S-adenosylhomocysteine hydrolase-like protein 1 (AHCYL1) inhibits lung cancer tumorigenesis by regulating cell plasticity.

BACKGROUND: Lung cancer is one of the most frequently diagnosed cancers characterized by high mortality, metastatic potential, and recurrence. Deregulated gene expression of lung cancer, likewise in many other solid tumors, accounts for their cell heterogeneity and plasticity. S-adenosylhomocysteine hydrolase-like protein 1 (AHCYL1), also known as Inositol triphosphate (IP(3)) receptor-binding protein released with IP(3) (IRBIT), plays roles in many cellular functions, including autophagy and apoptosis but AHCYL1 role in lung cancer is largely unknown. RESULTS: Here, we analyzed the expression of AHCYL1 in Non-Small Cell Lung Cancer (NSCLC) cells from RNA-seq public data and surgical specimens, which revealed that AHCYL1 expression is downregulated in tumors and inverse correlated to proliferation marker Ki67 and the stemness signature expression. AHCYL1-silenced NSCLC cells showed enhanced stem-like properties in vitro, which correlated with higher expression levels of stem markers POU5F1 and CD133. Also, the lack of AHCYL1 enhanced tumorigenicity and angiogenesis in mouse xenograft models highlighting stemness features. CONCLUSIONS: These findings indicate that AHCYL1 is a negative regulator in NSCLC tumorigenesis by modulating cell differentiation state and highlighting AHCYL1 as a potential prognostic biomarker for lung cancer.

Argentine consensus recommendations for lung cancer screening programmes: a RAND/UCLA-modified Delphi study.

BACKGROUND: Lung cancer (LC) screening improves LC survival; the best screening method in terms of improving survival is low-dose CT (LDCT), outpacing chest X-ray and sputum cytology. METHODS: A consensus of experts in Argentina was carried out to review the literature and generate recommendations for LC screening programmes. A mixed-method study was used with three phases: (1) review of the literature; (2) modified Delphi consensus panel; and (3) development of the recommendations. The Evidence to Decision (EtD) framework was used to generate 13 evaluation criteria. Nineteen experts participated in four voting rounds. Consensus among participants was defined using the RAND/UCLA method. RESULTS: A total of 16 recommendations scored ≥7 points with no disagreement on any criteria. Screening for LC should be performed with LDCT annually in the population at high-risk, aged between 55 and 74 years, regardless of sex, without comorbidities with a risk of death higher than the risk of death from LC, smoking ≥30 pack-years or former smokers who quit smoking within 15 years. Screening will be considered positive when finding a solid nodule ≥6 mm in diameter (or ≥113 mm3) on baseline LDCT and 4 mm in diameter if a new nodule is identified on annual screening. A smoking cessation programme should be offered, and cardiovascular risk assessment should be performed. Institutions should have a multidisciplinary committee, have protocols for the management of symptomatic patients not included in the programme and distribute educational material. CONCLUSION: The recommendations provide a basis for minimum requirements from which local institutions can develop their own protocols adapted to their needs and resources.

Resección de nódulo pulmonar en pulmón trasplantado bajo asistencia con membrana de oxigenación extracorpórea / Resection of a pulmonary nodule in a transplanted lung under extracorporeal membrane oxygenation

La utilización de soporte perioperatorio con sistema de oxigenación a través de membrana extracorpórea (ECMO) es un concepto novedoso en cirugía torácica general. Se presenta el caso de un paciente con trasplante pulmonar derecho por fibrosis pulmonar idiopática (FPI) que requirió la resección de un nódulo pulmonar homolateral con soporte de ECMO veno-venoso (VV). El soporte a través de ECMO VV es una opción viable cuando se prevén dificultades con la ventilación unipulmonar en casos seleccionados.

The use of perioperative support with extracorporeal membrane oxygenation (ECMO) systems is a novel concept in general thoracic surgery We report the case of a male patient with a history of right lung transplant due to idiopathic pulmonary fibrosis (IPF) who required resection of a right pulmonary nodule under veno-venous (VV) ECMO support. The use of VV-ECMO is a feasible option in selected cases when complications are expected to occur with one lung ventilation.

Lobectomía pulmonar: ¿Qué beneficios ofrece la videotoracoscopía? / Pulmonary Lobectomy. What are the Benefits of Video-assisted Thoracoscopy?

Introducción: A pesar del creciente uso de la lobectomía por videotoracoscopía, este abordaje resulta aún controvertido en algunos aspectos. El objetivo del presente trabajo es comparar los resultados quirúrgicos de la lobectomía pulmonar por videotoracoscopía y por toracotomía. Material y métodos: En el Hospital Universitario Fundación Favaloro, entre los años 2008 y 2017, fueron intervenidos quirúrgicamente 153 pacientes (n = 89 masculinos). Resultados: Se realizó lobectomía por videotoracoscopía a 39/89 pacientes. Los pacientes intervenidos por videotoracoscopía y con diagnóstico de cáncer de pulmón, tenían predominantemente tumores en estadío I (25/39 pacientes). La incidencia de complicaciones postoperatorias y mortalidad fueron similares en ambos grupos. En el grupo intervenido por videotoracoscopía la permanencia del drenaje pleural fue significativamente menor (4 versus 3 días, p = 0.004) y, también resultó más breve la estadía hospitalaria (6 versus 4 días de internación, p = 0.03). El número de estaciones ganglionares exploradas durante la cirugía fue mayor en los pacientes operados por toracotomía (4 versus 3.5 estaciones ganglionares, p < 0.001). Conclusión: La lobectomía por videotoracoscopía resultó al menos equivalente a la cirugía por toracotomía en términos de complicaciones postoperatorias. Los principales beneficios del abordaje por videotoracoscopía fueron una menor permanencia del drenaje pleural y menor estadía hospitalaria. Se recomienda tener especial cuidado con el muestreo ganglionar cuando la cirugía se realiza por videotoracoscopía.

Introduction: Despite the widespread adoption of video-assisted thoracoscopic lobectomy, this surgical approach still remains controversial. The objective of this paper is to compare the surgical results of video-assisted thoracoscopic lobectomy to open thoracotomy lobectomy, performed at the Hospital Universitario Fundación Favaloro between 2008 and 2017. Materials and Methods: One-hundred and fifty three patients (n = 89 males) had surgery during the study period; 39/153 had video-assisted thoracoscopic lobectomy. Results: Patients that had video-assisted thoracoscopic lobectomy were more likely to have stage I lung cancer (25/39). Postoperative complications and mortality rates were similar in both groups. Video-assisted thoracoscopic lobectomy patients had a shorter chest tube drainage time (4 vs. 3 days, p = 0.004) and length of hospital stay (6 vs. 4 days of stay, p = 0.03). The median number of lymph node stations sampled at surgery was significantly higher in the patients that had open thoracotomy lobectomy (4 vs. 3.5 lymph node stations, p < 0.001). Conclusion: Video-assisted thoracoscopic lobectomy is at least equivalent to open thoracotomy lobectomy in terms of postoperative complications and mortality. The main benefits of the video-assisted thoracoscopic approach are a shorter chest tube drainage time and length of hospital stay. Special attention should be taken at the time of nodal sampling when the surgery is performed by the video-assisted thoracoscopic approach.

Pulmonary Lobectomy: What are the Benefits of Video-assisted Thoracoscopy?

Introduction: Despite the increasing use of video-assisted thoracoscopic lobectomy, this surgical approach is still controversial in certain aspects. The purpose of this study is to compare the surgical results of video-assisted thoracoscopic pulmonary lobectomy to pulmonary lobectomy via thoracotomy. Materials and Methods: Between 2008 and 2017, 153 patients (n = 89 males) had surgery at the Hospital Universitario Fundación Favaloro. Results: 39/89 patients underwent video-assisted thoracoscopic lobectomy. Patients who had video-assisted thoracoscopy and were diagnosed with lung cancer mostly had stage I tumors (25/39 patients). Postoperative complications and mortality rates were similar in both groups. Video-assisted thoracoscopy patients had a significantly shorter pleural drainage time (4 vs. 3 days, p = 0.004) and a shorter length of hospital stay (6 vs. 4 days of stay, p = 0.03). The number of lymph node stations sampled during surgery was higher in the patients operated via thoracotomy (4 vs. 3.5 lymph node stations, p < 0.001). Conclusion: Video-assisted thoracoscopic lobectomy was at least equivalent to surgery by means of thoracotomy in terms of postoperative complications. The main benefits of the video-assisted thoracoscopy approach were shorter pleural drainage time and length of hospital stay. Special attention should be paid to nodal sampling when the surgery is performed via video-assisted thoracoscopy.

El valor predictivo negativo de la mediastinoscopía realizada por cirujanos torácicos / Negative Predictive Value of Mediastinoscopy Carried Out by Chest Surgeons

Antecedentes: A pesar de que la mediastinoscopía constituye el método de referencia en el diagnóstico prequirúrgico de enfermedad mediastinal en el cáncer pulmonar, recientemente su utilidad ha sido cuestionada debido a la aparición de métodos menos invasivos de los que se reporta serían al menos tan efectivos como la mediastinoscopía. Nuestro objetivo es revisar el índice de falsos negativos, valor predictivo negativo y sensibilidad de la mediastinoscopía cuando es realizada por cirujanos torácicos certificados. Métodos: Se seleccionaron del registro prospectivo de cirugía torácica del Hospital Universitario Fundación Favaloro todas las mediastinoscopías realizadas entre los años 2009 y 2015. De estos casos se revisaron las historias clínicas, reportes quirúrgicos y de anatomía patológica. Resultados: Se realizaron 82 mediastinoscopías en el período de estudio; 50 pacientes fueron hombres; la mediana de edad fue de 61 años. En el 100% de los casos se obtuvieron ganglios linfáticos. El porcentaje de falsos negativos de la mediastinoscopía fue de 7/82 pacientes. Tanto la sensibilidad como el valor predictivo negativo de la mediastinoscopía fueron del 84%. Hubo una complicación intraoperatoria. La mortalidad relacionada con el procedimiento fue del 0%. Conclusiones: La mediastinoscopía es un método seguro y de alto valor predictivo negativo cuando es realizada por cirujanos torácicos certificados. En todos los casos se obtienen ganglios linfáticos para su análisis. Estos valores son los que deberían tenerse en cuenta al momento de comparar este método con los nuevos métodos de muestra ganglionar mediastinal menos invasivos.

Background: Although mediastinoscopy is the gold standard in the preoperative diagnosis of lung cancer mediastinal disease, recent publications have addressed the role of newer less invasive methods, suggesting that they are at least, as valid as mediastinoscopy. Our objective was to report the false negative rate, negative predictive value and sensitivity of mediastinoscopy when performed by certified chest surgeons. Methods: The study included all patients who underwent mediastinoscopy at the General Thoracic Surgery Unit of the Hospital Universitario Fundación Favaloro from 2009 up to 2015. Medical, pathology and surgical reports were reviewed. Results: 82 patients underwent mediastinoscopy during the study period; 50 patients were men. Median age was 61 years. In all patients samples of lymph node tissue were obtained. The false negative rate of mediastinoscopy was 7/82 patients. The negative predictive value and the sensitivity of the procedure were 84%. There was one intraoperative complication. The mediastinoscopy related mortality rate was 0%. Conclusions: Mediastinoscopy is safe and has a high negative predictive value when it is performed by certifed chest surgeons. Samples of lymphatic tissue for biopsy can be obtained in 100% of the cases. These values should be used for comparisons with any newer minimally invasive methods designed to replace mediastinoscopy.

Surgical lung biopsy in transplant patients with diffuse lung disease: how much worse when the lung is the graft?

BACKGROUND: There are no data that compare the clinical presentation and results of surgical lung biopsy (SLB) for diffuse lung disease (DLD) in lung transplant patients, in contrast to individuals with other type of solid organ grafts. Our objective was to compare the clinical picture, radiologic pattern, pathology results, and outcomes of SLB for DLD in these two subsets of patients. METHODS: We retrospectively reviewed the clinical records of transplant patients undergoing SLB for DLD at our institution between 2004 and 2011. Patients with lung transplants and those with other transplants were compared. RESULTS: During the study period, 1,232 solid organ transplants were done at our institution. Of these, 49 patients (4%) had DLD that needed SLB for diagnosis, and 24 of these patients had a lung transplant. Dyspnea and a radiologic reticular pattern were more frequent in lung transplant patients, 21 of 24 vs 11 of 25 (p = 0.001) and 14 of 24 vs 7 of 25 (p = 0.03), respectively. Although postoperative complications and in-hospital deaths were more common in lung transplant patients, the differences were not statistically significant. Having the SLB performed for diagnosis, as opposed to being conducted for DLD that did not improve on medical treatment, had a protective effect on multivariate analysis (hazard ratio, 0.39; 95% confidence interval, 0.16 to 0.96; p = 0.042). A prior lung transplant was the only independent predictor of survival (hazard ratio, 4.62; 95% confidence interval, 1.53 to 13.92, p = 0.006). CONCLUSIONS: It is relatively uncommon for a solid organ transplant patient with DLD to require a SLB. Clinical and radiologic presentation differ in patients with lung transplants compared with other transplants. Postoperative outcomes are not significantly different between the groups. SLB performed early in the course of the disease might be beneficial. Having a lung transplant is a significant negative predictor of survival.

Successful circumferential free tracheal transplantation in a large animal model.

BACKGROUND: Long segment tracheobronchial stenoses are associated with high morbi-mortality rates and difficult treatment. Transplantation hasn't proved to be useful yet. Currently, the successful results achieved in small animal models couldn't be satisfactorily accomplished or extrapolated in large mammals. We aimed to evaluate the viability of orthotopic tracheal autoimplantation in an ovine model. METHODS: All animals underwent tracheal transplantation of 4 cm (5-7 rings) of the cervical trachea and were divided randomly in two groups: isolated autoimplantation (Group A/6) and autoimplantation with omental wrapping (Group B/6). Clinical follow up and weekly bronchoscopical examinations were performed. The grafts were macroscopically, histologically, and bacteriologically analyzed. RESULTS: In group A, four animals achieved their planed survival and were sacrificed up to 60 days after transplantation with viable grafts. In group B, only two sheep had successful results. Graft failure with infection, necrosis and severe stenosis was observed in the rest of the animals from both groups. Pseudomonas aeruginose was isolated in all cases. The main complication of the omental pedicle was vascular congestion and peritracheal hemorrhage. CONCLUSIONS: Contrary to the data reported to date, we found that tracheal transplantation is viable in a large mammal like the sheep. The main complication observed in this animal model was graft infection. The use of an omental pedicle with the technique applied worsened the grafts survival. The encouraging results obtained in this investigation justify further research in order to manage graft infection, leading us to establish a suitable large animal model for allotransplantation.

Mediastinoscopy in patients with lung cancer and negative endobronchial ultrasound guided needle aspiration.

BACKGROUND: Endobronchial ultrasound with transbronchial needle aspiration (EBUS-TBNA) has been proposed as a safe, less-invasive alternative to mediastinoscopy to stage mediastinal lymph nodes in patients with lung cancer. We evaluated the negative predictive value of EBUS-TBNA in lung cancer patients suspected of having N2 nodal metastases. METHODS: This study is a single-institution retrospective review of cases with suspected or confirmed lung cancer undergoing mediastinoscopy after a negative EBUS-TBNA between June 2006 and February 2008. RESULTS: A total of 494 patients underwent EBUS-TBNA during the study period. Twenty-nine patients with suspected or confirmed lung cancer had a negative EBUS-TBNA and underwent subsequent mediastinoscopy. Mediastinoscopy was performed for findings suspicious of N2 disease based on noninvasive imaging. Mediastinoscopy found metastatic nodes in eight of 29 patients (28%) for a patient-specific negative predictive value of EBUS-TBNA of 72% (95% CI, 56% to 89%). Mediastinal lymph node dissection found four further patients with positive N2 nodes (19%). The EBUS-TBNA and mediastinoscopy sampled the same lymph node station on 36 occasions in the 29 patients. The average lymph node size was 10 mm. Mediastinoscopy was positive in 5 of 36 stations, for a nodal-specific negative predictive value of EBUS-TBNA of 86% (95% CI, 75% to 97%). CONCLUSIONS: Endobronchial ultrasound with transbronchial needle aspiration can effectively sample mediastinal lymph node stations in patients with lung cancer. However, in this early experience, 28% of patients with high clinical suspicion of nodal disease had N2 mediastinal nodal metastases confirmed by mediastinoscopy despite negative EBUS-TBNA.

Open lung biopsy for diffuse disease in patients with and without previously transplanted solid organs.

BACKGROUND: Studies on whether surgical lung biopsy (SLB) modifies the treatment of patients with diffuse lung disease are conflicting, and information is limited on whether it alters treatment in solid-organ transplant recipients. Our objective was to determine and compare the rate of treatment change after SLB for diffuse lung disease in patients with and without a history of solid-organ transplantation. METHODS: Patients undergoing SLB for diffuse lung disease between March 2004 and March 2009 were identified. A retrospective review was performed. RESULTS: Sixty patients had SLB. Thirty-four patients (57%) had solid-organ transplantation. Twenty of 60 patients (33%) had a change in treatment as a result of the findings of the SLB. No significant differences in the treatment change rate were found between the transplant and nontransplant groups (10 of 34 versus 10 of 26; p = 0.46). Transplant patients were more likely to be on mechanical ventilation at the time of SLB (12 of 34 versus 3 of 26; p = 0.03). Mechanical ventilatory support at the time of SLB was associated with increased postoperative complications (odds ratio, 6.20; 95% confidence interval [CI], 1.70 to 22.66; p = 0.006) and in-hospital mortality (odds ratio, 9.75; 95% CI, 2.54 to 37.38; p = 0.001). Being on mechanical ventilation (hazard ratio, 3.91; 95% CI, 1.40 to 10.93; p = 0.009), a diagnosis of cancer (hazard ratio, 13.20; 95% CI, 2.87 to 60.78; p = 0.001), and a history of solid-organ transplantation (hazard ratio, 5.52; 95% CI, 1.08 to 28.14; p = 0.04) were independent predictors of survival. CONCLUSIONS: Surgical lung biopsy changes treatment in one third of patients, with no significant difference between patients without transplantation and solid-organ transplant recipients. Patients who undergo SLB while on mechanical ventilation have a significantly increased risk of postoperative complications and death.

N2 disease in T1 non-small cell lung cancer.

BACKGROUND: The optimal management strategy for mediastinal staging in early-stage non-small cell lung cancer (NSCLC) is not clearly defined. The true prevalence of mediastinal lymph node metastases (N2 disease) in resected pathologic T1 (pT1) NSCLC must be known to define the role of invasive mediastinal staging in these patients. METHODS: Data of patients with pT1 lesions resected at Mayo Clinic between 1998 and 2006 were retrospectively reviewed. Patients with N2 disease were identified from pathology and operative reports. We reviewed demographics, radiologic data, and surgical procedures for those with pathologic T1 N2 NSCLC. RESULTS: We identified 968 cases of pT1 lesions, 59 with pN2 disease (6.1%). For those with T1 N2 disease, the primary lung lesion was peripheral in 18 (31%) and central in 41 (69%). Of these, 36 had negative non-invasive mediastinal staging (3.7%) and were incidentally discovered. The most frequently affected lymph node station was 7 in 22 patients (37%), followed by 5,6 in 18 (31%). Mediastinoscopy found positive lymph nodes in 3 of 16 patients (19%) in which it was performed. Overall 5-year survival for pT1 N2 incidentally discovered during mediastinal lymph node dissection at the time of lung resection was 46% (95% confidence interval, 31% to 68%). CONCLUSIONS: True pT1 NSCLC harbors a relatively low rate of N2 disease. The rate of occult N2 disease not observed on noninvasive preoperative mediastinal staging is even lower. For patients with T1 NSCLC and negative mediastinal imaging, routine mediastinoscopy results in a low yield of occult N2 disease discovery.