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.

Evolution and complications of chest trauma.

OBJECTIVE: To describe the clinical characteristics and risk factors of patients with chest trauma, and to evaluate their correlation with the development of complications. METHODS: Descriptive, prospective and analytical study of a patient cohort with chest trauma who underwent follow-up for a period of 30 days. Excluded from the study were those patients with moderate to severe traumatic brain injury, long-bone fractures, abdominal trauma and patients requiring mechanical ventilation. RESULTS: A total of 376 patients met the inclusion criteria, 220 of whom were males (58.5%). The most frequent causes of trauma were falls (218 cases; 57.9%) and motor vehicle accidents (57 cases; 15.1%). The most frequent type of trauma was rib contusion (248 cases; 65.9%) and rib fractures (61 cases; 16.2%). Complications were observed in 43 patients (11.4%), mainly hemothorax (13 cases), pneumothorax (9 cases), pneumonia (6 cases) and acute renal failure (4 cases). Four patients died due to pneumonia and hemothorax. Thirty-three patients were hospitalized (8.7%) and 10 (2.6%) required later re-admittance. The risk for complications increased significantly in patients with more than 2 rib fractures, in those over the age of 85 and in the presence of certain comorbidities, such as COPD and pathologies requiring anticoagulation therapy. The risk for re-admittance is higher in patients over the age of 60. CONCLUSIONS: Patients with chest trauma who present certain comorbidities, are over the age of 85 and have more than 2 rib fractures may present more complications. These factors should be contemplated in the evaluation, management and follow-up of these subjects.

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.

Role of conservative medical management of tracheobronchial injuries.

BACKGROUND: The purpose of this study is to describe and assess the effectiveness of conservative treatment as the chosen treatment for tracheobronchial injury (TBI) management. This is a retrospective and descriptive study, which took place at a single center. METHODS: From January 1993 to July 2004, 33 TBIs were treated in our hospital. Eighteen (54.5%) were iatrogenic injuries and 15 (45.5%) were traumatic noniatrogenic injuries. Eighteen (55%) of the TBI patients were women and 15 (45.5%) were men, with a mean age of 46.7 +/- 23.4 years (range, 14-88 years). Eighteen (54.5%) of the injuries were caused by orotracheal intubation or tracheostomy, 13 (39.4%) by blunt trauma, and 2 (6.1%) by penetrating tracheal injuries. The average diagnostic delay was 18.29 +/- 19.8 hours. The mean injury size was 2.6 +/- 1.3 cm (range, 1-7 cm). Fourteen (42.4%) injuries were located in the cervical trachea, 8 (24.2%) in the thoracic trachea, 10 (30.3%) in the bronchi, and 1 (3%) involved both trachea and the main bronchi. Conservative treatment was applied in 20 (60.6%) of the 33 cases. Surgery should be performed in cases of esophageal-associated injuries, progressive subcutaneous or mediastinal emphysema, severe dyspnea requiring intubation, difficulty with mechanical ventilation, pneumothorax with an air leak through the chest drains, or mediastinitis. RESULTS: Conservative medical or surgical treatments achieved good outcomes in 28 (84.8%) cases. Five patients (15.2%) died while in the hospital; 4 of these were medically treated and 1 was surgically treated. Mortality was related to older patients and patients that had been diagnosed during mechanical ventilation. Major symptoms (progressive subcutaneous emphysema, dyspnea, sepsis) were detected more often in cartilaginous injuries (p < 0.05). Conservative treatment was considered more effective in membranous injuries (p < 0.05), and these sorts of injuries were not related to a high mortality rate (p > 0.05). Mortality was not related to conservative treatment, sex, diagnostic delay, injury mechanism, location, or length of the TBI (p < 0.05). CONCLUSIONS: Conservative treatment for TBI is effective regardless of the mechanism of production, length, or site of the injury. Conservative treatment should be carefully assessed in patients who meet strict selection criteria. Membranous injuries can be treated more often with a conservative approach, however, cartilaginous injuries should be treated surgically if major symptoms are detected.

[Tracheal injury from cervical stabbing]. / Lesión traqueal por puñalada cervical.

We report a case of isolated tracheal injury after a cervical stab without any other cervical damage. Diagnosis was performed by bronchoscopic and clinical examination. Plastic suture was performed with end-to-end anastomosis. The patient was discharged with good health status on the eleventh postoperative day.

Persistent cavitations in pulmonary mucormycosis after apparently successful amphotericin B.

A 67-year-old diabetic male developed bilateral pulmonary mucormycosis (PM). After long-term treatment with amphotericin B (cumulative dose of 30.6 g), clinical resolution was obtained, but small radiographic cavitations persisted. A late relapse occurred and bilateral lobectomy led to a definitive cure. Amphotericin B is not able to penetrate properly into PM cavitations. We suggest that persistence of cavitations should lead to consideration of surgery, even after a good response to amphotericin B.