Massimo De Filippo

Accuracy of Fine Needle Aspiration Cytology in the Pathological Typing of Non-small Cell Lung Cancer

Background: Histological typing of non-small cell lung cancer (NSCLC) has an increasing clinical relevance due to the emerging differences in medical treatment between squamous and nonsquamous tumors. However, most NSCLCs are diagnosed in an advanced stage, and the diagnosis is often obtained exclusively by cytology either exfoliative or following fine needle aspiration. We investigated the accuracy of fine needle aspiration cytology (FNAC) in NSCLC typing as compared with histology. Methods: Over the period 2000–2009, 1182 transbronchial needle aspirate or transthoracic needle aspirate samples were obtained from patients with suspicious thoracic lesions. In 474 patients, a cytological diagnosis of primary NSCLC was obtained, and 186 (39%) of them (108 transbronchial needle aspirates and 78 transthoracic needle aspirates) received a parallel or subsequent histologic diagnosis on endoscopic biopsy (112) or surgery (74). Results: At cytology, 158 (85%) NSCLC cases were typed (89 adenocarcinoma and 69 squamous cell carcinoma), while 28 (15%) were classified as NSCLC not otherwise specified. At histology, 183 (98%) cases were typed (109 adenocarcinoma, 69 squamous cell carcinoma, 3 adenosquamous carcinoma, and 2 large cell carcinoma), and only 3 (2%) were classified as NSCLC not otherwise specified. Cytological and histological typing was concordant in 137 of 156 (88%) cases (K = 0.755; p < 0.001). The positive predictive value of FNAC in typing NSCLC was 92% for adenocarcinoma and 82% for squamous cell carcinoma. Conclusion: FNAC in expert hands is fairly accurate for typing NSCLC and can be regarded as an acceptable procedure for diagnostic and medical treatment planning purposes in most NSCLC cases, especially when more invasive approaches are unfeasible. In poorly differentiated and doubtful cases, the use of ancillary techniques, such as immunocytochemistry, may be required to improve the diagnostic yield.

Relationship and Prognostic Value of Modified Coronary Artery Calcium Score, FEV1, and Emphysema in Lung Cancer Screening Population: The MILD Trial

PURPOSE To assess the relationship between a modified coronary artery calcium (mCAC) score and both forced expiratory volume in 1 second (FEV1) and pulmonary emphysema and the associations of such factors with all-cause mortality and cardiovascular events (CVEs) in a lung cancer computed tomographic (CT) screening trial. MATERIALS AND METHODS In this institutional review board-approved study, both clinical and low-dose CT data were evaluated in a cohort of heavy smokers consecutively recruited by the Multicentric Italian Lung Detection, or MILD, trial. Low-dose CT images were analyzed by using software that allowed quantification of mCAC, mean lung attenuation (MLA), and total extent of emphysema. The correlations between mCAC, percentage predicted FEV1, MLA, and emphysema extent were tested by using the Pearson correlation coefficient. Adjusted multiple logistic regression models were applied to assess the relationships between mCAC, FEV1, MLA, and emphysema extent and all-cause mortality and CVEs. RESULTS The final study cohort consisted of 1159 smokers. There were no significant correlations between mCAC score and FEV1 (r=-0.03, P=.4), MLA (r=-0.01, P=.7), or emphysema extent (r=0.02, P=.6). An mCAC score greater than 400 was the only factor that was independently associated with both all-cause mortality (odds ratio [OR]: 3.73; 95% confidence interval [CI]: 1.05, 13.32; P=.04) and CVEs (OR: 2.87; 95% CI: 1.13, 7.27; P=.03). CONCLUSION mCAC is a better predictor of CVE and all-cause mortality than FEV1 and emphysema extent and may contribute to the identification of high-risk individuals in a lung cancer screening setting.

Multidetector computed tomography arthrography of the knee: diagnostic accuracy and indications.

PURPOSE To evaluate the diagnostic accuracy and indications of arthrography with multidetector computed tomography (arthro-MDCT) of the knee, in patients with absolute or relative contraindications to MRI and in patients with periarticular metal implants using diagnostic arthroscopy as the gold standard. MATERIALS AND METHODS After intra-articular injection of iodixanol and volumetric acquisition, 68 knees in patients of both sexes (30 females, 38 males, age range 32-60 years) were examined with a 16-detector-row CT scanner. The patients had arthralgia but no radiologically detected fractures. They could not be studied by MRI either because of absolute contraindications (subcutaneous electronic implants), surgical metal implants or claustrophobia. In 37 of 68 patients who had had previous knee surgery, the arthro-CT examination was preceded by an MRI on the same day. All examinations were interpreted by two experienced musculoskeletal radiologists. The findings were compared with arthroscopic findings carried out within 28 days of the CT study. RESULTS In non-operated patients the comparison between arthro-MDCT and arthroscopy showed sensitivity and specificity ranging between 86% and 100%. In the 37 operated knees, arthro-MDCT had an accuracy of 95% compared with 53% of the MRI. Inter-observer agreement was almost perfect (K=0.97) in the evaluation of all types lesions, both on MDCT and MRI. When arthro-MDCT was compared with MRI in post-operative patients by a McNemar test, a significant difference (p<0.05) was found between these two techniques. CONCLUSIONS Arthro-MDCT of the knee is a safe technique that provides accurate diagnosis in identifying chondral, fibrocartilaginous and intra-articular ligamentous lesions, in patients that cannot be evaluated by MRI, and in patients after surgical.

Airway malacia in chronic obstructive pulmonary disease: prevalence, morphology and relationship with emphysema, bronchiectasis and bronchial wall thickening

The aim of this study was to determine the prevalence of airway malacia and its relationship with ancillary morphologic features in patients with chronic obstructive pulmonary disease (COPD). A retrospective review was performed of a consecutive series of patients with COPD who were imaged with inspiratory and dynamic expiratory multidetector computed tomography (MDCT). Airway malacia was defined as ≥50% expiratory reduction of the airway lumen. Both distribution and morphology of airway malacia were assessed. The extent of emphysema, extent of bronchiectasis and severity of bronchial wall thickness were quantified. The final study cohort was comprised of 71 patients. Airway malacia was seen in 38 of 71 patients (53%), and such proportion was roughly maintained in each stage of COPD severity. Almost all tracheomalacia cases (23/25, 92%) were characterised by an expiratory anterior bowing of the posterior membranous wall. Both emphysema and bronchiectasis extent did not differ between patients with and without airway malacia (p > 0.05). Bronchial wall thickness severity was significantly higher in patients with airway malacia and correlated with the degree of maximal bronchial collapse (p < 0.05). In conclusion, we demonstrated a strong association between airway malacia and COPD, disclosing a significant relationship with bronchial wall thickening.

MDCT arthrography of the wrist: Diagnostic accuracy and indications

PURPOSE To evaluate the diagnostic accuracy and indications of arthrography with Multidetector Computed Tomography (arthro-MDCT) of the wrist in patients with absolute or relative contraindications to magnetic resonance imaging (MRI) studies and in patients with periarticular metal implants using diagnostic arthroscopy as the gold standard. MATERIALS AND METHODS After intra-articular injection of iodixanol and volumetric acquisition, 43 wrists in patients of both genders (18 females, 25 males, age range 32-60 years) were examined with a 16-detector-row CT scanner. Fifteen patients had prior wrist surgery. The patients had arthralgia, degenerative and traumatic arthropathies as well as limited range of motion, but no radiologically detected fractures. All examinations were interpreted by two experienced musculoskeletal radiologists. The findings were compared with arthroscopic findings carried out within 28 days of the CT study. RESULTS In non-operated and operated wrists the comparison between arthro-MDCT and arthroscopy showed sensitivity, specificity and accuracy ranging between 92% and 94% for triangular fibrocartilage complex (TFCC), between 80% and 100% for intrinsic ligaments located within the proximal carpal compartment, and between 94% and 100% for articular cartilage. Inter-observer agreement between two radiologists, in the evaluation of all types of lesions, was almost perfect (k=0.96) and statistically significant (p<0.05). CONCLUSIONS Arthro-MDCT of the wrist provides an accurate diagnosis to identify chondral, fibrocartilaginous and intra-articular ligament lesions in patients who cannot be evaluated by MRI, and in post-surgical patients.

Sirolimus plus prednisone for Erdheim-Chester disease: an open-label trial

Erdheim-Chester disease (ECD) is a rare non-Langerhans cell histiocytosis, to whose pathogenesis neoplastic and immune-mediated mechanisms contribute. Mammalian target of rapamycin (mTOR)-inhibitors have antiproliferative and immunosuppressive properties. We tested in this study, the efficacy and safety of the mTOR-inhibitor sirolimus (SRL) plus prednisone (PDN) in patients with ECD. PDN was given initially at 0.75 mg/kg per day, tapered to 5 to 2.5 mg per day by month 6. Target SRL blood levels were 8 to 12 ng/mL. Treatment was continued for at least 24 months in patients who showed disease stabilization or improvement. Ten patients were enrolled; 8 achieved stable disease or objective responses, whereas 2 had disease progression. Responses were mainly observed at the following sites: retroperitoneum in 5/8 patients (62.5%), cardiovascular in 3/4 (75%), bone in 3/9 (33.3%), and central nervous system (CNS) in 1/3 (33.3%). The median follow-up was 29 months (interquartile range, 16.5-74.5); 2 patients died of progressive CNS disease and small-cell lung cancer, respectively. Treatment-related toxicity was mild. Using immunohistochemistry and immunofluorescence on ECD biopsies, we detected expression in foamy histiocytes of the phosphorylated forms of mTOR and of its downstream kinase p70S6K, which indicated mTOR pathway activation. In conclusion, SRL and PDN often induce objective responses or disease stabilization and may represent a valid treatment of ECD. The trial is registered at the Australia-New Zealand Clinical Trial Registry as #ACTRN12613001321730.

Predictive factors of diagnostic accuracy of CT-guided transthoracic fine-needle aspiration for solid noncalcified, subsolid and mixed pulmonary nodules

Purpose. The aim of this study was to analyse factors predicting the diagnostic accuracy of computed tomography (CT)-guided transthoracic fine-needle aspiration (TTFNA) for solid noncalcified, subsolid and mixed pulmonary nodules, with particular attention to those responsible for false negative results with a view to suggesting a method for their correction.PurposeThe aim of this study was to analyse factors predicting the diagnostic accuracy of computed tomography (CT)-guided transthoracic fine-needle aspiration (TTFNA) for solid noncalcified, subsolid and mixed pulmonary nodules, with particular attention to those responsible for false negative results with a view to suggesting a method for their correction.Materials and methodsFrom January 2007 to March 2010, we retrospectively reviewed the CT images of 198 patients of both sexes (124 males and 74 females; mean age, 70 years; range age, 44–90) used for the guidance of TTFNA of pulmonary nodules. Aspects considered were: lesion size and density, distance from the pleura, and lesion site. Multiplanar reformatted images (MPR) were retrospectively obtained in the sagittal and axial oblique planes relative to needle orientation.ResultsThe overall diagnostic accuracy of TTFNA CTguided biopsy was 86% for nodules between 0.7 and 3 cm, 83.3% for those between 0.7 and 1.5 cm, and 92% for those between 2 and 3 cm. Accuracy was 95.1% for solid pulmonary nodules, 84.6% for mixed nodules, and 66.6% for subsolid nodules. The diagnostic accuracy of CT-guided TTFNA in relation to the distance between the nodule and the pleural plane was 95.6% for lesions adhering to the pleura and 83.5% for central ones. The diagnostic accuracy was 84.2% for the pulmonary upper lobe nodules, 85.3% for the lower lobe and 90.9% for those in the lingula and middle lobe. In 75% of false negative and inadequate/insufficient cases the needle was found to lie outside the lesion, after reconstruction of the needle path by MPR.ConclusionsThe positive predictive factors of CT-guided TTFNA are related to the nodule size, density and distance from the pleural plane. The most common negative predictive factor of CT-guided TTFNA is the wrong position of the needle tip, as observed in the sagittal and axial oblique sections of the MPR reconstructions. The diagnostic accuracy of CT-guided TTFNA can therefore be improved by using the MPR technique to plan the needle path during the FNA procedure.RiassuntoObiettivoScopo del presente lavoro è stato individuare ed analizzare i fattori che predicono l’accuratezza diagnostica dell’ago-biopsia trans-toracica (TTFNA) guidata da tomografia computerizzata (TC) dei noduli polmonari solidi non calcifici, subsolidi e misti, con particolare attenzione ai fattori responsabili di falsi negativi, proponendo un metodo per la loro correzione.Materiali e metodiTra il 2007 ed il 2010 sono state analizzate retrospettivamente le immagini TC del torace di 198 pazienti di entrambi i sessi (124 maschi e 74 femmine, età media 70 anni, range età 44–90) utilizzate per l’esecuzione di TTFNA TC-guidata di noduli polmonari. I criteri analizzati sono stati: dimensione, densità, distanza dal piano pleurico e sede dei noduli polmonari. Sono state ottenute retrospettivamente immagini in ricostruzioni multiplanari (MPR) sui piani sagittali ed asssiali obliqui in relazione all’orientamento dell’ago.RisultatiL’accuratezza complessiva della TTFNA TC-guidata per noduli polmonari compresi tra 0,7 e 3 cm è stata 86%. L’accuratezza per i noduli polmonari compresi tra 7 e i 15 mm è stata del 83,3%, per quelli compresi tra 20 e 30 mm del 92%. L’accuratezza per i noduli polmonari solidi è stata del 95%, per i noduli misti 84,6% e per noduli subsolidi 66,6%. L’accuratezza per i noduli adesi al piano pleurico è stata del 95,6% e per quelli centrali 83,5%. Per i noduli dei lobi superiori è stata 84,2%, per quelli dei lobi inferiori 85,3%, per quelli della lingula e del lobo medio 90,9%. Nel 75% dei casi falsi negativi, inadeguati o insufficienti, la punta dell’ago dopo ricostruzione MPR era localizzata all’esterno o in periferia del nodulo polmonare.ConclusioniI fattori diagnostici predittivi positivi della TTFNA TC-guidata sono correlati con le dimensioni, la densità e la distanza del nodulo polmonare con il piano pleurico. Il fattore predittivo negativo ricorrente della TTFNA TC-guidata è l’errata localizzazione della punta dell’ago, mal evidente nelle scansioni assiali native, osservata retrospettivamente nelle sezioni sagittali ed assiali oblique MPR. Il ricorso alle immagini MPR sagittali e assiali oblique durante l’agoaspirazione è utile per il corretto planning della traiettoria dell’ago, quest’ultimo aspetto cruciale che influenza l’accuratezza diagnostica della procedura.

Reliability of EGFR and KRAS mutation analysis on fine-needle aspiration washing in non-small cell lung cancer.

INTRODUCTION Molecular profiling of advanced non-small cell lung cancer (NSCLC) has become essential for predicting customized medical treatment decision. In light of recent advances in non-invasive diagnostic procedures in NSCLC, we aimed to demonstrate the reliability of assessing molecular tests for epidermal growth factor receptor (EGFR) and KRAS genes on cytological samples by comparing the molecular profile obtained on cells from scraped smears with that on paired needle washing in a series of NSCLC cases. METHODS Thirty-two cytological specimens obtained by fine-needle aspiration biopsy procedures from primary or metastatic lesions of NSCLCs were Giemsa stained for a rapid on-site evaluation and, in case of an adequate sampling, the cellular material obtained from needle washing was collected into a saline solution. Scraped smears and needle washings were tested for EGFR and KRAS by polymerase chain reaction followed by direct sequencing. RESULTS The concordance between EGFR and KRAS mutational status in 29 paired scraped smears and needle washing was 100%, with 7 paired samples showing the same EGFR mutation (4 L858R mutation, 2 E746_A750 deletion and 1 A767_V769 duplication) and 8 paired samples showing the same KRAS mutations (4 G12D, 1 G12A, 1 G12V and 2 G12C). Three scraped smears, uninformative for poor DNA quality, resulted EGFR mutated on paired needle washings. CONCLUSIONS Needle washing obtained in the course of NSCLC non-invasive fine needle diagnostic procedures allows reliable mutation testing and can be regarded as an additional important source of biological material for molecular profiling of advanced NSCLC.

ALK and ROS1 rearrangements tested by fluorescence in situ hybridization in cytological smears from advanced non-small cell lung cancer patients.

The identification of ALK and ROS1 rearrangements and the availability of an effective target therapy, such as crizotinib, represent a new option in the treatment of advanced non‐small cell lung cancer (NSCLC) patients. In light of recent advances in non‐invasive diagnostic procedures, we aimed to demonstrate that direct cytological smears are suitable for assessing ALK and ROS1 rearrangements in patients with NSCLC.

Radiofrequency thermal ablation of renal tumors

Percutaneous radiofrequency ablation (PRFA) of renal malignancies is currently a therapeutic option for patients who are not able to undergo surgery. Some authors consider PRFA as the therapeutic standard in the treatment of renal neoplasms in non-operable patients due to comorbid conditions and in patients with mild-moderate renal failure, to preserve residual renal functionality. The use of PRFA has become more and more widespread due to a rise in the incidental detection of renal cell carcinomas with the ever-increasing use of Imaging for the study of abdominal diseases. Clinical studies indicate that RF ablation is an effective therapy with a low level of risk of complications, which provides good results in selected patients over short and medium term periods of time, however up to now few long-term studies have been carried out which can confirm the effectiveness of PRFA.