Integrating Biological and Radiological Data in a Structured Repository: a Data Model Applied to the COSMOS Case Study.

Integrating the information coming from biological samples with digital data, such as medical images, has gained prominence with the advent of precision medicine. Research in this field faces an ever-increasing amount of data to manage and, as a consequence, the need to structure these data in a functional and standardized fashion to promote and facilitate cooperation among institutions. Inspired by the Minimum Information About BIobank data Sharing (MIABIS), we propose an extended data model which aims to standardize data collections where both biological and digital samples are involved. In the proposed model, strong emphasis is given to the cause-effect relationships among factors as these are frequently encountered in clinical workflows. To test the data model in a realistic context, we consider the Continuous Observation of SMOking Subjects (COSMOS) dataset as case study, consisting of 10 consecutive years of lung cancer screening and follow-up on more than 5000 subjects. The structure of the COSMOS database, implemented to facilitate the process of data retrieval, is therefore presented along with a description of data that we hope to share in a public repository for lung cancer screening research.

Changes in thyroid fine needle aspiration practice during the COVID-19 pandemic.

PURPOSE: To investigate the diagnostic accuracy of a different sample preparation protocol for fine needle aspiration cytology (FNAC) of thyroid nodules established during the COVID-19 pandemic. METHODS: From April 2020, conventional smears during FNAC were ceased according to World Health Organization recommendations due to the increased infection risk for operators, and a new protocol using only liquid-based cytology (LBC) was adopted. FNACs performed between April and July 2020 (COVID-19 group) were retrospectively compared with those from December 2019 through March 2020 (Pre-COVID-19 group). The distribution of diagnoses based on SIAPEC-IAP categories and the concordance between cytological and histological results were compared using the chi-squared test. RESULTS: Categories based on FNAC for 90 and 82 thyroid nodules in the Pre-COVID-19 and COVID-19 groups showed no significant difference in distribution (P = .081), with the following respective cases (and percentages): TIR1, 7 (8%) and 8 (10%); TIR1C, 0 (0%) and 6 (7%); TIR2, 59 (66%) and 55 (67%); TIR3A, 8 (9%) and 5 (6%); TIR3B, 1 (1%) and 2 (3%); TIR4, 5 (6%) and 1 (1%); and TIR5, 10 (12%) and 5 (7%). Among patients with potentially malignant lesions, surgery was performed for 12/16 (75%) nodules in the Pre-COVID-19 and 7/8 (88%) nodules in the COVID-19 groups, with no significant differences between cytological and histological diagnoses (P = .931). CONCLUSION: The new LBC-only protocol provided similar diagnostic accuracy in comparison with conventional smears, and can be effectively applied during a viral pandemic improving operator safety.

COVID-19 and breast fine needle aspiration cytology method: What should we change?

INTRODUCTION: Air-dried slide preparation for fine needle aspiration cytology procedures is currently considered unsafe because of the risk of infectious aerosols of coronavirus 19. This study compares the safety and accuracy of two different protocols, one with and one without air-dried slides. METHODS: Starting from 3 March 2020, we discontinued the use of air-dried slides during breast fine needle aspiration procedures. We selected cases collected during two periods: 2 months before and 2 months after 3 March. In both groups, the number of procedures was recorded together with the distribution of the diagnostic categories and the concordance between cytological and histological results on surgical specimens for lesions suggestive of malignancy, using the chi-squared test. RESULTS: Of the 100 procedures performed during the pre-COVID-19 period, 55% were negative (C2), 3% were non-diagnostic (C1) and 40% were positive (C4 or C5). Of the 75 procedures obtained during the COVID-19 period, 44% were negative (C2), 2.7% were non-diagnostic (C1) and 52% were positive (C4 or C5). Despite the use of a new protocol during the COVID-19 period, we observed concordance between cytological and histological results for lesions suggestive of malignancy. There was no statistically significant difference concerning the distribution of the diagnostic categories in the two groups. CONCLUSIONS: Taking into account the slightly lower number of procedures being analysed during the COVID-19 period, the introduction of a new protocol that does not include air-dried slides is safe and reliable.

Ultrasound dye-assisted parathyroidectomy (USDAP): Experience of a tertiary center.

BACKGROUND: Primary hyperparathyroidism is primarily caused by parathyroid adenoma, followed by hyperplasia and parathyroid carcinoma. In the era of minimally invasive, targeted parathyroidectomy, the main challenge remains that of distinguishing intraoperatively pathological parathyroid from normal glands and peri-thyroid fat tissue. The aim of this study is to evaluate the surgical outcomes of a novel minimally invasive technique called ultrasound-guided dye-assisted parathyroidectomy (USDAP). METHODS: We perform a retrospective analysis of patients affected by parathyroid adenoma, treated with USDAP at our institution between 2014 and 2019. Data were collected on patient age and sex, tumor location and size, preoperative investigations, histopathology, perioperative complications and surgical outcomes. RESULTS: Between January 2014 and June 2019, 43 patients underwent parathyroidectomy in our Institute. Each case was discussed by the Institutional Multidisciplinary Board. All patients undergoing thyroidectomy together with USDAP or patients undergoing USDAP under endoscopic control were excluded from the present study. The final cohort, the largest to our knowledge, consisted of 29 patients. All patients were successfully treated with USDAP and remained disease-free during follow up. In all cases, pathological parathyroid was correctly identified and removed. There was no postoperative allergic reaction, nor were there neurotoxicity complications. USDAP permitted a shortening of operative and hospitalization time. CONCLUSIONS: USDAP is an effective and safe procedure both as first line treatment and as a re-operative procedure after previous surgical failures in selected cases.

The role of radiomics in tongue cancer: A new tool for prognosis prediction.

BACKGROUND: Radiomics represents an emerging field of precision-medicine. Its application in head and neck is still at the beginning. METHODS: Retrospective study about magnetic resonance imaging (MRI) based radiomics in oral tongue squamous cell carcinoma (OTSCC) surgically treated (2010-2019; 79 patients). All preoperative MRIs include different sequences (T1, T2, DWI, ADC). Tumor volume was manually segmented and exported to radiomic-software, to perform feature extraction. Statistically significant variables were included in multivariable analysis and related to survival endpoints. Predictive models were elaborated (clinical, radiomic, clinical-radiomic models) and compared using C-index. RESULTS: In almost all clinical-radiomic models radiomic-score maintained statistical significance. In all cases C-index was higher in clinical-radiomic models than in clinical ones. ADC provided the best fit to the models (C-index 0.98, 0.86, 0.84 in loco-regional recurrence, cause-specific mortality, overall survival, respectively). CONCLUSION: MRI-based radiomics in OTSCC represents a promising noninvasive method of precision medicine, improving prognosis prediction before surgery.

The European Institute of Oncology Thyroid Imaging Reporting and Data System for Classification of Thyroid Nodules: A Prospective Study.

BACKGROUND: To evaluate the performance, quality and effectiveness of "IEO-TIRADS" in assigning a TI-RADS score to thyroid nodules (TN) when compared with "EU-TIRADS" and the US risk score calculated with the S-Detect software ("S-Detect"). The primary objective is the evaluation of diagnostic accuracy (DA) by "IEO-TIRADS", "S-Detect" and "EU-TIRADS", and the secondary objective is to evaluate the diagnostic performances of the scores, using the histological report as the gold standard. METHODS: A radiologist collected all three scores of the TNs detected and determined the risk of malignancy. The results of all the scores were compared with the histological specimens. The sensitivity (SE), specificity (SP), and diagnostic accuracy (DA), with their 95% confidence interval (95% CI), were calculated for each method. RESULTS: 140 TNs were observed in 93 patients and classified according to all three scores. "IEO-TIRADS" has an SE of 73.6%, an SP of 59.2% and a DA of 68.6%. "EU-TIRADS" has an SE of 90.1%, an SP of 32.7% and a DA of 70.0%. "S-Detect" has an SE of 67.0%, an SP of 69.4% and a DA of 67.9%. CONCLUSION: "IEO-TIRADS" has a similar diagnostic performance to "S-Detect" and "EU-TIRADS". Providing a comparable DA with other reporting systems, IEO-TIRADS holds the potential of being applied in clinical practice.

A segmentation tool for pulmonary nodules in lung cancer screening: Testing and clinical usage.

PURPOSE: With the future goal of defining a large dataset based on low-dose CT with labelled pulmonary lesions for lung cancer screening (LCS) research, the aim of this work is to propose and evaluate into a clinical context a tool for semi-automatic segmentation able to facilitate the process of labels collection from a LCS study (COSMOS, Continuous Observation of SMOking Subjects). METHODS: Considering a preliminary set of manual annotations, a segmentation model based on a 2D-Unet was trained from scratch. Contour quality of the final 2D-Unet was assessed on an internal test set of manual annotations and on a subset of the public available LIDC dataset used as external test set. The tool for semi-automatic segmentation was then designed integrating the tested model into a Graphical User Interface. According to the opinion of two clinical users, the percentage of lesions properly contoured through the tool was quantified (Acceptance Rate, AR). The variability between segmentations derived by the two readers was estimated as mean percentage of difference (MPD) between the two sets of volumes and comparing the likelihood of malignancy derived from Volume Doubling Time (VDT). RESULTS: Performance in test sets were found similar (DICE ~ 0.75(0.15)). Accordingly, a good mean AR (80.1%) resulted from the two readers. Variability in terms of MPD was equal to 23.6% while 2.7% was the VDTs percentage of disagreement. CONCLUSIONS: A semi-automatic segmentation tool was developed and its applicability evaluated into a clinical context demonstrating the efficacy of the tool in facilitating the collection of labelled data.

Prevalence of Central Compartment Lymph Node Metastases in Papillary Thyroid Micro-Carcinoma: A Retrospective Evaluation of Predictive Preoperative Features.

Papillary thyroid micro-carcinomas are considered relatively indolent carcinomas, often occult and incidental, with good prognosis and favorable outcomes. Despite these findings, central lymph node metastases are common, and are related to a poor prognosis for the patient. We performed a retrospective analysis on patients treated with surgery for stage pT1a papillary thyroid micro-carcinomas. One hundred ninety-five patients were included in the analyses. The presence of central lymph node metastases was identified and studied. A multivariate analysis employing binary logistic regression was used to calculate adjusted odds ratios with 95% confidence intervals of possible central lymph node metastases risk factors. In the performed multivariate analysis, male gender, younger age, and histopathological characteristics, such as a tumor sub-capsular localization, were significantly associated with central lymph node metastases in pT1a patients. Central compartment lymph node metastases are present in a non-negligible number of cases in patients with papillary thyroid micro-carcinoma undergoing surgical resection. Studying these factors could be an effective tool for predicting patients' central lymph node metastases in papillary thyroid micro-carcinomas, defining a tailored surgical treatment in the future.

US-guided transcutaneous tru-cut biopsy of laryngo-hypopharyngeal lesions.

OBJECTIVE: To evaluate the feasibility and performance of ultrasound-guided transcutaneous tru-cut biopsy (USGTCB) in selected patients (with stenosis of airways or difficult intubation or contraindication to general anaesthesia) with untreated or previously treated suspicious laryngo-hypopharyngeal masses. METHODS: Biopsies were performed with a free-hand technique by a single radiologist. Thirty-six USGTCBs were scheduled in 34 patients (24 males, 10 females; age range 47-95 years). Two USGTCBs were not performed, as lesions were not detectable: therefore, 16 USGTCBs were performed for an untreated mass suspicious for malignancy and 18 were performed for a mass suspicious for recurrence after radiotherapy alone, or associated with endoscopic laser surgery or chemotherapy. RESULTS: USGTCB diagnosed 25 squamous cell carcinomas (73.5%) and nine benign lesions (26.5%); no false positives and two false negatives were reported, both in patients previously treated with radiotherapy. The sensitivity, specificity, positive and negative predictive value of the technique was 92.5%, 100%, 100% and 77.7% respectively, with no major complications. CONCLUSION: Although biopsy under microlaryngoscopy remains the "gold-standard" technique, USGTCB is feasible, carries the advantages of avoiding general anaesthesia, is suitable for outpatients and is cost-effective. If applied to selected patients, it could be considered for the histological diagnosis of both primary and recurrent laryngo-hypopharyngeal masses.

Pulmonary nodules: Contrast-enhanced volumetric variation at different CT scan delays.

OBJECTIVE: The purpose of this study was to assess the effects of IV contrast medium and different CT scan delays on volumetric measurements of pulmonary nodule. MATERIALS AND METHODS: Automated volumes of 35 pulmonary nodules were calculated with two dedicated software packages (designated as software A and software B) for each unenhanced and contrast-enhanced CT scan at 30-, 60-, 120-, 180-, and 300-second delays (injection protocol, 2 mL/s and 2 mL/kg). Nodule attenuation was also determined. Differences between unenhanced and contrast-enhanced volumes were analyzed by Wilcoxon's signed rank test. Contrast-enhanced volume ratio was calculated as the ratio between contrast-enhanced and unenhanced nodule volume. RESULTS: Contrast-enhanced volumes were significantly larger than unenhanced volumes (p < 0.05) for all the timing delays except at 30 seconds for software A, and no significant differences were found among volumes measured with both software programs at different contrast-enhanced delays. Median volume ratios between contrast-enhanced and unenhanced volumes were 1.04-1.07 for software A and 1.04-1.06 for software B, and median volume ratios within different contrast-enhanced delays were 0.99-1.03 for software A and 0.99-1.04 for software B. We did not find any significant association between contrast-enhanced volume ratio and nodule diameter, site, shape, unenhanced density, or contrast-enhanced density ratio (p > 0.05). CONCLUSION: We recommend comparing volume of pulmonary nodules obtained from CT examinations only if they are all performed with or without contrast material, whereas nodule volumes obtained by use of enhanced CT performed with different scan delays are comparable.

A subfascial variant of the deep inferior epigastric artery demonstrated by preoperative multidetector computed tomographic angiography: a case report.

Precise preoperative imaging by multidetector computed tomographic (MDCT) angiography for planning of deep inferior epigastric artery perforator (DIEP) flap dissection has been reported for enormous advantages in terms of reduced operative time and minimized flap-related complications. This case report shows a particularly rare anatomical subfascia variant of deep inferior epigastric artery (DIEA) which can be preoperatively demonstrated by MDCT angiogram. Therefore, the intraoperative finding also confirms the radiologic data and results in meticulous flap harvesting during incision on anterior rectus sheath. Additionally, the authors emphasize on performing preoperative high quality imaging for DIEP intervention precisely for specific vulnerable course of subfascial plane DIEP, which is rare but tends to be at risk without foreknowing its exact course.

Image-Guided Thermal Ablation as an Alternative to Surgery for Papillary Thyroid Microcarcinoma: Preliminary Results of an Italian Experience.

Purpose: To report the results of our preliminary experience in treating patients with papillary thyroid microcarcinoma (PTMC) with image-guided thermal ablation, in particular estimating the feasibility, safety and short-term efficacy. Materials and Methods: From 2018 patients with cytologically proven PTMC < 10 mm were discussed in a multidisciplinary team and evaluated for feasibility of image-guided thermal ablation. In case of technical feasibility, the three possible alternatives (i.e., image-guided thermal ablation, surgery, and active surveillance) were discussed with patients. Patients who agreed to be treated with image guided thermal ablation underwent radiofrequency (RFA) or laser ablation under local anesthesia and conscious sedation. Treatment feasibility, technical success, technique efficacy, change in thyroid function tests, side effects, minor and major complications, patients satisfaction and pain/discomfort perception during and after treatment, and disease recurrence during follow-up were recorded. Results: A total of 13 patients were evaluated, and 11/13 (84.6%) patients (9 female, 2 male, mean age 49.3 ± 8.7 years) resulted suitable for image-guided thermal ablation. All 11 patients agreed to be treated with image-guided thermal ablation. In addition, 3/11 (27.3%) were treated with laser ablation and 8/11 (72.7%) with RFA. All procedures were completed as preoperatively planned (technical success 100%). Technique efficacy was achieved in all 11/11 (100%) cases. Ablated volume significantly reduced from 0.87 ± 0.67 ml at first follow-up to 0.17 ± 0.36 at last follow-up (p = 0.003). No change in thyroid function tests occurred. No minor or major complications occurred. All patients graded 10 the satisfaction for the treatment, and mean pain after the procedure was reported as 1.4 ± 1.7, and mean pain after the procedure as 1.2 ± 1.1 At a median follow-up of 10.2 months (range 1.5-12 months), no local recurrence or distant metastases were found. Conclusions: Image guided thermal ablations appear to be feasible and safe in the treatment of PTMC. These techniques hold the potential to offer patients a minimally invasive curative alternative to surgical resection or active surveillance. These techniques appear to be largely preferred by patients.

In vivo repeatability of automated volume calculations of small pulmonary nodules with CT.

OBJECTIVE: The objectives of our study were to evaluate the in vivo reproducibility of automated volume calculations of small lung nodules with both low-dose and standard-dose CT and to assess whether repeatability within each technique varies according to the diameter, site, or morphology of the nodule or to percentage of emphysema. SUBJECTS AND METHODS: Sixty-six subjects with 83 solid pulmonary nodules between 5 and 10 mm in diameter were enrolled in this prospective study. Four consecutive MDCT data sets, two low dose and two standard dose, were obtained for each nodule on separate breath-holds during the same session. The volume of each nodule was calculated by automated software. Repeatability was evaluated by Bland-Altman's approach and the coefficient of repeatability. Associations of the percentage of volume variation between two measurements with nodule diameter, emphysema percentage, nodule site, and nodule morphology were assessed by Spearman's correlation coefficient and the Kruskal-Wallis test. A p value of < 0.05 was considered statistically significant. RESULTS: The range of variation of the volumes of pulmonary nodules between two subsequent measurements was -38% +/- 60% for low-dose CT and -27% +/- 40% for standard-dose CT. No significant statistical association was found between variation in volume measurements and nodule site, nodule diameter, nodule morphology, or emphysema percentage by semiautomated calculation of lung density. CONCLUSION: Automated volume calculations of small pulmonary nodules can significantly differ between two subsequent breath-holds with both low-dose and standard-dose CT techniques; in clinical practice we recommend that a volume variation of greater than 30% for nodules between 5 and 10 mm should be confirmed by follow-up CT to be sure that a nodule is actually growing.

A case of Warthin-like papillary thyroid carcinoma with diffuse sclerosing stroma and a novel RET mutation: a new entity or a combined tumour?

Activating mutations of the RET gene have been described for both papillary (chromosomal rearrangement) and medullary (missense mutations) thyroid carcinomas. Here, we describe a case of a Warthin-like variant of papillary thyroid carcinoma displaying some morphological aspects that mimic the diffuse sclerosing variant. The tumour harboured BRAF V600E mutation and a novel germline point mutation in the RET gene, with unknown clinical and pathological meaning.

Percutaneous laser ablation for benign and malignant thyroid diseases.

Minimally invasive image-guided thermal ablation is becoming increasingly common as an alternative to surgery for the treatment of benign thyroid nodules. Among the various techniques for thermal ablation, laser ablation (LA) is the least invasive, using the smallest applicators available on the market and enabling extremely precise energy deposition. However, in some cases, multiple laser fibers must be used simultaneously for the treatment of large nodules. In this review, the LA technique is described, and its main clinical applications and results are discussed and illustrated.

The role of ultrasound-guided transcutaneous tru-cut biopsy in diagnosing untreated and recurrent laryngo-hypopharyngeal masses.

OBJECTIVE: To evaluate the diagnostic performance of Ultrasound-guided Transcutaneous Tru-Cut biopsy (USGTCB) of laryngo-hypopharyngeal masses suspicious for malignancy. Furthermore we investigated whether USGTCB is accurate for both untreated masses and suspected recurrences. MATERIALS AND METHODS: From August 2004 to July 2014 we prospectively enrolled 66 patients for a total of 68 USGTCBs: 38 USGTCB were performed for a suspicious untreated mass and in 30 for a suspected recurrence. We calculated the sensitivity, specificity, positive predictive value and negative predictive value for all procedures and separately for untreated masses and suspected recurrences. RESULTS: USGTCB diagnosed 57 malignancies (51 squamous cell carcinomas, 6 other tumors) and 11 benign lesions. There were no false positives reported, whereas five false negatives were observed: two in patients with an untreated mass, three in patients with a suspected recurrence. Overall, the sensitivity of the technique was 91.9% (95% confidence interval [CI]: 82.2-97.3%); the specificity was 100% (95% CI: 54.1-100%); positive and negative predictive values were 100% (95% CI: 93.7-100%) and 54.5% (95% CI: 23.5-83.1%) respectively, with similar performances in untreated masses and suspected recurrences of SCC. CONCLUSION: USGTCB is an effective procedure for the histological diagnosis of laryngo-hypopharyngeal masses suspicious for malignancy in patients showing contraindications to biopsy via microlaryngoscopy under general, with similar performances for untreated masses and suspected recurrences.

Early lung-cancer detection with spiral CT and positron emission tomography in heavy smokers: 2-year results.

BACKGROUND: Low-dose spiral CT of the chest effectively detects early-stage lung cancer in high-risk individuals. The high rate of benign nodules and issues of making a differential diagnosis are critical factors that currently hamper introduction of large-scale screening programmes. We investigated the efficacy of repeated yearly spiral CT and selective use of positron emission tomography (PET) in a large cohort of high-risk volunteers. METHODS: We enrolled 1035 individuals aged 50 years or older who had smoked for 20 pack-years or more. All patients underwent annual low-dose CT, with or without PET, for 5 years. Lesions up to 5 mm were deemed non-suspicious and low-dose CT was repeated after 12 months (year 2). FINDINGS: By year 2, 22 cases of lung cancer had been diagnosed (11 at baseline, 11 at year 2). 440 lung lesions were identified in 298 (29%) participants, and 95 were recalled for high-resolution contrast CT. PET scans were positive in 18 of 20 of the identified cancer cases. Six patients underwent surgical biopsy for benign disease because of false-positive results (6% of recalls, 22% of invasive procedures). Complete resection was achieved in 21 (95%) lung cancers, 17 (77%) were pathological stage I (100% at year 2), and the mean tumour size was 18 mm. There were no interval lung cancers in the 2.5 years of follow-up (average time on study from randomisation to last contact), although 19 individuals were diagnosed with another form of cancer (two deaths and 17 non-fatal admissions). INTERPRETATION: Combined use of low-dose spiral CT and selective PET effectively detects early lung cancer. Lesions up to 5 mm can be checked again at 12 months without major risks of progression.

A case of NUT midline carcinoma with no HPV infection, slight EWSR1 rearrangement and strong expression of EGFR.

NUT midline carcinoma (NMC) is a rare neoplasm with a poor prognosis and involving mostly young patients. Here we describe a classic NMC with a BRD4-NUT fusion gene in a middle-aged woman. We also analyzed some biological features that could potentially influence its clinical behavior such as HPV infection, EWSR1 rearrangement, and the status of the EGFR gene.

Radio-guided ultrasound lymph node localization: feasibility of a new technique for localizing and excising nonpalpable lymph nodes ultrasound suspicious for melanoma metastases.

Identification of lymph nodes suspicious for metastases is crucial in melanoma patients during the follow-up. We propose a procedure called radio-guided ultrasound lymph node localization (RULL) for melanoma patients with ultrasound (US) suspicious, not palpable, lymph nodes. The aim of this study was to evaluate the feasibility of this technique, and to assess the efficacy of this new method. RULL was applied in 12 consecutive melanoma patients with non-palpable lymph nodes found suspicious for metastases during US follow-up. Macro-aggregates of human serum albumin labelled with diluted technetium-99m were injected into the suspected lymph node under US guidance and followed by a scintigraphy. The surgical treatment was carried out with the support of hand-held gamma-probe used for sentinel node biopsy. The tracer was correctly positioned in all 12 patients. Pathological examination revealed seven patients with metastatic lymph nodes, four with no metastatic lymph node, one patient with Hodgkin disease. No surgical complications were described. In conclusion, RULL may integrate the standard ultrasound-guided fine-needle aspiration to improve the diagnostic accuracy on US suspicious nodes and might replace the more logistically complicated wire identification or less accurate cutaneous marker identification of these nodes. Sensibility and specificity of this approach should be defined through a large multicentric study.