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BACKGROUND: The clinical pulmonary manifestations and genetic features of Birt-Hogg-Dubé syndrome (BHDS) in Asian patients remained unclear. We aimed to clarify the clinical features of BHDS-associated pneumothorax (PTX) and retrospectively investigate potential contributing factors in the largest Asian cohort to date. METHODS: We reviewed the clinical and genetic data collected in 2006-2017, from the BHDS patients who were Asian and presented with pulmonary cysts with or without a history of PTX. RESULTS: Data from 334 (41.3% males; 58.7% females) patients from 297 unrelated families were reviewed. Among them, 314 (94.0%) patients developed PTX. The median age at the first occurrence of PTX was 32 years, which was significantly lower in males (P = 0.003) and patients without notable skin manifestations (P < 0.001). Seventy-six (24.2%) patients experienced their first PTX episode before the age of 25 years. PTX simultaneously occurred in the bilateral lungs of 37 (11.8%) patients. Among 149 patients who had their first PTX episode at least 10 years before BHDS diagnosis, PTX occurred more frequently in males (P = 0.030) and light smokers than in nonsmokers (P = 0.014). The occurrence of PTX peaked in the early 30s and gradually decreased with age but remained high in females (P = 0.001). We identified 70 unique FLCN germline variants, including duplications (46.4%), substitutions (7.1%), insertions/deletions (30.0%), and variants affecting splicing (12.5%). Approximately 80% of Asian patients suspected of having BHDS could be genetically diagnosed by examining FLCN exons 7, 9, 11, 12, and 13. No apparent genotype-phenotype correlation regarding pulmonary manifestations was identified. CONCLUSIONS: Our findings indicate that sex, smoking history, and skin manifestations at BHDS diagnosis significantly influence the clinical features of BHDS-associated PTX. These findings may contribute to the appropriate management and treatment of BHDS-associated PTX.
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Síndrome de Birt-Hogg-Dubé , Quistes , Enfermedades Pulmonares , Neumotórax , Humanos , Masculino , Femenino , Neumotórax/genética , Neumotórax/diagnóstico , Síndrome de Birt-Hogg-Dubé/genética , Estudios Retrospectivos , Enfermedades Pulmonares/diagnóstico , Quistes/genéticaRESUMEN
Background: Robotic-assisted thoracic surgery (RATS) has gained increasing interest in recent years, with most procedures performed using the conventional multiportal approach. Uniportal RATS (URATS) approaches have recently been reported in the pursuit of minimally invasive procedures. However, URATS requires specific skills. Herein, we introduce dual-portal RATS (DRATS) performed with two incisions. Methods: Data of DRATS procedures performed from December 2022 to May 2023 were retrospectively reviewed. Twenty patients with lung cancer underwent anatomical lung resections via DRATS performed by our group at three institutes. Results: Among 20 cases of planned DRATS for anatomical pulmonary resections, there were no conversions to thoracotomy and no need for extra ports. The mean surgery time was 121±60 minutes and mean console time was 91±47 minutes. The mean intraoperative blood loss volume was 9.6±12.1 g. The mean duration of chest tube drainage and hospital stay were 2±1 and 5±2 days, respectively. The mean numerical rating scale for pain was 2±1 on the first postoperative day, 1±1 on the third day, and 1±1 at discharge. There were no postoperative complications or mortalities. Conclusions: Our primary experience shows that DRATS is safe and feasible for anatomical lung resection. We consider DRATS to be a very good preliminary step in the future transition to URATS.
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A male patient in his 60s at the time of the first medical examination had a smoking history of 50 years with 25 cigarettes a day. He was diagnosed with double urothelial cancers. In 200a, total left pelvic ureterectomy(pT2N0M0, Stage â ¡)and transurethral bladder tumorectomy(pTisN0M0, Stage â )were performed. For his gastric cancer with malignant pleural effusion(cT3N0M1, Stage â £b), in 200a plus 2, downstaging was acquired after chemotherapy. In 200a plus 5, subtotal gastrectomy D1 dissection was performed(W/D adenocarcinoma, pT2N0M0, Stage â A, Ef 1). For the first lung cancer, in 200a plus 5, thoracoscopic lung wedge resection of the left lower lobe was performed(P/D adenocarcinoma, pT1aN0M0, Stage â A1, R0, Ef 1). For the second lung cancer, in 200a plus 13, thoracoscopic lung wedge resection of the right upper lobe was performed after chemotherapy(P/D adenocarcinoma, pT1bN0M0, Stage â A2, R0). For the third lung cancer, in 200a plus 17, immunotherapy was performed for the left upper lobe lung cancer(P/D adenocarcinoma, cT3N1M1a, Stage â ¢A). All the cancers were diagnosed as primary lesions by immunohistological examination. For the metachronous multiple cancers, multidisciplinary treatment was necessary for each cancer considering the patient's physical condition. Moreover, strict follow-up was necessary because of the high risk of carcinogenesis.
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Adenocarcinoma , Neoplasias Pulmonares , Neoplasias Gástricas , Neoplasias de la Vejiga Urinaria , Humanos , Masculino , Adenocarcinoma/cirugía , Pulmón/patología , Neoplasias Pulmonares/tratamiento farmacológico , Factor 1 de Elongación Peptídica/uso terapéutico , Neoplasias Gástricas/tratamiento farmacológico , Neoplasias Gástricas/cirugía , Neoplasias de la Vejiga Urinaria/cirugía , Persona de Mediana Edad , AncianoRESUMEN
Birt-Hogg-Dubé syndrome (BHDS), an autosomal dominant inheritance disease caused by folliculin (FLCN) mutations, is associated with lung cysts and spontaneous pneumothorax. The possibility of FLCN haploinsufficiency in pleural mesothelial cells (PMCs) contributing to development of pneumothorax has not yet been clarified. Electron microscopy revealed exposed intercellular boundaries between PMCs on visceral pleura and decreased electron density around the adherens junctions in BHDS. To characterize cellular function of PMCs in BHDS patients (BHDS-PMCs), during surgery for pneumothorax, we established the flow cytometry-based methods of isolating high-purity PMCs from pleural lavage fluid. BHDS-PMCs showed impaired cell attachment and a significant decrease in proliferation and migration, but a significant increase in apoptosis compared with PMCs from primary spontaneous pneumothorax (PSP) patients (PSP-PMCs). Microarray analysis using isolated PMCs revealed a significant alteration in the expression of genes belonging to Gene Ontology terms "cell-cell adhesion junction" and "cell adhesion molecule binding". Gene set enrichment analysis demonstrated that CDH1, encoding E-cadherin, was identified in the down-regulated leading edge of a plot in BHDS-PMCs. AMPK and LKB1 activation were significantly impaired in BHDS-PMCs compared with PSP-PMCs. Our findings indicate that FLCN haploinsufficiency may affect the E-cadherin-LKB1-AMPK axis and lead to abnormal cellular function in BHDS-PMCs.
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Síndrome de Birt-Hogg-Dubé/patología , Líquido del Lavado Bronquioalveolar/citología , Haploinsuficiencia , Pleura/citología , Proteínas Proto-Oncogénicas/genética , Proteínas Supresoras de Tumor/genética , Adulto , Apoptosis , Síndrome de Birt-Hogg-Dubé/genética , Movimiento Celular , Proliferación Celular , Células Epiteliales/citología , Células Epiteliales/metabolismo , Femenino , Perfilación de la Expresión Génica , Regulación de la Expresión Génica , Humanos , Masculino , Microscopía Electrónica , Persona de Mediana Edad , Análisis de Secuencia por Matrices de Oligonucleótidos , Pleura/patología , Cultivo Primario de Células , Adulto JovenRESUMEN
Lymphangioleiomyomatosis (LAM) is a rare pulmonary disease characterised by the proliferation of smooth muscle-like cells (LAM cells), and an abundance of lymphatic vessels in LAM lesions. Studies reported that vascular endothelial growth factor-D (VEGF-D) secreted by LAM cells contributes to LAM-associated lymphangiogenesis, however, the precise mechanisms of lymphangiogenesis and characteristics of lymphatic endothelial cells (LECs) in LAM lesions have not yet been elucidated. In this study, human primary-cultured LECs were obtained both from LAM-affected lung tissues (LAM-LECs) and normal lung tissues (control LECs) using fluorescence-activated cell sorting (FACS). We found that LAM-LECs had significantly higher ability of proliferation and migration compared to control LECs. VEGF-D significantly promoted migration of LECs but not proliferation of LECs in vitro. cDNA microarray and FACS analysis revealed the expression of vascular endothelial growth factor receptor (VEGFR)-3 and integrin α9 were elevated in LAM-LECs. Inhibition of VEGFR-3 suppressed proliferation and migration of LECs, and blockade of integrin α9 reduced VEGF-D-induced migration of LECs. Our data uncovered the distinct features of LAM-associated LECs, increased proliferation and migration, which may be due to higher expression of VEGFR-3 and integrin α9. Furthermore, we also found VEGF-D/VEGFR-3 and VEGF-D/ integrin α9 signaling play an important role in LAM-associated lymphangiogenesis.
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Movimiento Celular , Proliferación Celular , Células Endoteliales/patología , Linfangioleiomiomatosis/patología , Adulto , Células Endoteliales/metabolismo , Femenino , Humanos , Cadenas alfa de Integrinas/metabolismo , Linfangioleiomiomatosis/metabolismo , Masculino , Persona de Mediana Edad , Transducción de Señal , Factor D de Crecimiento Endotelial Vascular/metabolismo , Receptor 3 de Factores de Crecimiento Endotelial Vascular/metabolismoRESUMEN
Lymphangioleiomyomatosis (LAM) is a rare destructive lung disease characterized by multiple thin-walled pulmonary cysts. The currently proposed diagnostic algorithm emphasizes the characteristic cystic appearance on high-resolution computed tomography (HRCT) so uncommon HRCT appearances present challenges to establishing the proper LAM diagnosis. The objective of this study is to accrue uncommon chest HRCT appearances, determine frequencies in both tuberous sclerosis complex (TSC)-associated LAM (TSC-LAM) and sporadic LAM (S-LAM) patients. 311 females referred to our hospital, including 272 S-LAM patients (mean age 39.2 years) and 39 TSC-LAM patients (mean age 38.3 years), were retrospectively evaluated. We found 2 types of radiologic findings likely to make HRCT cyst appearance atypical: characteristics of the cyst itself and uncommon findings in addition to cysts. We found that approximately 80% of LAM patients, whether TSC-associated or sporadic, showed typical HRCT appearance with mild to severe cystic destruction. The remaining 20% displayed unusual profiles in cyst appearance as well as additional findings aside from cyst: the former includes large cyst, thickened walls, and irregularly shaped whereas the latter includes ground glass attenuation and diffuse noncalcified nodules. It is important to be aware of various radiologic findings that make HRCT cystic appearance atypical of LAM.
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Neoplasias Pulmonares/diagnóstico , Pulmón/diagnóstico por imagen , Linfangioleiomiomatosis/diagnóstico , Esclerosis Tuberosa/complicaciones , Adulto , Anciano , Femenino , Humanos , Neoplasias Pulmonares/etiología , Linfangioleiomiomatosis/etiología , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Tomografía Computarizada por Rayos X , Adulto JovenRESUMEN
PURPOSE: To establish a method for quantitatively estimating the extent of the communication between the cyst and the airway in cystic lung diseases (CLDs) and evaluate its diagnostic utility in differentiating among CLDs. MATERIALS AND METHODS: Seventy-one patients (mean age, 49.9 years; age range, 25-79 years) with CLDs who underwent paired inspiratory and expiratory CT between July 2015 and July 2018 were enrolled in this prospective study. Participants were divided into three groups based on their diagnosis: Birt-Hogg-Dubé syndrome (BHDS) group (15 participants), lymphangioleiomyomatosis (LAM) group (43 participants), and other diseases (OT) group (13 participants). Total lung volume (TLV) and low-attenuation area volume (LAAV) were calculated at inspiration and expiration. The collapsibility of the LAAV was determined as the expiration-to-inspiration (E/I) ratio of LAAV (E/I ratio LAAV). The cyst-airway communicating index (CACI), the ratio of the LAAV change between inspiration and expiration to the TLV change between inspiration and expiration, was also determined. Receiver operating characteristic (ROC) analysis was used to evaluate the diagnostic utility for differentiating diseases. RESULTS: The E/I ratio LAAV was significantly higher in the BHDS group (0.69; 95% confidence interval [CI]: 0.61, 0.78) than in the LAM (0.33; 95% CI: 0.28, 0.38) (P < .001) and the OT (0.51; 95% CI: 0.38, 0.64) (P = .038) groups. The CACI was significantly lower in the BHDS group (0.89; 95% CI: 0.61, 1.17) than in the LAM (1.89; 95% CI: 1.76, 2.0) (P < .001) and the OT (1.539; 95% CI: 1.21, 1.86) (P = .003) groups. There was no significant difference in the area under the ROC curve of the CACI (0.881; 95% CI: 0.7749, 0.987) and the E/I ratio LAAV (0.877; 95% CI: 0.791, 0.963) for differentiating BHDS from other diseases. CONCLUSION: Quantitative analysis using paired inspiratory and expiratory CT for estimating the extent of cyst-airway communication in CLDs is useful when distinguishing BHDS from other diseases.Supplemental material is available for this article.© RSNA, 2020See also the commentary by Chung in this issue.
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AIM: To review the clinical features of the patient with cystic pulmonary light chain deposition disease(LCDD)and record high-resolution CT and histopathological findings. PATIENT: A 60-year-old woman who diagnosed multiple myeloma was admitted. There were diffuse proliferation of plasma cells by the bone marrow puncture that she received. And multiple cystic pulmonary tumors found in CT. We analyzed the method and result of the diagnosis. CT showed multiple cystic pulmonary tumors in the both lung which vessels traversing the cysts with thin wall ranged 5 to 30 millimeters. There were no abnormality in the heart, kidney and liver. Right upper lobe wedge resection was performed via video-assisted thoracic surgery( VATS)to establish a definitive diagnosis. Thoracoscopic findings revealed multiple white oval formed tumors in the visceral pleura. Histological HE staining findings of the surgical specimen revealed amyloid-like acidophilic material, and the immunohistochemical Congo red staining revealed monoclonal IgG with a kappa component. According to the above results these tumors had a diagnosis of pulmonary LCDD. CONCLUSION: VATS was effective to diagnose pulmonary LCDD in multiple cysts formation.
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Quistes , Neoplasias Pulmonares , Mieloma Múltiple , Quistes/cirugía , Femenino , Humanos , Pulmón , Neoplasias Pulmonares/diagnóstico , Persona de Mediana Edad , Cirugía Torácica Asistida por VideoRESUMEN
BACKGROUND: Birt-Hogg-Dubé syndrome (BHDS) is a recently recognized inherited multiple cystic lung disease causing recurrent pneumothoraces. Similarly to the lesions in patients with lymphangioleiomyomatosis (LAM), the pulmonary cysts are innumerable and widely dispersed and cannot all be removed. We recently described a total pleural covering (TPC) that covers the entire visceral pleura with oxidized regenerated cellulose (ORC) mesh. TPC successfully prevented the recurrence of pneumothorax in LAM patients. The purpose of this study was to evaluate the effect of an ORC pleural covering on pneumothorax recurrence in BHDS patients. RESULTS: This retrospective study enrolled a total of 81 pneumothorax patients with the diagnosis of BHDS who underwent 90 covering surgeries from January 2010 to August 2017 at Tamagawa Hospital. During the first half of the study period, a lower pleural covering (LPC) which covered the affected area with ORC mesh was mainly used to treat 38 pneumothoraces. During the second half of the study period, TPC was primarily performed for 52 pneumothoraces. All the thoracoscopic surgeries were successfully performed without serious complications (≥ Clavien-Dindo grade III). The median follow-up periods after LPC/TPC were 66/34 months, respectively. Pneumothorax recurrence rates after LPC at 2.5/5/7.5 years postoperatively were 5.4/12/42%, respectively; none of the patients who had underwent TPC developed postoperative pneumothorax recurrence (P = 0.032). CONCLUSIONS: TPC might be an effective option for surgical treatment of intractable pneumothorax in patients with BHDS.
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Síndrome de Birt-Hogg-Dubé/cirugía , Celulosa/química , Neumotórax/cirugía , Mallas Quirúrgicas , Fibrosis Quística/cirugía , Humanos , Pleura/cirugía , Estudios RetrospectivosRESUMEN
BACKGROUND AND OBJECTIVE: Birt-Hogg-Dubé syndrome (BHDS) is a rare hereditary disease that presents with multiple lung cysts and pneumothorax (PTX). Although some reports propose that findings from chest computed tomography enable one to distinguish BHDS from primary spontaneous pneumothorax (PSP), it is still unclear whether clinical features are useful for identifying patients with suspicion of BHDS from those with PTX. METHODS: We retrospectively reviewed the medical records of patients with PTX who underwent video-assisted thoracoscopic surgery at Nissan Tamagawa Hospital from January 2012 to December 2015. RESULTS: We identified a total of 1141 patients with PTX, including 54 with BHDS and 517 with PSP. Among them, logistic regression analysis segregated five features that were significantly associated with BHDS: familial history of PTX, past history of bilateral PTX, age at the first episode of PTX (≥25 years old (y.o.)), body mass index (≥18.5) and gender (female). We assigned scores of 3, 3, 2, 2 and 1 to the five features, respectively, to establish a system with a calculated score from 0 to 11. The cut-off value of a calculated score ≥ 4 yielded the highest sensitivity of 93% and specificity of 86%. Receiver operating characteristic (ROC) analysis showed the area under the curve reflecting an accuracy of this diagnostic test as 0.953. CONCLUSION: BHDS has several clinical features distinct from PSP. Our scoring system consists of only five clinical variables that are easily evaluated and efficiently separate BHDS patients from those who have PTX without relying on an imaging study. Further prospective study is needed to confirm our findings.
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Síndrome de Birt-Hogg-Dubé/diagnóstico , Neumotórax/diagnóstico , Adolescente , Adulto , Edad de Inicio , Anciano , Área Bajo la Curva , Síndrome de Birt-Hogg-Dubé/diagnóstico por imagen , Índice de Masa Corporal , Quistes/diagnóstico por imagen , Diagnóstico Diferencial , Femenino , Humanos , Enfermedades Pulmonares/complicaciones , Masculino , Persona de Mediana Edad , Neumotórax/diagnóstico por imagen , Neumotórax/genética , Curva ROC , Recurrencia , Estudios Retrospectivos , Factores Sexuales , Tomografía Computarizada por Rayos X , Adulto JovenRESUMEN
BACKGROUND: Birt-Hogg-Dubé syndrome (BHDS) (OMIM #135150) is an autosomal dominant disease, characterized by fibrofolliculomas (FFs) of the skin, pulmonary cysts with/without pneumothorax, and renal tumors. The prevalence of skin manifestations reported for Japanese BHDS patients is lower (<30%) compared with that of Western countries (75â¼90%), which appear to be underestimated. OBJECTIVE: To precisely examine the prevalence of skin lesions with dermoscopy and histopathology with reference to genetic analyses. METHODS: We studied 31 patients (47.0±13.2years old, range 15-71) consisting of 26 unrelated families consecutively from May 2013 to June 2015 specifically for skin-colored papules on their faces and cervicothoracic regions. Patients initially suspected of BHDS from multiple pulmonary cysts that resulted in pneumothorax (30/31; 96.8%) received dermoscopic examinations and skin biopsies if applicable. The diagnosis of BHDS was established by folliculin (FLCN) genetic testing, and the results were compared to the histopathological findings of FFs or trichodiscomas (TDs). RESULTS: FLCN germline mutation was demonstrated in 25/26 (96.2%) unrelated families tested and 28/29 patients (96.6%) tested. Skin lesions were recognized in 26/31 patients (83.9%); skin biopsies were performed in 23 patients of whom FFs and/or TDs were histologically demonstrated in 17 (73.9%). Although our study population included patients whose skin manifestations were evaluated prior to or after FLCN genetic testing, skin lesions were clearly prevalent and recognizable irrespective of whether genetic testing was or wasn't done. When examined with dermoscopy, distinct FFs appeared as well-demarcated areas of pallor with central follicular openings in 13 of 15 FF-bearing patients (86.7%); however, those manifestations were not recognized for TD. CONCLUSIONS: Skin lesions appear to be more prevalent than previously reported (<30% vs.73.9%) in Japanese BHDS patients. Dermoscopy is a useful diagnostic aid for finding FFs.
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Síndrome de Birt-Hogg-Dubé/patología , Quistes/patología , Dermoscopía/métodos , Neoplasias Pulmonares/patología , Neoplasias Cutáneas/diagnóstico por imagen , Adolescente , Adulto , Factores de Edad , Anciano , Biopsia , Síndrome de Birt-Hogg-Dubé/diagnóstico por imagen , Síndrome de Birt-Hogg-Dubé/genética , Quistes/diagnóstico por imagen , Quistes/genética , Femenino , Mutación de Línea Germinal , Humanos , Pulmón/patología , Neoplasias Pulmonares/diagnóstico por imagen , Neoplasias Pulmonares/genética , Masculino , Persona de Mediana Edad , Neumotórax/diagnóstico por imagen , Neumotórax/genética , Neumotórax/patología , Proteínas Proto-Oncogénicas/genética , Piel/diagnóstico por imagen , Piel/patología , Neoplasias Cutáneas/genética , Neoplasias Cutáneas/patología , Tomografía Computarizada por Rayos X , Proteínas Supresoras de Tumor/genética , Adulto JovenRESUMEN
PURPOSE: The pleural covering technique, i.e., wrapping a part of or the entire surface of the lung with oxidized regenerative cellulose (ORC), reinforces visceral pleura through pleural thickening for patients with pneumothorax and cystic lung diseases. However, it remains undetermined how ORC induces pleural thickening. METHODS: A histopathological examination was performed for lung specimens from patients who had recurrent pneumothoraces after pleural covering and re-operation (n = 5). To evaluate the influence of ORC on the pleura in vitro, we used MeT-5A cells (a human pleural mesothelial cell line). RESULTS: Pleural thickening was confirmed in all lung specimens examined. Three months after covering, the thickened pleura showed inflammatory cell infiltration, proliferation of myofibroblasts, and expression of fibronectin and TGF-ß. However, after 1 year, those findings virtually disappeared, and the thickened pleura was composed mainly of abundant collagen. When MeT-5A cells were cultured in ORC-immersed medium, their morphology changed from a cobblestone to spindle-shaped appearance. The expression of E-cadherin decreased, whereas that of N-cadherin, α-smooth muscle actin, and fibronectin increased, suggesting mesothelial-mesenchymal transition (Meso-MT). CONCLUSIONS: Our results suggest that Meso-MT may be involved as a mechanism of pleural thickening induced by pleural covering with ORC.
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Celulosa Oxidada , Transición Epitelial-Mesenquimal , Pleura/patología , Neumotórax/cirugía , Mallas Quirúrgicas , Procedimientos Quirúrgicos Torácicos/métodos , Actinas/metabolismo , Adolescente , Adulto , Cadherinas/metabolismo , Línea Celular , Medios de Cultivo , Células Epiteliales/metabolismo , Células Epiteliales/patología , Fibronectinas/metabolismo , Humanos , Masculino , Pleura/citología , Pleura/metabolismo , Recurrencia , Reoperación , Estudios Retrospectivos , Adulto JovenRESUMEN
Catamenial pneumothorax (CP) is generally caused by intraperitoneal air leaking from the uterus into the thoracic cavity via a defect in the endometrial tissue of the diaphragm and is usually detected in the right thorax. We report a case of left-sided CP caused by endometriosis in the visceral pleura and with no abnormal findings in the diaphragm. A 33-year-old female patient presented at the end of a course of low-dose contraceptive pills for pelvic endometriosis, with spontaneous pneumothorax in the left chest. Chest CT revealed a bulla in the left upper lung lobe. The patient underwent partial resection of the lung. Immunohistochemistry confirmed the presence of endometrial stromal tissue in the visceral pleura and confirmed this as the cause of pneumothorax since there were no observable abnormalities in the diaphragm. This case suggests that immunohistochemical examination of patients with spontaneous pneumothorax can detect alternative endometrial lesions.
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Vesícula/complicaciones , Endometriosis/complicaciones , Neumotórax/complicaciones , Neumotórax/etiología , Alveolos Pulmonares , Enfermedades Torácicas/complicaciones , Adulto , Biopsia , Vesícula/diagnóstico por imagen , Vesícula/cirugía , Endometriosis/diagnóstico por imagen , Endometriosis/cirugía , Femenino , Humanos , Inmunohistoquímica , Neumonectomía , Neumotórax/diagnóstico por imagen , Neumotórax/cirugía , Alveolos Pulmonares/diagnóstico por imagen , Alveolos Pulmonares/cirugía , Enfermedades Torácicas/diagnóstico por imagen , Enfermedades Torácicas/cirugía , Tomografía Computarizada por Rayos X , Resultado del TratamientoRESUMEN
Birt-Hogg-Dubé syndrome (BHDS) is an autosomal dominant inherited disorder caused by germline mutations in the FLCN gene, and characterized by skin fibrofolliculomas, multiple lung cysts, spontaneous pneumothorax, and renal neoplasms. Pulmonary manifestations frequently develop earlier than other organ involvements, prompting a diagnosis of BHDS However, the mechanism of lung cyst formation and pathogenesis of pneumothorax have not yet been clarified. Fibroblasts were isolated from lung tissues obtained from patients with BHDS (n = 12) and lung cancer (n = 10) as controls. The functional abilities of these lung fibroblasts were evaluated by the tests for chemotaxis to fibronectin and three-dimensional (3-D) gel contraction. Fibroblasts from BHDS patients showed diminished chemotaxis as compared with fibroblasts from controls. Expression of fibronectin and TGF-ß1 was significantly reduced in BHDS fibroblasts when assessed by qPCR Addition of TGF-ß1 in culture medium of BHDS lung fibroblasts significantly restored these cells' abilities of chemotaxis and gel contraction. Human fetal lung fibroblasts (HFL-1) exhibited reduced chemotaxis and 3-D gel contraction when FLCN expression was knocked down. To the contrary, a significant increase in chemotactic activity toward to fibronectin was demonstrated when wild-type FLCN was overexpressed, whereas transduction of mutant FLCN showed no effect on chemotaxis. Our results suggest that FLCN is associated with chemotaxis in lung fibroblasts. Together with reduced TGF-ß1 expression by BHDS lung fibroblasts, a state of FLCN haploinsufficiency may cause lung fibroblast dysfunction, thereby impairing tissue repair. These may reveal one mechanism of lung cyst formation and pneumothorax in BHDS patients.
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Síndrome de Birt-Hogg-Dubé/genética , Fibroblastos/metabolismo , Haploinsuficiencia/genética , Pulmón/metabolismo , Proteínas Proto-Oncogénicas/metabolismo , Proteínas Supresoras de Tumor/metabolismo , Adulto , Síndrome de Birt-Hogg-Dubé/patología , Quimiotaxis/fisiología , Quistes/patología , Femenino , Fibroblastos/patología , Mutación de Línea Germinal , Humanos , Pulmón/patología , Enfermedades Pulmonares/diagnóstico , Enfermedades Pulmonares/genética , Masculino , Microscopía Confocal/métodos , Persona de Mediana Edad , Neumotórax/diagnóstico , Neumotórax/genética , Neumotórax/cirugía , Proteínas Proto-Oncogénicas/genética , Piel/patología , Enfermedades de la Piel/diagnóstico , Enfermedades de la Piel/genética , Factor de Crecimiento Transformador beta1/metabolismo , Proteínas Supresoras de Tumor/genéticaRESUMEN
BACKGROUND: Spontaneous pneumothorax is a major and frequently recurrent complication of lymphangioleiomyomatosis (LAM). Despite the customary use of pleurodesis to manage pnenumothorax, the recurrence rate remains high, and accompanying pleural adhesions cause serious bleeding during subsequent lung transplantation. Therefore, we have developed a technique of total pleural covering (TPC) for LAM to wrap the entire visceral pleura with sheets of oxidized regenerated cellulose (ORC) mesh, thereby reinforcing the affected visceral pleura and preventing recurrence. METHODS: Since January 2003, TPC has been applied during video-assisted thoracoscopic surgery for the treatment of LAM. The medical records of LAM patients who had TPC since that time and until August 2014 are reviewed. RESULTS: TPC was performed in 43 LAM patients (54 hemithoraces), 11 of whom required TPC bilaterally. Pneumothorax recurred in 14 hemithoraces (25.9%) from 11 patients (25.6%) after TPC. Kaplan-Meier estimates of recurrence-free hemithorax were 80.8% at 2.5 years, 71.7% at 5 years, 71.7% at 7.5 years, and 61.4% at 9 years. The recurrence-free probability was significantly better when 10 or more sheets of ORC mesh were utilized for TPC (P = 0.0018). TPC significantly reduced the frequency of pneumothorax: 0.544 ± 0.606 episode/month (mean ± SD) before TPC vs. 0.008 ± 0.019 after TPC (P<0.0001). Grade IIIa postoperative complications were found in 13 TPC surgeries (24.1%). CONCLUSIONS: TPC successfully prevented the recurrence of pneumothorax in LAM, was minimally invasive and rarely caused restrictive ventilatory impairment.
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Lymphangioleiomyomatosis (LAM) is a rare neoplastic disease entailing cystic destruction of the lungs and progressive respiratory failure. LAM lungs are histologically characterized by the proliferation of smooth muscle-like cells (LAM cells) and an abundance of lymphatic vessels. To elucidate the pathophysiological processes of LAM, cell-type-specific analyses are required. However, no method exists for isolating the individual types of cells in LAM lesions. Therefore, we established a fluorescence-activated cell sorting (FACS)-based method for the direct isolation of LAM cells and other various cellular components from LAM-affected lung tissue. We obtained LAM-affected lung tissue from resections or transplant recipients and prepared single-cell suspensions. FACS, immunohistochemical, and molecular analysis were used cooperatively to isolate HMB45-positive LAM cells with tuberous sclerosis complex (TSC) 2 loss of heterozygosity (LOH). Using a combination of antibodies against an epithelial cell adhesion molecule (EpCAM) and podoplanin, we fractionated CD45-negative lung cells into three groups: lymphatic endothelial cells (LEC) (EpCAM(-)/podoplanin(hi) subset), alveolar type II cells (EpCAM(hi)/podoplanin(-) subset), and mesenchymal cells (EpCAM(-)/podoplanin(-/low) subset). During subsequent analysis of HMB45 expression, as a LAM-specific marker, we clearly identified LAM cells in the mesenchymal cell population. We then discovered that CD90(+)/CD34(-) cells in the mesenchymal cell population are not only positive for HBM45 but also had TSC2 LOH. These isolated cells were viable and subsequently amenable to cell culture. This method enables us to isolate LAM cells and other cellular components, including LAM-associated LEC, from LAM-affected lung tissues, providing new research opportunities in this field.
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Pulmón/patología , Linfangioleiomiomatosis/patología , Adulto , Antígenos CD34/metabolismo , Biomarcadores/metabolismo , Separación Celular , Forma de la Célula , Células Cultivadas , Femenino , Humanos , Receptores de Hialuranos/metabolismo , Pulmón/metabolismo , Linfangioleiomiomatosis/metabolismo , Persona de Mediana EdadRESUMEN
Birt-Hogg-Dubé syndrome (BHDS) is a rare hereditary disease that presents with multiple lung cysts and recurrent pneumothorax. These cysts occupy predominantly the lower-medial zone of the lung field adjacent to the interlobar fissure, and some of them abut peripheral pulmonary vessels. For the surgical management of pneumothorax with BHDS, the conventional approach of resecting all subpleural cysts and bullae is not feasible. Thus, after handling several bullae by using a stapler or performing ligation as a standardized treatment, we applied to a pleural covering technique to thicken the affected visceral pleura and then to prevent recurrence of pneumothorax. We herein report the successful application of a pleural covering technique via thoracoscopic surgery to treat the recurrent pneumothorax of a 30-year-old man with BHDS. This technique is promising for the management of intractable pneumothorax secondary to BHDS.
Asunto(s)
Síndrome de Birt-Hogg-Dubé/cirugía , Adhesivo de Tejido de Fibrina/uso terapéutico , Pleura/cirugía , Neumotórax/cirugía , Cirugía Torácica Asistida por Video/instrumentación , Adulto , Síndrome de Birt-Hogg-Dubé/complicaciones , Síndrome de Birt-Hogg-Dubé/diagnóstico , Humanos , Masculino , Neumotórax/diagnóstico , Neumotórax/etiología , Recurrencia , Mallas Quirúrgicas , Tomografía Computarizada por Rayos X , Resultado del TratamientoRESUMEN
BACKGROUND AND OBJECTIVE: A major pathogenic factor for catamenial pneumothorax is thoracic endometriosis. However, thoracic endometriosis-related pneumothorax (TERP) can develop as either catamenial or non-catamenial pneumothorax (CP). Therefore, the aim of this study was to elucidate the clinical differences between catamenial and non-catamenial TERP. METHODS: The clinical and pathological data in female patients who underwent video-assisted thoracoscopic surgery at the Pneumothorax Research Center during an 8-year period were retrospectively reviewed. This study included 150 female patients with surgico-pathologically confirmed TERP. The subjects were divided into two groups, those having all of the pneumothorax episodes in the catamenial period (CP group) and those who did not (non-CP group). We compared the clinical characteristics and surgico-pathological findings between these two groups. RESULTS: Of the 150 TERP patients, 55 (36.7%) were classified in the CP group, and 95 (63.3%) in the non-CP group. In regard to the locations of endometriosis, all TERP patients had diaphragmatic endometriosis, while pleural implantation was recognized in 34 of the 55 (61.8%) patients in the CP group and 42 of the 95 (44.2%) patients in the non-CP group (P < 0.05). CONCLUSIONS: A significant difference in the proportion of patients with pleural endometriosis was observed between catamenial and non-catamenial TERP. The ectopic sites of the endometriosis may be responsible for the timing of the pneumothorax episodes.
Asunto(s)
Endometriosis/complicaciones , Endometriosis/patología , Enfermedades Musculares/complicaciones , Enfermedades Pleurales/complicaciones , Neumotórax/etiología , Adulto , Diafragma , Endometriosis/cirugía , Femenino , Humanos , Menstruación , Persona de Mediana Edad , Enfermedades Musculares/patología , Enfermedades Musculares/cirugía , Enfermedades Pleurales/patología , Enfermedades Pleurales/cirugía , Estudios Retrospectivos , Cirugía Torácica Asistida por Video , Adulto JovenRESUMEN
PURPOSE: Thoracic endometriosis-related pneumothorax (TERP) is a secondary condition specific for females, but in a clinical setting, TERP often is difficult to distinguish from primary spontaneous pneumothorax (PSP) based on a relationship between the dates of pneumothorax and menstruation. The purpose of this study was to clarify the clinical features of TERP compared with PSP. METHODS: We retrospectively reviewed the clinical and histopathological files of female patients with pneumothorax who underwent video-assisted thoracoscopic surgery in the Pneumothorax Research Center during the 6-year period from January 2005 to December 2010. We analyzed the clinical differences between TERP and PSP. RESULTS: The study included a total of 393 female patients with spontaneous pneumothorax, of whom 92 (23.4 %) were diagnosed as having TERP and 33.6 % (132/393) as having PSP. We identified four factors (right-sided pneumothorax, history of pelvic endometriosis, age ≥31 years, and no smoking history) that were statistically significant for predicting TERP and assigned 6, 5, 4, and 3 points, respectively, to establish a scoring system with a calculated score from 0 to 18. The cutoff values of a calculated score ≥12 yielded the highest positive predictive value (86 %; 95 % confidence interval (CI) 81.5-90.5 %) for TERP and negative predictive value (95.2 %; 95 % CI 92.3-98 %) for PSP. CONCLUSIONS: TERP has several distinct clinical features from PSP. Our scoring system consists of only four clinical variables that are easily obtainable and enables us to suspect TERP in female patients with pneumothorax.