices. In multivariable Cox proportional hazard model, lower FEV1 and higher Fres were associated with shorter time to first exacerbation in patients with group A and B independent of ABCD classification(A vs B), age, BMI, smoking status, emphysema and airway disease. Conclusions: Adding FEV1 or Fres to ABCD tool could help identifying patients with higher risk of exacerbation. Physiological evaluation including spirometry or respiratory oscillometry and ABCD classification tool should be used together to estimate exacerbations risk for preventive intervention in patients with COPD.

The full-iterative model reconstruction generates ultra-high-resolution computed tomography (U-HRCT) images comprising a 1024 × 1024 matrix and 0.25 mm thickness while suppressing image noises, allowing evaluating small airways 1–2 mm in diameter. However, this technique imposes huge computational burdens and requires a long reconstruction time. This study evaluated whether a recently-established deep learning-based reconstruction, Advanced intelligent Clear-IQ Engine (AiCE), allows quantitative morphological analyses of smaller airways with equal or better quality than the full-iterative model reconstruction while shortening the reconstruction time. In phantom tubes mimicking small airways, the measurement error of 0.5-mm-thickness wall was smaller on the AiCE-based than the full-iterative model-based U-HRCT. Moreover, in five patients with chronic obstructive pulmonary disease, the AiCE-based U-HRCT decreased the reconstruction time approximately by 90% with a modest improvement in image noise, contrast, and sharpness compared to the full-iterative model-based U-HRCT. Therefore, the AiCE-based U-HRCT can be readily used clinically for morphologically evaluating peripheral small airways.

Background Detailed differences in clinical information between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pneumonia (CP), which is the main phenotype of SARS-CoV-2 disease, and influenza pneumonia (IP) are still unclear. Methods A prospective, multicenter cohort study was conducted by including patients with CP who were hospitalized between January and June 2020 and a retrospective cohort of patients with IP hospitalized from 2009 to 2020. We compared the clinical presentations and studied the prognostic factors of CP and IP. Results Compared with the IP group (n = 66), in the multivariate analysis, the CP group (n = 362) had a lower percentage of patients with underlying asthma or chronic obstructive pulmonary disease (P < .01), lower neutrophil-to-lymphocyte ratio (P < .01), lower systolic blood pressure (P < .01), higher diastolic blood pressure (P < .01), lower aspartate aminotransferase level (P < .05), higher serum sodium level (P < .05), and more frequent multilobar infiltrates (P < .05). The diagnostic scoring system based on these findings showed excellent differentiation between CP and IP (area under the receiver operating characteristic curve, 0.889). Moreover, the prognostic predictors were different between CP and IP. Conclusions Comprehensive differences between CP and IP were revealed, highlighting the need for early differentiation between these 2 pneumonias in clinical settings.

[Background] The prevalence and clinical impacts of expiratory central airway collapse (ECAC) in smokers remain controversial. Although studies have shown associations of ECAC with airflow limitation and symptoms, others have shown that higher tracheal collapsibility is associated with lower expiratory-to-inspiratory ratio of lung volume (E/I-LV), but not airflow limitation. This study tested whether ECAC of the trachea and main bronchi could occur exclusively in smokers with lower E/I-LV and affect their symptoms independent of emphysema and intrapulmonary airway disease. [Methods] ECAC was defined as the expiratory-to-inspiratory ratio of cross-sectional lumen area

INTRODUCTION AND OBJECTIVE:In various malignancies, increased expression of programmed cell death protein 1 (PD-1) on programmed cell death ligand 1 (PD-L1) or lymphocytes on antigen-presenting cel...

To investigate the efficacy and safety of first-line Pazopanib advanced or metastatic renal cell carcinoma (RCC): a single-institution study. (Patients and methods) We gathered 23 RCC patients treated between April 2014 and February 2018 in our institution and examined the treatments outcome and adverse events (AEs). (Results) Their risk criteria were categorized as follows: Favorable (n=2), Intermediate (n=12) and Poor (n=9) by International mRCC Database Consortion (IMDC). Median progression free survival (PFS) was 8.6 months and median overall survival (OS) was unreached. Best response (BR) of Pazopanib was partial response (PR): n=10, 50.0%, stable disease (SD): n=8, 40.0% and progression disease (PD): n=2, 10.0% (Three patients had no evaluable data,). AEs of Grade3 had liver dysfunction (n=3), thrombocytopenia (n=2), hand-foot syndrome (n=1), vomiting (n=1) and bowel bleeding (n=1). (Conclusion) The fist-line pazopanib demonstrated good clinical benefit with well-tolerance.

Association between pulmonary disease and IgA nephropathy (IgAN) has been previously reported. However, no association has been reported between hypersensitivity pneumonitis (HP) and IgAN. Here, we report about a patient with no particular medical history, who experienced worsening dyspnoea in the course of 1 month, with ground-glass opacity on chest CT and no improvement after antibiotic therapy. The patient was diagnosed as having HP based on the history of antigen exposure, detection of Trichosporon asahii-specific antibodies and bronchoscopy findings. Concomitantly, findings of renal biopsy revealed the IgAN diagnosis. The patient underwent corticosteroid therapy, with good outcomes for both HP and IgAN. This is the first report in the literature to describe summer-type HP complicated with IgAN.

Anaplastic lymphoma kinase (ALK) translocation renal cell carcinomas (RCCs) have been reported by several independent groups in recent times. The clinical behavior and histopathologic characteristics of these carcinomas are not fully understood because of the paucity of cases reported. Here, we describe 2 cases of RCC harboring a novel striatin (STRN)-ALK fusion. The first case was a 33-year-old woman with no sickle cell trait who underwent nephrectomy for right renal mass and had late recurrence in para-aortic lymph nodes twice 10 and 12 years after initial surgery. After the second recurrence, she was carefully observed without any treatment. Twenty-six years after the initial nephrectomy, the second para-aortic lymphadenectomy was performed, and gastrectomy was performed for newly developed primary gastric cancer. The resected para-aortic lymph nodes were largely replaced by metastatic carcinoma. The second case was a 38-year-old man with no sickle cell trait who underwent cytoreductive nephrectomy followed by sunitinib therapy for metastatic RCC. In both cases, the tumor showed solid, papillary, tubular, and mucinous cribriform structures. Psammoma bodies were occasionally seen in the stroma. Tumor cells had a large nucleus and prominent nucleoli with predominantly eosinophilic cytoplasm. Rhabdoid cells and signet-ring cells were also observed. Intracytoplasmic mucin deposition and background mucinous stroma were confirmed. In the second case, tumor necrosis was seen in some areas. Tumor cells exhibited diffuse positive staining for ALK in both cases. ALK translocation was confirmed by fluorescent in situ hybridization, and further gene analysis revealed a STRN-ALK fusion. These cases provide great insights into ALK translocation RCCs.

(Purpose) We investigated the outcome of external-beam radiotherapy (EBRT) with neoadjuvant androgen deprivation therapy (NeoADT) for high-risk prostate cancer defined by National Comprehensive Cancer Network (NCCN) guideline. (Patients and method) From 2002 to 2013, 70 patients with high-risk prostate cancer (PSA ≥20 ng/ml or clinical T stage ≥T3a, Gleason score ≥8) were treated with NeoADT and EBRT. EBRT consisted of three-dimensional conformal or intensity modulated radiotherapy with or without whole-pelvic radiation. Biochemical failure was defined according to the Phoenix definition. Biochemical progression-free survival (bPFS) and overall survival (OS) were calculated by Kaplan-Meier method, and prognostic factors for bPFS were analyzed by using the Cox proportional hazard model. (Result) The median age and initial prostate-specific antigen (PSA) level were 72 years old and 25.2 ng/ml, respectively. 43 patients had PSA level ≥20 ng/ml, 51 patients had clinical stage ≥T3a, 27 patients had Gleason score ≥8. The number of risk factors patients possessed was 1 (RiskN-1) in 31 patients, 2 (RiskN-2) in 27 patients and 3 (RiskN-3) in 12 patients. Median EBRT dose and duration of Neo ADT were 74 Gy and13.0 months, respectively. Whole-pelvic radiation was administered in 7 patients. After median follow-up of 4.8 years, biochemical and clinical failure occurred in 23 and 2 patients, respectively. No patients died of cancer. Five-year/8-year bPFS and OS were 63%/54% and 100%/91%, respectively. In multivariate analysis, three high-risk factor of NCCN guideline (PSA, clinical stage, Gleason score) did not predict outcome after EBRT independently, but RiskN (-1 vs -2, 3, HR 35.35, 95%CI 2.51-498.05, p

Background To compare the prevalence of nephrotoxicity between patients with a solitary-functioning kidney versus those with bilateral-functioning kidneys during the administration of cisplatin-based chemotherapy for advanced urothelial carcinoma. Methods We retrospectively analyzed 244 advanced urothelial carcinoma patients treated with cisplatin-based chemotherapy between 2004 and 2010 at 17 institutes in Japan. The 24 h creatinine clearance, Cockcroft–Gault formula, and estimated glomerular filtration rate equation (eGFR), were compared before all chemotherapies. The urinary tract function status was determined based on the data of nephroureterectomy, hydronephrosis, and relief of upper urinary tract obstruction. A total of 244 patients were divided into four groups according to their urinary tract functioning status and eGFR results, including bilateral-functioning kidneys with pretreatment eGFR ≥60 mL/min/1.73 m2 group (n = 83, 34.0%); a solitary-functioning kidney with pretreatment eGFR ≥60 mL/min/1.73 m2 group (n = 36, 14.8%); bilateral-functioning kidneys with pretreatment eGFR 10% and 30% from baseline in the post-third-course of chemotherapy was significantly higher in patients with bilateral-functioning kidneys than in those with a solitary-functioning kidney, among patients with pretreatment eGFR 20% from baseline were significantly higher in patients with bilateral-functioning kidneys than those with a solitary-functioning kidney among patients with pretreatment eGFR

Purpose We investigated the impact of lower urinary tract symptoms (LUTS) on generic health-related quality of life (HRQOL) in male patients without co-morbidity. Patients and method From 2003 to 2011, a total 567 men who presented out urological department completed the questionnaires including International Prostate Symptom Score (IPSS), incontinence-frequency score (IFS) from the UCLA prostate cancer index, MOS 36-Item Short-Form Health Survey (SF-36). Among 230 patients with no coexisting morbidity, the relations between each LUTS score of IPSS indices and IFS and 8 domain scores of SF-36 were analyzed by Pearson's product-moment correlation and stepwise multiple regression analysis. Result Univariate analysis showed that the IFS had a significant correlation with all of 8 domain scores of SF-36, and also the IPSS item scores of urgency, nocturia and straining correlated significantly with multiple domain scores of SF-36. In multiple regression analysis, the proportionate contributions of LUTS to each SF-36 domain scores were low (R2 was 10% or less). Incontinence was considered as the most influential factor that had a negative impact on HRQOL in 7 SF-36 domains of physical functioning, role-physical, bodily pain, general health perception, vitality, social functioning and mental health. Additionally, nocturia, straining and urgency were significantly associated with deficit of HRQOL in 4 SF-36 domains (role-physical, general health perception, role-emotional, mental health), 2 domains (bodily pain, social functioning) and 1 domain (role-emotional) of SF-36, respectively. CONCLUSION; Among LUTS, incontinence, nocturia and straining were the most important symptoms in association with the negative impact on generic HRQOL measured by SF-36.

Myxoid/round cell liposarcomas are rare mesenchymal neoplasms. They preferentially occur in the lower extremity, and most of them have type 1 or type 2 DDIT3-FUS fusion gene. We report here a very rare case of myxoid/round cell liposarcoma of the paratesticular region with type 3 DDIT3-FUS fusion gene. A 46-year-old Japanese man noticed a gradually enlarged intrascrotal mass without pain. Surgical resection of 3.4 cm × 2.1 cm oval mass was carried out, and it was located in the right paratesticular region apart from the spermatic cord and epididymis. Histological examination of the tumor revealed ovoid cell proliferation with anastomosing vascular network and scattered lipoblasts. Genetic analysis elucidated that the tumor had a chromosomal translocation, type 3 DDIT3-FUS chimeric gene. The tumor was definitely diagnosed as myxoid/round cell liposarcoma of the paratesticular region.

A 27-year-old man visited our hospital with painless swelling of the left scrotum. Hematologic studies showed the following levels of lactate dehydrogenase, 3,171 IU/l ; alpha-fetoprotein, 2.2 ng/ml ; and β- human chorionic gonadotropin, 0.4 ng/ml, and abdominal computed tomography revealed a mass of 10×8 ×4 cm in the left testis, and that of 3.5×3.0×5.0 cm in the left renal hilar lymph node, without any other metastasis. Left high inguinal orchiectomy was performed, and histopathological examination revealed mixed form with seminoma and teratoma. He was diagnosed to have a left germ cell tumor with left renal hilar lymph node metastases, pT1, N3, M0, stage II C, indicating poor prognosis with IGCCC. The patient received four cycles of chemotherapy, COMPE regimen (CDDP, VCR, MTX, PEP, VP-16 [etoposide]). After lactate dehydrogenase, alpha-fetoprotein, and β -human chorionic gonadotropin all normalized, retroperitoneal lymph node dissection was performed. Histopathological examination revealed only a mature teratoma. Two and half years later, hematologic studies showed blast transformation. Bone marrow biopsy revealed acute myeloblastic lymphoma (M2). The patient received one cycle of AraC and daunorubicin, one cycle of high dose AraC, and three cycles of AraC and mitoxantrone. After chemotherapy, he has maintained a disease-free status for 11 years. In this case, etoposide, a topoisomerase II inhibitor, was the presumed cause of therapy-related acute myeloid leukemia. After administering chemotherapeutic agents especially etoposide, it is important to check blood count periodically for a long time.

Using a photoaffinity labeling technique, Nakamaru-Ogiso et al. demonstrated that fenpyroximate, a strong inhibitor of bovine heart mitochondrial NADH-ubiquinone oxidoreductase (complex I), binds to the ND5 subunit [Nakamaru-Ogiso, E., et al. (2003) Biochemistry 42, 746-754]. Considering that the main body of the ND5 subunit composed of transmembrane helixes 1-15 is located at the distal end of the membrane domain [Efremov, R. G., et al. (2010) Nature 465, 441-445], however, their result may be questionable. Because establishing the number and location of inhibitors and/or quinone binding sites in the membrane domain is necessary to elucidate the function of the enzyme, it is critical to clarify whether there is an additional inhibitor and/or quinone binding site besides the interface between the hydrophilic and membrane domains. We therefore performed photoaffinity labeling experiments using two newly synthesized fenpyroximate derivatives [[(125)I]-4-azidophenyl fenpyroximate ([(125)I]APF) and [(125)I]-3-azido-5-iodobenzyl fenpyroximate ([(125)I]AIF)] possessing a photoreactive azido group at and far from the pharmacophoric core moiety, respectively. Doubled sodium dodecyl sulfate-polyacrylamide gel electrophoresis revealed that [(125)I]APF and [(125)I]AIF bind to the PSST and 49 kDa subunits, respectively. Careful examination of the fragmentation patterns of the labeled PSST and 49 kDa subunits generated by limited proteolysis indicated that the residues labeled by [(125)I]APF and [(125)I]AIF are located in the Ser43-Arg66 (PSST) and Asp160-Arg174 (49 kDa) regions, respectively, which face the supposed quinone-binding pocket formed at the interface of the PSST, 49 kDa, and ND1 subunits. We conclude that fenpyroximate does not bind to the distal end of the membrane domain but rather resides at the interface between the two domains in a manner such that the pharmacophoric pyrazole ring and side chain of the inhibitor orient toward the PSST and 49 kDa subunits, respectively. This study answers a critical question relating to complex I.