Juliana Guarize

A 10-Year Single-Center Experience on 708 Lung Metastasectomies: The Evidence of the “International Registry of Lung Metastases”

Introduction: The International Registry of Lung Metastases defined a new staging system based on identified prognostic factors for long-term survival after metastasectomy. The aim of our study was to confirm the validity of the International Registry of Lung Metastases classification system in patients who underwent curative lung metastasectomy in a single center. Methods: We retrospectively reviewed 575 patients who underwent 708 lung metastasectomies from January 1998 to October 2008. Complete curative pulmonary resections were performed in 490 cases (85%). Three hundred seventy-two patients developed lung metastases from epithelial tumors, 80 from sarcomas, 27 from melanomas, and 11 from germ cell tumors. The mean disease-free interval (DFI) was 46.6 months. Open surgical resection was performed in 479 patients. One hundred eighty-five patients had a single-lung metastasis. Lymph node dissection was performed in 353 cases. Results: After a mean follow-up of 34 months, 247 patients (43%) had died. Multivariate analysis disclosed that completeness of resection (p < 0.0001), patients with germ cell tumors (p = 0.04), and DFI ≥36 months (p = 0.01) were also associated with a better prognosis. The actuarial survival after complete metastasectomy was 74% at 2 years and 46% at 5 years. Conclusions: We confirmed completeness of surgery, histology, and DFI ≥36 months as independent prognostic factors. Number of metastases, presence of lymph node metastases, surgical approach, and number of metastasectomies did not statistically influence long-term survival.

Non-small-cell lung cancer

Lung cancer is one of the most frequently diagnosed cancers and is the leading cause of cancer-related death worldwide. Non-small-cell lung cancer (NSCLC), a heterogeneous class of tumours, represents approximately 85% of all new lung cancer diagnoses. Tobacco smoking remains the main risk factor for developing this disease, but radon exposure and air pollution also have a role. Most patients are diagnosed with advanced-stage disease owing to inadequate screening programmes and late onset of clinical symptoms; consequently, patients have a very poor prognosis. Several diagnostic approaches can be used for NSCLC, including X-ray, CT and PET imaging, and histological examination of tumour biopsies. Accurate staging of the cancer is required to determine the optimal management strategy, which includes surgery, radiochemotherapy, immunotherapy and targeted approaches with anti-angiogenic monoclonal antibodies or tyrosine kinase inhibitors if tumours harbour oncogene mutations. Several of these driver mutations have been identified (for example, in epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK)), and therapy continues to advance to tackle acquired resistance problems. Also, palliative care has a central role in patient management and greatly improves quality of life. For an illustrated summary of this Primer, visit: http://go.nature.com/rWYFgg

Difficulties encountered managing nodules detected during a computed tomography lung cancer screening program

OBJECTIVE The main challenge of screening a healthy population with low-dose computed tomography is to balance the excessive use of diagnostic procedures with the risk of delayed cancer detection. We evaluated the pitfalls, difficulties, and sources of mistakes in the management of lung nodules detected in volunteers in the Cosmos single-center screening trial. METHODS A total of 5201 asymptomatic high-risk volunteers underwent screening with multidetector low-dose computed tomography. Nodules detected at baseline or new nodules at annual screening received repeat low-dose computed tomography at 1 year if less than 5 mm, repeat low-dose computed tomography 3 to 6 months later if between 5 and 8 mm, and fluorodeoxyglucose positron emission tomography if more than 8 mm. Growing nodules at the annual screening received low-dose computed tomography at 6 months and computed tomography-positron emission tomography or surgical biopsy according to doubling time, type, and size. RESULTS During the first year of screening, 106 patients underwent lung biopsy and 91 lung cancers were identified (70% were stage I). Diagnosis was delayed (false-negative) in 6 patients (stage IIB in 1 patient, stage IIIA in 3 patients, and stage IV in 2 patients), including 2 small cell cancers and 1 central lesion. Surgical biopsy revealed benign disease (false-positives) in 15 cases (14%). Positron emission tomography sensitivity was 88% for prevalent cancers and 70% for cancers diagnosed after first annual screening. No needle biopsy procedures were performed in this cohort of patients. CONCLUSION Low-dose computed tomography screening is effective for the early detection of lung cancers, but nodule management remains a challenge. Computed tomography-positron emission tomography is useful at baseline, but its sensitivity decreases significantly the subsequent year. Multidisciplinary management and experience are crucial for minimizing misdiagnoses.

Multidisciplinary treatment of malignant thymoma

Purpose of review Thymomas are the most common tumors of the anterior mediastinum. Although surgery remains the only curative treatment, the use of multimodality therapy for primary unresectable thymomas has led to change the clinical management of these tumors. Recent findings Nowadays Masaoka stage, WHO, and radical surgical resection are considered by many authors as independent prognostic factors for long-term survival. Radiotherapy may be useful as adjuvant therapy in cases of incomplete surgical resection with microscopic or macroscopic residual disease, or for those patients with locally advanced or metastatic unresectable disease. Chemotherapy is considered a valid option in selected patients with residual disease after local treatments or as a neoadjuvant approach to improve resectability in Masaoka stages III or IV-a thymomas. Currently, no standardized regimen for chemotherapy or agreed timing exists. Summary So far, multimodality treatment has been related to low morbidity and long survival rate, but there are still many concerns regarding a different regimen of therapy and the correct timing.

Lymph node involvement in T1 non-small-cell lung cancer: could glucose uptake and maximal diameter be predictive criteria?

OBJECTIVE The introduction of modern staging systems such as computed tomography (CT) and positron emission tomography/CT (PET/CT) with fluorodeoxyglucose ([(18)F]FDG) has increased the detection of small peripheral lung cancers at an early stage. We analyzed the behavior of pathological T1 non-small-cell lung cancer (NSCLC) to identify criteria predictive of nodal involvement, and the role of cancer size in lymph node metastases. METHODS We retrospectively analyzed 219 patients with pathological T1 NSCLC. All patients were staged by high-resolution CT and PET as stage I, and underwent anatomical resection and radical lymphadenectomy. Our data were collected based on pathological nodule size (0-10 mm; 11-20 mm; and 21-30 mm); morphological features of lung nodule and FDG uptake of the tumor measured by standardized uptake value (SUV). RESULTS A total of 190 patients (87%) were pN0, 14 (6%) pN1, and 15 (7%) pN2. No nodal involvement was observed in any of the 62 patients with nodule size less than 10 mm, in 20 out of 120 patients (17%) with nodule size 11-20 mm, and in nine out of 37 tumors (28%) 21-30 mm in size (p=0.0007). All 55 patients with nodule SUV<2.0 and all 26 non-solid lesions were pN0 (respectively, p=0.0001 and p=0.03). All nodal metastases occurred among the group of 132 patients with size larger than 10 mm and SUV higher than 2.0 with a 22% rate of nodal involvement of (29 patients) (p<0.0001). CONCLUSIONS The low probability of lymph node involvement in NSCLC <1 cm or showing glucose uptake <2 suggests lymphadenectomy could be avoided. A randomized trial should be performed to validate our data.

Airway Fistula Closure after Stem-Cell Infusion

Investigators observed the healing of a broncholpeural fistula soon after the injection of mesenchymal stem cells into the area surrounding the fistula.

The Role of Extended Pulmonary Metastasectomy

Background: The role of extended pulmonary resection for lung metastases is still unclear, and little information is available in the literature. This study was performed to analyze the outcomes and prognostic factors of patients who underwent extended resections for pulmonary metastases. Methods: From 1998 to 2013, 1027 patients underwent lung metastasectomy procedures. Twenty-nine patients had extended pulmonary resections: three resections of the chest wall, one azygos, one diaphragm, four vascular resections/reconstructions, six sleeve resections, and 14 pneumonectomies. Results: Extended resection was performed for metastatic disease mainly from epithelial (62.1%) and sarcomatous (20.7%) tumors. Complete resection was obtained in all patients. Thirty-day operative morbidity and mortality rates were 38% (11 of 29) and 0%, respectively. Only one patient had a major complication due to a bronchopleural fistula. Mean hospital stay was 6.3 days. After a median follow-up of 27 months, 16 patients (55%) had died. At univariate analysis, survival was determined by primary tumor histology (p = 0.03); the number of metastases, nodal status, disease-free interval or extension of surgery (pneumonectomy vs. lobar resection) were not related to survival probably due to the low number of patients. Overall survival after a complete extended metastasectomy was 66% at 2 years, 42% at 5 years, and 36% at 10 years. Conclusions: Extended resections performed during pulmonary metastasectomies are associated with low mortality and morbidity rates and an acceptable long-term survival when performed in selected patients susceptible to complete resection.

Operative rigid bronchoscopy: indications, basic techniques and results

Palliative airway treatments are essential to improve quality and length of life in lung cancer patients with central airway obstruction. Rigid bronchoscopy has proved to be an excellent tool to provide airway access and control in this cohort of patients. The main indication for rigid bronchoscopy in adult bronchology remains central airway obstruction due to neoplastic or non-neoplastic disease. We routinely use negative pressure ventilation (NPV) under general anaesthesia to prevent intraoperative apnoea and respiratory acidosis. This procedure allows opioid sparing, a shorter recovery time and avoids manually assisted ventilation, thereby reducing the amount of oxygen needed, while maintaining optimal surgical conditions. The major indication for NPV rigid bronchoscopy at our institution has been airway obstruction by neoplastic tracheobronchial tissue, mainly treated by laser-assisted mechanical dissection. When strictly necessary, we use silicone stents for neoplastic or cicatricial strictures, reserving metal stents to cover tracheo-oesophageal fistulae. NPV rigid bronchoscopy is an excellent tool for the endoscopic treatment of locally advanced tumours of the lung, especially when patients have exhausted the conventional therapeutic resources. Laser-assisted mechanical resection and stent placement are the most effective procedures for preserving quality of life in patients with advanced stage cancer.

Endobronchial ultrasound for mediastinal staging in lung cancer patients

Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) has changed the way mediastinal staging is performed in lung cancer patients. EBUS-TBNA is probably the most important non-invasive procedure for mediastinal staging and the currently preferred approach in many reference cancer centres worldwide. EBUS-TBNA is a less invasive technique than mediastinoscopy with low morbidity and no mortality and can be performed in an outpatient setting with excellent results. This study describes the technical aspects of EBUS-TBNA and our personal experience with the procedure.

MicroRNA expression profile in primary lung cancer cells lines obtained by endobronchial ultrasound transbronchial needle aspiration

Background Novel cancer biomarkers like microRNA (miRNA) are promising tools to gain a better understanding of lung cancer pathology and yield important information to guide therapy. In recent years, new less invasive methods for the diagnosis and staging of NSCLC have become key tools in thoracic oncology and the worldwide spread of endobronchial ultrasound transbronchial needle aspiration (EBUS-TBNA). However, appropriate specimen handling is mandatory to achieve adequate results and reproducibility. The aim of this single centre prospective study was to evaluate the feasibility of a complete miRNA expression profile in fresh NSCLC cell lines obtained by EBUS-TBNA. Methods Patients with proven NSCLC underwent EBUS-TBNA for the diagnosis of suspect lymph node metastasis, and cytological specimens were collected for epithelial cell culture and miRNA expression analysis. To validate the miRNA expression profile, we compared the results from EBUS-TBNA NSCLC specimens with those obtained from formalin-fixed paraffin-embedded (FFPE) mediastinoscopy specimens. Results Analysis of the miRNA expression profiles of three independent EBUS-TBNA-derived primary cell lines allowed the screening of 377 different human miRNAs. One hundred and fifty miRNAs were detected in all cell lines. Analysis of the miRNA expression profile in mediastinoscopy specimens showed a strong similarity in the clusters analysed. Conclusions The miRNA expression profile is feasible and reliable in EBUS-TBNA specimens. Validation of this protocol in fresh cytological specimens represents an effective and reproducible method to correlate translational and clinical research.