BACKGROUND Clinical data of patients with Langerhans cell histiocytosis are well established, alt... more BACKGROUND Clinical data of patients with Langerhans cell histiocytosis are well established, although new diagnostic methods and specially long term evolution of the disease with lung involvement are not well-known. METHODS In all cases, patients were diagnosed by means of pathologic study of the lung samples, either by transbronchial biopsy in 7 patients, or by surgical lung biopsy in 8 patients. Six patients were diagnosed by bone biopsy. Other patients were diagnosed by bronchoalveolar lavage (BAL). In 4 patients, who underwent BAL, the study of antibodies CD1 (CD1a) was positive (> 5%). Lymphocytopenia was detected in 28% of patients, whereas no decrease in delayed cutaneous hypersensitivity tests was detected in any of them. After a follow-up study of 12.8 years (range: 4-22 years), 7 patients had dead, 6 patients showed severe lung involvement and other 5 patients did not have lung affection. CONCLUSIONS The diagnosis of Langerhans cell histiocytosis has improved by detect...
Molecular evidence has linked the pathophysiology of lymphangioleiomyomatosis (LAM) to that of me... more Molecular evidence has linked the pathophysiology of lymphangioleiomyomatosis (LAM) to that of metastatic breast cancer. Following on this observation, we assessed the association between LAM and subsequent breast cancer. An epidemiological study was carried out using three LAM country cohorts, from Japan, Spain, and the United Kingdom. The number of incident breast cancer cases observed in these cohorts was compared with the number expected on the basis of the country-specific incidence rates for the period 2000-2014. Immunohistochemical studies and exome sequence analysis were performed in two and one tumors, respectively. All cohorts revealed breast cancer standardized incidence ratios (SIRs) ≥ 2.25. The combined analysis of all cases or restricted to pre-menopausal age groups revealed significantly higher incidence of breast cancer: SIR = 2.81, 95 % confidence interval (CI) = 1.32-5.57, P = 0.009; and SIR = 4.88, 95 % CI = 2.29-9.99, P = 0.0007, respectively. Immunohistochemical...
Lymphangioleiomyomatosis (LAM) is a rare lung-metastasizing neoplasm caused by the proliferation ... more Lymphangioleiomyomatosis (LAM) is a rare lung-metastasizing neoplasm caused by the proliferation of smooth muscle-like cells that commonly carry loss-of-function mutations in either the tuberous sclerosis complex 1 or 2 (TSC1 or TSC2) genes. While allosteric inhibition of the mechanistic target of rapamycin (mTOR) has shown substantial clinical benefit, complementary therapies are required to improve response and/or to treat specific patients. However, there is a lack of LAM biomarkers that could potentially be used to monitor the disease and to develop other targeted therapies. We hypothesized that the mediators of cancer metastasis to lung, particularly in breast cancer, also play a relevant role in LAM. Analyses across independent breast cancer datasets revealed associations between low TSC1/2 expression, altered mTOR complex 1 (mTORC1) pathway signaling, and metastasis to lung. Subsequently, immunohistochemical analyses of 23 LAM lesions revealed positivity in all cases for the ...
The aim is to correlate pulmonary arterial (PA) remodeling estimated by PA fibrosis in PA hyperte... more The aim is to correlate pulmonary arterial (PA) remodeling estimated by PA fibrosis in PA hypertension (PAH) with clinical follow-up. Histology of PA specimens is also performed. 19 patients, aged 54±16 (4 men), functional class II-III were studied with right heart catheterization, PA Intravascular Ultrasound and optical coherence tomography (OCT) in inferior lobe segment. PA wall fibrosis was obtained by OCT ( area of fibrosis/PA cross sectional area × 100). Patients follow-up was blind to OCT. Events were defined as mortality, lung transplantation, need of intravenous prostaglandins or onset of right ventricular failure. OCT measurements showed high intra- and interobserver agreement. There was a good correlation between OCT and histology in PA fibrosis from explanted lungs. Area of fibrosis was 1.4±0.8 mm(2), % fibrosis was 22.3±8. Follow-up was 3.5 years (2.5-4.5). OCT %Fib was significantly correlated with PA capacitance (r=-0.536) and with pulmonary vascular rsistance (r=0.55)...
COPD and emphysema due to alpha-1 antitrypsin deficiency (AATD) are the first and fourth indicati... more COPD and emphysema due to alpha-1 antitrypsin deficiency (AATD) are the first and fourth indications for lung transplantation worldwide, respectively. Despite this, there is little information regarding the health status of these patients at the time of transplantation. Patients who received a lung transplant in the Hospital Vall d'Hebron between July 1993 and August 2013 were identified and data from the evaluation prior to the transplant were collected. A total of 217 patients who received a lung transplant for COPD and 19 in whom the indication was AATD were included. These patients were severely impaired at the time of the evaluation for lung transplantation, although the trend in recent years has been to evaluate patients at earlier stages of the disease. Baseline characteristics were similar in both groups except that patients with AATD were younger [43 (7.7) vs. 53.6 (6.1) years old, P<.001], with less exposure to tobacco [23.9 (15) vs. 50 (29) packs-year, P<002] an...
Direct delivery of amphotericin B (AMB) to the respiratory tract may be an alternative to intrave... more Direct delivery of amphotericin B (AMB) to the respiratory tract may be an alternative to intravenous administration. The use of inhalation allows high AMB concentrations to be achieved at the site of infection. A reversed-phase high-performance liquid chromatographic method with a 30-mm-long column is described for assaying AMB in respiratory secretions obtained by bronchoaspiration (BAS) and bronchoalveolar lavage (BAL). Sample clean-up involved treatment with methanol (BAS) and solid-phase extraction onto Sep-Pak C18 cartridges (BAL). The mobile phase consisted of 2.5 mM Na2EDTA-acetonitrile (70:30, v/v). The retention time of AMB was 1.5 min. The range of the assay was from 0.1 to 5 micrograms/ml. The mean recovery was over 90% for both fluids. Within-day and between-day RSDs ranged from 3.10 to 11.87%. AMB in the BAS samples was stable for two days at 20-25 degrees C and for three months at -20 degrees C. The drug in the BAL fluid was stable for one day at 20-25 degrees C, seven days at 4 degrees C and for one month at -20 degrees C.
BACKGROUND Clinical data of patients with Langerhans cell histiocytosis are well established, alt... more BACKGROUND Clinical data of patients with Langerhans cell histiocytosis are well established, although new diagnostic methods and specially long term evolution of the disease with lung involvement are not well-known. METHODS In all cases, patients were diagnosed by means of pathologic study of the lung samples, either by transbronchial biopsy in 7 patients, or by surgical lung biopsy in 8 patients. Six patients were diagnosed by bone biopsy. Other patients were diagnosed by bronchoalveolar lavage (BAL). In 4 patients, who underwent BAL, the study of antibodies CD1 (CD1a) was positive (> 5%). Lymphocytopenia was detected in 28% of patients, whereas no decrease in delayed cutaneous hypersensitivity tests was detected in any of them. After a follow-up study of 12.8 years (range: 4-22 years), 7 patients had dead, 6 patients showed severe lung involvement and other 5 patients did not have lung affection. CONCLUSIONS The diagnosis of Langerhans cell histiocytosis has improved by detect...
Molecular evidence has linked the pathophysiology of lymphangioleiomyomatosis (LAM) to that of me... more Molecular evidence has linked the pathophysiology of lymphangioleiomyomatosis (LAM) to that of metastatic breast cancer. Following on this observation, we assessed the association between LAM and subsequent breast cancer. An epidemiological study was carried out using three LAM country cohorts, from Japan, Spain, and the United Kingdom. The number of incident breast cancer cases observed in these cohorts was compared with the number expected on the basis of the country-specific incidence rates for the period 2000-2014. Immunohistochemical studies and exome sequence analysis were performed in two and one tumors, respectively. All cohorts revealed breast cancer standardized incidence ratios (SIRs) ≥ 2.25. The combined analysis of all cases or restricted to pre-menopausal age groups revealed significantly higher incidence of breast cancer: SIR = 2.81, 95 % confidence interval (CI) = 1.32-5.57, P = 0.009; and SIR = 4.88, 95 % CI = 2.29-9.99, P = 0.0007, respectively. Immunohistochemical...
Lymphangioleiomyomatosis (LAM) is a rare lung-metastasizing neoplasm caused by the proliferation ... more Lymphangioleiomyomatosis (LAM) is a rare lung-metastasizing neoplasm caused by the proliferation of smooth muscle-like cells that commonly carry loss-of-function mutations in either the tuberous sclerosis complex 1 or 2 (TSC1 or TSC2) genes. While allosteric inhibition of the mechanistic target of rapamycin (mTOR) has shown substantial clinical benefit, complementary therapies are required to improve response and/or to treat specific patients. However, there is a lack of LAM biomarkers that could potentially be used to monitor the disease and to develop other targeted therapies. We hypothesized that the mediators of cancer metastasis to lung, particularly in breast cancer, also play a relevant role in LAM. Analyses across independent breast cancer datasets revealed associations between low TSC1/2 expression, altered mTOR complex 1 (mTORC1) pathway signaling, and metastasis to lung. Subsequently, immunohistochemical analyses of 23 LAM lesions revealed positivity in all cases for the ...
The aim is to correlate pulmonary arterial (PA) remodeling estimated by PA fibrosis in PA hyperte... more The aim is to correlate pulmonary arterial (PA) remodeling estimated by PA fibrosis in PA hypertension (PAH) with clinical follow-up. Histology of PA specimens is also performed. 19 patients, aged 54±16 (4 men), functional class II-III were studied with right heart catheterization, PA Intravascular Ultrasound and optical coherence tomography (OCT) in inferior lobe segment. PA wall fibrosis was obtained by OCT ( area of fibrosis/PA cross sectional area × 100). Patients follow-up was blind to OCT. Events were defined as mortality, lung transplantation, need of intravenous prostaglandins or onset of right ventricular failure. OCT measurements showed high intra- and interobserver agreement. There was a good correlation between OCT and histology in PA fibrosis from explanted lungs. Area of fibrosis was 1.4±0.8 mm(2), % fibrosis was 22.3±8. Follow-up was 3.5 years (2.5-4.5). OCT %Fib was significantly correlated with PA capacitance (r=-0.536) and with pulmonary vascular rsistance (r=0.55)...
COPD and emphysema due to alpha-1 antitrypsin deficiency (AATD) are the first and fourth indicati... more COPD and emphysema due to alpha-1 antitrypsin deficiency (AATD) are the first and fourth indications for lung transplantation worldwide, respectively. Despite this, there is little information regarding the health status of these patients at the time of transplantation. Patients who received a lung transplant in the Hospital Vall d'Hebron between July 1993 and August 2013 were identified and data from the evaluation prior to the transplant were collected. A total of 217 patients who received a lung transplant for COPD and 19 in whom the indication was AATD were included. These patients were severely impaired at the time of the evaluation for lung transplantation, although the trend in recent years has been to evaluate patients at earlier stages of the disease. Baseline characteristics were similar in both groups except that patients with AATD were younger [43 (7.7) vs. 53.6 (6.1) years old, P<.001], with less exposure to tobacco [23.9 (15) vs. 50 (29) packs-year, P<002] an...
Direct delivery of amphotericin B (AMB) to the respiratory tract may be an alternative to intrave... more Direct delivery of amphotericin B (AMB) to the respiratory tract may be an alternative to intravenous administration. The use of inhalation allows high AMB concentrations to be achieved at the site of infection. A reversed-phase high-performance liquid chromatographic method with a 30-mm-long column is described for assaying AMB in respiratory secretions obtained by bronchoaspiration (BAS) and bronchoalveolar lavage (BAL). Sample clean-up involved treatment with methanol (BAS) and solid-phase extraction onto Sep-Pak C18 cartridges (BAL). The mobile phase consisted of 2.5 mM Na2EDTA-acetonitrile (70:30, v/v). The retention time of AMB was 1.5 min. The range of the assay was from 0.1 to 5 micrograms/ml. The mean recovery was over 90% for both fluids. Within-day and between-day RSDs ranged from 3.10 to 11.87%. AMB in the BAS samples was stable for two days at 20-25 degrees C and for three months at -20 degrees C. The drug in the BAL fluid was stable for one day at 20-25 degrees C, seven days at 4 degrees C and for one month at -20 degrees C.
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Papers by Antonio Román