Acute myocardial infarction as presenting symptom of thymoma with compression on a coronary stent.

We report the clinical case of a patient with acute myocardial infarction due to coronary stent compression as first manifestation of a large thymoma. The patient underwent a coronarography and thrombus aspiration + plain old balloon angioplasty restoring the stent patency. The mass resection was performed through left robotic-assisted thoracic surgery (RATS), resulting in a type A thymoma pT1a, IIb Masaoka-Koga. An uncommon presentation led to early diagnosis and treatment of a thymoma with both oncological and functional significance.

Combining Piezo and Power Tools for a Better Outcome in Hybrid Structural-Preservation Rhinoplasty.

INTRODUCTION: Over the past decade, rhinoplasty has seen an unprecedented evolution in concepts, techniques and tools. New concepts have led to new techniques, prevalently but not exclusively related to preservation rhinoplasty, and the use of new tools has made such techniques easier, more precise and thus better reproducible. Power tools can presently be considered only relatively new, while Piezo has gained great popularity over the last years. MATERIALS AND METHOD: This article is focused on how power tools (diverse burrs with specific spherical, cylindrical, conical, discoid tips) can be integrated efficiently together with the use of Piezo and its different inserts in a logical and effective manner. DISCUSSION: This combination should be implemented in a progressive fashion into specific steps of surgery, although, in general, burrs should be used for reshaping and piezo for cutting bone. Specific and notable exceptions to this rule will be mentioned in the paper. Obviously, cost should be considered, but the benefits are evident: heightened control, reduced asymmetries, smoother bony and middle vault contour, and a more precise management of septum and turbinates. We have come to this conclusion following the combined experience of the two centers participating in the study, with over 350 patients over the last three years. CONCLUSIONS: The article focuses on the modified dorsal split preservation hybrid rhinoplasty favored by the senior author, but its principles will easily apply to any structural, preservation, or hybrid rhinoplasty. LEVEL OF EVIDENCE V: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Durvalumab Plus Gemcitabine and Cisplatin Versus Gemcitabine and Cisplatin in Biliary Tract Cancer: a Real-World Retrospective, Multicenter Study.

BACKGROUND: The TOPAZ-1 phase III trial reported a survival benefit with the anti-programmed cell death ligand 1 (anti-PD-L1) durvalumab in combination with gemcitabine and cisplatin in patients with advanced biliary tract cancer (BTC). OBJECTIVE: The present study investigated for the first time the impact on survival of adding durvalumab to cisplatin/gemcitabine compared with cisplatin/gemcitabine in a real-world setting. PATIENTS AND METHODS: The analyzed population included patients with unresectable, locally advanced, or metastatic BTC treated with durvalumab in combination with cisplatin/gemcitabine or with cisplatin/gemcitabine alone. The impact of adding durvalumab to chemotherapy in terms of overall survival (OS) and progression free survival (PFS) was investigated with univariate and multivariate analysis. RESULTS: Overall, 563 patients were included in the analysis: 213 received cisplatin/gemcitabine alone, 350 received cisplatin/gemcitabine plus durvalumab. At the univariate analysis, the addition of durvalumab was found to have an impact on survival, with a median OS of 14.8 months versus 11.2 months [hazard ratio (HR) 0.63, 95% confidence interval (CI) 0.50-0.80, p = 0.0002] in patients who received cisplatin/gemcitabine plus durvalumab compared to those who received cisplatin/gemcitabine alone. At the univariate analysis for PFS, the addition of durvalumab to cisplatin/gemcitabine demonstrated a survival impact, with a median PFS of 8.3 months and 6.0 months (HR 0.57, 95% CI 0.47-0.70, p < 0.0001) in patients who received cisplatin/gemcitabine plus durvalumab and cisplatin/gemcitabine alone, respectively. The multivariate analysis confirmed that adding durvalumab to cisplatin/gemcitabine is an independent prognostic factor for OS and PFS, with patients > 70 years old and those affected by locally advanced disease experiencing the highest survival benefit. Finally, an exploratory analysis of prognostic factors was performed in the cohort of patients who received durvalumab: neutrophil-lymphocyte ratio (NLR) and disease stage were to be independent prognostic factors in terms of OS. The interaction test highlighted NLR ≤ 3, Eastern Cooperative Oncology Group Performance Status (ECOG PS) = 0, and locally advanced disease as positive predictive factors for OS on cisplatin/gemcitabine plus durvalumab. CONCLUSION: In line with the results of the TOPAZ-1 trial, adding durvalumab to cisplatin/gemcitabine has been confirmed to confer a survival benefit in terms of OS and PFS in a real-world setting of patients with advanced BTC.

Multidisciplinary Management of Descending Necrotizing Mediastinitis: Is Thoracoscopic Treatment Feasible?

Background: Descending necrotizing mediastinitis (DNM) is a life-threatening condition, generally caused by downward dissemination of oropharyngeal infections through cervical fascial planes. Mediastinal drainage is conventionally achieved by thoracotomy, but a Video-Assisted Thoracoscopic Surgery (VATS) approach is gaining interest due to the reduced invasiveness of procedure. We aimed to evaluate the effectiveness of VATS treatment in patients with DNM. Methods: We conducted a retrospective multicenter study including patients with descending mediastinitis that underwent mediastinal drainage through VATS (VATS group) or thoracotomy (thoracotomy group), both in association with cervical drainage. Patients with mediastinitis secondary to cardiac, pulmonary, or esophageal surgery were excluded. The intergroup differences regarding surgical outcome and postoperative morbidity and mortality were compared. Results: A total of 21 patients were treated for descending mediastinitis during the study period. Cervicotomy and thoracotomy were performed in 15 patients (71%), while cervicotomy and VATS were performed in 6 patients (29%). There were no significant differences in surgical outcome, postoperative morbidity, and mortality between groups. VATS treatment was not associated with a higher complication rate. Patients in the VATS group had a shorter operative time (p = 0.016) and shorter ICU stay (p = 0.026). Conclusions: VATS treatment of DNM is safe and effective. The comparison with thoracotomy showed no significant differences in postoperative morbidity and mortality. The VATS approach is associated with a shorter operative time and ICU stay than thoracotomy.

Modified blade: an interventional option in rigid bronchoscopy for non-resectable benign tracheal stenosis.

INTRODUCTION: Benign tracheobronchial stenosis is a abnormal tracheal lumen narrowing that may incur progressive dyspnea and life-threatening hypoxemia. There is no consensus on which patients should be treated with endoscopic or surgical method. This study investigates the outcomes of bronchoscopic dilatation in the treatment of benign tracheal stenosis using a device equipped with a blade to cut the stenotic lesions with dense fibrosis. MATERIALS AND METHODS: The procedure was carried out in an operating room under general anesthesia. All patients were intubated with a Rigid Bronchoscope (RB) placed just above the stenosis. Through Rigid Bronchoscopy combined modalities were used as needed: radial incisions of the mucosal stenosis with blade at the levels of 4, 8 and 12 o'clock, with back and forth movements, then the stenotic area was dilated more easily with a rigid bronchoscope. Dilatation was performed by passing the RB of increasing diameter through stenotic areas and then Balloon dilatation of increasing diameter. There were no complications during the procedure. RESULT: We conducted an observational, retrospective, single-centre study in the Thoracic Surgery Unit of the University of 'Luigi Vanvitelli' of Naples from November 2011 to September 2021. We included all consecutive patients with benign tracheal stenosis inoperable. During the study period, 113 patients were referred to our department with benign tracheal stenosis inoperable. 61 patients were treated with the blade. During the follow-up, a recurrence of the stenosis was observed in 8 patients in the first month and in 4 patients in the third month. Instead in the patients treated with the use of laser (52 patients), during the follow-up a recurrence was observed in 16 patients in the first month and in 6 patients in the third month; no patient relapsed after 6 months and after 1 year. Long term successful bronchoscopic management with blade was attained by 99% in simple and 93% in mixed stenosis and in complex type stenosis. CONCLUSION: Our study underlines the importance of the use of the blade in bronchoscopic treatment as a valid conservative approach in the management of patients with inoperable benign tracheal stenosis as an alternative to the use of the laser, reducing the abnormal inflammatory reaction in order to limit recurrences.

Influence of the level of compliance with preventive maintenance therapy upon the prevalence of peri-implant diseases.

BACKGROUND: A study was made to evaluate peri-implant conditions in compliers and erratic compliers with peri-implant maintenance therapy (PIMT), and to assess the role of site-specific confounders. METHODS: Erratic PIMT compliers (EC) were defined as presenting attendance < 2×/year, while regular compliers (RC) attended ≥ 2×/year. Generalized estimating equations (GEE) were employed to perform a multivariable multilevel analysis in which the peri-implant condition was established as dependent variable. RESULTS: Overall, 86 non-smoker patients (42 RC and 44 EC) attending the Department of Periodontology of the Universitat Internacional de Catalunya were recruited consecutively on a cross-sectional basis. The mean period of loading was 9.5 year. An implant placed in an erratic patient has 88% higher probability of presenting peri-implant diseases versus RC. Furthermore, the probability of diagnosis of peri-implantitis was significantly higher in EC versus RC (odds ratio [OR] 5.26; p = 0.009). Among other factors, history of periodontitis, non-hygienic prosthesis, period of implant loading, and modified plaque index (mPI) at implant level were shown to significantly increase the risk of peri-implantitis diagnosis. Although not associated with peri-implantitis diagnosis risk, keratinized mucosa (KM) width, and vestibular depth (VD) were significantly associated to plaque accumulation (mPI). CONCLUSIONS: Compliance with PIMT was found to be significantly associated with peri-implant condition. In this sense, attending PIMT < 2×/year may be ineffective to prevent peri-implantitis.

Three-dimensional lung reconstructions for the localization of lung nodules to be resected during surgery.

BACKGROUND: The localization of lung nodules is challenging during thoracoscopy. In this study, we evaluated the use of three-dimensional (3D) lung reconstruction for use in the operating room to guide the identification of lung nodules during thoracoscopy. METHODS: This was a single-center retrospective study. All consecutive patients undergoing thoracoscopic resection of lung nodules were included in the study. Patients were retrospectively divided into two groups based upon whether the thoracoscopic resection was performed with the assistance (3D group) or not (standard group) of 3D lung reconstruction. The operative time (minutes) to detect lung nodules was statistically compared between the two study groups in relation to the characteristics of lung nodules as size, localization, and distance from the visceral pleura. RESULTS: Our study population consisted of 170 patients: 85 in the 3D group and 85 in the standard group. No intergroup difference differences were found regarding the characteristics and histological diagnosis of lesions. The standard group compared to the 3D group was associated with a significantly longer operative time for the detection of lesions <10 mm (13.87 ± 2.59 vs. 5.52 ± 1.01, p < 0.001), lesions between 10 and 20 mm (5.05 ± 0.84 vs. 3.89 ± 0.92; p = 0.03), lesions localized in complex segments (7.49 ± 4.25 vs. 5.11 ± 0.97; p < 0.001), and deep lesions (9.58 ± 4.82 vs. 5.4 ± 1.01, p < 0.001). CONCLUSIONS: Our 3D lung reconstruction model for use in the operating room may be an additional tool for thoracic surgeons to guide the detection of small and deep nodules during thoracoscopy. It is a noninvasive and cost saving procedure and may be widely used.

Inter-Rater Agreement for Diagnosing Adenomyosis Using Magnetic Resonance Imaging and Transvaginal Ultrasonography.

Our aim was to compare the inter-rater agreement about transvaginal ultrasonography (TVS) with magnetic resonance imaging (MRI) with regard to diagnosing adenomyosis and for assessing various predefined imaging features of adenomyosis, in the same set of women. The study cohort included 51 women, prospectively, consecutively recruited based on a clinical suspicion of adenomyosis. MRIs and TVS videoclips and 3D volumes were retrospectively assessed by four experienced radiologists and five experienced sonographers, respectively. Each rater subjectively evaluated the presence or absence of adenomyosis, as well as imaging features suggestive of adenomyosis. Fleiss kappa (κ) was used to reflect inter-rater agreement for categorical data, and the intraclass correlation coefficient (ICC) was used to reflect the reliability of quantitative data. Agreement between raters for diagnosing adenomyosis was higher for TVS than for MRI (κ = 0.42 vs. 0.28). MRI had a higher inter-rater agreement in assessing wall asymmetry, irregular junctional zone (JZ), and the presence of myometrial cysts, while TVU had a better agreement for assessing globular shape. MRI showed a moderate to good reliability for measuring the JZ (ICC = 0.57-0.82). For TVS, the JZ was unmeasurable in >50% of cases, and the remaining cases had low reliability (ICC = -0.31-0.08). We found that inter-rater agreement for diagnosing adenomyosis was higher for TVS than for MRI, despite the fact that MRI showed a higher inter-rater agreement in most specific features. Measurements of JZ in the coronal plane with 3D TVS were unreliable and thus unlikely to be useful for diagnosing adenomyosis.

Intrathoracic neurogenic tumors (ITNs): Management of solid and cystic lesions.

BACKGROUND: Intrathoracic neurogenic tumors (INTs) are derived from nerve tissue and grow within the chest. Preoperative diagnosis can be challenging and only complete surgical exeresis enables confirmation of the suspected diagnosis. Here, we analyzed our experience on management of paravertebral lesions with solid and cystic patterns. METHODS: A monocentric retrospective study was conducted, which included 25 consecutive cases of ITNs in the period from 2010 to 2022. These cases had been surgically treated by thoracoscopic resection alone, or in combination with neurosurgery in the case of dumbbell tumors. The demographic and operative data along with complications were recorded and analyzed. RESULTS: Twenty-five patients were diagnosed with a paravertebral lesion of which 19 (76%) had solid features and six (24%) had cystic features. The most common diagnosis was schwannoma (72%), followed by neurofibroma (20%) and malignant schwannoma (8%). In four cases (12%) the tumor showed an intraspinal extension. None of the patients had recurrence until 6 months of follow-up. Comparison between the VATS and thoracotomy procedures showed that outcome of discharge on the postoperative day, on average, was 2.61 ± 0.5 versus 3.51 ± 0.53, respectively (p-value <0.001). CONCLUSION: The treatment of choice for INTs is complete resection which is tailored to tumor size, location, and extension. In our study, paravertebral tumors with cystic characteristics were not associated with an intraspinal extension and did not show a different behavior from solid tumors.

RIB Plaster: a versatile, moldable derivative from scraping the periphery of the rib.

A simple technique is described for obtaining "rib plaster" by scraping the whitish peripheral portion of residual segments of rib after the perichondrium is removed and appropriate multiple laminations are derived This putty-like substance tends to conglomerate appropriately due to its high density and has unique properties: readily compacted into diced cartilage inserters, smoothly injected, easily moldable. "Rib plaster" serves well for camouflage of irregularities of the dorsum and tip as well as for mild augmentation. It comes to no further cost and in an adequate supply once a full-thickness rib segment is harvested for secondary rhinoplasty.

Survival trends over 20 years in patients with advanced cholangiocarcinoma: Results from a national retrospective analysis of 922 cases in Italy.

Cholangiocarcinoma is a rare group of tumors that involve the hepatic biliary tree. Prognosis for patients with cholangiocarcinoma remains dismal. Herein, we present survival trends over a long time period spanning almost 20 years in patients with advanced cholangiocarcinoma receiving systemic chemotherapy. We retrospectively analyzed a large multicenter dataset of cholangiocarcinoma outpatients evaluated in 14 centers within the Cholangiocarcinoma Italian Group Onlus (Gruppo Italiano Colangiocarcinoma Onlus, G.I.C.O.) between 2000 and 2017 (first-line), and 2002 and 2017 (second-line). Three time periods were considered: 2000-2009, 2010-2013, and 2014-2017. A total of 922 patients (51.19% male) with cholangiocarcinoma undergoing first-line therapy were evaluated. The median durations of follow-up for progression-free survival (PFS) and overall survival (OS) were 37 and 57 months, respectively. PFS at 12 months in the three periods of starting first-line therapy was similar, ranging from 11.71% to 15.25%. OS at 12 months progressively improved (38.30%, 44.61% and 49.52%, respectively), although the differences were not statistically significant after adjusting for age, disease status, and primary tumor site. A total of 410 patients (48.5% male) underwent second-line chemotherapy. The median durations of follow-up for PFS and OS were 47.6 and 41.90 months, respectively. An OS of 24.3%, 32.3%, and 33.1% was observed in 2002-2009, 2010-2013, and 2014-2017, respectively. Despite incremental benefits across years, our clinical experience confirms that modest overall advances have been achieved with first- and second-line chemotherapy in advanced cholangiocarcinoma. Efforts should focus on the identification of patients who derive the greatest benefit from treatment.

Outcomes of Thoracoscopic Lobectomy after Recent COVID-19 Infection.

BACKGROUND: The COVID-19 outbreak had a massive impact on lung cancer patients with the rise in the incidence and mortality of lung cancer. METHODS: We evaluated whether a recent COVID-19 infection affected the outcome of patients undergoing thoracoscopic lobectomy for lung cancer using a retrospective observational mono-centric study conducted between January 2020 and August 2022. Postoperative complications and 90-day mortality were reported. We compared lung cancer patients with a recent history of COVID-19 infection prior to thoracoscopic lobectomy to those without recent COVID-19 infection. Univariable and multivariable analyses were performed. RESULTS: One hundred and fifty-three consecutive lung cancer patients were enrolled. Of these 30 (19%), had a history of recent COVID-19 infection prior to surgery. COVID-19 was not associated with a higher complication rate or 90-day mortality. Patients with recent COVID-19 infection had more frequent pleural adhesions (p = 0.006). There were no differences between groups regarding postoperative complications, conversion, drain removal time, total drainage output, and length of hospital stay. CONCLUSIONS: COVID-19 infection did not affect the outcomes of thoracoscopic lobectomy for lung cancer. The treatment of these patients should not be delayed in case of recent COVID-19 infection and should not differ from that of the general population.

Modified Dorsal Split Preservation Hybrid Rhinoplasty for Cartilaginous Pushdown and Full Letdown Applications: A PROM-Based Review of 100 Consecutive Cases.

Splitting the middle vault on an anatomical plane along the "Septal T" allows a new hybrid perspective on the many modifications of "surface" preservation techniques. The "dorsal split preservation" concept can be applied both to cartilaginous pushdown as well as to full letdown techniques. The dorsal keystone area is maintained, while the middle vault is reshaped. The septum is addressed by conventional L strut septoplasty. Precise direct suture fixation of the high-middle strip is easily accomplished after flexing the osseous-chondral junction at the K area. Specific technical points are described to allow exact and stable configuration of the dorsum.A retrospective analysis on 100 consecutive patients demonstrated aesthetic and functional improvement.

Primary Tumor Resection for Metastatic Colorectal, Gastric and Pancreatic Cancer Patients: In Search of Scientific Evidence to Inform Clinical Practice.

The management of the primary tumor in metastatic colorectal, gastric and pancreatic cancer patients may be challenging. Indeed, primary tumor progression could be associated with severe symptoms, compromising the quality of life and the feasibility of effective systemic therapy, and might result in life-threatening complications. While retrospective series have suggested that surgery on the primary tumor may confer a survival advantage even in asymptomatic patients, randomized trials seem not to definitively support this hypothesis. We discuss the evidence for and against primary tumor resection for patients with metastatic gastrointestinal (colorectal, gastric and pancreatic) cancers treated with systemic therapies and put in context the pros and cons of the onco-surgical approach in the time of precision oncology. We also evaluate current ongoing trials on this topic, anticipating how these will influence both research and everyday practice.

Fluoropyrimidine­induced cardiotoxicity in colorectal cancer patients: a prospective observational trial (CHECKPOINT).

Fluoropyrimidines (FP) are the backbone chemotherapy in colorectal cancer (CRC) treatment; however, their use is associated with cardiotoxicity, which is underreported. In the present study, it was aimed to prospectively determine the incidence rates and related risk factors of FP­induced cardiotoxicity (FIC) in CRC patients and at identifying predictive biomarkers. A total of 129 consecutive previously untreated CRC patients underwent active cardiological monitoring, including 5­items simplified questionnaire on symptoms, electrocardiogram (ECG) and plasma sample collection during FP chemotherapy. FIC was defined as the presence of ECG alterations and/or the arising of at least one symptom of chest pain, dyspnoea, palpitations or syncope. The primary objective was the evaluation of FIC incidence. Secondary objectives were the correlation of FIC with well­known cardiological risk factors and the identification of circulating biomarkers (serum levels of troponin I, pro hormone BNP; miRNA analysis) as predictors of FIC. A total of 20 out of 129 (15.5%) patients experienced FIC. The most common symptoms were dyspnoea (60%) and chest pain (40%), while only 15% of patients presented ECG alterations, including one acute myocardial infarction. Retreatment with FP was attempted in 90% of patients with a favourable outcome. Despite 48% of patients having cardiological comorbidities, an increased FIC was not observed in this subgroup. Only the subgroup of females with the habit of alcohol consumption showed an increased risk of FIC. None of the circulating biomarkers evaluated demonstrated a clinical utility as FIC predictors. FIC can be an unexpected, life­threatening adverse event that can limit the subsequent treatment choices in patients with CRC. In this prospective study, well­known cardiological comorbidities were not related to higher FIC risk and circulating biomarkers predictive of toxicity could not be found. With careful monitoring, mainly based on symptoms, almost all patients completed the FP treatment.

One-lung ventilation in obese patients undergoing thoracoscopic lobectomy for lung cancer.

BACKGROUND: We evaluated the safety and feasibility of one-lung ventilation in obese patients undergoing thoracoscopic lobectomy and whether obesity affected peri- and postoperative outcomes. METHODS: This was a retrospective single center study including consecutive patients undergoing thoracoscopic lobectomy between October 2019 and February 2022. Obese patients were statistically compared to a control group to evaluate any differences in relation to one-lung ventilation and peri- and postoperative outcomes. RESULTS: Our study population included 111 patients; of these, 26 (23%) were included in the obese group, while 85 (77%) were included within the nonobese group. To obtain one-lung ventilation in nonobese patients, a double-lumen tube was more frequently used than a single-lumen tube with bronchial blocker (61% vs. 39%; p = 0.02), while in obese patients a single-lumen tube with bronchial blocker was used more than a double-lumen tube (81% vs. 19%, p = 0.001). Intergroup comparison showed that a double-lumen tube was the preferred method in nonobese patients, while a single-lumen tube with bronchial blockers was the strategy of choice in obese patients (p = 0.0002). Intubation time was longer in the obese group than in the nonobese group (94.0 ± 6.1 vs. 85.0 ± 7.0 s; p = 0.0004) and failure rate of first attempt at intubation was higher in the obese group (23% vs. 5%; p = 0.01). Obesity was not associated with increased intra-, peri- and postoperative complications and/or mortality. CONCLUSIONS: One-lung ventilation is a feasible and safe procedure also in obese patients and obesity did not negatively affect peri- and postoperative outcomes after lung resection.

External Validation of the Ovarian-Adnexal Reporting and Data System (O-RADS) Lexicon and the International Ovarian Tumor Analysis 2-Step Strategy to Stratify Ovarian Tumors Into O-RADS Risk Groups.

Importance: Correct diagnosis of ovarian cancer results in better prognosis. Adnexal lesions can be stratified into the Ovarian-Adnexal Reporting and Data System (O-RADS) risk of malignancy categories with either the O-RADS lexicon, proposed by the American College of Radiology, or the International Ovarian Tumor Analysis (IOTA) 2-step strategy. Objective: To investigate the diagnostic performance of the O-RADS lexicon and the IOTA 2-step strategy. Design, Setting, and Participants: Retrospective external diagnostic validation study based on interim data of IOTA5, a prospective international multicenter cohort study, in 36 oncology referral centers or other types of centers. A total of 8519 consecutive adult patients presenting with an adnexal mass between January 1, 2012, and March 1, 2015, and treated either with surgery or conservatively were included in this diagnostic study. Twenty-five patients were excluded for withdrawal of consent, 2777 were excluded from 19 centers that did not meet predefined data quality criteria, and 812 were excluded because they were already in follow-up at recruitment. The analysis included 4905 patients with a newly detected adnexal mass in 17 centers that met predefined data quality criteria. Data were analyzed from January 31 to March 1, 2022. Exposures: Stratification into O-RADS categories (malignancy risk <1%, 1% to <10%, 10% to <50%, and ≥50%). For the IOTA 2-step strategy, the stratification is based on the individual risk of malignancy calculated with the IOTA 2-step strategy. Main Outcomes and Measures: Observed prevalence of malignancy in each O-RADS risk category, as well as sensitivity and specificity. The reference standard was the status of the tumor at inclusion, determined by histology or clinical and ultrasonographic follow-up for 1 year. Multiple imputation was used for uncertain outcomes owing to inconclusive follow-up information. Results: Median age of the 4905 patients was 48 years (IQR, 36-62 years). Data on race and ethnicity were not collected. A total of 3441 tumors (70%) were benign, 978 (20%) were malignant, and 486 (10%) had uncertain classification. Using the O-RADS lexicon resulted in 1.1% (24 of 2196) observed prevalence of malignancy in O-RADS 2, 4% (34 of 857) in O-RADS 3, 27% (246 of 904) in O-RADS 4, and 78% (732 of 939) in O-RADS 5; the corresponding results for the IOTA 2-step strategy were 0.9% (18 of 1984), 4% (58 of 1304), 30% (206 of 690), and 82% (756 of 927). At the 10% risk threshold (O-RADS 4-5), the O-RADS lexicon had 92% sensitivity (95% CI, 87%-96%) and 80% specificity (95% CI, 74%-85%), and the IOTA 2-step strategy had 91% sensitivity (95% CI, 84%-95%) and 85% specificity (95% CI, 80%-88%). Conclusions and Relevance: The findings of this external diagnostic validation study suggest that both the O-RADS lexicon and the IOTA 2-step strategy can be used to stratify patients into risk groups. However, the observed malignancy rate in O-RADS 2 was not clearly below 1%.

Identification of a minimum number of genes to predict triple-negative breast cancer subgroups from gene expression profiles.

BACKGROUND: Triple-negative breast cancer (TNBC) is a very heterogeneous disease. Several gene expression and mutation profiling approaches were used to classify it, and all converged to the identification of distinct molecular subtypes, with some overlapping across different approaches. However, a standardised tool to routinely classify TNBC in the clinics and guide personalised treatment is lacking. We aimed at defining a specific gene signature for each of the six TNBC subtypes proposed by Lehman et al. in 2011 (basal-like 1 (BL1); basal-like 2 (BL2); mesenchymal (M); immunomodulatory (IM); mesenchymal stem-like (MSL); and luminal androgen receptor (LAR)), to be able to accurately predict them. METHODS: Lehman's TNBCtype subtyping tool was applied to RNA-sequencing data from 482 TNBC (GSE164458), and a minimal subtype-specific gene signature was defined by combining two class comparison techniques with seven attribute selection methods. Several machine learning algorithms for subtype prediction were used, and the best classifier was applied on microarray data from 72 Italian TNBC and on the TNBC subset of the BRCA-TCGA data set. RESULTS: We identified two signatures with the 120 and 81 top up- and downregulated genes that define the six TNBC subtypes, with prediction accuracy ranging from 88.6 to 89.4%, and even improving after removal of the least important genes. Network analysis was used to identify highly interconnected genes within each subgroup. Two druggable matrix metalloproteinases were found in the BL1 and BL2 subsets, and several druggable targets were complementary to androgen receptor or aromatase in the LAR subset. Several secondary drug-target interactions were found among the upregulated genes in the M, IM and MSL subsets. CONCLUSIONS: Our study took full advantage of available TNBC data sets to stratify samples and genes into distinct subtypes, according to gene expression profiles. The development of a data mining approach to acquire a large amount of information from several data sets has allowed us to identify a well-determined minimal number of genes that may help in the recognition of TNBC subtypes. These genes, most of which have been previously found to be associated with breast cancer, have the potential to become novel diagnostic markers and/or therapeutic targets for specific TNBC subsets.