Advances in multimodal treatment for stage IIIA-N2 non-small cell lung cancer.

BACKGROUND AND AIM: In Stage IIIA-N2 non-small cell lung cancer (NSCLC), the accuracy of combined positron-emission tomography/computed tomography imaging (PET-CT), together with mediastinal staging techniques, has led to a wide range of challenging clinical scenarios in terms of therapeutic management. Concurrent chemoradiotherapy followed by consolidation immunotherapy remains the standard of care. In patients with potentially-resectable disease, surgery plays an important role in multimodal therapy. The introduction of targeted therapies and immune-checkpoint inhibitors has revolutionized multimodal treatment. In the present article, we review current treatment options and future trends in stage IIIA-N2 NSCLC. RELEVANCE FOR PATIENTS: This article provides insight into the current status of multimodal treatment for NSCLC to support decision-making in routine clinical practice.

High-dose neoadjuvant chemoradiotherapy versus chemotherapy alone followed by surgery in potentially-resectable stage IIIA-N2 NSCLC. A multi-institutional retrospective study by the Oncologic Group for the Study of Lung Cancer (Spanish Radiation Oncology Society).

BACKGROUND: The optimal induction treatment in potentially-resectable stage IIIA-N2 NSCLC remains undefined. AIM: To compare neoadjuvant high-dose chemoradiotherapy (CRT) to neoadjuvant chemotherapy (CHT) in patients with resectable, stage IIIA-N2 non-small-cell lung cancer (NSCLC). METHODS: Retrospective, multicentre study of 99 patients diagnosed with stage cT1-T3N2M0 NSCLC who underwent neoadjuvant treatment (high-dose CRT or CHT) followed by surgery between January 2005 and December 2014. RESULTS: 47 patients (47.5%) underwent CRT and 52 (52.5%) CHT, with a median follow-up of 41 months. Surgery consisted of lobectomy (87.2% and 82.7%, in the CRT and CHT groups, respectively) or pneumonectomy (12.8% vs. 17.3%). Nodal downstaging (to N1/N0) and Pathologic complete response (pCR; pT0pN0) rates were significantly higher in the CRT group (89.4% vs. 57.7% and 46.8% vs. 7.7%, respectively; p < 0.001)). Locoregional recurrence was significantly lower in the CRT group (8.5% vs. 13.5%; p = 0.047) but distant recurrence rates were similar in the two groups. Median PFS was 45 months (CHT) vs. "not reached" (CRT). Median OS was similar: 61 vs. 56 months (p = 0.803). No differences in grade ≥3 toxicity were observed. On the Cox regression analysis, advanced pT stage was associated with worse OS and PFS (p < 0.001) and persistent N2 disease (p = 0.002) was associated with worse PFS. CONCLUSIONS: Compared to neoadjuvant chemotherapy alone, a higher proportion of patients treated with preoperative CRT achieved nodal downstaging and pCR with better locoregional control. However, there were no differences in survival. More studies are needed to know the optimal treatment of these patients.

Functional Chest Wall Reconstruction With a Biomechanical Three-Dimensionally Printed Implant.

Chest wall resection and reconstruction for neoplastic diseases has unique oncologic, structural, and functional challenges. In a young and fit patient with a mediastinal mass and extensive anterior chest wall invasion, purely structural solutions were deemed insufficient. We hereby present a novel three-dimensionally printed patient-specific titanium implant of sternum and ribs. This osteointegrable implant was designed with biomechanical capabilities using a unique "Greek wave" folding pattern. Postoperative dynamic computed tomography showed that the implant allowed for controlled flexing during the respiratory cycle. Three-dimensional printing with biocompatible materials could enable a new generation of chest wall implants strongly focused on functional reconstruction.

Estenosis traqueal y enfermedad por IgG4 / Tracheal stenosis and IgG4-related disease

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Experiencia de los Servicios de Cirugía Torácica españoles en el tratamiento del pectus excavatum mediante la técnica de Nuss / Experience with the Nuss technique for the treatment of Pectus Excavatum in Spanish Thoracic Surgery Departments

INTRODUCCIÓN: Aunque la introducción de la técnica de Nuss revolucionó el tratamiento quirúrgico del pectus excavatum, no se ha generalizado su uso en nuestro medio. El objetivo de este estudio es conocer la situacion actual del uso de esta técnica en una selección de Servicios de Cirugía Torácica de España. MÉTODOS: Estudio observacional retrospectivo multicéntrico que analiza los principales aspectos epidemiológicos y resultados clínicos tras 10 años de experiencia empleando técnica de Nuss. RESULTADOS: Entre 2001 y 2010 se intervino a 149 pacientes (media de edad 21,2 años), 74% varones. Los resultados estéticos iniciales fueron excelentes o buenos en el 93,2%, regulares en el 4,1% y malos en el 2,7% de los casos. Un total de 45 pacientes (30,6%) presentaron complicaciones tras la primera intervención. Las más frecuentes fueron la presencia de seroma en las heridas quirúrgicas, desplazamiento de la barra, rotura del estabilizador, neumotórax, hemotórax, infección de la herida, neumonía, pericarditis y un taponamiento pericárdico que requirió la extracción de la barra de urgencia. El dolor postoperatorio fue referido por todos los pacientes y 3 de ellos (2%) requirieron la extracción precoz de la barra por dolor intratable. Tras una media de 39,2 meses, se había retirado la barra a 72 pacientes (49%), con dificultades en la extracción en 5 (7%). Tras un seguimiento medio de 1,6 años se constató buen resultado en 145 pacientes (98,7%). CONCLUSIONES: La técnica de Nuss en adultos ha tenido buenos resultados en los Servicios de Cirugía Torácica españoles aunque no se ha generalizado su utilización. Las posibles complicaciones se han de tener en cuenta, por lo que la indicación debe ser muy bien valorada. La posibilidad de un tratamiento conservador previo es valorado por alguno de los servicios en la actualidad

INTRODUCTION: Up to 93% of patients undergoing abdominal surgery will develop intra-abdominal adhesions with the subsequent morbidity that they represent. Various substances have been tested for the prevention of adhesions with controversial results; the aim of our study is to compare the capability of pirfenidone in adhesion prevention against sodium hyaluronate/carboxymethylcellulose. METHODS: A randomized, prospective, longitudinal experimental study with Winstar rats. They were divided into 3 groups. The subjects underwent an exploratory laparotomy and they had a 4 cm2 cecal abrasion. The first group received saline on the cecal abrasion, and groups 2 and 3 received pirfenidone and sodium hyaluronate/carboxymethylcellulose respectively. All rats were sacrificed on the 21st day after surgery and the presence of adhesions was evaluated with the modified Granat scale. Simple frequency, central tendency and dispersion measures were recorded. For the statistical analysis we used Fisher's test. RESULTS: To evaluate adhesions we used the Granat's modified scale. The control group had a median adhesion formation of 3 (range 0-4). The pirfenidone group had 1.5 (range 0-3), and the sodium hyaluronate/carboxymethylcellulose group had 0 (range 0-1). There was a statistically significant difference to favor sodium hyaluronate/carboxymethylcellulose against saline and pirfenidone (P< 0 .009 and P< .022 respectively). CONCLUSIONS: The use of sodium hyaluronate/carboxymethylcellulose is effective for the prevention of intra-abdominal adhesions. More experimental studies are needed in search for the optimal adhesion prevention drug

Experience with the Nuss technique for the treatment of Pectus Excavatum in Spanish Thoracic Surgery Departments.

INTRODUCTION: Although the Nuss technique revolutionized the surgical treatment of pectus excavatum, its use has not become widespread in our country. The aim of this study was to analyze the current use of this technique in a sample of Thoracic Surgery Departments in Spain. METHODS: Observational rectrospective multicentric study analyzing the main epidemiological aspects and clinical results of ten years experience using the Nuss technique. RESULTS: Between 2001 and 2010 a total of 149 patients were operated on (mean age 21.2 years), 74% male. Initial aesthetic results were excellent or good in 93.2%, mild in 4.1% and bad in 2.7%. After initial surgery there were complications in 45 patients (30.6%). The most frequent were wound seroma, bar displacement, stabilizer break, pneumothorax, haemothorax, wound infection, pneumonia, pericarditis and cardiac tamponade that required urgent bar removal. Postoperative pain appeared in all patients. In 3 cases (2%) it was so intense that it required bar removal. After a mean follow-up of 39.2 months, bar removal had been performed in 72 patients (49%), being difficult in 5 cases (7%). After a 1.6 year follow-up period good results persisted in 145 patients (98.7%). CONCLUSION: Nuss technique in adults has had good results in Spanish Thoracic Surgery Departments, however its use has not been generalized. The risk of complications must be taken into account and its indication must be properly evaluated. The possibility of previous conservative treatment is being analyzed in several departments at present.

Normothermic perfusion of donor lungs for preservation and assessment with the Organ Care System Lung before bilateral transplantation: a pilot study of 12 patients.

BACKGROUND: Cold flush and static cold storage is the standard preservation technique for donor lungs before transplantations. Several research groups have assessed normothermic perfusion of donor lungs but all devices investigated were non-portable. We report first-in-man experience of the portable Organ Care System (OCS) Lung device for concomitant preservation, assessment, and transport of donor lungs. METHODS: Between Feb 18, and July 1, 2011, 12 patients were transplanted at two academic lung transplantation centres in Hanover, Germany and Madrid, Spain. Lungs were perfused with low-potassium dextran solution, explanted, immediately connected to the OCS Lung, perfused with Steen's solution supplemented with two red-cell concentrates. We assessed donor and recipient characteristics and monitored extended criteria donor lung scores; primary graft dysfunction scores at 0, 24, 48, and 72 h; time on mechanical ventilation after surgery; length of stays in hospital and the intensive-care unit after surgery; blood gases; and survival of grafts and patients. FINDINGS: Eight donors were female and four were male (mean age 44·5 years, range 14-72). Seven recipients were female and five were male (mean age 50·0 years, range 31-59). The preharvest donor ratio of partial pressure of oxyen (PaO(2)) to fractional concentration of oxygen in inspired air (F(I)O(2)) was 463·9 (SD 91·4). The final ratio of PaO(2) to F(I)O(2) measured with the OCS Lung was 471·58 (127·9). The difference between these ratios was not significant (p=0·72). All grafts and patients survived to 30 days; all recipients recovered and were discharged from hospital. INTERPRETATION: Lungs can be safely preserved with the OCS Lung, resulting in complete organ use and successful transplantation in our series of high-risk recipients. In November, 2011, we began recruitment for a prospective, randomised, multicentre trial (INSPIRE) to compare preservation with OCS Lung with standard cold storage. FUNDING: TransMedics and German Federal Ministry of Education and Research.

Clinical lung transplantation from uncontrolled non-heart-beating donors revisited.

BACKGROUND: The aim of our study is to review and update the long-term results from our previously published series of lung transplantation in uncontrolled non-heart-beating donors (NHBDs). METHODS: A prospective collection of data was undertaken from all lung transplants performed among uncontrolled NHBDs between 2002 and December 2009. The statistical analysis was performed using SPSS software and survival was estimated using the Kaplan-Meier method. RESULTS: Twenty-nine lung transplants were performed. Mean total ischemic times for the first and second lung were 575 minutes (SD 115.6) and 701 minutes (SD 111.3), respectively. Primary graft dysfunction (PGD) G1, G2 and G3 occurred in 5 cases (17%), 5 cases (17%) and 11 cases (38%), respectively. Overall hospital mortality rate was 17% (5 patients). Statistical analysis revealed a statistically significant association of mortality with ischemic times and with PGD. In terms of overall survival, 3-month, 1-year, 2-year and 5-year survival rates were 78%, 68%, 57% and 51%, respectively, and the conditional survival rates in those who survived the first 3 months were 86%, 72% and 65%, respectively. The cumulative incidence of bronchiolitis obliterans syndrome (BOS) was 11%, 35% and 45% at 1, 3 and 5 years, respectively. CONCLUSIONS: Lung transplantation from uncontrolled non-heart-beating donors shows acceptable results for both mid- and long-term survival and BOS; however, the higher rates of PGD and its impact on early mortality must make us more demanding with respect to the acceptance criteria and methods of evaluation used with these donors.

Trasplante de pulmón con donantes no controlados a corazón parado. Factores pronósticos dependientes del donante y evolución inmediata postrasplante / Lung Transplantation with Uncontrolled Non-Heart-Beating Donors. Transplantation. Donor Prognostic Factor and Immediate Evolution Post Transplant

Introducción: La donación en asistolia no controlada (DANC) constituye una alternativa al trasplantepulmonar con donantes en muerte encefálica. El objetivo principal del estudio es describir la incidenciade eventos al mes tras el trasplante con pulmones de DANC, y la influencia de los factores dependientesdel donante y del proceso de donación.Pacientes y métodos: Estudio de una cohorte histórica de 33 receptores de trasplante pulmonar realizadosen los hospitales Puerta de Hierro y Marqués de Valdecilla con 32 DANC procedentes del Hospital ClínicoSan Carlos durante el periodo 2002-2008. Se estudiaron los siguientes eventos: complicaciones quirúrgicasy médicas, disfunción primaria del injerto, rechazo agudo, neumonía y mortalidad. Se evaluaron lascaracterísticas del donante y los tiempos del proceso de donación (minutos).Resultados: La mediana de edad de los receptores fue 50,5 años (rango intercuartílico, 38,5-58); 28 hombresy 5 mujeres. La incidencia acumulada de los eventos al mes fue: neumonía, 10 (31,3%); disfunciónprimaria del injerto, 15 (46,9%); rechazo, 12 (37,5%); mortalidad, 4 (12,1%); complicaciones médicas,25 (78,1%), y quirúrgicas, 18 (56,3%). La mediana del tiempo de asistolia fue mayor en los sujetos conneumonía (15 vs. 7,5; p = 0,027), la mediana del tiempo de isquemia fría fue superior en los sujetos quepresentaron complicaciones quirúrgicas y mortalidad (436 vs. 343,5; p = 0,04; 505 vs. 410; p = 0,033, respectivamente),y las medianas de los tiempos de isquemia total fueron superiores en los receptores quefallecieron (828 vs. 695; p = 0,036).Conclusiones: Los DANC constituyen una alternativa válida para expandir el pool de donantes pulmonaresante la carencia actual de pulmones válidos para el trasplante. La incidencia de complicaciones escomparable con los datos publicados en la literatura(AU)

Introduction: Uncontrolled donation after cardiac death (DACD) has become an alternative to lung transplantationwith encephalic-death donation. The main objective of this study is to describe the incidenceof clinically relevant events in the period of thirty days after lung transplant with uncontrolled DACD andthe influence of factors depending on the donor and donation process as well.Patients and methods: Historical cohort study of 33 lung transplant receivers at Hospital Puerta de Hierro and Hospital Marqués de Valdecilla with 32 DACD from Hospital Clínico San Carlos from 2002 to 2008.We studied surgical and medical complications, primary graft dysfunction, acute rejection, pneumonia and mortality. We made an evaluation of the donor characteristics and donation procedure times (minutes). Results: Median age of recipients was 50.5 years (interquartile range, 38.5-58). There were 28 malesand 5 females. Cumulative incidence of events in the first month was: pneumonia 10 (31.3%); primarygraft dysfunction 15 (46.9%); rejection 12 (37.5%); mortality 4 (12.1%); medical complications 25 (78.1%);and surgical complications 18(56.3%). Median time of cardiac arrest was higher in those who presentedpneumonia (15 vs. 7.5; p = 0.027). Median time of cold ischemia was higher in those who presentedsurgical complications and mortality (436 vs. 343.5; p = 0.04; 505 vs. 410; p = 0.033, respectively), andmedian of total ischemia times were longer in the recipients who died (828 vs. 695; p = 0.036).Conclusions: Uncontrolled DACD are a valid alternative for expanding the donor pool in order to mitigatethe current shortage of lungs that are valid for transplantation. The incidence of complications iscomparable with published data in the literature(AU)

[Lung transplantation with uncontrolled non-heart-beating donors. Transplantation. Donor prognostic factor and immediate evolution post transplant]. / Trasplante de pulmón con donantes no controlados a corazón parado. Factores pronósticos dependientes del donante y evolución inmediata postrasplante.

INTRODUCTION: Uncontrolled donation after cardiac death (DACD) has become an alternative to lung transplantation with encephalic-death donation. The main objective of this study is to describe the incidence of clinically relevant events in the period of thirty days after lung transplant with uncontrolled DACD and the influence of factors depending on the donor and donation process as well. PATIENTS AND METHODS: Historical cohort study of 33 lung transplant receivers at Hospital Puerta de Hierro and Hospital Marqués de Valdecilla with 32 DACD from Hospital Clínico San Carlos from 2002 to 2008. We studied surgical and medical complications, primary graft dysfunction, acute rejection, pneumonia and mortality. We made an evaluation of the donor characteristics and donation procedure times (minutes). RESULTS: Median age of recipients was 50.5 years (interquartile range, 38.5-58). There were 28 males and 5 females. Cumulative incidence of events in the first month was: pneumonia 10 (31.3%); primary graft dysfunction 15 (46.9%); rejection 12 (37.5%); mortality 4 (12.1%); medical complications 25 (78.1%); and surgical complications 18 (56.3%). Median time of cardiac arrest was higher in those who presented pneumonia (15 vs. 7.5; p = 0.027). Median time of cold ischemia was higher in those who presented surgical complications and mortality (436 vs. 343.5; p = 0.04; 505 vs. 410; p = 0.033, respectively), and median of total ischemia times were longer in the recipients who died (828 vs. 695; p = 0.036). CONCLUSIONS: Uncontrolled DACD are a valid alternative for expanding the donor pool in order to mitigate the current shortage of lungs that are valid for transplantation. The incidence of complications is comparable with published data in the literature.

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.

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.