First case of lung cancer with pneumoconiosis and endobronchial leiomyoma complicating the diagnosis.

BACKGROUND: In the treatment of lung cancer, the presence or absence of mediastinal lymph node involvement has a significant bearing on the indication for surgery. In addition, if a tumor is found in the trachea during preoperative scrutiny of lung cancer, the possibility of intratracheal metastasis should be considered, since this kind of metastasis is a contraindication for surgery. In the present study, we experienced a case of lung cancer associated with pneumoconiosis and a rare intratracheal leiomyoma. In this case, preoperative staging was difficult, but endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) and intratracheal tumor biopsy were helpful in determining the treatment strategy. CASE PRESENTATION: A 65-year-old man was referred to our hospital for evaluation of abnormal chest X-ray shadows. Sputum cytology indicated squamous cell carcinoma. PET-CT scan showed fluorodeoxyglucose uptake in a right upper lobe mass and the hilar, mediastinal and right supraclavicular lymph nodes, and bronchoscopy revealed a protuberant lesion in the left bronchus. Hence, EBUS-TBNA for the mediastinal lymph nodes and simultaneous evaluation of the protuberant lesion in the left bronchus were performed. The bronchial tumor was histopathologically diagnosed as leiomyoma. Since mediastinal lymph node biopsy showed no malignant cells, a right upper lobectomy and a right S6 segmentectomy were performed. Postoperative pathological evaluation of the dissected lymph nodes revealed pneumoconiosis but no metastasis. He was, thus, diagnosed with squamous cell lung carcinoma (pT2bN0M0, pStage IIA). CONCLUSIONS: We report a patient with lung cancer and coexistence of a rare endobronchial leiomyoma and pneumoconiosis, who underwent surgery after preoperative evaluation using EBUS-TBNA.

Trafficking of newly synthesized surfactant protein B to the lamellar body in alveolar type II cells.

Lung surfactant accumulates in the lamellar body (LB) via not only the secretory (anterograde) pathway but also the endocytic (retrograde) pathway. Our previous studies suggested that the major surfactant components, phosphatidylcholine and surfactant protein A take independent trafficking routes in alveolar type II cells. Thus, trafficking of surfactant protein B (SP-B), a major hydrophobic surfactant apoprotein, should be re-evaluated by a straightforward method. Radiolabeling of cells and subsequent cell fractionation were employed to pursue the sequential trafficking of newly synthesized SP-B in rabbit alveolar type II cells. The LB fraction was prepared by gradient ultracentrifugation. Immunoprecipitation from the culture medium, total cells, and LB fraction was carried out with anti-SP-B antibody. Newly synthesized [35S]-pro-SP-B (~ 42 kDa) was detected in the cells after 1 h. An ~ 8-kDa mature form of [35S]-SP-B was detected in the cells after 3 h and in the LB after 6 h. Mature [35S]-SP-B was predominant in the cells after 24 h, and the dominant portion was present in the LB. In contrast, only a small amount of mature [35S]-SP-B was present in the culture medium. Molecular processing of ~ 42 kDa [35S]-pro-SP-B and transport to the LB was inhibited by brefeldin A, which disassembles the Golgi apparatus. These results suggest that newly synthesized SP-B is sorted to the LB via the Golgi and stored until exocytosis. This pathway is distinct from the pathways reported for phosphatidylcholine and surfactant protein A.

ADRB2 gene polymorphism and emphysema heterogeneity can modulate bronchodilator response in patients with emphysema.

BACKGROUND: Genetic variation in the ß2-adrenergic receptor (ADRB2) gene has been thought to have an important role in the differential response to ß2-agonist therapy for asthma. However, previous studies have shown little evidence for an association between these ADRB2 variants and the bronchial dilator response (BDR) in chronic obstructive pulmonary disease (COPD) patients. This discrepancy could be explained by differences in the distribution and heterogeneity of pulmonary emphysema in COPD patients, since emphysema distribution and heterogeneity are thought to have a role in pulmonary function in COPD patients. We hypothesized that differences in emphysema distribution and heterogeneity may have masked significant alterations of the bronchodilator response among ADRB2 genotypes in COPD patients in previous studies. METHODS: The BDR (induced by 20 µg of procaterol) was measured in 211 patients who had a smoking history of more than 10 pack/years and had undergone chest high resolution computed tomography examination. A low attenuations area (<960 Hounsfield Units) was identified and the emphysema heterogeneity index (EHI%) was calculated with a range in value from -100% to 100%. ADRB2 Arg16Gly genotyping was performed using polymerase chain reaction-restriction fragment length polymorphism analysis. RESULTS: The BDR was augmented in patients with homogenous emphysema compared with those with upper-dominant emphysema. In patients carrying the AA genotype of ADRB2, the BDR was significantly increased in patients with upper-dominant emphysema, but not in patients with lower-dominant emphysema. CONCLUSION: Combination analysis of ADRB2 Arg16Gly polymorphism and EHI% may predict the effectiveness of ß2-adrenergic receptor agonist treatment in patients with COPD and emphysema.

Exogenous gene transfer of Rab38 small GTPase ameliorates aberrant lung surfactant homeostasis in Ruby rats.

BACKGROUND: Rab38 small GTPase regulates intracellular transport in melanocytes and alveolar type II epithelial cells. Ruby rats carrying Rab38 and other gene mutations exhibit oculocutaneous albinism, bleeding diathesis, and hence, are a rat model of human Hermansky-Pudlak syndrome (HPS). We previously showed that Long Evans Cinnamon (LEC) rats, one strain of the Ruby rats, developed aberrant lung surfactant homeostasis with remarkably enlarged lamellar bodies in alveolar type II cells. METHODS: A replication-deficient recombinant adenovirus expressing rat Rab38 (Ad-Rab38) was constructed. Alveolar type II cells were isolated from the LEC rats and tested for lung surfactant phosphatidylcholine secretion. The rats were also examined whether exogenous expression of Ad- Rab38 could rescue the altered lung surfactant homeostasis in the lungs. RESULTS: Isolated type II cells infected with Ad-Rab38 exhibited improved secretion patterns of [3H]phosphatidylcholine, i.e. increased basal hyposecretion and decreased agonist-induced hypersecretion. Endobronchial administration of Ad-Rab38 improved the morphology of type II cells and lamellar bodies, reducing their sizes close to those of wild-type rats. The increased amounts of phosphatidylcholine and surfactant protein B in the lamellar body fractions were decreased in the Ad-Rab38 infected lungs. CONCLUSIONS: These results provide strong evidence that the aberrant lung surfactant homeostasis in the LEC rats is caused by Rab38 deficit, and suggest that endobronchial delivery of the responsive transgene could be an effective method to ameliorate the abnormal lung phenotype in the animal model of HPS.

Sirt1 expression is associated with CD31 expression in blood cells from patients with chronic obstructive pulmonary disease.

BACKGROUND: Cigarette smoke induced oxidative stress has been shown to reduce silent information regulator 1 (Sirt1) levels in lung tissue from smokers and patients with COPD patients. Sirt1 is known to inhibit endothelial senescence and may play a protective role in vascular cells. Endothelial progenitor cells (EPCs) are mobilized into circulation under various pathophysiological conditions, and are thought to play an important role in tissue repair in chronic obstructive lung disease (COPD). Therefore, Sirt1 and EPC-associated mRNAs were measured in blood samples from patients with COPD and from cultured CD34+ progenitor cells to examine whether these genes are associated with COPD development. METHODS: This study included 358 patients with a smoking history of more than 10 pack-years. RNA was extracted from blood samples and from CD34+ progenitor cells treated with cigarette smoke extract (CSE), followed by assessment of CD31, CD34, Sirt1 mRNA, miR-34a, and miR-126-3p expression by real-time RT-PCR. RESULTS: The expression of CD31, CD34, Sirt1 mRNAs, and miR-126-3p decreased and that of miR-34a increased in moderate COPD compared with that in control smokers. However, no significant differences in these genes were observed in blood cells from patients with severe COPD compared with those in control smokers. CSE significantly decreased Sirt1 and increased miR-34a expression in cultured progenitor cells. CONCLUSION: Sirt1 expression in blood cells from patients with COPD could be a biomarker for disease stability in patients with moderate COPD. MiR-34a may participate in apoptosis and/or senescence of EPCs in smokers. Decreased expression of CD31, CD34, and miR-126-3p potentially represents decreased numbers of EPCs in blood cell from patients with COPD.

Iloprost reverses established fibrosis in experimental right ventricular failure.

Prostacyclin and its analogues improve cardiac output and functional capacity in patients with pulmonary arterial hypertension (PAH); however, the underlying mechanism is not fully understood. We hypothesised that prostanoids have load-independent beneficial effects on the right ventricle (RV). Angio-obliterative PAH and RV failure were induced in rats with a single injection of SU5416 followed by 4 weeks of exposure to hypoxia. Upon confirmation of RV dysfunction and PAH, rats were randomised to 0.1 µg·kg(-1) nebulised iloprost or drug-free vehicle, three times daily for 2 weeks. RV function and treadmill running time were evaluated pre- and post-iloprost/vehicle treatment. Pulmonary artery banded rats were treated 8 weeks after surgery to allow for significant RV hypertrophy. Inhaled iloprost significantly improved tricuspid annulus plane systolic excursion and increased exercise capacity, while mean pulmonary artery pressure and the percentage of occluded pulmonary vessels remained unchanged. Rats treated with iloprost had a striking reduction in RV collagen deposition, procollagen mRNA levels and connective tissue growth factor expression in both SU5416/hypoxia and pulmonary artery banded rats. In vitro, cardiac fibroblasts treated with iloprost showed a reduction in transforming growth factor (TGF)-ß1-induced connective tissue growth factor expression, in a protein kinase A-dependent manner. Iloprost decreased TGF-ß1-induced procollagen mRNA expression as well as cardiac fibroblast activation and migration. Iloprost significantly induced metalloproteinase-9 gene expression and activity and increased the expression of autophagy genes associated with collagen degradation. Inhaled iloprost improves RV function and reverses established RV fibrosis partially by preventing collagen synthesis and by increasing collagen turnover.

Adenovector-mediated gene transfer of lysophosphatidylcholine acyltransferase 1 attenuates oleic acid-induced acute lung injury in rats.

OBJECTIVE: Lysophosphatidylcholine is generated through the hydrolysis of phosphatidylcholine by phospholipase A2 and reversely converted to phosphatidylcholine by lysophosphatidylcholine acyltransferase 1. Although lysophosphatidylcholine is a potent proinflammatory mediator and increased in several types of acute lung injuries, the role of lysophosphatidylcholine acyltransferase 1 has not yet been addressed. We aimed to investigate whether the exogenous expression of lysophosphatidylcholine acyltransferase 1 could attenuate acute lung injury. DESIGN: Randomized, prospective animal study, including in vitro primary cell culture test. SETTING: University medical center research laboratory. SUBJECTS: Adult male Sprague-Dawley rats. INTERVENTIONS: Recombinant adenoviruses carrying complementary DNA encoding lysophosphatidylcholine acyltransferase 1 or lacZ (Ad-lacZ) as a control was constructed. Alveolar type II cells were isolated from rats and cultured on tissue-culture inserts. Rats were pretreated with an endobronchial administration of the recombinant adenovirus. One week later, they were IV injected with oleic acid. The lungs were examined 4 hours post oleic acid. MEASUREMENTS AND MAIN RESULTS: Adenoviruses carrying complementary DNA encoding lysophosphatidylcholine acyltransferase 1-infected alveolar type II cells showed lower lysophosphatidylcholine levels and a decreased percentage of cell death compared with Ad-lacZ-infected cells or noninfected cells after exposure to hydrogen peroxide for 1 hour. Compared with Ad-lacZ plus oleic acid-treated lungs, adenoviruses carrying complementary DNA encoding lysophosphatidylcholine acyltransferase 1 plus oleic acid-treated lungs showed a lower wet-to-dry lung weight ratio, a higher lung compliance, lower lysophosphatidylcholine contents, higher phosphatidylcholine contents, and a lower apoptosis ratio of alveolar type II cells. Histological scoring revealed that the adenoviruses carrying complementary DNA encoding lysophosphatidylcholine acyltransferase 1-treated lungs developed oleic acid-induced lung injuries that were attenuated compared with those of Ad-lacZ-treated lungs. CONCLUSIONS: Exogenous expression of lysophosphatidylcholine acyltransferase 1 protects alveolar type II cells from oxidant-induced cell death in vitro, and endobronchial delivery of a lysophosphatidylcholine acyltransferase 1 transgene effectively attenuates oleic acid-induced acute lung injury in vivo. These results suggest that lysophosphatidylcholine acyltransferase 1 plays a protective role in acute lung injury.

Prognostic value of the serum creatinine/cystatin C ratio in patients with chronic obstructive pulmonary disease.

BACKGROUND: Sarcopenia, characterized by skeletal muscle atrophy and physical inactivity, is a manifestation of chronic obstructive pulmonary disease (COPD) and is associated with a poor prognosis. The serum creatinine (Cr)/cystatin C (CysC) ratio has been proposed as a marker of sarcopenia, given its correlation with total skeletal muscle mass, and as a prognostic indicator in COPD. This study aimed to evaluate the usefulness of the serum Cr/CysC ratio as a prognostic determinant in these patients. METHODS: A total of 124 outpatients with COPD were enrolled in this study. Their serum Cr and CysC levels were measured. Survival time analyses were conducted to compare mortality rates between the low and high serum Cr/CysC ratio groups. Multivariate analysis was performed to investigate the association between various factors. RESULTS: Using a serum Cr/CysC cut-off value of 0.885, the mortality rate (per 1000 person-years) for overall mortality was significantly higher in the low serum Cr/CysC ratio group (69.2 versus 28.6; hazard ratio, 2.47; 95% confidence interval, 1.06-5.79; p < 0.05). Similarly, the mortality rate due to respiratory disease was also higher (37.8 versus 8.2; hazard ratio, 4.68; 95% confidence interval, 1.05-20.9; p < 0.05). Multivariate Cox proportional hazards analysis revealed that serum Cr/CysC was an independent risk factor for respiratory disease mortality, regardless of age and airflow limitations. CONCLUSIONS: The serum Cr/CysC ratio could be a valuable clinical parameter for identifying sarcopenia and severe airflow obstruction. The study findings highlight the utility of this ratio as a prognostic predictor in patients with COPD.

The role of hypoxia in pulmonary vascular diseases: a perspective.

From the discovery of hypoxic pulmonary vasoconstriction, responses to hypoxia have been considered as representative for the many alterations in lung vessels that occur in several chronic lung diseases, including pulmonary hypertension, interstitial pulmonary fibrosis, acute respiratory distress syndrome, and chronic obstructive pulmonary disease. An essential part of preclinical research to explain the pathobiology of these diseases has been centered on the exposure of small and large animals to hypoxia. This review aims to summarize pivotal results of clinical and preclinical research on hypoxia, which still have important implications for researchers today.

Thyroid hormone is highly permissive in angioproliferative pulmonary hypertension in rats.

Epidemiological evidence links pulmonary arterial hypertension (PAH) with thyroid disease, but a mechanistic explanation for this association is lacking. Because a central hallmark of vascular remodelling in pulmonary hypertension is lumen obliteration by endothelial cell growth and because thyroid hormones are known to be angiogenic, we hypothesised that thyroid hormones play a role in the control of endothelial cell proliferation in experimental PAH in rats. Hypothyroidism was induced by subtotal thyroidectomy and treatment with propylthiouracil (PTU) in rats with experimental PAH after combined exposure to vascular endothelial growth factor receptor inhibition and hypoxia (the Sugen-chronic hypoxia (SuHx) model). Subtotal thyroidectomy prevented and PTU treatment reversed the development of severe experimental PAH. Thyroxin repletion restored the PAH phenotype in thyroidectomised SuHx rats. The prevention of PAH by thyroidectomy was associated with a reduced rate of cell turnover, reduced extracellular signal-regulated protein kinases 1 and 2 phosphorylation, and reduced expression of α(v)ß(3) integrin, fibroblast growth factor (FGF)-2 and FGF receptor. Thyroidectomy mitigated hypoxia-induced pulmonary hypertension, but this effect was not associated with a decreased pulmonary vascular resistance. These data suggest that thyroid hormone permits endothelial cell proliferation in PAH. A causal link between thyroid diseases and the onset or progression of vascular remodelling in PAH patients remains to be determined.

A case of severe pneumonia caused by Legionella longbeachae with positive results by a Legionella urinary antigen detection kit.

Legionella longbeachae is a Legionella bacteria often detected in soil, and is known as a rare cause of Legionella infections in Japan. In addition, detection of this Legionella species is often overlooked due to negative results from Legionella urinary antigen tests, which could lead to errors in the therapeutic approach. An 80-year-old woman was admitted to our hospital because of fever and dyspnea. Her blood tests showed elevated white blood cells, increased C-reactive protein and transaminases, and hyponatremia. Chest computed tomography showed dense consolidation in the right lung. We diagnosed Legionella pneumonia because the Legionella urinary antigen test was positive on the day after her admission. The patient was intubated and mechanically ventilated on the third day of hospitalization, because of respiratory failure. However, her condition did not improve and she died on the 10th day after admission. After her death, L. longbeachae was detected from sputum culture from her tracheal tube, and was diagnosed as the causative organism of her pneumonia. L. longbeachae infection reportedly rarely produces positive urinary antigen test results. Our experience suggests that the urinary antigen test using Ribotest Legionella might be able to detect Legionella spp. other than L. pneumophila.

Differential response in patients with large cell neuroendocrine carcinoma of the lung to initial therapy: A case series.

BACKGROUND: Large cell neuroendocrine tumors of the lung (LCNEC) are rare. Chemotherapy with the small cell lung carcinoma (SCLC) regimen is the most appropriate treatment for LCNEC. However, there is evidence that the non-small cell lung cancer regimen is also effective in some reported cases. Due to the differences in response to LCNEC treatment, a standard of care for LCNEC has not been established. CASES: The clinical records of nine patients with LCNEC who were treated with anticancer drugs based on an SCLC regimen from March 2016 to March 2022 were retrospectively reviewed. The patients who responded to treatment after one cycle of systemic chemotherapy were compared to those who did not respond. All patients in the responder group had a performance status (PS) of 0 or 1. However, 5 of the 6 patients in the non-responder group had a PS of 2 or 3, indicating that many patients were in poor general condition. Although patients with multiple metastases to more than one organ prior to treatment were not identified in the responder group, five of these patients were in the non-responder group. In the non-responder group, all patients discontinued treatment due to deterioration of general condition during first-line treatment. Thus, none of them were able to start the second-line treatment. CONCLUSION: The results of this study may suggest that early diagnosis and initiation of treatment before multiple organ metastasis development and PS decline may have clinical implications that could lead to improved treatment response in patients with LCNEC.

Influencing factors of efficacy and long-term use of amrubicin in patients with small cell lung cancer.

BACKGROUND: Amrubicin (AMR) has become the standard of care for post-relapse small cell lung cancer (SCLC). It has also been reported to achieve long-term disease control in patients with good treatment response. However, the optimal patient population for whom AMR is effective and the factors associated with long-term disease control are yet to be identified. The aim of the study was to identify the clinical characteristics and factors associated with long-term disease control in patients with recurrent SCLC who would benefit from AMR therapy. METHODS: The clinical records of 33 patients diagnosed with recurrent SCLC and treated with AMR were retrospectively reviewed. Clinical information was compared between patients who achieved disease control (effective group) and who developed disease progression (noneffective group) on the first efficacy assessment after AMR and between patients who continued AMR for more than seven cycles (maintenance group) and those who terminated treatment after 1-6 cycles (discontinuation group). RESULTS: The noneffective group included significantly more patients with AMR dose reductions after the second cycle (p = 0.006). AMR dose reduction was an independent risk factor for disease progression. The maintenance group had significantly lower pretreatment lactate dehydrogenase (LDH) levels than the discontinuation group (p = 0.046). A high LDH level was an independent risk factor for short AMR discontinuation. Overall survival was significantly longer in the effective group than in the noneffective group (p < 0.001). CONCLUSIONS: In AMR therapy for patients with relapsed SCLC, continuation of AMR without dose reduction after the second cycle may contribute to disease control and prolonged survival.

Copper dependence of angioproliferation in pulmonary arterial hypertension in rats and humans.

Obliteration of the vascular lumen by endothelial cell growth is a hallmark of many forms of severe pulmonary arterial hypertension. Copper plays a significant role in the control of endothelial cell proliferation in cancer and wound-healing. We sought to determine whether angioproliferation in rats with experimental pulmonary arterial hypertension and pulmonary microvascular endothelial cell proliferation in humans depend on the proangiogenic action of copper. A copper-depleted diet prevented, and copper chelation with tetrathiomolybdate reversed, the development of severe experimental pulmonary arterial hypertension. The copper chelation-induced reopening of obliterated vessels was caused by caspase-independent apoptosis, reduced vessel wall cell proliferation, and a normalization of vessel wall structure. No evidence was found for a role of super oxide-1 inhibition or lysyl-oxidase-1 inhibition in the reversal of angioproliferation. Tetrathiomolybdate inhibited the proliferation of human pulmonary microvascular endothelial cells, isolated from explanted lungs from control subjects and patients with pulmonary arterial hypertension. These data suggest that the inhibition of endothelial cell proliferation by a copper-restricting strategy could be explored as a new therapeutic approach in pulmonary arterial hypertension. It remains to be determined, however, whether potential toxicity to the right ventricle is offset by the beneficial pulmonary vascular effects of antiangiogenic treatment in patients with pulmonary arterial hypertension.

Severe pulmonary arterial hypertension induced by SU5416 and ovalbumin immunization.

The combination of chronic hypoxia and treatment of rats with the vascular endothelial growth factor (VEGF) receptor blocker, SU5416, induces pulmonary angio-obliteration, resulting in severe pulmonary arterial hypertension (PAH). Inflammation is thought to contribute to the pathology of PAH. Allergic inflammation caused by ovalbumin (OVA) immunization causes muscularization of pulmonary arteries, but not severe PAH. Whether disturbance of the immune system and allergic inflammation in the setting of lung endothelial cell apoptosis causes PAH is unknown. We investigated the effects of OVA-allergic inflammation on the development of PAH initiated by VEGF blockade-induced lung endothelial cell apoptosis. OVA-immunized rats were treated with SU5416 to induce pulmonary vascular endothelial cell apoptosis. The combination of OVA and SU5416 treatment resulted in severe angio-obilterative PAH, accompanied by increased IL-6 expression in the lungs. c-Kit(+) and Sca-1(+) cells were found in and around the lung vascular lesions. Pan-caspase inhibiton, dexamethasone treatment, and depletion of B-lymphocytes using an anti-CD20 antibody suppressed this remodeling. OVA immunization also increased lung tissue hypoxia-induced factor-1α and VEGF expression. Our results also suggest that the increased expression of hypoxia-induced factor-1α and IL-6 induced by the allergic lung inflammation may be a component of the pathogenesis of PAH.

A brief overview of mouse models of pulmonary arterial hypertension: problems and prospects.

Many chronic pulmonary diseases are associated with pulmonary hypertension (PH) and pulmonary vascular remodeling, which is a term that continues to be used to describe a wide spectrum of vascular abnormalities. Pulmonary vascular structural changes frequently increase pulmonary vascular resistance, causing PH and right heart failure. Although rat models had been standard models of PH research, in more recent years the availability of genetically engineered mice has made this species attractive for many investigators. Here we review a large amount of data derived from experimental PH reports published since 1996. These studies using wild-type and genetically designed mice illustrate the challenges and opportunities provided by these models. Hemodynamic measurements are difficult to obtain in mice, and right heart failure has not been investigated in mice. Anatomical, cellular, and genetic differences distinguish mice and rats, and pharmacogenomics may explain the degree of PH and the particular mode of pulmonary vascular adaptation and also the response of the right ventricle.

Suppression of histone deacetylases worsens right ventricular dysfunction after pulmonary artery banding in rats.

RATIONALE: Inhibitors of histone deacetylases (HDACs) reduce pressure-overload-induced left ventricular hypertrophy and dysfunction, but their effects on right ventricular (RV) adaptation to pressure overload are unknown. OBJECTIVES: Determine the effect of the broad-spectrum HDAC inhibitors trichostatin A (TSA) and valproic acid (VPA) on RV function and remodeling after pulmonary artery banding (PAB) in rats. METHODS: Chronic progressive RV pressure-overload was induced in rats by PAB. After establishment of adaptive RV hypertrophy 4 weeks after surgery, rats were treated for 2 weeks with vehicle, TSA, or VPA. RV function and remodeling were determined using echocardiography, invasive hemodynamic measurements, immunohistochemistry, and molecular analyses after 2 weeks of HDAC inhibition. The effects of TSA were determined on the expression of proangiogenic and prohypertrophic genes in human myocardial fibroblasts and microvascular endothelial cells. MEASUREMENTS AND MAIN RESULTS: TSA treatment did not prevent the development of RV hypertrophy and was associated with RV dysfunction, capillary rarefaction, fibrosis, and increased rates of myocardial cell death. Similar results were obtained with the structurally unrelated HDAC inhibitor VPA. With TSA treatment, a reduction was found in expression of vascular endothelial growth factor and angiopoietin-1, which proteins are involved in vascular adaptation to pressure-overload. TSA dose-dependently suppressed vascular endothelial growth factor, endothelial nitric oxide synthase, and angiopoietin-1 expression in cultured myocardial endothelial cells, which effects were mimicked by selective gene silencing of several class I and II HDACs. CONCLUSIONS: HDAC inhibition is associated with dysfunction and worsened remodeling of the pressure-overloaded RV. The detrimental effects of HDAC inhibition on the pressure-overloaded RV may come about via antiangiogenic or proapoptotic effects.

Lung cancer with post-fracture healing changes causing difficulty in staging.

In cases wherein metastatic disease diagnosis in lung cancer is difficult with imaging, tissue biopsy should be performed. A 77-year-old woman presented with a complaint of cough. Positron emission tomography-computed tomography showed a left lung tumor with fluorodeoxyglucose accumulation, multiple lymphadenopathies, and right-rib sclerotic lesion. Although the diagnosis was lung adenocarcinoma, the bone lesion required differentiation from traumatic changes. A costal biopsy showed bone lesions as post-fracture healing changes, leading to variation in the therapeutic strategy to curative. In patients with lung cancer, history of trauma, and bone lesions with fluorodeoxyglucose accumulation, aggressive tissue biopsy is recommended for accurate staging.

Laryngeal papilloma-induced chronic airway obstruction: A case report.

Laryngeal papilloma is a benign tumor characterized by minimal symptoms; however, in rare cases, it can cause airway obstruction and should be treated with caution. A 65-year-old woman presented to the clinic with a history of dyspnea for the past 20 years. Chest computed tomography revealed the presence of a tracheal diverticulum with an internal septum on the right side of the trachea at the apex of the lung. Upon examination, an otorhinolaryngologist revealed a wart-like tumor at the base of the tongue. However, it was ruled out to be the cause of dyspnea owing to the small size of the tumor. Thereafter, the patient was placed under observation. Brochoscopy was performed to investigate the tracheal diverticulum. Bronchoscopy revealed a pedunculated papilloma entering the glottis because of inhalation in the supine position, indicating a high risk of airway obstruction by the papilloma. The patient underwent papilloma resection. Papillomas must be considered in the differential diagnosis of dyspnea. The risk of airway obstruction should not be underestimated in patients with papilloma with reported history of dyspnea, even in the case of small tumors. The patient had a rare tracheal diverticulum, which further complicated the diagnosis of dyspnea.

Acquired pulmonary arteriovenous malformation associated with bronchiectasis: a case report.

BACKGROUND: Pulmonary arteriovenous malformations are mostly caused by congenitally abnormal shunts between pulmonary arteries and pulmonary veins. CASE PRESENTATION: A 74-year-old Japanese woman with a history of bronchiectasis was admitted to our hospital because of dyspnea on exertion. Pulmonary angiography and reconstructed three-dimensional contrast-enhanced computed tomography images showed shunts between pulmonary arteries and pulmonary veins, indicating a diagnosis of pulmonary arteriovenous malformations. Coil embolization of the shunts was successful. CONCLUSIONS: Our findings imply that bronchiectasis can cause pulmonary arteriovenous malformations, and thus patients who present with hypoxemia with bronchiectasis should be carefully evaluated.