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1.
Artigo em Inglês | MEDLINE | ID: mdl-32201002

RESUMO

OBJECTIVE: Improvement in ex vivo lung perfusion protocols could increase the number of donors available for transplantation and protect the lungs from primary graft dysfunction. We hypothesize that perfusate adsorption during ex vivo lung perfusion reconditions the allograft to ischemia-reperfusion injury after lung transplantation. METHODS: Donor pig lungs were preserved for 24 hours at 4°C, followed by 6 hours of ex vivo lung perfusion according to the Toronto protocol. The perfusate was additionally adsorbed through a CytoSorb adsorber (CytoSorbents, Berlin, Germany) in the treatment group, whereas control lungs were perfused according to the standard protocol (n = 5, each). Ex vivo lung perfusion physiology and biochemistry were monitored. Upon completion of ex vivo lung perfusion, a left single lung transplantation was performed. Oxygenation function and lung mechanics were assessed during a 4-hour reperfusion period. The inflammatory response was determined during ex vivo lung perfusion and reperfusion. RESULTS: The cytokine concentrations in the perfusate were markedly lower with the adsorber, resulting in improved ex vivo lung perfusion physiology and biochemistry during the 6-hour perfusion period. Post-transplant dynamic lung compliance was markedly better during the 4-hour reperfusion period in the treatment group. Isolated allograft oxygenation function and dynamic compliance continued to be superior in the adsorber group at the end of reperfusion, accompanied by a markedly decreased local inflammatory response. CONCLUSIONS: Implementation of an additional cytokine adsorber has refined the standard ex vivo lung perfusion protocol. Furthermore, cytokine removal during ex vivo lung perfusion improved immediate post-transplant graft function together with a less intense inflammatory response to reperfusion in pigs. Further studies are warranted to understand the beneficial effects of perfusate adsorption during ex vivo lung perfusion in the clinical setting.

2.
Artigo em Inglês | MEDLINE | ID: mdl-31919516

RESUMO

OBJECTIVES: No significant data are available to assess whether complex sleeve lobectomy (complex-SL) can be considered comparable to conventional lobectomy (CL) in terms of surgical outcome. The purpose of this study was to compare surgical and oncological outcomes of complex-SL with CL in patients with lung cancer. METHODS: Between 2000 and 2015, a total of 568 patients who underwent open CL (defined as resection of only 1 lobe) and 187 patients who underwent SL were analysed. The SL group was divided into 2 subgroups: standard-SL (bronchial SL, n = 106) and complex-SL (n = 81) (defined as bronchial sleeve resection together with another surgical intervention: bronchovascular SL, n = 40; vascular SL, n = 26; atypical bronchoplasty with resection of more than 1 lobe, n = 12; bronchial SL + chest wall resection, n = 3). RESULTS: The complex-SL group had more patients with chronic obstructive pulmonary disease (COPD) (25.9% vs 12.5%, P = 0.001), neoadjuvant treatment (39.5% vs 12.0%, P < 0.001), advanced-stage non-small-cell lung cancer (53.2% vs 33.1%, P = 0.001) and low preoperative forced expiratory volume in 1 s (77.2% vs 84.3%, P = 0.004) than the CL group. The overall surgical mortality (in-hospital or 30-day) was 2.6% (n = 20); it was 2.8% for CL and 2.8% for complex-SL. Postoperative complications occurred in 34.9% of the CL group and 39.5% of the complex-SL group (P = 0.413). The pulmonary complication rate was similar between the groups (24.1% for CL, 27.2% for complex-SL, P = 0.552). The 5-year survival in the CL group was 57.1%, and in the complex-SL group it was 56.2% (P = 0.888). Multivariate analysis showed that TNM stage (P < 0.001) and N status (P < 0.001) were significant and independent negative prognostic factors for survival. CONCLUSIONS: Complex-SL had a comparable outcome to CL, although the complex-SL group had more patients with advanced-stage NSCLC, low preoperative forced expiratory volume in 1 s and COPD.

3.
J Heart Lung Transplant ; 38(12): 1235-1245, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31777330

RESUMO

BACKGROUND: This study aimed to examine intermediate-term outcomes of lung transplantation (LTx) recipients from donors after circulatory death (DCD). METHODS: We examined the International Society for Heart and Lung Transplantation (ISHLT) Thoracic Transplant Registry data for patients transplanted between January 2003 and June 2017 at 22 centers in North America, Europe, and Australia participating in the DCD Registry. The distribution of continuous variables was summarized as median and interquartile range (IQR) values. Wilcoxon rank sum test was used to compare distribution of continuous variables and chi-square or Fisher's exact test for categorical variables. Kaplan-Meier survival rates after LTx from January 2003 to June 2016 were compared between DCD-III (Maastricht category III withdrawal of life-sustaining therapy [WLST]) only and donors after brain death (DBD) using the log-rank test. Risk factors for 5-year mortality were investigated using Cox multivariate proportional-hazards model. RESULTS: The study cohort included 11,516 lung transplants, of which 1,090 (9.5%) were DCD lung transplants with complete data. DCD-III comprised 94.1% of the DCD cohort. Among the participating centers, the proportion of DCD-LTx performed each year increased from 0.6% in 2003 to 13.5% in 2016. DCD donor management included extubation in 91%, intravenous heparin in 53% and pre-transplant normothermic ex vivo donor lung perfusion in 15%. The median time interval from WLST to cardiac arrest was 15 minutes (IQR: 11-22 minutes) and to cold flush 32 minutes (IQR: 26-41minutes). Compared with DBD, donor age was higher in DCD-III donors (46 years [IQR: 34-55] vs 40 years [IQR: 24-52]), bilateral LTx was performed more often (88.3% vs 76.6%), and more recipients had chronic obstructive pulmonary disease and emphysema as their transplant indication. Five-year survival rates were comparable (63% vs 61%, p = 0.72). In multivariable analysis, recipient and donor ages, indication diagnosis, procedure type (single vs bilateral and double LTx), and transplant era (2003-2009 vs 2010-2016) were independently associated with survival (p < 0.001), but donor type was not (DCD-III vs DBD; hazard ratio, 1.04 [0.90-1.19], p = 0.61). CONCLUSION: This ISHLT DCD Registry report with 5-year follow-up demonstrated similar favorable long-term survival in DCD-III and DBD lung donor recipients at 22 experienced centers globally. These data indicate that more extensive use of DCD-LTx would increase donor organ availability and may reduce waiting list mortality.

4.
Artigo em Inglês | MEDLINE | ID: mdl-31499540

RESUMO

BACKGROUND: Primary pulmonary sarcoma (PPS) is a rare malignant lung neoplasm, and there is very little medical evidence about treatment of PPS. The aim of this study is to clarify the clinical characteristics and therapeutic outcome of patients who underwent surgical resection for PPS. METHODS: We retrospectively reviewed the records of patients who underwent surgical resection for PPS in our institution between 1995 and 2014. Cases who only underwent biopsy were excluded. RESULTS: A total of 24 patients (18 males, 6 females), with a median age of 60 (interquartile range: 44-67) years, were analyzed. The surgical procedures performed in these patients were pneumonectomy (n = 10), lobectomy (n = 11), and wedge resection (n = 3). Complete resection was achieved in 16 patients. The pathological stages (tumor, node, metastases lung cancer classification, 8th edition) of the patients were I (n = 4), II (n = 12), III (n = 2), and IV (n = 5), and there were four cases of lymph node metastasis. The 5-year overall survival rate of the patients was 50% (95% confidence interval [CI]: 29-72). Adverse prognostic factors for overall survival were incomplete resection (hazard ratio [HR]: 4.4, 95% CI: 2.1-42), advanced pathological stage (HR 14, 95% CI: 2.8-66), higher pathological grade (HR 4.5, 95% CI: 1.2-17), and tumor size ≥ 7 cm (HR 4.7, 95% CI: 1.1-21). CONCLUSIONS: Our series of PPS revealed that incomplete resection, advanced pathological stage, higher pathological grade, and tumor size were unfavorable factors for long-term survival.

5.
Curr Opin Organ Transplant ; 24(3): 288-296, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31090638

RESUMO

PURPOSE OF REVIEW: The current review presents a concise update on published literature on donation after circulatory death (DCD) and lung transplantation (LTx). Worldwide an increasing need for lungs is evident, however the utilization rate of DCD lung donors is still considerably low. In this summary article, we reviewed both the experimental background and international clinical experience. RECENT FINDINGS: Our analysis confirmed satisfactory results for LTx from DCD donors, which equals the results from donation after brain death. Although most studies reported on short-term results, some confirmed these results on the long-term and development of chronic lung allograft dysfunction. Our review summarizes the different DCD categories and underlines the potential of the DCD V category. We analyze the barriers to implement a DCD program, discuss the more recent advances like ex-vivo lung perfusion and describe the future challenges. SUMMARY: Based on the current short-term and long-term clinical results, we believe that barriers for DCD utilization should be overcome, resulting in a safe implementation of more DCD LTx programs worldwide. VIDEO ABSTRACT.

6.
Artigo em Inglês | MEDLINE | ID: mdl-30964773

RESUMO

PURPOSE OF REVIEW: The current review presents a concise update on published literature on donation after circulatory death (DCD) and lung transplantation (LTx). Worldwide an increasing need for lungs is evident, however the utilization rate of DCD lung donors is still considerably low. In this summary article, we reviewed both the experimental background and international clinical experience. RECENT FINDINGS: Our analysis confirmed satisfactory results for LTx from DCD donors, which equals the results from donation after brain death. Although most studies reported on short-term results, some confirmed these results on the long-term and development of chronic lung allograft dysfunction. Our review summarizes the different DCD categories and underlines the potential of the DCD V category. We analyze the barriers to implement a DCD program, discuss the more recent advances like ex-vivo lung perfusion and describe the future challenges. SUMMARY: Based on the current short-term and long-term clinical results, we believe that barriers for DCD utilization should be overcome, resulting in a safe implementation of more DCD LTx programs worldwide. VIDEO ABSTRACT.

8.
Lung ; 197(2): 217-226, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30739218

RESUMO

PURPOSE: Acute allograft rejection after lung transplantation remains an unsolved hurdle. The pathogenesis includes an inflammatory response during and after transplantation. Ropivacaine, an amide-linked local anesthetic, has been shown to attenuate lung injury due to its anti-inflammatory effects. We hypothesized that the drug would also be able to attenuate acute rejection (AR) after allogeneic lung transplantation. METHODS: Allogeneic, orthotopic, single left lung transplantation was performed between BALB/c (donors) and C57BL/6 (recipients) mice. Prior to explantation, lungs were flushed with normal saline with or without ropivacaine (final concentration 1 µM). Plasma levels of tumor necrosis factor-α and interleukins - 6 and - 10 were measured 3 h after transplantation by ELISA. Lung function was assessed on postoperative day five and transplanted lungs were analyzed using histology (AR), immunohistochemistry (infiltrating leukocytes) and Western blot (phosphorylation and expression of Src and caveolin-1). RESULTS: Ropivacaine pre-treatment significantly reduced AR scores (median 3 [minimum-maximum 2-4] for control vs. 2 [1-2] for ropivacaine, p < 0.001) and plasma levels of tumor necrosis factor-α (p = 0.01) compared to control, whereas plasma concentrations of interleukin - 6 (p = 0.008) and - 10 (p < 0.001) were increased by ropivacaine. The number of T-lymphocytes infiltrating the transplanted lung was attenuated (p = 0.02), while no differences in macrophage or B-lymphocyte numbers could be observed after ropivacaine pre-treatment. Caveolin-1 phosphorylation in ropivacaine-treated lungs was diminished (p = 0.004). CONCLUSIONS: Pre-treatment of donor lungs with the local anesthetic ropivacaine diminished histological signs of AR after orthotopic left lung transplantation in mice, most likely due to reduced infiltration of T-lymphocytes into the graft.


Assuntos
Anestésicos Locais/farmacologia , Anti-Inflamatórios/farmacologia , Rejeição de Enxerto/prevenção & controle , Sobrevivência de Enxerto/efeitos dos fármacos , Transplante de Pulmão/efeitos adversos , Pulmão/efeitos dos fármacos , Ropivacaina/farmacologia , Doença Aguda , Aloenxertos , Animais , Caveolina 1/metabolismo , Quimiotaxia de Leucócito/efeitos dos fármacos , Citocinas/sangue , Modelos Animais de Doenças , Rejeição de Enxerto/imunologia , Rejeição de Enxerto/metabolismo , Rejeição de Enxerto/patologia , Mediadores da Inflamação/sangue , Pulmão/imunologia , Pulmão/metabolismo , Pulmão/patologia , Masculino , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Fosforilação , Linfócitos T/efeitos dos fármacos , Linfócitos T/imunologia , Linfócitos T/metabolismo , Fatores de Tempo
9.
J Thorac Dis ; 10(Suppl 23): S2704-S2710, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30210822

RESUMO

Background: Radiotherapy is recommended as primary local therapy for inoperable patients with non-small cell lung cancer (NSCLC). We hypothesized that selected patients with advanced emphysema could be candidates for surgery and improved functional outcome might result in addition to low mortality and morbidity and successful cancer control when sublobar resection in a lung volume reduction surgery (LVRS) concept is applied. Methods: All patients with NSCLC and severe emphysema who underwent cancer resection in a LVRS concept between 2003 and 2015 were included for analysis. Postoperative 90-day mortality, complications, survival and lung function with forced expiratory volume in one second pre-operatively and three months postoperatively served as endpoints. Results: Fourteen patients were included. Three procedures were bilateral and eleven unilateral, eight have been performed with thoracoscopy and six with conversion to an open procedure due to adhesions. In ten patients, tumor resection was atypical and in four patients an anatomic segmentectomy was performed. All patients had lung volume reduction. Prolonged air leak occurred in three patients. Perioperative 90-mortality was zero. Median pre-operative forced expiratory volume in one second was 32.5% and increased to 37% (P=0.002) 3 months following surgery. Three and 5-year survival rates were 50% and 35%, respectively. Conclusions: Sublobar resection of NSCLC combined with LVRS in patients with severely impaired lung function due to emphysema can be performed with low mortality and morbidity making it an alternative treatment modality to radiotherapy. This approach allows cancer resection in marginal patients and improves emphysema symptoms simultaneously.

10.
J Thorac Dis ; 10(6): 3845-3848, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30069385

RESUMO

Lung transplantation is an established therapeutic procedure for end stage lung diseases. Its success may be impaired by perioperative complications. Intraoperative blood loss and the resulting blood transfusion are among the most common complications. The various factors contributing to increased blood loss during lung transplantation are only scarcely investigated and not yet completely understood. This is in sharp contrast to other surgical fields, as in orthopedic surgery, liver transplantation and cardiac surgery the contributors to blood loss are well identified. This narrative review article aims to highlight the acknowledged factors influencing blood loss in lung transplantation (such as double vs. single lung transplant) and to discuss potential factors that may be of interest for further research or helpful to develop strategies targeting risk factors in order to minimize blood loss during lung transplantation and finally improve patient outcome.

11.
Ann Thorac Cardiovasc Surg ; 24(6): 296-302, 2018 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-29962390

RESUMO

PURPOSE: Utilization of donation after circulatory death (DCD) donors has the potential to decrease donor shortage in lung transplantation (LTx). This study reviews the long-term outcome of LTx from DCD donors. METHODS: We included all consecutive DCD (Maastricht Category III) and all donations after brain death (DBD) donor lung transplants at our Center performed between January 2012 and February 2017. Data were analyzed comparing the two groups in regard of survival after LTx as primary outcome. RESULTS: Median withdrawal to cardiac arrest time was 17 min (interquartile range [IQR]: 11.5-20.5). Median cardiac arrest to cold perfusion was 32 min (IQR: 24.5-36.5). Primary graft dysfunction (PGD) grade 3 at T72 occurred in three recipients. Chronic lung allograft dysfunction (CLAD) led to death in two cases. In DCD group, there was no 90-day mortality. In DCD, group 1- and 3-year survival rates were 100% and 80%. In DBD group, 1- and 3-year survival rates were 85% and 69% (p = 0.4). CONCLUSIONS: Our report confirmed the comparable outcome from DCD donors compared with DBD donors. Utility of DCD donors is a safe option to overcome donor shortage.


Assuntos
Morte Encefálica , Seleção do Doador , Transplante de Pulmão/métodos , Doadores de Tecidos/provisão & distribução , Adulto , Feminino , Sobrevivência de Enxerto , Humanos , Transplante de Pulmão/efeitos adversos , Transplante de Pulmão/mortalidade , Masculino , Pessoa de Meia-Idade , Países Baixos , Complicações Pós-Operatórias/etiologia , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento
12.
J Thorac Dis ; 10(3): E175-E178, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29707367

RESUMO

We present an exemplary case of an immunocompromised patient with pulmonary mucormycosis successfully treated by a combination of surgical removal of the mucor and urokinase to control the recurring hemothorax. The use of urokinase in hemothoraces is a way to reduce repetitive surgeries in weak patients.

13.
Interact Cardiovasc Thorac Surg ; 27(5): 727-732, 2018 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-29846608

RESUMO

OBJECTIVES: Abdominal surgery after lung transplantation is an important factor for major morbidity and mortality. Herein, we describe the incidence and outcome of abdominal surgery occurring early or late after transplantation. METHODS: Overall, 315 patients who underwent lung transplantation between January 2000 and December 2013 at our institution were included in a prospective database. Perioperative parameters were assessed, and complications were graded according to the Clavien-Dindo Classification. RESULTS: Among 315 patients after lung transplantation, 52 patients underwent abdominal surgery, 16 during the early postoperative phase and 42 at later time points. Bowel ischaemia and perforation of the right colon were the most common reason for early surgery, with a median interval of 7 days after lung transplantation. The median survival time for patients with early abdominal surgery was 31 months compared to 40 and 90 months for patients with no or late abdominal surgery (P = 0.001 and P = 0.002, respectively). The most common late indications for surgery were perforated diverticulitis, ileus and hernia, with a median interval of 37.9 months after lung transplantation and a median survival comparable with patients without any abdominal surgery (P = 0.9). However, prior hospitalization due to a non-abdominal disease was associated with increased morbidity (P = 0.006) after late surgery. CONCLUSIONS: Early abdominal surgeries after lung transplantation are associated with a significant mortality risk. Abdominal operations at late time points have a favourable outcome unless patients were hospitalized prior to the abdominal complication. Clinical trial registration number: ZH-KEK-Nr. 2014-0244.


Assuntos
Procedimentos Cirúrgicos do Sistema Digestório/métodos , Gastroenteropatias/cirurgia , Transplante de Pulmão/efeitos adversos , Complicações Pós-Operatórias/cirurgia , Adulto , Causas de Morte/tendências , Feminino , Seguimentos , Gastroenteropatias/epidemiologia , Humanos , Transplante de Pulmão/mortalidade , Masculino , Pessoa de Meia-Idade , Morbidade/tendências , Complicações Pós-Operatórias/epidemiologia , Estudos Prospectivos , Estudos Retrospectivos , Taxa de Sobrevida/tendências , Suíça/epidemiologia , Fatores de Tempo
14.
Swiss Med Wkly ; 148: w14614, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29689119

RESUMO

AIM: Various scoring systems aim to assess the quality of organs donated for transplantation on the basis of patient characteristics, clinical examination and laboratory results. How well such scoring systems reflect the practice in lung transplantation in Switzerland has never been studied. Therefore, we evaluated two scoring systems for their ability to predict whether or not donor lungs are accepted by the two Swiss lung transplant centres. METHODS: We retrospectively analysed patient data of adult deceased organ donors in Switzerland between 1 July 2007 and 30 June 2014. Included were all donors from whom at least one organ was transplanted. We evaluated two lung donor quality scores, the multicentre-developed Eurotransplant donor score (EDS), and the single-centre-developed Zurich donor score (ZDS). Both scores were slightly adapted to be applicable to Swiss deceased organ donor data. We evaluated whether these scores can predict whether lungs were transplanted or refused by Swiss transplant centres, using univariate logistic regression. We further assessed their discriminative power by calculating the area under the receiver operating characteristic curve (AUC). RESULTS: Of the 635 donors included in our analysis, 295 (46%) were accepted as lung donors by one of the two lung transplant centres in Switzerland. Our analysis showed that both scores can predict whether or not a donor lung is likely to be accepted for transplantation in Switzerland. As the score value of a donor increases, the odds of the lung being transplanted significantly decreases (odds ratio [OR] 0.58, 95% confidence interval [CI] 0.51-0.65 for the adapted EDS; OR 0.35, 95% CI 0.28-0.43 for the adapted ZDS). This effect is slightly more pronounced in the adapted ZDS than in the adapted EDS. The discriminatory power of the scores from the AUC was 0.719 (95% CI 0.680-0.758) for the adapted EDS, and 0.723 (95% CI 0.681-0.760) for the adapted ZDS, which for both was deemed fair discrimination. CONCLUSIONS: Both scoring systems are able to predict whether or not donor lungs are accepted by the two Swiss lung transplant centres. As an alternative to adapting an established scoring system, a national lung quality score could be derived de novo. This could be based on a logistic regression analysis including the most relevant donor characteristics. However, such a new score would need to be validated on an independent sample and ideally tested for its predictive value in terms of post-transplantation outcome.


Assuntos
Algoritmos , Seleção do Doador/normas , Transplante de Pulmão , Obtenção de Tecidos e Órgãos/normas , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Alocação de Recursos/normas , Estudos Retrospectivos , Fatores de Risco , Suíça , Resultado do Tratamento
15.
Eur J Cardiothorac Surg ; 54(3): 565-571, 2018 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-29538689

RESUMO

OBJECTIVES: Pulmonary hypertension (PH) is considered a contraindication for lung volume reduction surgery (LVRS). Because, it has been reported that endobronchial lung volume reduction may have a beneficial effect without increased mortality in patients with emphysema and PH, we evaluated its effect on PH in patients undergoing LVRS. METHODS: From January 2014 until June 2016, 119 LVRSs were performed at Zurich University Hospital. PH was a contraindication for patients with homogeneous emphysema but was acceptable for those with heterogeneous emphysema. Thirty patients underwent echocardiography before and after LVRS, 10 of whom had preoperative systolic pulmonary artery pressures >35 mmHg and 20 of whom had normal systolic pulmonary artery pressure. The effect of LVRS on pulmonary artery pressure, lung function and survival was analysed. RESULTS: Ninety-day mortality for all 30 patients was 0, and the postoperative course did not differ significantly between the 2 groups. In patients with PH, the median systolic pulmonary artery pressure decreased from 41 mmHg [interquartile range (IQR) 39-47] to 37 mmHg (IQR 36-38, P = 0.04). These patients had an improvement of forced expiratory volume in 1 s from the median 27% predicted (IQR 23-34) to 33% (IQR 28-40, P = 0.007) 3 months postoperatively. CONCLUSIONS: If further confirmed in other cohorts, mild to moderate PH may no longer be considered a contraindication for LVRS in patients with heterogeneous emphysema.


Assuntos
Hipertensão Pulmonar , Pulmão , Pneumonectomia , Enfisema Pulmonar , Adulto , Idoso , Ecocardiografia , Feminino , Humanos , Hipertensão Pulmonar/diagnóstico por imagem , Hipertensão Pulmonar/mortalidade , Hipertensão Pulmonar/cirurgia , Estimativa de Kaplan-Meier , Pulmão/diagnóstico por imagem , Pulmão/cirurgia , Masculino , Pessoa de Meia-Idade , Pneumonectomia/mortalidade , Pneumonectomia/estatística & dados numéricos , Enfisema Pulmonar/diagnóstico por imagem , Enfisema Pulmonar/mortalidade , Enfisema Pulmonar/cirurgia
16.
Interact Cardiovasc Thorac Surg ; 26(5): 859-864, 2018 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-29300898

RESUMO

OBJECTIVES: Human leucocyte antigen (HLA) mismatch between donor and recipient has a differential impact on the outcome after transplant (Tx) among transplantable solid organs. Although the lung is considered a highly antigenic organ, the impact of HLA matching between the donor and the recipient has been shown to be heterogeneous on lung Tx outcome. To provide further evidence that HLA matching should be considered in the decision process prior to lung Tx, we evaluated the impact of donor/recipient HLA mismatch on the outcome after lung Tx at our institution. METHODS: All patients who underwent lung Tx were analysed in this retrospective single-cohort study between 1994 and 2013 for HLA (-A, -B or -DR) matching between the donor and the recipient and their association with overall survival, the incidence of acute cellular rejection (ACR) and the development of chronic lung allograft dysfunction (CLAD). RESULTS: In total, 371 (197 men) patients were included. Of these, 117 patients had no HLA match (0/6), 143 had a 1/6 match, 77 had 2/6 matches, 28 had 3/6 matches and 6 had 4/6 matches. One hundred and twenty-two (33%) patients experienced at least 1 episode of ACR and 172 (46%) patients developed CLAD. Univariate analysis showed a significant correlation between HLA mismatch and the development of CLAD, whereas multivariate analysis revealed that the number of HLA matches (hazard ratio 0.76; P = 0.002), antibodies to cytomegalovirus in either donors or recipients (hazard ratio 1.52; P = 0.036) and donor age (hazard ratio 1.03; P < 0.001) were independent risk factors for the development of CLAD. On the other hand, HLA matches did not correlate with the incidence of ACR and with the overall survival rate. CONCLUSIONS: The number of HLA mismatches between donors and recipients after lung Tx did not correlate with ACR or with the overall survival. In contrast, HLA mismatch correlated with the development of CLAD and should therefore be considered a risk factor.


Assuntos
Rejeição de Enxerto/epidemiologia , Antígenos HLA/imunologia , Pneumopatias/mortalidade , Transplante de Pulmão/efeitos adversos , Adolescente , Adulto , Fatores Etários , Idoso , Anticorpos Antivirais , Citomegalovirus/imunologia , Feminino , Histocompatibilidade , Teste de Histocompatibilidade , Humanos , Incidência , Pneumopatias/imunologia , Pneumopatias/cirurgia , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Fatores de Risco , Taxa de Sobrevida , Adulto Jovem
17.
Pediatr Transplant ; 22(3): e13145, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29380491

RESUMO

ECP is an established "second-line" treatment for CLAD/BOS. Recently, ECP was used for the first time in an adolescent CF patient as a "second-line" treatment therapy in life-threatening primary graft dysfunction following lung transplantation who deteriorated despite extensive treatment including ECMO and ATG. Within 10 days after initiation of ECP twice weekly, allograft function and clinical status improved significantly and the patient was weaned from mechanical ventilation support. ECP has been continued every 2 weeks since. Two hundred days after lung transplantation, the patient has an acceptable allograft function (FEV1 67%) and no signs of allograft rejection. We advocate that use of ECP and its immunomodulatory effects should be evaluated in the early period following lung transplantation.


Assuntos
Transplante de Pulmão , Fotoferese/métodos , Disfunção Primária do Enxerto/terapia , Feminino , Humanos , Adulto Jovem
18.
Ann Thorac Surg ; 105(2): 379-385, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29223424

RESUMO

BACKGROUND: Lung volume reduction surgery (LVRS) has been proven to be a successful procedure and can be performed with low mortality when defined selection criteria are met. We hypothesized good outcome and low mortality after LVRS for selected patients with severe hyperinflation and nonhomogeneous morphology even when diffusion capacity of the lung for carbon monoxide (Dlco) is less than 20%. METHODS: The study included all patients scheduled for LVRS between March 2005 and May 2014 with a preoperative Dlco of less than 20%. Postoperative 90-day mortality was the primary end point. Secondary end points were postoperative lung function and surgical morbidity at 3, 6, and 12 months. RESULTS: Included were 33 patients with a median forced expiratory volume in 1 second of 23% (interquartile range, 19% to 28%), a median diffusion capacity of 15% (interquartile range, 13% to 18%), and a median hyperinflation of 76% (residual volume-to-total lung capacity ratio of 70% to 76%). Mean follow-up was 44.8 months (range, 10 to 141 months). Heterogeneous emphysema was present in 26 patients, and 7 showed intermediately heterogeneous morphology. Sixteen procedures were bilateral, and 31 were performed by video-assisted thoracoscopic surgery. The 90-day mortality was 0%. Median forced expiratory volume in 1 second percentage predicted at 3 months increased from 23% to 29% (p < 0.001). Median Dlco increased from 15% to 24% (p < 0.001), and median hyperinflation decreased from 76% to 63% (p < 0.001). A prolonged air leak exceeding 7 days occurred in 16 patients (48.5%), and 6 required reoperation for fistula closure. The 7 patients with intermediately heterogeneous emphysema showed a median increase in forced expiratory volume in 1 second from 20% preoperatively to 28% postoperatively (p = 0.028). CONCLUSIONS: Selected patients with severely impaired Dlco of less than 20% can cautiously be considered as potential candidates if hyperinflation is severe and the lungs show areas with advanced destruction as targets for resection.


Assuntos
Pulmão/cirurgia , Pneumonectomia/métodos , Capacidade de Difusão Pulmonar/fisiologia , Enfisema Pulmonar/cirurgia , Cirurgia Torácica Vídeoassistida/métodos , Idoso , Feminino , Volume Expiratório Forçado , Humanos , Pulmão/diagnóstico por imagem , Pulmão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/epidemiologia , Enfisema Pulmonar/diagnóstico , Enfisema Pulmonar/fisiopatologia , Reoperação , Taxa de Sobrevida/tendências , Suíça/epidemiologia , Tomografia Computadorizada por Raios X , Resultado do Tratamento
19.
Eur J Cardiothorac Surg ; 53(3): 596-602, 2018 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-28957998

RESUMO

OBJECTIVES: Lung volume reduction surgery (LVRS) and lung transplantation (LTx) are the treatments of choice in selected patients with end-stage emphysema. Recently, the history of LVRS has been questioned due to reduced post-transplant survival. We aim to address this question by reviewing our experience, which is the largest single-centre series of LVRS followed by LTx. METHODS: We reviewed our prospectively recorded database in patients with emphysema undergoing LTx between 1993 and 2014. Preoperative workup and postoperative outcomes were compared according to previous LVRS status. The Kaplan-Meier test was used for survival analysis and compared with a log-rank test. RESULTS: One hundred and seventeen patients (66 men; mean age 56 ± 7 years) underwent LTx during the study period, 52 of whom had previous LVRS (LVRS + LTx). The mean time from LVRS to LTx was 45 ± 31 months. Patients were slightly older and had extensive smoking history in the LVRS + LTx group. Overall, in-hospital mortality was 10%, which did not differ significantly regardless of the history of LVRS (P = 0.8). The median survival for the LTx-only and LVRS + LTx groups was 86 [95% confidence interval (CI) 56-116] and 107 (95% CI 77-137) months, respectively (P = 0.6). CONCLUSIONS: Previous LVRS does not negatively affect short-term and long-term outcomes following LTx in patients with end-stage emphysema. The history of LVRS should not preclude the candidacy for LTx. Considering the limited number of donors available, the LVRS option should be kept in mind for the postponement of LTx in carefully selected patients.


Assuntos
Transplante de Pulmão/mortalidade , Transplante de Pulmão/estatística & dados numéricos , Pulmão/cirurgia , Pneumonectomia/estatística & dados numéricos , Enfisema/cirurgia , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
20.
Transplantation ; 102(2): e49-e58, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-28825953

RESUMO

BACKGROUND: Several mouse lung transplantation (Tx) models have been proposed for the study of chronic airway fibrosis (CAF), the most prevalent complication seen in human lung transplant recipients, termed chronic lung allograft dysfunction. Alternatively, it has been called for to establish an experimental animal model for restrictive allograft syndrome, another phenotype of chronic lung allograft dysfunction. However, these mouse transplant models exhibit significant heterogeneity in consistency and reproducibility. We therefore aimed at reevaluating current available models. METHODS: Four different Tx combinations were used that manifest CAF: 2 minor antigen-mismatched Tx combinations (MINOR, donor: C57BL/10, recipient: C57BL/6J); or MINOR-N using recipient C57BL/6N, major histocompatibility antigen-mismatched immunosuppressed Tx (MAJOR, donor: BALB/c, recipient: C57BL/6J), and syngeneic Tx (donor and recipient: C57BL/6J) as control. The recipients were harvested and analyzed at week 8. Oxygenation, histology, reverse transcription polymerase chain reaction, and magnetic resonance imaging were performed to analyze outcome of those models. RESULTS: The most prominent manifestation of CAF, thickest subepithelial fibrotic changes, worst oxygenation, and the most severe acute rejection were detected in the MAJOR group compared with all other (P < 0.05). Gene expressions of TNF-α and TGF-ß1 were higher, and IL-10 was lower in the MAJOR group. Immunohistochemistry found pleuroparenchymal fibrotic change in both the MAJOR and MINOR-J groups. CONCLUSIONS: We propose the major mismatch model under mild immunosuppression as the most suitable model for studying posttransplant CAF, and both the major and minor mismatch models for the restrictive phenotype.


Assuntos
Bronquiolite Obliterante/etiologia , Transplante de Pulmão/efeitos adversos , Pulmão/patologia , Complicações Pós-Operatórias/etiologia , Animais , Bronquiolite Obliterante/diagnóstico por imagem , Doença Crônica , Modelos Animais de Doenças , Fibrose , Imagem por Ressonância Magnética , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Complicações Pós-Operatórias/diagnóstico por imagem
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