RESUMO
Although cytomegalovirus (CMV) viremia/DNAemia has been associated with reduced survival after lung transplantation, its association with chronic lung allograft dysfunction (CLAD) and its phenotypes is unclear. We hypothesized that, in a modern era of CMV prophylaxis, CMV DNAemia would still remain associated with death, but also represent a risk factor for CLAD and specifically restrictive allograft syndrome (RAS)/mixed phenotype. This was a single-center retrospective cohort study of all consecutive adult, first, bilateral-/single-lung transplants done between 2010-2016, consisting of 668 patients. Risks for death/retransplantation, CLAD, or RAS/mixed, were assessed by adjusted cause-specific Cox proportional-hazards models. CMV viral load (VL) was primarily modeled as a categorical variable: undetectable, detectable to 999, 1000 to 9999, and ≥10 000 IU/mL. In multivariable models, CMV VL was significantly associated with death/retransplantation (≥10 000 IU/mL: HR = 2.65 [1.78-3.94]; P < .01), but was not associated with CLAD, whereas CMV serostatus mismatch was (D+R-: HR = 2.04 [1.30-3.21]; P < .01). CMV VL was not associated with RAS/mixed in univariable analysis. Secondary analyses with a 7-level categorical or 4-level ordinal CMV VL confirmed similar results. In conclusion, CMV DNAemia is a significant risk factor for death/retransplantation, but not for CLAD or RAS/mixed. CMV serostatus mismatch may have an impact on CLAD through a pathway independent of DNAemia.
Assuntos
Infecções por Citomegalovirus , Citomegalovirus , Rejeição de Enxerto , Sobrevivência de Enxerto , Transplante de Pulmão , Complicações Pós-Operatórias , Viremia , Humanos , Transplante de Pulmão/efeitos adversos , Infecções por Citomegalovirus/virologia , Infecções por Citomegalovirus/epidemiologia , Masculino , Feminino , Estudos Retrospectivos , Pessoa de Meia-Idade , Viremia/virologia , Viremia/epidemiologia , Citomegalovirus/isolamento & purificação , Fatores de Risco , Seguimentos , Rejeição de Enxerto/etiologia , Rejeição de Enxerto/virologia , Prognóstico , Complicações Pós-Operatórias/virologia , Complicações Pós-Operatórias/epidemiologia , Adulto , Carga Viral , Taxa de Sobrevida , Transplantados/estatística & dados numéricosRESUMO
BACKGROUND: Survival after lung transplantation (LTx) is hampered by uncontrolled inflammation and alloimmunity. Regulatory T-cells (Tregs) are being studied as a cellular therapy in solid organ transplantation. Whether these systemically administered Tregs can function at the appropriate location and time is an important concern. We hypothesised that in vitro-expanded recipient-derived Tregs can be delivered to donor lungs prior to LTx via ex vivo lung perfusion (EVLP), maintaining their immunomodulatory ability. METHODS: In a rat model, Wistar Kyoto (WKy) CD4+CD25high Tregs were expanded in vitro prior to EVLP. Expanded Tregs were administered to Fisher 344 (F344) donor lungs during EVLP; left lungs were transplanted into WKy recipients. Treg localisation and function post-transplant were assessed. In a proof-of-concept experiment, cryopreserved expanded human CD4+CD25+CD127low Tregs were thawed and injected into discarded human lungs during EVLP. RESULTS: Rat Tregs entered the lung parenchyma and retained suppressive function. Expanded Tregs had no adverse effect on donor lung physiology during EVLP; lung water as measured by wet-to-dry weight ratio was reduced by Treg therapy. The administered cells remained in the graft at 3â days post-transplant where they reduced activation of intra-graft effector CD4+ T-cells; these effects were diminished by day 7. Human Tregs entered the lung parenchyma during EVLP where they expressed key immunoregulatory molecules (CTLA4+, 4-1BB+, CD39+ and CD15s+). CONCLUSIONS: Pre-transplant Treg administration can inhibit alloimmunity within the lung allograft at early time points post-transplant. Our organ-directed approach has potential for clinical translation.
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Transplante de Pulmão , Linfócitos T Reguladores , Animais , Pulmão , Transplante de Pulmão/efeitos adversos , Perfusão/efeitos adversos , Ratos , Doadores de TecidosRESUMO
Definitions for chronic lung allograft dysfunction (CLAD) phenotypes were recently revised (2019 ISHLT consensus). Post-CLAD onset phenotype transition may occur as a result of change in obstruction, restriction, or RAS-like opacities (RLO). We aimed to assess the prevalence and prognostic implications of these transitions. This was a single-center, retrospective cohort study of bilateral lung transplants performed in 2009-2015. CLAD phenotypes were determined per ISHLT guidelines. CLAD phenotype transition was defined as a sustained change in obstruction, restriction or RLO. We specifically focused on phenotype changes based on RLO emergence. Association of RLO development with time to death or retransplant were assessed using Kaplan-Meier and Cox proportional hazards models. Among 211 patients with CLAD, 47 (22.2%) experienced a phenotype transition. Nineteen patients developed RLO. Development of RLO phenotype after CLAD onset was associated with a shorter time to death/retransplant when considering the entire CLAD patient cohort (HR = 4.00, CI 2.74-5.83, P < 0.001) and also when restricting the analysis to only patients with a Non-RLO phenotype at CLAD onset (HR 9.64, CI 5.52-16.84, P < 0.0001). CLAD phenotype change based on emergence of RAS-like opacities implies a worse outcome. This highlights the clinical importance of imaging follow-up to monitor for phenotype transitions after CLAD onset.
Assuntos
Transplante de Pulmão , Disfunção Primária do Enxerto , Aloenxertos , Humanos , Pulmão , Transplante de Pulmão/efeitos adversos , Fenótipo , Disfunção Primária do Enxerto/epidemiologia , Disfunção Primária do Enxerto/etiologia , Estudos RetrospectivosRESUMO
Delayed immunological rejection after human lung transplantation causes chronic lung allograft dysfunction, which is associated with high mortality. Delayed rejection may be attributable to indirect alloantigen presentation by host antigen-presenting cells; however, its pathophysiology is not fully understood. The mitogen-activated protein kinase pathway is activated in T cells upon stimulation, and we previously showed that the MEK inhibitor, trametinib, suppresses graft-versus-host disease after murine bone marrow transplantation. We investigated whether trametinib suppresses graft rejection after two types of rat lung transplantation and analyzed its immunological mode of action. Major histocompatibility complex-mismatched transplantation from brown Norway rats into Lewis rats and minor histocompatibility antigen-mismatched transplantation from Fischer 344 rats into Lewis rats were performed. Cyclosporine (CsA) and/or trametinib were administered alone or consecutively. Acute and delayed rejection, lymphocyte infiltration, and pulmonary function were evaluated. Administration of trametinib after CsA suppressed delayed rejection, reduced inflammatory cell infiltration and fibrosis within the graft, and preserved pulmonary functions at Day 28. Trametinib suppressed functional differentiation of T and B cells in the periphery but preserved thymic T cell differentiation. Donor B cells within the graft disappeared by Day 14, indicating that delayed graft rejection at Day 28 was mainly due to indirect presentation by host antigen-presenting cells. Finally, trametinib administration without CsA preconditioning suppressed rejection after minor histocompatibility antigen-mismatched transplantation. Trametinib attenuates delayed rejection upon major histocompatibility complex-mismatched transplantation by suppressing indirect presentation and is a promising candidate to treat chronic lung allograft dysfunction in humans.
Assuntos
Rejeição de Enxerto/tratamento farmacológico , Transplante de Pulmão , Piridonas/farmacologia , Pirimidinonas/farmacologia , Animais , Ciclosporina/farmacologia , Rejeição de Enxerto/imunologia , Pulmão/efeitos dos fármacos , Transplante de Pulmão/métodos , Ratos Endogâmicos Lew , Transplante Homólogo/métodosRESUMO
Thymic epithelial tumors (TETs), encompassing thymoma and thymic carcinoma, represent a rare and heterogeneous group of thoracic malignancies with varying prognoses and treatment strategies. Surgical resection is the cornerstone of therapy for localized stages, but the management of locally advanced or unresectable TETs often involves induction therapy, including chemotherapy and/or radiation therapy, as a neoadjuvant approach aimed at downstaging the tumor to facilitate subsequent resection. This review synthesizes current knowledge on the re-evaluation process and operative indications following induction therapy for TETs, highlighting the pivotal role of accurate assessment in guiding surgical decisions and optimizing patient outcomes. Induction therapy's efficacy is contingent upon precise re-evaluation methods to accurately gauge treatment response and assess resectability post-therapy. This review discusses the various modalities employed in re-evaluation, including computed tomography (CT), magnetic resonance imaging (MRI), positron emission tomography-CT (PET-CT), and the significance of tumor markers, underlining their strengths and limitations. The adoption of modified RECIST criteria for TETs by the International Thymic Malignancy Interest Group (ITMIG) underscores the necessity for standardized assessment guidelines to ensure consistency and reliability across studies and clinical practices. Furthermore, we explore the implications of induction therapy on surgical decision-making, emphasizing the criteria for determining the suitability of patients for surgical intervention post-therapy. The review addresses the challenges and future perspectives associated with the re-evaluation process, including the potential for advanced imaging techniques and the integration of molecular and genetic markers to enhance the precision of treatment response assessment. In conclusion, the re-evaluation of TETs post-induction therapy is a complex but critical component of the multidisciplinary management approach for these patients. Standardizing re-evaluation methodologies and incorporating novel diagnostic tools could significantly improve the prognostication and treatment stratification, ultimately enhancing the therapeutic outcomes for patients with advanced TETs.
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Lung transplantation results are compromised by ischemia-reperfusion injury and alloimmune responses. Ex vivo lung perfusion (EVLP) is used to assess marginal donor lungs before transplantation but is also an excellent platform to apply novel therapeutics. We investigated donor lung immunomodulation using genetically engineered mesenchymal stromal cells with augmented production of human anti-inflammatory hIL-10 (MSCsIL-10). Pig lungs were placed on EVLP for 6 h and randomized to control (n = 7), intravascular delivery of 20 × 106 (n = 5, low dose) or 40 × 106 human MSCs IL-10 (n = 6, high dose). Subsequently, single-lung transplantation was performed, and recipient pigs were monitored for 3 days. hIL-10 secretion was measured during EVLP and after transplantation, and immunological effects were assessed by cytokine profile, T and myeloid cell characterization and mixed lymphocyte reaction. MSCIL-10 therapy rapidly increased hIL-10 during EVLP and resulted in transient hIL-10 elevation after lung transplantation. MSCIL-10 delivery did not affect lung function but was associated with dose-related immunomodulatory effects, with the low dose resulting in a beneficial decrease in apoptosis and lower macrophage activation, but the high MSCIL-10 dose resulting in inflammation and cytotoxic CD8+ T cell activation. MSCIL-10 therapy during EVLP results in a rapid and transient perioperative hIL-10 increase and has a therapeutic window for its immunomodulatory effects.
Assuntos
Imunomodulação , Interleucina-10 , Transplante de Pulmão , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais , Transplante de Pulmão/métodos , Animais , Interleucina-10/metabolismo , Células-Tronco Mesenquimais/metabolismo , Células-Tronco Mesenquimais/imunologia , Células-Tronco Mesenquimais/citologia , Suínos , Transplante de Células-Tronco Mesenquimais/métodos , Humanos , Engenharia Genética , Pulmão/metabolismo , Pulmão/patologia , Pulmão/imunologiaRESUMO
BACKGROUND: Both visceral pleural invasion (VPI) and lymphovascular invasion (LVI) have been shown to be adverse prognostic factors for early-stage non-small-cell lung cancer (NSCLC). Positive VPI upstages the T category of tumors ≤ 2 cm (T1a) to T2a, whereas LVI is not adapted as a descriptor for the Tumor, Node, Metastasis classification system. This study was conducted to evaluate the prognostic impacts of VPI and LVI in patients with pN0 NSCLC and a tumor diameter of ≤ 2 cm. METHODS: We reviewed records of a total of 142 patients with pN0 NSCLC and a tumor diameter of ≤ 2 cm, who underwent lobectomy with hilar and mediastinal lymph node dissection between January 2001 and December 2009. We conducted univariate and multivariate analyses to evaluate the impact of VPI, LVI, and other clinicopathologic factors on survival. RESULTS: Visceral pleural invasion and LVI were diagnosed as positive in 18 (12.7%) and 22 (15.5%) patients, respectively. Male sex, squamous cell carcinoma, positive VPI, and positive LVI were risk factors for overall survival. Squamous cell carcinoma, positive VPI, and positive LVI were risk factors for relapse-free survival. In multivariate analysis, squamous cell carcinoma and positive LVI were independent risk factors for overall survival, and positive LVI was an independent risk factor for relapse-free survival. CONCLUSIONS: Positive LVI was more important than VPI as a prognostic factor in patients with pN0 NSCLC and a tumor diameter of ≤ 2 cm. Adjuvant chemotherapy should be considered for such patients, to improve the treatment outcomes.
Assuntos
Vasos Sanguíneos/patologia , Carcinoma Pulmonar de Células não Pequenas/patologia , Neoplasias Pulmonares/patologia , Sistema Linfático/patologia , Pleura/patologia , Idoso , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/cirurgia , Feminino , Humanos , Estimativa de Kaplan-Meier , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/cirurgia , Excisão de Linfonodo , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica/patologia , Recidiva Local de Neoplasia/mortalidade , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Pneumonectomia , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Carga TumoralRESUMO
We describe an extremely rare case of pulmonary abscess caused by fish bone which stabbed the lung from transesophageal route. A 60-year-old woman referred to our hospital complaining of fever. Three days before, she had swallowing pain while eating the bony parts of a fish. An examination on admission showed that C-reactive protein (CRP) is 9.70 mg/dl. Chest computed tomography (CT)revealed, 4 cm mass shadow in the right upper lobe and fish bone material in the mass shadow. Esophagography showed no abnormal findings. Right upper lobectomy was performed under the diagnosis of pulmonary abscess by fish bone. Post operative course was uneventful. The cause was suspected of migration of a fish bone into the right upper lobe via mediasinum and thoracic cavity from esophagus.
Assuntos
Abscesso Pulmonar/etiologia , Animais , Feminino , Peixes , Migração de Corpo Estranho/cirurgia , Humanos , Abscesso Pulmonar/cirurgia , Pessoa de Meia-IdadeRESUMO
BACKGROUND: Chronic lung allograft dysfunction (CLAD) is a heterogeneous condition. Characterization of CLAD phenotypes is essential to enhance the understanding of pathogenesis and guide new therapies. The study objective was to validate the new International Society for Heart and Lung Transplantation (ISHLT) CLAD classification system and further explore patients who do not fall into the defined CLAD sub-categories. METHODS: We performed a single-center, retrospective cohort study of adult, first, bilateral lung transplants performed from 2010 to 2015. Patients with CLAD were classified on the basis of the 2019 ISHLT consensus document. CLAD phenotypes and other potential predictors of survival after CLAD onset were assessed using Kaplan-Meier and Cox proportional hazards models. RESULTS: Among the 174 subjects with CLAD, 104 (59.8%) had bronchiolitis obliterans syndrome (BOS), 16 (9.2%) restrictive allograft syndrome (RAS), 9 (5.2%) mixed, and 19 (10.9%) undefined phenotype. A total of 26 patients (14.9%) did not match any of these 4 categories and remained unclassified. Allograft survival post-CLAD onset was longer for patients with BOS (median, 500 days) than patients with RAS (median, 372 days) or mixed (median, 328 days). The 45 patients (26.8%) with undefined/unclassified phenotype were combined and recategorized on the basis of the presence or absence of characteristic RAS-like opacities on chest imaging; those with RAS-like opacities had significantly worse allograft survival than patients with BOS (hazard ratio, 2.14; 95% confidence interval, 1.17-3.93; pâ¯=â¯0.014) and similar survival to RAS or mixed phenotype. CONCLUSIONS: The new ISHLT CLAD phenotype classification is informative with regards to post-CLAD outcomes. Chest imaging demonstrating persistent parenchymal or pleural fibrosis may be used for risk-stratification of patients who do not match the major CLAD phenotypes.
Assuntos
Transplante de Coração-Pulmão/efeitos adversos , Disfunção Primária do Enxerto/epidemiologia , Medição de Risco/métodos , Adulto , Aloenxertos , Feminino , Seguimentos , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Ontário/epidemiologia , Fenótipo , Estudos Retrospectivos , Fatores de Risco , Taxa de Sobrevida/tendências , Fatores de Tempo , Adulto JovemRESUMO
BACKGROUND: Localization of inflammatory stimuli may direct lung allografts to different phenotypes of chronic dysfunction, such as bronchiolitis obliterans syndrome (BOS) or restrictive allograft syndrome (RAS). We hypothesized that airway stimulation with lipopolysaccharide (LPS) in rats leads to airway-centered inflammation similar to human BOS. METHODS: Rat left lung transplantation was conducted (donor: Brown Norway, recipient: Lewis). Allotransplant recipients received cyclosporine A (CsA) until postoperative day 56 with airway instillation of LPS (Allo-LPS, n = 8), phosphate buffered saline (Allo-PBS, n = 5) from days 35 to 46 (3 times a wk), or no further treatment (n = 4). Some allotransplant recipients received CsA until day 14 and were immunosuppression free after day 15 until day 56. Bronchial and pleural fibrosis were semiquantified; alveolar fibrosis was evaluated with a histological scale. RESULTS: The Allo-LPS group had significantly increased International Society for Heart and Lung Transplantation rejection grades (grade A, P = 0.005; grade B, P = 0.004), bronchial obstructive proportion (0.34 ± 0.04% [Allo-LPS] versus 0.11 ± 0.04% [Allo-PBS], P = 0.006), and airway resistance (3.05 ± 1.78 cm H2O·s/mL [Allo-LPS] versus 0.83 ± 0.58 cm H2O·s/mL [Allo-PBS], P = 0.007) compared with other groups. Allotransplant recipients that underwent a short course of CsA developed RAS-like fibrosis involving the airways, alveoli, and pleura. CONCLUSIONS: Airway instillation of LPS in allografts under immunosuppression resulted in BOS-like airway-centered inflammation and fibrosis distinct from RAS-like diffuse fibrosis, which was induced by a shortened course of immunosuppression. We propose novel animal models for BOS and RAS after lung transplantation.
Assuntos
Remodelação das Vias Aéreas/imunologia , Bronquiolite Obliterante/imunologia , Modelos Animais de Doenças , Rejeição de Enxerto/imunologia , Transplante de Pulmão/efeitos adversos , Aloenxertos/imunologia , Aloenxertos/patologia , Animais , Bronquiolite Obliterante/patologia , Fibrose , Rejeição de Enxerto/patologia , Rejeição de Enxerto/prevenção & controle , Humanos , Terapia de Imunossupressão/métodos , Lipopolissacarídeos/imunologia , Pulmão/imunologia , Pulmão/patologia , Masculino , Ratos , Ratos Endogâmicos BN , Ratos Endogâmicos Lew , Transplante Homólogo/efeitos adversosRESUMO
OBJECTIVE: Lung ischemia-reperfusion injury is among the complications seen after lung transplantation, resulting in morbidity and mortality. Pirfenidone, an antifibrotic agent for the treatment of idiopathic pulmonary fibrosis, is reported to have cytoprotective properties in various disease models. The purpose of this study was to investigate the effect of pirfenidone on lung ischemia-reperfusion injury. METHODS: Male Lewis rats (260-290 g) were divided into 3 groups: sham group (n = 5), warm ischemia (WI) group (n = 10), and WI plus pirfenidone (WI+PFD) group (n = 10). The sham group underwent 210 minutes of perfusion without ischemia. The WI and WI+PFD groups underwent 90 minutes of warm ischemia and 120 minutes of reperfusion. In the WI+PFD group, pirfenidone (300 mg/kg) was administered orally by gavage 30 minutes before ischemia. After reperfusion, arterial blood gas analysis, lung mechanics, lung wet-to-dry weight ratio, and histologic findings were obtained. The gene expressions of proinflammatory cytokines in lung tissue were measured by quantitative reverse transcription polymerase chain reaction. RESULTS: Compared with the WI group, the WI+PFD group had significantly better dynamic pulmonary compliance (P < .01) and oxygenation levels (P < .05). The wet-to-dry ratio was lower in the WI+PFD group (P < .05). Histologic analysis showed that the WI+PFD group had reduced perivascular edema and neutrophil infiltration. The expression of tumor necrosis factor-α messenger RNA was decreased in the WI+PFD group (P < .05). CONCLUSIONS: Our results revealed that in a rat hilar clamp model, pirfenidone alleviated lung ischemia-reperfusion through anti-inflammatory effects.
Assuntos
Anti-Inflamatórios/metabolismo , Lesão Pulmonar/prevenção & controle , Transplante de Pulmão/efeitos adversos , Pulmão/efeitos dos fármacos , Piridonas/farmacologia , Traumatismo por Reperfusão/prevenção & controle , Isquemia Quente/efeitos adversos , Animais , Citocinas/genética , Citocinas/metabolismo , Citoproteção , Modelos Animais de Doenças , Mediadores da Inflamação/metabolismo , Pulmão/metabolismo , Pulmão/patologia , Pulmão/fisiopatologia , Lesão Pulmonar/metabolismo , Lesão Pulmonar/patologia , Lesão Pulmonar/fisiopatologia , Masculino , Ratos Wistar , Traumatismo por Reperfusão/metabolismo , Traumatismo por Reperfusão/patologia , Traumatismo por Reperfusão/fisiopatologia , Transdução de SinaisRESUMO
BACKGROUND: We have developed a novel method for native upper lobe-sparing living-donor lobar lung transplantation (LDLLT) to overcome a small-for-size graft in standard LDLLT with acceptable results. We hypothesized that grafts implanted with this procedure might work more efficiently than those in standard lobe transplantation. METHODS: Bilateral LDLLT was performed in 31 patients with a functional graft matching of less than 60% at our institution between August 2008 and December 2015. Of these, 22 patients were available for evaluation of pulmonary function more than 1 year later: 15 undergoing standard LDLLT with less than 60% functional matching and 7 undergoing native upper lobe-sparing LDLLT. RESULTS: Overall survival at 2 years was 87.5% in the lobe-sparing LDLLT patients and 79.0% in the standard LDLLT patients (pâ¯=â¯0.401). The median forced vital capacity size-matching levels were 50.7% ± 1.6% in the standard LDLLT and 45.2% ± 2.3% in the sparing LDLLT group (pâ¯=â¯0.074). The 1-year and 2-year post-operative volume ratios of inspiration to expiration were significantly different between the 2 groups, at 1.76 and 1.45 after standard LDLLT (pâ¯=â¯0.019) vs 2.41 and 2.23 after lobe-sparing LDLLT (pâ¯=â¯0.015). CONCLUSIONS: The grafts in lobe-sparing LDLLT functioned more effectively than those in standard LDLLT. This advantage was associated with the improvement of pulmonary functions.
Assuntos
Doadores Vivos , Transplante de Pulmão/métodos , Pulmão/fisiopatologia , Pneumonectomia/métodos , Capacidade Vital/fisiologia , Adulto , Feminino , Seguimentos , Sobrevivência de Enxerto , Humanos , Pulmão/cirurgia , Masculino , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
OBJECTIVES: Extended thymectomy is a treatment option for myasthenia gravis (MG), but the surgical indications are controversial. Pathologic features of the thymus can be used to predict surgical outcomes, but there is no reliable method for evaluating these characteristics preoperatively. The purpose of this study was to determine whether anterior mediastinal tissue volume, as measured via 3-dimensional computed tomography (3DCT) volumetry, correlates with serum anti-acetylcholine receptor antibody (AChRAb) levels in patients undergoing thymectomy for myasthenia gravis. Therefore, we investigated the relationships among anterior mediastinal tissue volume determined by 3DCT volumetry and AChRAb levels. METHODS: The subjects were 28 patients who underwent extended thymectomy and were enrolled retrospectively. We measured volume of the anterior mediastinum and calculated the volumes of more than -30 Hounsfield units (V-30) by using 3DCT volumetry and compared them with perioperative AChRAb levels. The significance of their volumes in MG was examined by comparison with 53 patients without MG. RESULTS: V-30 values were related to age and were significantly greater in patients with MG than in patients without MG (P < .001). V-30 values were correlated positively with preoperative AChRAb levels (ρ = 0.505, P = .006) and inversely with the post/preoperative AChRAb ratio (ρ = -0.453, P = .018). The histologic nonadipose tissue ratio was correlated with the V-30/volume of the anterior mediastinum (ρ = 0.700, P < .001). CONCLUSIONS: This method for evaluation of the anterior mediastinal tissue volume and AChRAb production may be helpful in establishing a treatment plan for MG.
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Autoanticorpos/sangue , Mediastino , Miastenia Gravis , Receptores Colinérgicos/imunologia , Adulto , Feminino , Humanos , Masculino , Mediastino/diagnóstico por imagem , Mediastino/patologia , Pessoa de Meia-Idade , Miastenia Gravis/epidemiologia , Miastenia Gravis/patologia , Miastenia Gravis/fisiopatologia , Miastenia Gravis/cirurgia , Estudos Retrospectivos , TimectomiaRESUMO
BACKGROUND: Early diagnosis of unilateral chronic lung allograft dysfunction (CLAD) is difficult because the unaffected contralateral lung functions as a reservoir in bilateral living-donor lobar lung transplantation (LDLLT). We previously reported the usefulness of 133Xe ventilation scintigraphy for detection of unilateral change, but the supply of 133Xe has been stopped globally. The present study aimed to examine the usefulness of inspiratory and expiratory computed tomography (I/E CT) volumetry for detection of unilateral change in CLAD patients. METHODS: This was a retrospective single-center, observational study using prospectively collected data. A total of 58 patients who underwent bilateral LDLLT from August 2008 to February 2017 were analyzed. Respiratory function tests, I/E CT were prospectively conducted. ΔLung volume was defined as the value obtained by subtracting expiratory lung volume from inspiratory lung volume. RESULTS: Fourteen (24%) cases were clinically diagnosed with CLAD, of which 10 (71%) were diagnosed as unilateral CLAD. ΔLung volume of bilateral lungs strongly correlated with forced vital capacity (r = 0.92, P < 0.01) and forced expiratory volume in 1 second (r = 0.80, P < 0.01). Regardless the phenotypes (bronchiolitis obliterans syndrome or restrictive allograft syndrome) of CLAD, Δlung volume onset/baseline significantly decreased compared with that in the non-CLAD group. Among the 10 unilateral CLAD patients, 3 with clinically suspected unilateral rejection yet did not show a 20% decline in forced expiratory volume in 1 second. In 2 of these, Δlung volume of unilateral lungs on the rejection side decreased by 20% or more. CONCLUSIONS: Our findings suggest that I/E CT volumetry may be useful for assessment and early diagnosis of unilateral CLAD after bilateral LDLLT.
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BACKGROUND: Severe chest wall deformation is generally a contraindication for lung transplantation; however, it is not known whether patients with flat chests have reduced postoperative exercise capacity and pulmonary function. This study's purpose was to investigate the relationship between preoperative thoracic shape and postoperative exercise capacity and pulmonary function in patients undergoing lung transplantation. METHODS: Twenty recipients who underwent successful bilateral living-donor lobar lung transplantation were evaluated. To analyze postoperative graft function in relation to preoperative thoracic shape, 40 donor grafts implanted into 20 recipients were divided into two groups: flat chest group and normal chest group. Flat chest is diagnosed when the thoracic anteroposterior diameter to transverse diameter ratio is 1:3 or less. RESULTS: The ratio of the postoperative forced vital capacity to the preoperatively estimated forced vital capacity was significantly lower in the flat chest group than in the normal chest group 1 year after lung transplantation (p = 0.002). However, there were no significant differences in postoperative 6-minute walk distances between the two groups. Furthermore, the thoracic anteroposterior diameter to transverse diameter ratio in the flat chest group significantly increased after lung transplantation (p = 0.02). CONCLUSIONS: Although postoperative pulmonary function was significantly poorer for patients with flat chests than for patients with normal chests, their postoperative exercise capacity was equivalent. We also found that flat chest severity significantly improved after lung transplantation. Our study, the first investigating postoperative functional status in patients with flat chests, clearly shows that it is possible to perform lung transplantation in such patients with acceptable outcomes.
Assuntos
Tolerância ao Exercício/fisiologia , Tórax em Funil/diagnóstico por imagem , Tórax em Funil/cirurgia , Imageamento Tridimensional , Doadores Vivos , Transplante de Pulmão/métodos , Adulto , Estudos de Casos e Controles , Feminino , Sobrevivência de Enxerto , Humanos , Transplante de Pulmão/efeitos adversos , Masculino , Pessoa de Meia-Idade , Segurança do Paciente , Cuidados Pós-Operatórios/métodos , Cuidados Pré-Operatórios/métodos , Prognóstico , Valores de Referência , Testes de Função Respiratória , Estudos Retrospectivos , Medição de Risco , Tomografia Computadorizada por Raios X/métodos , Resultado do TratamentoRESUMO
BACKGROUND: Antibody-mediated rejection may lead to chronic lung allograft dysfunction, but antibody-mediated rejection may develop in the absence of detectable donor-specific antibody (DSA) in recipient serum. This study investigated whether humoral immune responses develop not only systemically but locally within rejected lung allografts, resulting in local production of DSA. METHODS: Lewis rats received orthotopic left lung transplantation from Lewis (syngeneic control) or Brown-Norway (major histocompatibility complex-mismatched allogeneic) donor rats. Rats that underwent allogeneic lung transplantation were subsequently administered cyclosporine until day 14 (short immunosuppression) or day 35 (long immunosuppression). The lung grafts and spleens of recipient animals were tissue cultured for 4 days, and the titer of antibody against donor major histocompatibility complex molecules was assayed by flow cytometry. Explanted lung grafts were also evaluated pathologically. RESULTS: By day 98, DSA titers in supernatants of lung graft (P = 0.0074) and spleen (P = 0.0167) cultures, but not serum, from the short immunosuppression group were significantly higher than titers in syngeneic controls. Cultures and sera from the long immunosuppression group showed no production of DSA. Microscopically, the lung grafts from the short immunosuppression group showed severe bronchiole obliteration and parenchymal fibrosis, along with lymphoid aggregates containing T and B cells, accompanying plasma cells. These findings suggestive of local humoral immune response were not observed by days 28 and 63. CONCLUSIONS: DSA can be locally produced in chronically rejected lung allografts, along with intragraft immunocompetent cells. Clinical testing of DSA in serum samples alone may underestimate lung allograft dysfunction.
Assuntos
Rejeição de Enxerto/imunologia , Antígenos de Histocompatibilidade Classe I/imunologia , Isoanticorpos/metabolismo , Transplante de Pulmão , Pulmão/imunologia , Animais , Biomarcadores/metabolismo , Citometria de Fluxo , Rejeição de Enxerto/diagnóstico , Masculino , Ratos , Ratos Endogâmicos Lew , Baço/imunologiaRESUMO
BACKGROUND: Successful living-donor lobar lung transplantation largely depends on the donor's outcome. Because surgical skills and peri-operative management have evolved over time, this study evaluated the recent outcomes of donor lobectomies. METHODS: Between 2008 and 2014, 48 consecutive living-donor lobar lung transplantations with 85 donor lobectomies were performed at Kyoto University. All donors were prospectively followed up regularly until 1 year after surgery. RESULTS: Right and left lower lobectomies were performed in 49 and 36 donors, respectively. Pulmonary arterial branches were sacrificed at equal frequency in both lobectomies, whereas pulmonary arterioplasty was only performed in left lower lobectomy (n = 9). All donors were discharged after the lobectomies, and none died during follow-up. Post-operative complications occurred in 24 donors (28%) overall, without a significant difference between donor sides. Intraoperative complications were found in 2 donors. Early and late post-operative complications were noted in 17 and 6 donors, respectively. Pneumothorax, pleuritis, and pleural effusion were the most frequent. Post-operative pulmonary function sequentially recovered more than expected and was not significantly affected by the sacrifice of pulmonary arterial branches during lobectomy. By contrast, pulmonary function at 1 year after donor lobectomy in the donors who had peri-operative complications was significantly lower than that in the donors who did not, although even post-operative pulmonary function in the donors with peri-operative complications still recovered more than expected. CONCLUSIONS: Living-donor lobectomies have been safely performed in recent decades with low morbidities and without mortality.
Assuntos
Doadores Vivos , Transplante de Pulmão , Pneumonectomia/efeitos adversos , Coleta de Tecidos e Órgãos/efeitos adversos , Obtenção de Tecidos e Órgãos/organização & administração , Adulto , Estudos de Coortes , Feminino , Volume Expiratório Forçado/fisiologia , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Recuperação de Função Fisiológica , Capacidade Vital/fisiologia , Adulto JovemRESUMO
Pulmonary cryptococcosis is most likely to occur in immunocompromised patients. The radiological manifestations generally include pulmonary parenchymal lesions, namely, pulmonary nodules, cavitary lesions, and consolidation; thus, multiple pleural nodules are unusual presentation. Here, we report a woman who presented with multiple pleural cryptococcosis without pleural effusion. The patient had previously undergone surgery for stage II rectal cancer. In addition, she received 6 cycles of chemotherapy for follicular lymphoma. Computed tomography (CT) revealed multiple small nodules involving the pleura without pleural effusion, which suggested possible recurrence of rectal cancer or malignant lymphoma as pleural dissemination. Thoracoscopic examination was performed, and pleural cryptococcosis was diagnosed. Although pleural cryptococcosis without pleural effusion is extremely rare presentation, clinicians should consider it when an immunocompromised patient presents with multiple pleural nodules. Thoracoscopic exploration should be the best procedure for the definitive diagnosis of multiple pleural nodules.