Gastroesophageal Reflux and Esophageal Motility Disorder After Lung Transplant: Influence on the Transplanted Graft.

BACKGROUND: Esophageal pathology has been identified as a bad prognostic factor in lung transplantation (LTx). This study aims to assess the esophageal disorders present post-LTx, under treatment with proton pump inhibitors, and their putative impact on the graft. METHODS: Prospective, observational study of LTx patients. Digestive factors were assessed by manometry and pH-metry at 6 months post-LTx and under proton pump inhibitor treatment. We assessed the association between esophageal disorders and graft function and acute rejection (AR) and chronic lung allograft dysfunction (CLAD). RESULTS: Out of 76 post-LTx patients, 27% showed gastroesophageal reflux disease (GERD), 55% showed inadequate gastric inhibition, and 59% showed esophageal motility disorders (EMDs). We observed a greater incidence of AR from 3 months post-LTx in the presence of EMD (P ≤ .05). No significant differences were observed in GERD or EMD prevalence or in survival between patients with or without CLAD. The maximum forced expiratory volume in 1 second (FEV1) achieved after bilateral LTx was significantly (P = .022) lower in patients with EMD vs without EMD. CONCLUSION: At 6 months post-LTx, there is a high percentage of esophageal disorders (GERD and EMDs). No esophageal disorder is associated with CLAD or with survival, although EMDs are associated with a greater incidence of AR and lower graft function.

Prospective Clinical Integration of an Amplicon-Based Next-Generation Sequencing Method to Select Advanced Non-Small-Cell Lung Cancer Patients for Genotype-Tailored Treatments.

INTRODUCTION: A substantial fraction of non-small-cell lung cancers (NSCLCs) harbor targetable genetic alterations. In this study, we analyzed the feasibility and clinical utility of integrating a next-generation sequencing (NGS) panel into our routine lung cancer molecular subtyping algorithm. PATIENTS AND METHODS: After routine pathologic and molecular subtyping, we implemented an amplicon-based gene panel for DNA analysis covering mutational hot spots in 22 cancer genes in consecutive advanced-stage NSCLCs. RESULTS: We analyzed 109 tumors using NGS between December 2014 and January 2016. Fifty-six patients (51%) were treatment-naive and 82 (75%) had lung adenocarcinomas. In 89 cases (82%), we used samples derived from lung cancer diagnostic procedures. We obtained successful sequencing results in 95 cases (87%). As part of our routine lung cancer molecular subtyping protocol, single-gene testing for EGFR, ALK, and ROS1 was attempted in nonsquamous and 3 squamous-cell cancers (n = 92). Sixty-nine of 92 samples (75%) had sufficient tissue to complete ALK and ROS1 immunohistochemistry (IHC) and NGS. With the integration of the gene panel, 40 NSCLCs (37%) in the entire cohort and 30 NSCLCs (40%) fully tested for ALK and ROS1 IHC and NGS had actionable mutations. KRAS (24%) and EGFR (10%) were the most frequently mutated actionable genes. Ten patients (9%) received matched targeted therapies, 6 (5%) in clinical trials. CONCLUSION: The combination of IHC tests for ALK and ROS1 and amplicon-based NGS is applicable in routine clinical practice, enabling patient selection for genotype-tailored treatments.

Agreement Between Computed Tomography and Pathologic Nodule Counts in Colorectal Lung Metastases.

BACKGROUND: Computed tomography is the most common technique used to estimate the number of pulmonary metastases and their resectability. A lack of agreement between radiologic and surgical pathologic findings could potentially lead to incomplete resection or to rejection of patients for potentially curative treatments. The objective of this study was to estimate the disagreement between the number of radiologic lesions and the number of histologically confirmed malignant lesions excised from patients with pulmonary metastases from colorectal cancer. METHODS: This was a multicenter longitudinal study using a national registry. All patients underwent open surgery for pulmonary metastasectomy. RESULTS: Radiologic unilateral involvement was documented in 345 of 404 patients (85%); 253 (73%) presented with single nodules. The radiologic and malignant pathologic findings were concordant in 316 (78%) patients. The two independent predictors of discordance between computed tomography and the number of pathologic metastases were the bilateral involvement and the number of radiologic nodules. This model explained 28% of the variability in the disagreement frequency and discriminated between agreement and disagreement in 85% of the patients. Discrepancies increased with the nodule count with an odds ratio of 6.17 (95% confidence interval, 4.08 to 9.33) per additional nodule. For similar nodule counts, a lower disagreement frequency was observed among bilateral cases (odds ratio, 0.2; 95% confidence interval, 0.07 to 0.55). CONCLUSIONS: Differences between the radiologic and pathologic findings were documented in 1 of every 5 patients. The correlation was very accurate in patients with single radiologic nodules. However, half of the patients with more nodules showed discrepancies.

Tratamiento del carcinoma broncogénico de célula no pequeña en estadios precoces / Treatment of non-small cell lung carcinoma in early stages

El tratamiento del carcinoma brongénico es multidisciplinar. Se dispone de diferentes estrategias terapéuticas, siendo la cirugía la que presenta mejores resultados en aquellos pacientes con carcinoma broncogénico en estadios precoces. Otras opciones como la radioterapia estereotáctica quedan relegadas a pacientes con pequeños tumores y mala reserva cardiopulmonar, o a aquellos que rechacen la cirugía. La quimioterapia adyuvante no está justificada en pacientes con enfermedad en estadio i , planteándose doble quimioterapia adyuvante basada en cisplatino tras la cirugía en aquellos con estadios ii y III A (AU)

Treatment of lung carcinoma is multidisciplinary. There are different therapeutic strategies available, although surgery shows the best results in those patients with lung carcinoma in early stages. Other options such as stereotactic radiation therapy are relegated to patients with small tumors and poor cardiopulmonary reserve or to those who reject surgery. Adjuvant chemotherapy is not justified in patients with stage i of the disease and so double adjuvant chemotherapy should be considered. This adjuvant chemotherapy should be based on cisplatin after surgery in those patients with stages ii and IIIA (AU)

[Treatment of non-small cell lung carcinoma in early stages]. / Tratamiento del carcinoma broncogénico de célula no pequeña en estadios precoces.

Treatment of lung carcinoma is multidisciplinary. There are different therapeutic strategies available, although surgery shows the best results in those patients with lung carcinoma in early stages. Other options such as stereotactic radiation therapy are relegated to patients with small tumors and poor cardiopulmonary reserve or to those who reject surgery. Adjuvant chemotherapy is not justified in patients with stage i of the disease and so double adjuvant chemotherapy should be considered. This adjuvant chemotherapy should be based on cisplatin after surgery in those patients with stages ii and IIIA.

Registro Español de Trasplante Pulmonar: primer informe de resultados (2006-2010) / The Spanish Lung Transplant Registry: First Report of Results (2006-2010)

El Registro Español de Trasplante Pulmonar (RETP) inició su actividad en 2006, participando en él todos los equipos de trasplante pulmonar (TP) con un programa activo en España. Este informe presenta por primera vez de forma global la descripción y resultados de los pacientes trasplantados de pulmón en España entre los años 2006 y 2010. La actividad de TP ha ido en progresivo aumento, trasplantándose en este periodo 951 adultos y 31 niños. La media de edad del receptor fue de 48,2 años, siendo 41,7 años en el donante pulmonar. En el TP adulto, la causa más frecuente de trasplante fue el enfisema/EPOC, seguido de la fibrosis pulmonar idiopática, representando ambas más del 60% del total de las indicaciones. La probabilidad de supervivencia tras el TP adulto a uno y 3 años es del 72 y del 60%, respectivamente, si bien en los pacientes que sobreviven al tercer mes postrasplante estas supervivencias son del 89,7 y del 75,2%. Los factores que más claramente inciden en la supervivencia del paciente son la edad del receptor y el diagnóstico que indicó el trasplante. En los trasplantes pediátricos, la fibrosis quística es la principal causa de trasplante (68%), y la supervivencia al año es del 80, y del 70% a los 3 años. Tanto en el trasplante adulto como en el pediátrico, la causa más frecuente de fallecimiento es la infección. Estos datos confirman la consolidación del TP en España como una opción terapéutica para la enfermedad respiratoria crónica avanzada, tanto en niños como en adultos(AU)

The Spanish Lung Transplant Registry (SLTR) began its activities in 2006 with the participation of all the lung transplantation (LT) groups with active programs in Spain. This report presents for the first time an overall description and results of the patients who received lung transplants in Spain from 2006 to 2010. LT activity has grown progressively, and in this time period 951 adults and 31 children underwent lung transplantation. The mean age of the recipients was 48.2, while the mean age among the lung donors was 41.7. In adult LT, the most frequent cause for lung transplantation was emphysema/COPD, followed by idiopathic pulmonary fibrosis, both representing more than 60% the total number of indications. The probability for survival after adult LT to one and three years was 72% and 60%, respectively, although in patients who survived until the third month post-transplantation, these survival rates reached 89.7% and 75.2%. The factors that most clearly influenced patient survival were the age of the recipient and the diagnosis that indicated the transplantation. Among the pediatric transplantations, cystic fibrosis was the main cause for transplantation (68%), with a one-year survival of 80% and a three-year survival of 70%. In adult as well as pediatric transplantations, the most frequent cause of death was infection. These data confirm the consolidated situation of LT in Spain as a therapeutic option for advanced chronic respiratory disease, both in children as well as in adults(AU)

The Spanish Lung Transplant Registry: first report of results (2006-2010).

The Spanish Lung Transplant Registry (SLTR) began its activities in 2006 with the participation of all the lung transplantation (LT) groups with active programs in Spain. This report presents for the first time an overall description and results of the patients who received lung transplants in Spain from 2006 to 2010. LT activity has grown progressively, and in this time period 951 adults and 31 children underwent lung transplantation. The mean age of the recipients was 48.2, while the mean age among the lung donors was 41.7. In adult LT, the most frequent cause for lung transplantation was emphysema/COPD, followed by idiopathic pulmonary fibrosis, both representing more than 60% the total number of indications. The probability for survival after adult LT to one and three years was 72% and 60%, respectively, although in patients who survived until the third month post-transplantation, these survival rates reached 89.7% and 75.2%. The factors that most clearly influenced patient survival were the age of the recipient and the diagnosis that indicated the transplantation. Among the pediatric transplantations, cystic fibrosis was the main cause for transplantation (68%), with a one-year survival of 80% and a three-year survival of 70%. In adult as well as pediatric transplantations, the most frequent cause of death was infection. These data confirm the consolidated situation of LT in Spain as a therapeutic option for advanced chronic respiratory disease, both in children as well as in adults.

Desarrollo de un programa de donación pulmonar en asistolia con «preservación en bitermia» y resultados tras un año de experiencia clínica / Development of a Non-Heart-Beating Lung Donor Program With «Bithermia Preservation», and Results After One Year of Clinical Experience

El número de trasplantes pulmonares que se realizan en España continúa en ascenso, con 235 pacientes trasplantados en 2010. Los programas de donantes en asistolia han contribuido a esta progresión. Nuestra Unidad de Trasplante Pulmonar comenzó su actividad en octubre de 2008, y en estos 3 años se han trasplantado con éxito el 97% de los pacientes intervenidos. Para obtener un mayor número de donantes hemos desarrollado un programa de donación pulmonar en asistolia a partir del programa existente en nuestro hospital. Fue necesario la elaboración de una metodología de preservación multiorgánica (pulmonar, hepática y renal) que hemos denominado «preservación en bitermia». Presentamos la experiencia de su aplicación clínica durante el primer año. Hemos trasplantado 3 pacientes utilizando este tipo de donantes en asistolia. Ninguno de los pacientes desarrolló disfunción primaria del injerto, todos fueron dados de alta, realizan vida activa y sin datos de síndrome de bronquiolitis obliterante (AU)

The number of lung transplantations that are performed in Spain continues to grow, with 235 transplant recipients 2010. Non-heart-beating donations have contributed to this upward progression. Our Lung Transplant Unit began its activity in October 2008 and during these last three years 97% of the transplant interventions performed have been successful. In order to increase the number of donations, we have developed a non-heart-beating donor program as part of the existing organs program in our hospital. In doing so, the development of a multi-organic preservation method (lung, liver and kidney), which we call «Bithermia Preservation», was necessary. This paper presents this methodology as well as the first year of clinical application experience. During this time, 3 patients have been transplanted using such non-heart-beating donations. None of them developed primary graft dysfunction; all the patients have been discharged and lead active lives without any evidence of bronchiolitis obliterans syndrome (AU)

Development of a non-heart-beating lung donor program with «Bithermia Preservation¼, and results after one year of clinical experience.

The number of lung transplantations that are performed in Spain continues to grow, with 235 transplant recipients 2010. Non-heart-beating donations have contributed to this upward progression. Our Lung Transplant Unit began its activity in October 2008 and during these last three years 97% of the transplant interventions performed have been successful. In order to increase the number of donations, we have developed a non-heart-beating donor program as part of the existing organs program in our hospital. In doing so, the development of a multi-organic preservation method (lung, liver and kidney), which we call «Bithermia Preservation¼, was necessary. This paper presents this methodology as well as the first year of clinical application experience. During this time, 3 patients have been transplanted using such non-heart-beating donations. None of them developed primary graft dysfunction; all the patients have been discharged and lead active lives without any evidence of bronchiolitis obliterans syndrome.

Normativa para la selección de pacientes candidatos a trasplante pulmonar / Guidelines for the Selection of Lung Transplantation Candidates

La presente normativa ha sido elaborada con el consenso de, al menos, un representante de cada uno delos hospitales con programa de trasplante pulmonar en España. Además, previamente a su publicación,ha sido revisada por un grupo de revisores destacados por su reconocida trayectoria en el campo del trasplantepulmonar. En las siguientes páginas, el lector encontrará los criterios de selección de pacientescandidatos a trasplante pulmonar, cuándo y cómo remitir un paciente a un centro trasplantador y, finalmente,cuándo incluir al paciente en lista de espera. Se ha atribuido un nivel de evidencia a las cuestionesmás relevantes. Este documento pretende ser una guía práctica para los neumólogos que no participandirectamente en el trasplante pulmonar pero que deben considerar este tratamiento para sus pacientes.Finalmente, se ha propuesto de una forma consensuada un documento que recoge de forma estructuradalos datos del paciente potencial candidato a trasplante pulmonar que son relevantes para poder tomar lamejor decisión(AU)

The present guidelines have been prepared with the consensus of at least one representative of eachof the hospitals with lung transplantation programs in Spain. In addition, prior to their publication,these guidelines have been reviewed by a group of prominent reviewers who are recognized for theirprofessional experience in the field of lung transplantation. Within the following pages, the reader willfind the selection criteria for lung transplantation candidates, when and how to remit a patient to atransplantation center and, lastly, when to add the patient to the waiting list. A level of evidence hasbeen identified for the most relevant questions. Our intention is for this document to be a practical guide for pulmonologists who do not directly participate in lung transplantations but who should consider thistreatment for their patients. Finally, these guidelines also propose an information form in order to compilein an organized manner the patient data of the potential candidate for lung transplantation, which arerelevant in order to be able to make the best decisions possible(AU)

Guidelines for the selection of lung transplantation candidates.

The present guidelines have been prepared with the consensus of at least one representative of each of the hospitals with lung transplantation programs in Spain. In addition, prior to their publication, these guidelines have been reviewed by a group of prominent reviewers who are recognized for their professional experience in the field of lung transplantation. Within the following pages, the reader will find the selection criteria for lung transplantation candidates, when and how to remit a patient to a transplantation center and, lastly, when to add the patient to the waiting list. A level of evidence has been identified for the most relevant questions. Our intention is for this document to be a practical guide for pulmonologists who do not directly participate in lung transplantations but who should consider this treatment for their patients. Finally, these guidelines also propose an information form in order to compile in an organized manner the patient data of the potential candidate for lung transplantation, which are relevant in order to be able to make the best decisions possible.

Causa intratorácica poco frecuente de neumoperitoneo espontáneo / An uncommon intrathoracic cause of spontaneous pneumoperitoneum

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Graft pneumonectomy and delayed contralateral lung transplantation.

We believe that contralateral single lung transplantation after graft pneumonectomy has not been reported yet in the literature. We present the case of an emphysematous patient who received a unilateral left lung transplant and had severe stenosis in bronchial anastomosis and bronchiectasis develop. Four years after transplantation we decided to perform a left pneumonectomy and a delayed right lung transplantation. Nine months after the procedure the patient is ambulatory and is not dependent on oxygen support.

Results of clinical lung transplant from uncontrolled non-heart-beating donors.

BACKGROUND: The scarcity of grafts for lung transplant and the growing number of candidates expecting an organ has led to an increase of deaths in patients waiting for lung transplantation. Non-heart-beating donors (NHBD) represent a promising source of grafts for those who are involved in clinical lung transplantation. We present the results of our series of 17 out-of-hospital NHBD lung transplantations performed since 2002. METHODS: We have collected data from 17 donors and recipients involved in NHBD lung transplants since 2002, as well as data referring to the type of procedure and peri-operative events. We describe the incidence of post-operative complications with special attention to primary graft disfunction (PGD), bronchial healing, bronchiolitis obliterans syndrome (BOS), and survival. We used Kaplan-Meier method to obtain the survival curve. RESULTS: G2-G3 PGD was reported in 9 patients (53%), with a complete restoration of the partial pressure of arterial oxygen/fraction of inspired oxygen ratio in 170 hours for G2 and 168 hours for G3. There were no deaths directly related to PGD. Acute rejection was detected in 7 patients (41%), 4 of which exceeded grade 1. The incidence of BOS after transplantation was 1 (7%) of 14 patients during the first year, 2 (11%) of 9 in the second year, and 2 (50%) of 4 in the third year. Hospital mortality rate was 17%. The survival rates were 82% at 3 months, 69%, at 1 year, and 58% at 3 years. CONCLUSIONS: Mid-term results confirm the adequacy of uncontrolled NHBD as a promising complementary source of lung donors for clinical transplant.

[Is endoscopic treatment of bronchopleural fistula useful?]. / 'Es útil el tratamiento endoscópico de las fístulas bronquiales?

OBJECTIVE: New endoscopic techniques have been developed as an alternative to surgical treatment of bronchopleural fistula. The objective of this study was to analyze our experience with endoscopic treatment of such fistulas. MATERIAL AND METHODS: We conducted a retrospective study of patients with bronchopleural fistula diagnosed by fiberoptic bronchoscopy. Patient characteristics, underlying disease, fistula size, and outcome of endoscopic treatment were analyzed. The endoscopic technique consisted of injection of fibrin sealants (Histoacryl and/or Tissucol) through the catheter of the fiberoptic bronchoscope. RESULTS: Between 1997 and 2004, 18 patients were diagnosed with bronchopleural fistula by fiberoptic bronchoscopy. All were men with a mean (SD) age of 62 (12) years. Bronchopleural fistula was diagnosed after neoplastic surgery in 16 patients, in the bronchial suture after lung transplantation in 1 patient, and concurrently with pleural effusion due to hydatidosis in the remaining patient. The size of the fistula ranged from 1 mm to 10 mm (mean 3.6 [2.7] mm). Fibrin sealants were applied in 14 patients, 2 underwent direct surgery after diagnosis, and the bronchopleural fistula closed spontaneously in the remaining 2. The fibrin sealant used was Histoacryl in 12 patients and Tissucol in 2. Pleural drainage was employed simultaneously and antibiotic therapy was administered at the discretion of the surgeon. The 4 patients whose bronchopleural fistula was associated with empyema also underwent pleural lavage. In 12 patients the fistulas closed as a result of the endoscopic technique (85.7%), and no complications were observed. For 85.7%, fewer than 3 applications of fibrin sealant were necessary. CONCLUSIONS: The success rate of closure of bronchopleural fistula with fibrin sealants injected under guidance with fiberoptic bronchoscopy is high and there are no complications. This technique can render surgery unnecessary.