BL-MOL-AR Project, Preliminary Results about Liquid Biopsy: Molecular Approach Experience and Research Activity in Oncological Settings.

Background Liquid biopsy is mainly used to identify tumor cells in pulmonary neoplasms. It is more often used in research than in clinical practice. The BL-MOL-AR study aims to investigate the efficacy of next-generation sequencing (NGS) and clinical interpretation of the circulating free DNA (cfDNA) levels. This study reports the preliminary results from the first samples analyzed from patients affected by various neoplasms: lung, intestinal, mammary, gastric, biliary, and cutaneous. Methods The Biopsia Liquida-Molecolare-Arezzo study aims to enroll cancer patients affected by various malignancies, including pulmonary, intestinal, advanced urothelial, biliary, breast, cutaneous, and gastric malignancies. Thirty-nine patients were included in this preliminary report. At time zero, a liquid biopsy is executed, and two types of NGS panels are performed, comprising 17 genes in panel 1, which is already used in the routine tissue setting, and 52 genes in panel 2. From the 7th month after enrollment, 10 sequential liquid biopsies are performed up to the 17th month. The variant allele frequency (%) and cfDNA levels (ng/mL) are measured in every plasmatic sample. Results The NGS results obtained by different panels are similar even though the number of mutations is more concordant for lung pathologies. There are no significant differences in the actionability levels of the identified variants. Most of the molecular profiles of liquid biopsies reflect tissue data. Conclusions Preliminary data from this study confirm the need to clarify the limitations and potential of liquid biopsy beyond the lung setting. Overall, parameters related to cfDNA levels and variant allele frequency could provide important indications for prognosis and disease monitoring.

Usefulness of 18-F FDG PET/CT in the pre-treatment evaluation of thymic epithelial neoplasms.

BACKGROUND: To assess the usefulness of (18)fluorine-fluorodeoxyglucose positron emission tomography/computed tomography ((18)F-FDG PET/CT) for differentiating the grade of malignancy of thymic epithelial neoplasm, and to determine whether (18)F-FDG PET/CT can have a role in pretreatment evaluation and possibly modify treatment strategy. MATERIALS AND METHODS: The data of 26 consecutive patients (14 males and 12 females) diagnosed with a thymic epithelial neoplasm were prospectively collected and analyzed retrospectively. All patients underwent standard clinical assessment and (18)F-FDG PET/CT. The patients were divided into two subgroups according to a simplified histologic classification: low-risk thymoma (types A, AB and B1) and high-risk thymoma (types B2, B3 and C). The maximum standardized uptake value (SUV(max)) of the tumor, the mean SUV of mediastinum, and the tumor/mediastinum (T/M) ratio (ratio of peak SUV of the tumor to mean SUV of mediastinum) were compared to determine whether the two subgroups (low-risk versus high-risk tumors) could be distinguished by (18)F-FDG PET/CT, and to test for possible correlations between (18)F-FDG uptake and disease stage. RESULTS: There was a strong statistical correlation between SUV(max) and patient subgroup and between SUV(max) and disease stage, and an even stronger correlation between SUV(max) and patient subgroup and the T/M ratio; a T/M ratio of 2.75 emerged as the cut-off value for differentiating between low-risk and high-risk thymomas. CONCLUSIONS: (18)F-FDG PET/CT can be used a "metabolic biopsy" to divide thymic epithelial neoplasm into two subgroups of high and low risk and is useful in pretreatment staging.

Oxygen pulse as a predictor of cardiopulmonary events in lung resection.

Traditional algorithms suggest a stepwise approach to the functional evaluation of candidates for lung resection. A cardiopulmonary exercise test is incorporated as a supplementary test for patients with borderline pulmonary predicted values, and sometimes as a first screening test for cardiac risk evaluation. To assess the predictive weight of exercise tests in noncardiac thoracic surgery, we retrospectively analyzed 99 patients (80 males) aged 67.8 +/-8.1 years who underwent lung resection after a cardiopulmonary exercise test. During basal spirometry, the mean predicted forced expiratory volume in the first second was 69.9% +/-18.6%, and predicted carbon monoxide diffusing capacity was 71.6% +/-20.5%. Peak oxygen consumption was 11.1 +/-3.2 mL.kg(-1).min(-1), oxygen pulse was 9 +/-2.8 mL.beat(-1), and minute ventilation/CO(2) output was 45.2 +/- 7.7. Mean hospital stay was 10.4 days, and intensive care unit stay was 0.3 days. Postoperative complications occurred in 20 (20%) patients. On multivariate analysis, body mass index, a high level of exercise achieved during the cardiopulmonary exercise test, lower heart rate at peak exercise, and oxygen pulse correlated significantly with better postoperative outcome. Cardiopulmonary exercise tests are helpful for stratifying patients undergoing thoracic surgery. Perioperative complications seem to be strongly related to left ventricular function and physical performance.

Paraneoplastic extra limbic encephalitis associated with thymoma.

We report the case of a 55-year-old woman with thymoma diagnosed after finding of extra limbic encephalitis. She presented neurologic symptoms as seizure and aphasia; magnetic resonance imaging (MRI) of the brain showed multiple lesions located in insular, parietal and temporal lobes (in cortical and sub-cortical area). Brain biopsies confirmed the diagnosis of encephalitis and CT-scan of the thorax showed an anterior mediastinal mass suspected for thymoma. The patient was submitted to thymectomy through a median sternotomy and we assisted to secondary reduction of cerebral lesions and total remission of symptoms.

Pulmonary angiosarcoma presenting as spontaneous recurrent hemothorax.

An incidental diagnosis of pulmonary angiosarcoma was made after surgical exploration for repeated episodes of bleeding in an 85-year-old woman. Spontaneous hemothorax is uncommon and deserves detailed investigation.

Role of fluorine-flurodeoxyglucose positron emission tomography/computed tomography in preoperative assessment of anterior mediastinal masses.

OBJECTIVE: The purpose of the study was to explore the usefulness of fluorine-fluorodeoxyglucose positron emission tomography/computed tomography (F-FDG PET-CT) in the preoperative assessment of isolated anterior mediastinal lesions, especially in the planning of operative strategy (biopsy or upfront resection). METHODS: During the last 36 months, 19 consecutive patients (10 males, mean age 54+/-16 years) underwent PET-CT in the preoperative work-up of isolated anterior mediastinal diseases. Maximal transverse diameter at CT and the postoperative histology and Masaoka staging for thymomas were collected and related to the maximum standardised uptake values (SUVs). Thymomas were divided into low-risk thymoma (LRT=A, AB and B1) and high-risk thymoma (HRT=B2, B3 and C). RESULTS: There were 13 thymomas (six LRT and seven HRT), three lymphomas and three other primitive thymic tumours (one paraganglioma, two non-seminomatous germ cell tumours). In LRT, the mean SUV was 3.3+/-0.5 resulting significantly lower than HRT, 13.5+/-7 (p=0.009). The SUV in LRT was also significantly lower with respect to lymphoma, 12.4+/-4 (p=0.001), and the other primitive anterior mediastinal tumours, 8+/-0.8 (p=0.001). Between thymomas we found a significant correlation between Masaoka stage and SUV, r=0.718, p=0.006. No correlation was found between transverse diameters and SUV, r=0.141, p=0.6. CONCLUSIONS: In our experience, low SUV (<5) is associated with LRT and minimal invasive thymoma (Masaoka stages I-II) and, therefore, susceptible to upfront surgery. For lesions with an infiltrative aspect on CT scan associated with a higher SUV (>5), an open biopsy is mandatory to exclude mediastinal lymphomas or, in case of HRT, to address a neoadjuvant treatment.

The split latissimus dorsi muscle flap to protect a bronchial stump at risk of bronchial insufficiency.

Consistent branching of the thoracodorsal vessels to the latissimus dorsi makes it possible to split the muscle into independent branched units. The use of the lateral split latissimus dorsi muscle flap to protect the bronchial stump in case of bronchus at risk of insufficiency is described.

Impact of size, histology, and gender on stage IA non-small cell lung cancer.

The aim of this study was to assess which prognostic factors could influence survival in surgically treated stage IA non-small cell lung cancer. The records of 224 consecutive patients with pathological stage IA after radical surgery were reviewed retrospectively. Overall 1, 3 and 5-year survival rates were 89%, 76%, and 66%. Nearly half of the deaths were unrelated to the original cancer. There was no difference in survival attributable to preoperative pulmonary function, age at operation, or extent of resection. However, patients with limited resections had a higher rate of local recurrence. Survival was better with a smaller size of tumor (= 2 cm), in the female sex, and in cases of bronchoalveolar adenocarcinoma.