Cytomolecular Classification of Thyroid Nodules Using Fine-Needle Washes Aspiration Biopsies.

Fine-needle aspiration biopsies (FNA) represent the gold standard to exclude the malignant nature of thyroid nodules. After cytomorphology, 20-30% of cases are deemed "indeterminate for malignancy" and undergo surgery. However, after thyroidectomy, 70-80% of these nodules are benign. The identification of tools for improving FNA's diagnostic performances is explored by matrix-assisted laser-desorption ionization mass spectrometry imaging (MALDI-MSI). A clinical study was conducted in order to build a classification model for the characterization of thyroid nodules on a large cohort of 240 samples, showing that MALDI-MSI can be effective in separating areas with benign/malignant cells. The model had optimal performances in the internal validation set (n = 70), with 100.0% (95% CI = 83.2-100.0%) sensitivity and 96.0% (95% CI = 86.3-99.5%) specificity. The external validation (n = 170) showed a specificity of 82.9% (95% CI = 74.3-89.5%) and a sensitivity of 43.1% (95% CI = 30.9-56.0%). The performance of the model was hampered in the presence of poor and/or noisy spectra. Consequently, restricting the evaluation to the subset of FNAs with adequate cellularity, sensitivity improved up to 76.5% (95% CI = 58.8-89.3). Results also suggest the putative role of MALDI-MSI in routine clinical triage, with a three levels diagnostic classification that accounts for an indeterminate gray zone of nodules requiring a strict follow-up.

Ex vivo thyroid fine needle aspirations as an alternative for MALDI-MSI proteomic investigation: intra-patient comparison.

Fine needle aspiration (FNA) is the reference standard for the diagnosis of thyroid nodules. Matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) has been successfully used to discriminate the proteomic profiles of benign and malignant thyroid FNAs within the scope of providing support to pathologists for the classification of morphologically borderline cases. However, real FNAs provide a limited amount of material due to sample collection restrictions. Ex vivo FNAs could represent a valuable alternative, increasing sample size and the power of statistical conclusions. In this study, we compared the real and ex vivo MALDI-MSI proteomic profiles, extracted from thyrocyte containing regions of interest, of 13 patients in order to verify their similarity. Statistical analysis demonstrated the mass spectra similarity of the proteomic profiles by performing intra-patient comparison, using statistical similarity systems. In conclusion, these results show that post-surgical FNAs represent a possible alternative source of material for MALDI-MSI proteomic investigations in instances where pre-surgical samples are unavailable or the number of cells is scarce.

Role of Complete Duplex Ultrasound to Diagnose Deep Vein Thrombosis in COVID-19 Critical Patients.

An increased risk of deep vein thrombosis (DVT) has been reported in critical COVID-19 patients, despite adequate thromboprophylaxis, and most of DVT are probably asymptomatic. As a screening approach has been advocated, the best examination protocol is unknown. The objective of this study is to assess the role of a Complete Duplex Ultrasound (CDUS) examination in detecting DVT in a large population of COVID-19 patients admitted to intensive care unit (ICU) for respiratory failure. Single-center retrospective study of 145 COVID-19 patients admitted to ICU. DVT was assessed with a CDUS performed by experienced radiologist after ICU admission. DVT was confirmed in 38 patients (26%). Most DVT were distal to the knee (66%), while only 16% were proximal. At the time of the examination, 55% of the patients received full-dose anticoagulation, while 45% received thromboprophylaxis, and there were no differences in anticoagulation regimen between positive and negative patients. Patients with DVT had higher dimers compared with those with negative CDUS (P < .002). The observed frequency of DVT is high despite adequate anticoagulation. A comprehensive and experienced ultrasound examination protocol can allow to recognize a large number of distal DVT otherwise missed, albeit their clinical significance is unknown.

The spectrum of the cytopathological features of primary effusion lymphoma and human herpes virus 8-related lymphoproliferative disorders.

INTRODUCTION: Human herpes virus 8-related lymphoproliferative disorders are a complex and heterogeneous group of entities and some of them are eminently diagnosed by cytopathology. In a routine laboratory, these lesions account for less than 1% of the effusion fluids samples. However, they represent up to 30% of all the lymphoma diagnosis from effusion cytological samples and their consideration in the diagnostic flow chart is mandatory, especially in human immunodeficiency virus-positive patients. METHODS: A retrospective series of cytological specimens from cavity effusions (n = 605) were analysed. Five human herpes virus 8-related lymphoproliferative processes were recruited. A combination of morphological criteria (enhanced with May-Grünwald Giemsa staining), cell block-based immunocytochemistry and flow cytometry were undertaken for final characterisation. RESULTS: The identification of malignant cells may be difficult. Some specimens are particularly rich, easily leading to suspect a lymphoproliferative process, whereas in other cases, the presence of abundant reactive mesothelial cells, histiocytes, neutrophils, small reactive T and B lymphocytes may obscure the neoplastic process. The biological behaviour may be very heterogeneous and a standardised therapy for these cases is still lacking, although some patients may benefit from antiretroviral therapy in a human immunodeficiency virus setting. CONCLUSIONS: The present case series highlights some characteristic findings of these entities to reaffirm useful cytopathological diagnostic criteria, stressing the crucial role of the appropriate technical processing of effusion fluids to obtain the best performances.

The management of haemoglobin interference for the MALDI-MSI proteomics analysis of thyroid fine needle aspiration biopsies.

MALDI-MSI represents an ideal tool to explore the spatial distribution of proteins directly in situ, integrating molecular and cytomorphological information, enabling the discovery of potential diagnostic markers in thyroid cytopathology. However, red cells present in the fine needle aspiration biopsy (FNAB) specimens caused ion suppression of other proteins during the MALDI-MSI analysis due to large amount of haemoglobin. Aim of this study was to set up a sample preparation workflow able to manage this haemoglobin interference. Three protocols were compared using ex vivo cytological samples collected from fresh thyroid nodules of 9 patients who underwent thyroidectomy: (A) conventional air-dried smears, (B) cytological smears immediately fixed in ethanol, and (C) ThinPrep liquid-based preparation. Protocols C and A were also evaluated using real FNABs. Results show that protocol C markedly decreased the amount of haemoglobin, with respect to protocols A and B. Protein profiles obtained with protocols A and B were characterised by high inter-patient variability, probably related to the abundance of the haemoglobin, whereas similar spectra were observed for protocol C, where haemoglobin contents were lower. Our findings suggest protocol C as the sample preparation method for MALDI-MSI analysis. Graphical abstract.

Use of Shear Wave Elastography in the Sonographic Triage of Thyroid Nodules: Feasibility Study in a Series of Lesions Already Selected for Fine Needle Aspiration.

OBJECTIVES: The aim of this study was to evaluate the application of shear wave elastography (SWE) in the routine management of thyroid nodules, as a possible additional tool to the standard sonographic triage. METHODS: A total of 248 consecutive patients scheduled for ultrasound-guided thyroid fine-needle aspiration were included in the study. The presence of a pure colloid lesion was an exclusion criterion. Absolute and relative SWE stiffness measurements on color-coded elastograms, expressed in kilopascals and meters per second, were correlated with radiologic and pathologic features. RESULTS: SWE values in thyroid nodules were significantly higher than normal thyroid tissue (P = .0001), proving the different elastic properties of the pathologic tissues. Regarding the radiologic characteristics of the nodules, SWE highest values were associated with the largest lesions (P = .0105) but independent from sonographic and Doppler findings. The SWE elasticity was not influenced by the characteristics of the biopsy smears. The final correlation between the SWE results and the pathologic diagnoses showed a trend in stiffness from tender tumors (follicular adenoma) to papillary thyroid carcinoma (P = .016). CONCLUSIONS: SWE allows the identification of nodules within normal parenchyma; however, the present study does not confirm the potential role in differentiating between benign and malignant thyroid nodules.

Update on: proteome analysis in thyroid pathology - part II: overview of technical and clinical enhancement of proteomic investigation of the thyroid lesions.

INTRODUCTION: An accurate diagnostic classification of thyroid lesions remains an important clinical aspect that needs to be addressed in order to avoid 'diagnostic' thyroidectomies. Among the several 'omics' techniques, proteomics is playing a pivotal role in the search for diagnostic markers. In recent years, different approaches have been used, taking advantage of the technical improvements related to mass spectrometry that have occurred. Areas covered: The review provides an update of the recent findings in diagnostic classification, in genetic definition and in the investigation of thyroid lesions based on different proteomics approaches and on different type of specimens: cytological, surgical and biofluid samples. A brief section will discuss how these findings can be integrated with those obtained by metabolomics investigations. Expert commentary: Among the several proteomics approaches able to deepen our knowledge of the molecular alterations of the different thyroid lesions, MALDI-MSI is strongly emerging above all. In fact, MS-imaging has also been demonstrated to be capable of distinguishing thyroid lesions, based on their different molecular signatures, using cytological specimens. The possibility to use the material obtained by the fine needle aspiration makes MALDI-MSI a highly promising technology that could be implemented into the clinical and pathological units.

Proteomics in thyroid cytopathology: Relevance of MALDI-imaging in distinguishing malignant from benign lesions.

Several proteomic strategies are used extensively for the purpose of biomarker discovery and in order to obtain insights into the molecular aspects of cancers, using either body fluids or tissue as samples. Among them, MALDI-imaging can be applied to cytological thyroid specimens to investigate the molecular signatures of different pathological conditions and highlight differences in the proteome that are of relevance for diagnostic and pathogenetic research. In this study, 26 ex-vivo fine needle aspirations from benign thyroid nodules (n = 13) and papillary thyroid carcinomas (n = 13) were analyzed by MALDI-imaging. Based on the specific protein signatures capable of distinguishing the aforementioned patients, MALDI-imaging was able to correctly assign, in blind, the specimens from ten additional FNABs to a malignant or benign class, as later confirmed by the morphological classification. Moreover, some proteins presented a progressive overexpression in malignant phenotypes when compared with Hashimoto's thyroiditis and hyperplastic/follicular adenoma. This data not only suggests that a MALDI-imaging based approach can be a valuable tool in the diagnosis of thyroid lesions but also in the detection of proteins that have a possible role in the promotion of tumorigenic activity.

Safe ECMO femoral decannulation by placement of inferior vena cava filter via internal jugular vein.

Veno-arterial extracorporeal membrane oxygenation (ECMO) is a lifesaving treatment in patients with cardiogenic shock or cardiac arrest caused by massive pulmonary embolism. In these patients, positioning an inferior vena cava filter is often advisable, especially if deep venous thrombosis is not resolved at the time of the ECMO suspension. Moreover, in ECMO patients, a high incidence of deep venous thrombosis at the site of venous cannulation has been reported, and massive pulmonary embolism following ECMO decannulation has been described. Nonetheless, an inferior vena cava filter cannot be positioned as long as an ECMO cannula is inside the inferior vena cava. Thus, we developed a strategy to allow placement of an inferior vena cava filter through the internal jugular concurrently with the removal of the femoral venous ECMO cannula. In two women supported by veno-arterial ECMO for cardiac arrest secondary to pulmonary embolism, this novel approach allowed for safe ECMO decannulation.

Use of "Time-Out" checklist in interventional radiology procedures as a tool to enhance patient safety.

PURPOSE: This study was done to evaluate the feasibility and effectiveness of adopting a safety checklist (SC) in the angiography suite during interventional radiology (IR) procedures to enhance patient safety. MATERIALS AND METHODS: Surgical SC was successfully introduced in 2009 with the aim of drastically reducing the morbidity and mortality caused by human error on patients during their stay in the operating room. Even CIRSE, the Cardiovascular and Interventional Radiological Society of Europe, recently published its own SC recommending its use in IR suites. Since January 2012, in our routine practice in the angiographic unit, we have used a 20-item checklist named "Time-Out" derived from the CIRSE SC. The main items are: in the Time-Out phase, active verbal communication within the team; correct identification of the patient and of the procedure site and side. Additionally, during the preprocedure (Sign-In) and postprocedure (Sign-Out) stages a series of clinical data are collected such as administration of prophylaxis against contrast allergy or contrast-induced nephropathy (CIN), when needed informed consent, discontinuation of anticoagulation therapy, fasting, correct labelling of biological samples, etc. RESULTS: Preliminary educational sessions were held to sensitise all the staff involved in the Time-Out project (physicians, nurses, radiographers) and ensure satisfactory compliance from the outset in consideration of the increased time and paperwork that checklist implementation would involve. CONCLUSIONS: The use of a checklist in IR, named "Time-Out" in our experience was feasible and effective allowing elimination of adverse events in the first year of use and promoting significant involvement and awareness of patient safety among the health-care team. The level of implementation, completeness and acceptability of the SC within the team increased after adequate training had been provided.

Viable residual tumor tissue after radiofrequency ablation treatment in hepatocellular carcinoma: evaluation with CT perfusion.

PURPOSE: To assess the role of CT perfusion technique in detection of blood flow changes related to the therapeutic effects in HCC lesion treated with RFA. METHODS: 14 cirrhotic patients with known HCC underwent a perfusion study about 4 months (range 1-13 months) after RFA on a 16-slice MDCT scanner (Brilliance, Philips). Dynamic CT was performed acquiring 8 dynamic slice/scan, after injection of 50 mL of contrast media. In treated lesion, surrounding parenchyma and hypervascular tissue suspicious for residual disease/recurrence, the following perfusion parameters were analyzed: perfusion (P, mL/100 g min); arterial perfusion (AP, mL/min); blood volume (BV, mL/100 mg); hepatic perfusion index (HPI, %), and time to peak (TTP, s). Univariate Wilcoxon signed rank test was used for statistical analysis. RESULTS: In patients with residual disease (8/14) values of perfusion parameters measured within tumor were: P, median = 45.2; AP, median = 48.2; BV, median = 18.9; HPI, median = 35.8; and TTP, median = 19.4. The values calculated in ablated area were: P, median = 10.9; AP, median = 9.6; BV, median = 5.5; HPI, median = 14.6; TTP, median = 39.6. The parameters calculated in the surrounding parenchyma were: P, median = 15.8; AP, median = 14.2; BV, median = 12.0; HPI, median = 17.9; TTP, median = 43.2. A significant difference (P < 0.05) was observed in mean values of P, AP, and HPI, calculated between treated lesions with residual tumor and those successfully treated. CONCLUSION: Perfusion CT enables assessment of HCC vascularity after RFA treatment, by adding quantitative information about the presence of residual arterial vessels within the viable residual neoplastic tissue.

The Complex Cyto-Molecular Landscape of Thyroid Nodules in Pediatrics.

Thyroid fine-needle aspiration (FNA) is a commonly used diagnostic cytological procedure in pediatric patients for the evaluation of thyroid nodules, triaging them for the detection of thyroid cancer. In recent years, greater attention has been paid to thyroid FNA in this setting, including the use of updated ultrasound score algorithms to improve accuracy and yield, especially considering the theoretically higher risk of malignancy of these lesions compared with the adult population, as well as to minimize patient discomfort. Moreover, molecular genetic testing for thyroid disease is an expanding field of research that could aid in distinguishing benign from cancerous nodules and assist in determining their clinical management. Finally, artificial intelligence tools can help in this task by performing a comprehensive analysis of all the obtained data. These advancements have led to greater reliance on FNA as a first-line diagnostic tool for pediatric thyroid disease. This review article provides an overview of these recent developments and their impact on the diagnosis and management of thyroid nodules in children.

Spontaneous Soft Tissue Hematomas in Patients with Coagulation Impairment: Safety and Efficacy of Transarterial Embolization.

The aim of this study is to report the authors' experience of percutaneous transarterial embolization (TAE) in patients with spontaneous soft tissue hematomas (SSTH) and active bleeding with anticoagulation impairment. The study retrospectively identified 78 patients who received a diagnosis of SSTH by CT scan and underwent TAE between 2010 and 2019 in a single trauma center. The patients were stratified using Popov classification into categories: 2A, 2B, 2C, and 3. The patient's 30-day survival after TAE was considered the primary outcome; immediate technical success, the need for additional TAE, and TAE-related complications were considered secondary outcomes. Immediate technical success, complication rate, and risk factors for death were analyzed. Follow-up stopped on day 30 from TAE. 27 patients (35%) fell into category 2A, 8 (10%) into category 2B, 4 (5%) into category 2C, and 39 (50%) into category 3. Immediate technical success was achieved in 77 patients (98.7%). Complications included damage at the arterial puncture site (2 patients, 2.5%) and acute kidney injury (24 patients, 31%). Only 2 patients (2.5%) had been discharged with a new diagnosis of chronic kidney disease. The 30-day overall mortality rate was 19% (15 patients). The mortality rate was higher in hemodynamically unstable patients, in Popov categories 2B, 2C, and 3, and in patients with an initial eGFR < 30 mL/min × 1.73 m2. The study demonstrated a higher mortality risk for categories 2B, 2C, and 3 compared to category 2A. Nonetheless, TAE has proven effective and safe in type 2A patients. Even though it is unclear whether type 2A patients could benefit from conservative treatment rather than TAE, in the authors' opinion, a TAE endovascular approach should be promptly considered for all patients in ACT with active bleeding demonstrated on CT scans.

An Indeterminate for Malignancy FNA Report Does Not Increase the Surgical Risk of Incidental Thyroid Carcinoma.

Incidental thyroid carcinomas (ITCs) are a fairly frequent finding in daily routine practice, with papillary thyroid microcarcinoma being the most frequent entity. In our work, we isolated incidental cases arising in thyroids removed for other cytologically indeterminate and histologically benign nodules. We retrospectively retrieved cases with available thyroid Fine Needle Aspiration (FNA, 3270 cases), selecting those with an indeterminate cytological diagnosis (Bethesda classes III−IV, 652 cases). Subsequently, we restricted the analysis to surgically treated patients (163 cases) finding an incidental thyroid carcinoma in 22 of them. We found a 13.5% ITC rate, with ITCs representing 46.8% of all cancer histologically diagnosed in this indeterminate setting. Patients received a cytological diagnosis of Bethesda class III and IV in 41% and 59% of cases, respectively. All ITC cases turned out to be papillary thyroid microcarcinomas; 36% of cases were multifocal, with foci bilaterally detected in 50% of cases. We found an overall ITC rate concordant with the literature and with our previous findings. The assignment of an indeterminate category to FNA did not increase the risk of ITCs in our cohort. Rather, a strong statistical significance (p < 0.01) was found comparing the larger size of nodules that underwent FNA and the smaller size of their corresponding ITC nodule.

Compressive ultrasound can predict early pulmonary embolism onset in COVID patients.

PURPOSE: To evaluate the usefulness of compressive ultrasound (CUS) for the diagnosis of deep vein thrombosis (DVT) in patients with SARS-CoV-2-related infection. METHODS: 112 hospitalized patients with confirmed SARS-CoV-2 infection were retrospectively enrolled. CUS was performed within 2 days of admission and consisted in the assessment of the proximal and distal deep venous systems. Lack of compressibility, or direct identification of an endoluminal thrombus, were the criteria used for the diagnosis of DVT. Pulmonary embolism (PE) events were investigated at computed tomography pulmonary angiography (CTPA) within 5 days of follow-up. Logistic binary regression was computed to determine which clinical and radiological parameters were independently associated with PE onset. RESULTS: Overall, the incidence of DVT in our cohort was about 43%. The most common district involved was the left lower limb (68.7%) in comparison with the right one (58.3%) while the upper limbs were less frequently involved (4.2% the right one and 2.1% the left one, respectively). On both sides, the distal tract of the popliteal vein was the most common involved (50% right side and 45.8% left side). The presence of DVT in the distal tract of the right popliteal vein (OR = 2.444 95%CIs 1.084-16.624, p = 0.038), in the distal tract of the left popliteal vein (OR = 4.201 95%CIs 1.484-11.885, p = 0.007), and D-dimer values (OR = 2.122 95%CIs 1.030-5.495, p = 0.003) were independently associated with the onset on PE within 5 days. CONCLUSIONS: CUS should be considered a useful tool to discriminate which category of patients can develop PE within 5 days from admission.

Diagnostic Performances of the ACR-TIRADS System in Thyroid Nodules Triage: A Prospective Single Center Study.

Ultrasound scores are used to determine whether thyroid nodules should undergo Fine Needle Aspiration (FNA) or simple clinical follow-up. Different scores have been proposed for this task, with the American College of Radiology (ACR) TIRADS system being one of the most widely used. This study evaluates its ability in triaging thyroid nodules deserving FNA on a large prospective monocentric Italian case series of 493 thyroid nodules from 448 subjects. In ACR 1-2, cytology never prompted a surgical indication. In 59% of cases classified as TIR1c-TIR2, the FNA procedure could be ancillary, according to the ACR-TIRADS score. A subset (37.9%) of cases classified as TIR4-5 would not undergo FNA, according to the dimensional thresholds used by the ACR-TIRADS. Applying the ACR score, a total of 46.5% thyroid nodules should be studied with FNA. The ACR system demonstrated a sensitivity and specificity of 58.9% and 59% in the identification of patients with cytology ≥TIR3A, with a particularly high false negative rate for ACR classes ≥3 (44.8%, 43/96), which would dramatically decrease (7.3%, 7/96) if the dimensional criteria were not taken into account. In ACR 3-4-5, a correspondence with the follow-up occurred in 60.3%, 50.2% and 51.9% of cases. The ACR-TIRADS is a useful risk stratification tool for thyroid nodules, although the current dimensional thresholds could lead to an underestimation of malignant lesions. Their update might be considered in future studies to increase the screening performances of the system.

Use of Diagnostic Criteria from ACR and EU-TIRADS Systems to Improve the Performance of Cytology in Thyroid Nodule Triage.

Objective: The American College of Radiology (ACR) and the European Thyroid Association (EU) have proposed two scoring systems for thyroid nodule classification. Here, we compared the ability of the two systems in triaging thyroid nodules for fine-needle aspiration (FNA) and tested the putative role of an approach that combines ultrasound features and cytology for the detection of malignant nodules. Design and Methods: The scores obtained with the ACR and EU Thyroid Imaging Reporting and Data Systems (TIRADS) from a prospective series of 480 thyroid nodules acquired from 435 subjects were compared to assess their performances in FNA triaging on the final cytological diagnosis. The US features that showed the highest contribution in discriminating benign nodules from malignancies were combined with cytology to improve its diagnostic performance. Results: FNA was recommended on 46.5% and 51.9% of the nodules using the ACR and EU-TIRADS scores, respectively. The ACR system demonstrated a higher specificity as compared to the EU-TIRADS (59.0% vs. 52.4%, p = 0.0012) in predicting ≥ TIR3A/III (SIAPEC/Bethesda) nodules. Moreover, specific radiological features (i.e., echogenic foci and margins), combined with the cytological classes improved the specificity (97.5% vs. 91%, p < 0.0001) and positive predictive values (77.5% vs. 50.7%, p < 0.0001) compared to cytology alone, especially in the setting of indeterminate nodules (TIR3A/III and TIR3B/IV), maintaining an excellent sensitivity and negative predictive value. Conclusions: The ACR-TIRADS system showed a higher specificity compared to the EU-TIRADS in triaging thyroid nodules. The use of specific radiological features improved the diagnostic ability of cytology.

Analysis of Hashimoto's thyroiditis on fine needle aspiration samples by MALDI-Imaging.

Matrix-Assisted Laser Desorption/Ionization (MALDI)-Mass Spectrometry imaging (MSI) has been applied in various diseases aimed to biomarkers discovery. In this study diagnosis and prognosis of Hashimoto Thyroiditis (HT) in cytopathology by MALDI-MSI has been investigated. Specimens from a routine series of subjects who underwent UltraSound-guided thyroid Fine Needle Aspirations (FNAs) were used. The molecular classifier trained in a previous study was modified to include HT as a separate entity in the group of benign lesions, in the diagnostic proteomic triage of thyroid nodules. The statistical analysis confirmed the existence of signals that HT shares with hyperplastic lesions and others that are specific and characterize this subgroup. Statistically relevant HT-related peaks were included in the model. Then, the discriminatory capability of the classifier was tested in a second validation phase, showing a good agreement with cytological diagnoses. The possibility to overlap the molecular signatures of both the lymphocytes and epithelial cells components (ROIs or pixel-by-pixel analysis) confirmed the composite proteomic background of HT. These results open the way to their possible translation as alternative serum biomarkers of this autoimmune condition.

Molecular trait of follicular-patterned thyroid neoplasms defined by MALDI-imaging.

In the field of thyroid neoplasms, the most interesting recent change regards the introduction of a new terminology for follicular-patterned thyroid tumors, named Noninvasive Thyroid Neoplasm with Papillary-like Nuclear Features (NIFTP). This pre-malignant tumor is considered to be the putative precursor of invasive carcinoma. However, given that several issues are still unresolved, the application of ancillary tools, based on omics-techniques, may improve the clinical management of these challenging cases. The present paper highlights the proteomic profiles of a series of NIFTPs submitted to Fine Needle Aspirations (FNAs) and analysed by MALDI-imaging in order to confirm the heterogeneous phenotype of nodules included in the present NIFTP terminology and to underline the necessity of more accurate biomarkers that can be used for their characterization. Ethical and economic implications in terms of healthcare costs, operative risks, morbidity, as well as the potential need for lifelong hormone replacement therapy, seem to be significant reasons to approach the characterization of NIFTPs using alternative tools such as MALDI-MSI.

Virtual Guidance of Percutaneous Transthoracic Needle Biopsy with C-Arm Cone-Beam CT: Diagnostic Accuracy, Risk Factors and Effective Radiation Dose.

PURPOSE: C-arm cone-beam computed tomography-guided transthoracic lung core needle biopsy (CBCT-CNB) is a safe and accurate procedure for the evaluation of patients with pulmonary nodules. The purpose of our study was to evaluate the diagnostic performance, complication rates and effective radiation dose of CBCT-CNB with virtual guidance. MATERIALS AND METHODS: We retrospectively collected data regarding 375 CBCT-CNBs performed with virtual guidance (XperGuide-Philips Healthcare, Best, The Netherlands) from January 2010 to June 2015 on 355 patients (mean age, 68.1 years ± 11.8; age range, 31-88 years). Patients were divided into groups and compared based on the diagnostic failure and lesion size (15 mm cutoff). Diagnostic performance, complication rate and effective radiation dose were investigated. Variables influencing diagnostic performance and complications were assessed using Student's T test and Pearson's χ2 test. RESULTS: The sensitivity, specificity, positive and negative predictive value and accuracy for patients subjected to CNBs were 96.8%, 100%, 100%, 100% and 97.2%, respectively. Considering risk factors for pneumothorax, no significant differences were found regarding patient and lesion characteristics. Perilesional hemorrhage occurred more frequently in older patients (p = 0.046) and in smaller lesions (p = 0.001). Hemoptysis was significantly more frequent in patients with perilesional hemorrhage (p = 0.01). Mean effective radiation dose in CBCT-CNB was 7.12 ± 8.78 mSv. CONCLUSIONS: CBCT-CNB combined with virtual guidance is a reliable and accurate technique that allows exact localization of pulmonary lesions, effective preprocedural planning and real-time fluoroscopy altogether.