Implementation of an AI Algorithm in Clinical Practice to Reduce Missed Incidental Pulmonary Embolisms on Chest CT and Its Impact on Short-Term Survival.

OBJECTIVES: A substantial number of incidental pulmonary embolisms (iPEs) in computed tomography scans are missed by radiologists in their daily routine. This study analyzes the radiological reports of iPE cases before and after implementation of an artificial intelligence (AI) algorithm for iPE detection. Furthermore, we investigate the anatomic distribution patterns within missed iPE cases and mortality within a 90-day follow-up in patients before and after AI use. MATERIALS AND METHODS: This institutional review board-approved observational single-center study included 5298 chest computed tomography scans performed for reasons other than suspected pulmonary embolism (PE). We compared 2 cohorts: cohort 1, consisting of 1964 patients whose original radiology reports were generated before the implementation of an AI algorithm, and cohort 2, consisting of 3334 patients whose scans were analyzed after the implementation of an Food and Drug Administration-approved and CE-certified AI algorithm for iPE detection (Aidoc Medical, Tel Aviv, Israel). For both cohorts, any discrepancies between the original radiology reports and the AI results were reviewed by 2 thoracic imaging subspecialized radiologists. In the original radiology report and in case of discrepancies with the AI algorithm, the expert review served as reference standard. Sensitivity, specificity, prevalence, negative predictive value (NPV), and positive predictive value (PPV) were calculated. The rates of missed iPEs in both cohorts were compared statistically using STATA (Version 17.1). Kaplan-Meier curves and Cox proportional hazards models were used for survival analysis. RESULTS: In cohort 1 (mean age 70.6 years, 48% female [n = 944], 52% male [n = 1020]), the prevalence of confirmed iPE was 2.2% (n = 42), and the AI detected 61 suspicious iPEs, resulting in a sensitivity of 95%, a specificity of 99%, a PPV of 69%, and an NPV of 99%. Radiologists missed 50% of iPE cases in cohort 1. In cohort 2 (mean age 69 years, 47% female [n = 1567], 53% male [n = 1767]), the prevalence of confirmed iPEs was 1.7% (56/3334), with AI detecting 59 suspicious cases (sensitivity 90%, specificity 99%, PPV 95%, NPV 99%). The rate of missed iPEs by radiologists dropped to 7.1% after AI implementation, showing a significant improvement (P < 0.001). Most overlooked iPEs (61%) were in the right lower lobe. The survival analysis showed no significantly decreased 90-day mortality rate, with a hazards ratio of 0.95 (95% confidence interval, 0.45-1.96; P = 0.88). CONCLUSIONS: The implementation of an AI algorithm significantly reduced the rate of missed iPEs from 50% to 7.1%, thereby enhancing diagnostic accuracy. Despite this improvement, the 90-day mortality rate remained unchanged. These findings highlight the AI tool's potential to assist radiologists in accurately identifying iPEs, although its implementation does not significantly affect short-term survival. Notably, most missed iPEs were located in the right lower lobe, suggesting that radiologists should pay particular attention to this area during evaluations.

Automatic Detection of Post-Operative Clips in Mammography Using a U-Net Convolutional Neural Network.

BACKGROUND: After breast conserving surgery (BCS), surgical clips indicate the tumor bed and, thereby, the most probable area for tumor relapse. The aim of this study was to investigate whether a U-Net-based deep convolutional neural network (dCNN) may be used to detect surgical clips in follow-up mammograms after BCS. METHODS: 884 mammograms and 517 tomosynthetic images depicting surgical clips and calcifications were manually segmented and classified. A U-Net-based segmentation network was trained with 922 images and validated with 394 images. An external test dataset consisting of 39 images was annotated by two radiologists with up to 7 years of experience in breast imaging. The network's performance was compared to that of human readers using accuracy and interrater agreement (Cohen's Kappa). RESULTS: The overall classification accuracy on the validation set after 45 epochs ranged between 88.2% and 92.6%, indicating that the model's performance is comparable to the decisions of a human reader. In 17.4% of cases, calcifications have been misclassified as post-operative clips. The interrater reliability of the model compared to the radiologists showed substantial agreement (κreader1 = 0.72, κreader2 = 0.78) while the readers compared to each other revealed a Cohen's Kappa of 0.84, thus showing near-perfect agreement. CONCLUSIONS: With this study, we show that surgery clips can adequately be identified by an AI technique. A potential application of the proposed technique is patient triage as well as the automatic exclusion of post-operative cases from PGMI (Perfect, Good, Moderate, Inadequate) evaluation, thus improving the quality management workflow.

Dual role of GRHL3 in bladder carcinogenesis depending on histological subtypes.

The effect of grainyhead-like transcription factor 3 (GRHL3) on cancer development depends on the cancer subtypes as shown in tumor entities such as colorectal or oral squamous cell carcinomas. Here, we analyzed the subtype-specific role of GRHL3 in bladder carcinogenesis, comparing common urothelial carcinoma (UC) with squamous bladder cancer (sq-BLCA). We examined GRHL3 mRNA and protein expression in cohorts of patient samples, its prognostic role and its functional impact on tumorigeneses in different molecular and histopathological subtypes of bladder cancer. We showed for GRHL3 a reverse expression in squamous and urothelial bladder cancer subtypes. Stably GRHL3-overexpressing EJ28, J82, and SCaBER in vitro models revealed a tumor-suppressive function in squamous and an oncogenic role in the urothelial cancer cells affecting cell and colony growth, and migratory and invasive capacities. Transcriptomic profiling demonstrated highly subtype-specific GRHL3-regulated expression networks coined by the enrichment of genes involved in integrin-mediated pathways. In SCaBER, loss of ras homolog family member A (RHOA) GTPase activity was demonstrated to be associated with co-regulation of eukaryotic translation initiation factor 4E family member 3 (EIF4E3), a potential tumor suppressor gene. Thus, our data provide for the first time a detailed insight into the role of the transcription factor GRHL3 in different histopathological subtypes of bladder cancer.

Heterogenous NECTIN4 expression in urothelial high-risk non-muscle-invasive bladder cancer.

High-grade non-muscle-invasive bladder cancer (HG NMIBC) patients are at high risk (HR) of progression to muscle-invasion. Bladder-preserving therapies for this patient subgroup are limited, and additional treatments are desirable. Recently, enfortumab vedotin, targeting cancer-associated NECTIN4, has been approved for the treatment of advanced urothelial carcinoma. However, data on the expression of NECTIN4 and its therapeutic potential for HR NMIBC are scarce. Here, NECTIN4 was immunohistochemically analyzed in urothelial HG NMIBC by studying cohorts of carcinoma in situ (CIS)/T1HG (N = 182 samples), HG papillary tumors from mixed-grade lesions (mixed TaHG) (N = 87) and papillary HG tumors without a history of low-grade disease (pure TaHG/T1HG) (N = 98) from overall 225 patients. Moreover, inter-lesional NECTIN4 heterogeneity in multifocal HG NMIBC tumors was determined. A high prevalence of NECTIN4 positivity was noted across HG NMIBC subgroups (91%, N = 367 samples), with 77% of samples showing moderate/strong expression. Heterogenous NECTIN4 levels were observed between HG NMIBC subgroups: non-invasive areas of CIS/T1HG and pure TaHG/T1HG samples showed NECTIN4 positivity in 96% and 99%, with 88% and 83% moderate/strong expressing specimens, respectively, whereas significantly lower NECTIN4 levels were detected in mixed TaHG lesions (72% positivity, 48% of samples with moderate/strong NECTIN4 expression). Moreover, higher NECTIN4 heterogeneity was observed in patients with multifocal mixed TaHG tumors (22% of patients) compared to patients with multifocal CIS/T1HG and pure TaHG/T1HG tumors (9% and 5%). Taken together, NECTIN4-directed antibody-drug conjugates might be promising for the treatment of HR NMIBC patients, especially for those exhibiting CIS/T1HG and pure TaHG/T1HG tumors without a history of low-grade disease.

Pure high-grade papillary urothelial bladder cancer: a luminal-like subgroup with potential for targeted therapy.

PURPOSE: Non-invasive high-grade (HG) bladder cancer is a heterogeneous disease that is characterized insufficiently. First-line Bacillus Calmette-Guérin instillation fails in a substantial amount of cases and alternative bladder-preserving treatments are limited, underlining the need to promote a further molecular understanding of non-invasive HG lesions. Here, we characterized pure HG papillary urothelial bladder cancer (pure pTa HG), a potential subgroup of non-invasive HG bladder carcinomas, with regard to molecular subtype affiliation and potential for targeted therapy. METHODS: An immunohistochemistry panel comprising luminal (KRT20, ERBB2, ESR2, GATA3) and basal (KRT5/6, KRT14) markers as well as p53 and FGFR3 was used to analyze molecular subtype affiliations of 78 pure pTa HG/papillary pT1(a) HG samples. In 66 of these, ERBB2 fluorescence in situ hybridization was performed. Additionally, targeted sequencing (31 genes) of 19 pTa HG cases was conducted, focusing on known therapeutic targets or those described to predict response to targeted therapies noted in registered clinical trials or that are already approved. RESULTS: We found that pure pTa HG/papillary pT1(a) HG lesions were characterized by a luminal-like phenotype associated with frequent (58% of samples) moderate to high ERBB2 protein expression, rare FGFR3 alterations on genomic and protein levels, and a high frequency (89% of samples) of chromatin-modifying gene alterations. Of note, 95% of pTa HG/papillary pT1 HG cases harbored at least one potential druggable genomic alteration. CONCLUSIONS: Our data should help guiding the selection of targeted therapies for investigation in future clinical trials and, additionally, may provide a basis for prospective mechanistic studies of pTa HG pathogenesis.