18-Fluorine fluorodeoxyglucose positron emission tomography in the pretreatment evaluation of thymic epithelial neoplasms: a metabolic biopsy confirmed by Ki-67 expression.

OBJECTIVES: To investigate the usefulness of 18-fluorine fluorodeoxyglucose ((18)F-FDG) positron emission tomography/computed tomography (PET-CT) in the pretreatment evaluation of thymic epithelial neoplasms (TENs). We previously demonstrated that the ratio between standardized uptake value of the tumour and aortic arch (SUV T/M) correlates with World Health Organization (WHO) classification. We now focused our evaluation on thymomas only, excluding carcinomas. We also searched for the expression of a pathological biomarker, Ki-67, that gained both diagnostic and prognostic relevance for various solid tumours. Its correlation with SUV T/M and WHO classification was evaluated. METHODS: We performed a retrospective dynamic cohort study of data from January 2006 to December 2012, on 23 consecutive patients with pathologically proven TEN, excluding thymic carcinomas, evaluated with PET-CT. For each patient, SUV T/M was calculated. The patients were then categorized, according to WHO classification, into two groups (low-risk: 3 A, 9 AB, 5 B1; high-risk: 5 B2, 1 B3) and Ki-67 labelling index (LI) was defined. We employed the Spearman rank non-linear correlation coefficient (ρ) to estimate the correlations between variables. RESULTS: SUV T/M proved to be significantly higher for high-positive Ki-67 samples, indicating a strong correlation between SUV T/M and Ki-67 LI (ρ = 0.8). Furthermore, high Ki-67 LI samples correlate with the higher-risk WHO subgroup (ρ = 0.9). CONCLUSIONS: FDG PET-CT can provide a useful tool in the preoperative work-up of TEN, reflecting its proliferation capacity, as described also by the Ki-67 expression. In particular, SUV T/M could provide a 'metabolic biopsy' to divide TEN into high-risk and low-risk neoplasms.

Results of Li-Tho trial: a prospective randomized study on effectiveness of LigaSure® in lung resections.

OBJECTIVE: The role of electro-thermal bipolar tissue sealing system (LigaSure(®), (LS); Covidien, Inc., CO, USA) in thoracic surgery is still undefined. Reports of its use are still limited. The objective of the trial was to evaluate the cost and benefits of LS in major lung resection surgery. METHODS: A randomized blinded study of a consecutive series of 100 patients undergoing lobectomy was undertaken. After muscle-sparing thoracotomy and classification of lung fissures according to Craig-Walker, patients with fissure Grade 2-4 were randomized to Stapler group or LS group fissure completion. Recorded parameters were analysed for differences in selected intraoperative and postoperative outcomes. Statistical analysis was performed with the bootstrap method. Pearson's χ(2) test and Fisher's exact test were used to calculate probability value for dichotomous variables comparison. Cost-benefit evaluation was performed using Pareto optimal analysis. RESULTS: There were no significant differences between groups, regarding demographic and baseline characteristics. No patient was withdrawn from the study; no adverse effect was recorded. There was no mortality or major complications in both groups. There were no statistically significant differences as to operative time or morbidity between patients in the LS group compared with the Stapler group. In the LS group, there was a not statistically significant increase of postoperative air leaks in the first 24 postoperative hours, while a statistically significant increase of drainage amount was observed in the LS group. No statistically significant difference in hospital length of stay was observed. Overall, the LS group had a favourable multi-criteria analysis of cost/benefit ratio with a good 'Pareto optimum'. CONCLUSIONS: LS is a safe device for thoracic surgery and can be a valid alternative to Staplers. In this setting, LS allows functional lung tissue preservation. As to costs, LS seems equivalent to Staplers.

The significance of intrapulmonary metastasis in non-small cell lung cancer: upstaging or downstaging? A re-appraisal for the next TNM staging system.

OBJECTIVE: The management of patients with non-small cell lung cancer (NSCLC) with intrapulmonary metastases (PM) is controversial. In TNM classification, PM are designed as T4 when in the same lobe of the primary tumour (PM1) and M1 when in a different lobe(s) (PM2). Some authors have questioned the negative prognostic impact of PM. The present study assessed prevalence, correlation with clinico-pathologic variables and impact on survival of PM, along with a review of the literature. METHODS: From January 1993 to December 2006, 2013 NSCLC patients underwent surgical resection at our institution. Of these, 74 presented with PM (39 PM1, 35 PM2). Patients with bronchioloalveolar carcinoma (BAC), carcinoid tumours, contralateral disease and preoperative chemo/radiotherapy were excluded from the analysis. A logistic regression analysis was undertaken to evaluate a relationship between the presence of PM and different clinico-pathologic variables. Survival analysis was undertaken to investigate the prognostic significance of PM. RESULTS: PM represent 3.6% of our patient population of operated NSCLC. Metastases were multiple in 36 cases and single in 38. Thirty-six patients had node-negative disease. Among all the variables for the logistic regression analysis only vascular invasion (OR: 0. 45; 95% CI 0.24-0.85, p=0.01) and N status (OR: 0. 6; 95% CI 0.43-0.82, p=0.001) were significantly correlated with the presence of PM. Median survival rates of PM1, PM2, other T4 and other M1 patients were 25, 23, 15 and 14 months, respectively. A survival advantage was observed in patients with PM as compared to other T4/M1 patients, although the difference was not significant either overall (p=0.21) or in the N0 disease group (p=0.12). CONCLUSIONS: The presence of PM in NSCLC patients is a rare occurrence. Risk factors for the development of PM are a microscopic vascular invasion and a high nodal status. A survival advantage over other T4/M1 patients is evident from our experience, although not significant. The results of the literature which have been accumulating in the most recent years including ours bend to the conclusion that there is sufficient validated information to consider a downstaging in the presence of intrapulmonary metastases from NSCLC for the seventh edition of the TNM classification.

Subwavelength size determination by spatially modulated illumination virtual microscopy.

A new approach for determining the sizes of individual, small fluorescent objects with diameters considerably below the optical resolution limit is described in which spatially modulated illumination (SMI) microscopy and 360-647-nm excitation wavelengths are used. The results of SMI virtual microscopy computer simulations indicate that, in this wavelength range, reliable measurements of sizes as small as approximately 20 nm are feasible if the low numbers of fluorescence photons that are usually detected from such small objects are taken into account. This method is based on the well-known fact that the modulation of the diffraction image in a SMI microscope is disturbed by the size of the object. Using appropriately calculated calibration functions, one can use this disturbance of the modulation to determine the size of the original object.

Spatial preservation of nuclear chromatin architecture during three-dimensional fluorescence in situ hybridization (3D-FISH).

3D-FISH has become a major tool for studying the higher order chromatin organization in the cell nucleus. It is not clear, however, to what extent chromatin arrangement in the nucleus after fixation and 3D-FISH still reflects the order in living cells. To study this question, we compared higher order chromatin arrangements in living cells with those found after the 3D-FISH procedure. For in vivo studies we employed replication labeling of DNA with Cy3-conjugated nucleotides and/or chromatin labeling by GFP-tagged histone 2B. At the light microscope level, we compared the intranuclear distribution of H2B-GFP-tagged chromatin and the positions of replication-labeled chromatin domains in the same individual cells in vivo, after fixation with 4% paraformaldehyde, and after 3D-FISH. Light microscope data demonstrate a high degree of preservation of the spatial arrangement of approximately 1-Mb chromatin domains. Subsequent electron microscope investigations of chromatin structure showed strong alterations in the ultrastructure of the nucleus caused mainly by the heat denaturation step. Through this step chromatin acquires the appearance of a net with mesh size of 50-200 nm roughly corresponding to the average displacement of the chromatin domains observed at light microscope level. We conclude that 3D-FISH is a useful tool to study chromosome territory structure and arrangements down to the level of approximately 1-Mb chromatin domain positions. However, important ultrastructural details of the chromatin architecture are destroyed by the heat denaturation step, thus putting a limit to the usefulness of 3D-FISH analyses at nanometer scales.

Stage I non-small cell lung carcinoma: really an early stage?

OBJECTIVE: We review our results on surgical treatment of patients with stage I non-small cell lung carcinoma and we attempted to clarify the prognostic significance of some surgical--pathologic variables. METHODS: From 1993 to 1999, 667 patients received curative lung resection and complete hilar and mediastinal lymphadenectomy for non-small cell lung cancer. Of these, there were 436 Stage I disease (65%), of whom 144 T1N0 and 292 T2N0. No patients had pre- or postoperative radio- or chemotherapy. Prognostic significance of the following independent variables was tested using univariate (log-rank) and multivariate (Cox proportional-hazards) analysis: type of resection (sublobar vs lobectomy vs pneumonectomy), histology (squamous cell vs adenocarcinoma), tumour size (3cm), histologic vascular invasion, visceral pleura involvement, positive bronchial resection margin, general T status. RESULTS: Overall 5-year survival was 63%. In both univariate and multivariate survival analysis, significant prognostic factors were histology (adenocarcinoma 65% vs squamous cell carcinoma 51%), tumour size (3cm 46%), and the presence of negative resection margin. Five-year survival by general T status was 66% in T1N0 vs 55% in T2N0 disease (P=0.19). CONCLUSIONS: Despite advances in early diagnosis and surgical technique, 5-year survival of stage I non-small cell lung carcinoma remains low as compared to survival of other solid organ neoplasm. Tumour size