Search Results (162)

Background: The causation of type 2 diabetes remains under debate, but evidence supports both abdominal lipid and ectopic lipid overspill into tissues including muscle as key. How these depots differentially alter cardiometabolic profile and change during body weight and fat loss is not known. Methods: Women with obesity scheduled to undergo bariatric surgery were assessed at baseline (BL, n = 28) and at 6-month follow-up (6m_FU, n = 26) after weight loss. Fasting plasma (Pla), subcutaneous thigh adipose (STA), subcutaneous abdominal adipose, (SAA), and thigh vastus lateralis muscle (VLM) samples were collected at BL through surgery and at 6m_FU using needle biopsy. An untargeted liquid chromatography mass spectrometry metabolomics platform was used. Pla and tissue-specific lipid and polar metabolite profiles were modelled as changes from BL and 6m_FU. Results: There was significant body weight (−24.5 kg) loss at 6m_FU (p < 0.05). BL vs. 6m_FU tissue metabolomics profiles showed the largest difference in lipid profiles in SAA tissue in response to surgery. Conversely, polar metabolites were more susceptible to change in STA and VLM. In Pla samples, both lipid and polar metabolite profiles showed significant differences between timepoints. Jaccard–Tanimoto coefficient t-tests identified a sub-group of gut microbiome and dietary-derived omega-3-fatty-acid-containing lipid species and core energy metabolism and adipose catabolism-associated polar metabolites that are trafficked between sample types in response to bariatric surgery. Conclusions: In this first report on channelling of lipids and polar metabolites to alternative tissues in bariatric-induced weight loss, adaptive shuttling of small molecules was identified, further promoting adipose processing and highlighting the dynamic and coordinated nature of post-surgical metabolic regulation. Full article

Background and Objectives: The accuracy of breast cancer diagnosis depends on the concordance between imaging features and pathological findings. While BI-RADS (Breast Imaging Reporting and Data System) provides standardized risk stratification, its correlation with histologic grade and immunohistochemical markers remains underexplored. This study assessed the diagnostic performance of BI-RADS 3, 4, and 5 classifications and their association with tumor grade and markers such as ER, PR, HER2, and Ki-67. Materials and Methods: In this prospective study, 67 women aged 33–82 years (mean 56.4) underwent both mammography and ultrasound. All lesions were biopsied using ultrasound-guided 14G core needles. Imaging characteristics (e.g., margins, echogenicity, calcifications), histopathological subtype, and immunohistochemical data were collected. Statistical methods included logistic regression, Chi-square tests, and Spearman’s correlation to assess associations between BI-RADS, histology, and immunohistochemical markers. Results: BI-RADS 5 lesions showed a 91% malignancy rate. Evaluated features included spiculated margins, pleomorphic microcalcifications, and hypoechoic masses with posterior shadowing, and were correlated with histological and immunohistochemical results. Invasive tumors typically appeared as irregular, hypoechoic masses with posterior shadowing, while mucinous carcinomas mimicked benign features. Higher BI-RADS scores correlated significantly with increased Ki-67 index (ρ = 0.76, p < 0.001). Logistic regression yielded an AUC of 0.877, with 93.8% sensitivity and 80.0% specificity. Conclusions: BI-RADS scoring effectively predicts malignancy and correlates with tumor proliferative markers. Integrating imaging, histopathology, and molecular profiling enhances diagnostic precision and supports risk-adapted clinical management in breast oncology. Full article

Introduction: The multigene molecular testing of prostate cancer tissue after biopsy provides individualized information to guide further management. The utility of selective genetic testing for MRI-visible target versus systematic cancer in patients as well as during different time points of active surveillance (AS) is unknown. The objective of this study was to compare Prolaris^TM results of MRI-target cancers versus systematic cancers on prostate needle biopsy as well as both during consideration for initial AS candidacy and candidacy for remaining on AS. Methods: Our prospectively maintained institutional multiparametric (mp) MRI prostate cancer active surveillance database (2013–2024) was queried for patients that underwent Prolaris^TM genetic testing of positive biopsy cores. Baseline information for PSA, PSA density, and Prolaris^TM calculated data were collected. Information on the timing of the Prolaris testing, defined as during the initial cancer diagnostic biopsy or on a subsequent confirmatory biopsy was collected. SPSS v29.0 was used to compare the selective Prolaris^TM results of MRI-target cancers versus systematic cancers during different points of AS. Results: 264 patients with a Prolaris^TM test were identified, 86 with MRI-target and 178 on systematic cancers. 182 Prolaris^TM tests were sent on a diagnostic biopsy and 81 on a subsequent biopsy. Overall, MRI-target cancers had similar risk scores (3.23 vs. 3.14, p = 0.18). Prolaris^TM scores were higher for GG2 systematic than GG1 target cancers (3.40 vs. 3.18, p = 0.023). The GG2 systematic lesion cohort also had higher predicted the 10-year disease-specific mortality (DSM) (3.40% vs. 2.30%, p < 0.01) and 10-year metastasis risk (1.90% vs. 1.20%, p = 0.013), and more aggressive recommended treatment. Analyses of the Prolaris^TM results sent during a diagnostic biopsy yielded similar results. Finally, on an analysis of the Prolaris^TM results sent during subsequent biopsy, a systematic GG2 biopsy was noted to have a higher 10-year DSM and metastasis rate, but similar risk scores and treatment recommendations. Conclusions: Prolaris^TM tests can be sent at multiple time points of AS, and selectively for MRI-visible versus higher grade cancers. There is no consistent association between MRI-visible cancer and Prolaris risk profile. When utilizing multigene molecular testing in prostate cancer, each individual patient must be evaluated to decide the appropriate level of care. Full article

Background: Supraclavicular lymph nodes (SCLNs) are often indicative of malignancy, but the effectiveness of ultrasound (US) and hematological parameters in their assessment and the prognosis of patients with malignant SCLNs need further study. Methods: We retrospectively reviewed 348 patients with SCLNs from July 2007 to June 2023, including patients over 18 years of age who underwent fine needle aspiration (FNA) or core needle biopsy (CNB). Our analysis focused on clinical characteristics, US features and hematological parameters to differentiate between benign and malignant SCLNs and to assess their prognostic value, especially in the Asian population. Results: The malignancy rate was 49%, with lung cancer (22%) and lymphoma (16%) being the most common. The malignant nodes were larger and had a greater short-to-long axis ratio, irregular margins, and abnormal vascular patterns (p < 0.01). The 5-year survival rate for patients with malignant SCLNs was 40%. Blood markers, such as the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and systemic immune–inflammation index (SII) (SII ≥ 970), were significant prognostic factors for overall survival (OS). Compared with lymphoma patients, patients with malignancies of supraclavicular and infraclavicular origins had significantly worse OS. Conclusions: Our findings highlight the importance of ultrasound in evaluating SCLNs. Furthermore, hematological markers (NLR, PLR, and SII) and the origin of SCLNs have important prognostic value. Full article

Introduction: A potential prognostic biomarker for predicting the response to immunotherapy in breast cancer (BC) is tumor-infiltrating lymphocytes (TILs). The purpose of this research is to examine if preoperative characteristics of breast magnetic resonance imaging (MRI) may be used to predict TIL levels in a group of BC patients. In addition, we aimed to assess any potential relationship between the various tumor biology subgroups and MR imaging characteristics. Materials and Methods: This retrospective analysis comprised 145 participants with histologically confirmed BC who had preoperative DCE MRI. We collected and examined patient information as well as tumor MRI features, such as size and shape, edema, necrosis, multifocality/multicentricity, background parenchymal enhancement (BPE), and apparent diffusion coefficient (ADC) values. We divided patients into two groups based on their TIL levels: low-TIL (<10%) and high-TIL groups (≥10%). Following core needle biopsy, tumors were categorized as Luminal A, Luminal B, HER2+, and Triple Negative using immunohistochemical analysis. TIL levels were correlated with tumor biological profiles and MRI features using both parametric and non-parametric tests. Results: Patients were categorized as having a high TIL level (≥10%; 54/145 patients) and a low TIL level (<10%; 91/145 patients) based on the median TIL level of 10%. Of the lesions, 13 were HER2-positive, 16 were Triple Negative, 49 were Luminal A, and 67 were Luminal B. Higher TIL levels were statistically correlated with TNBC (11/16 individuals, p: 0.007). ADC values (p = 0.01), BPE levels (p = 0.008), and TIL levels were all significantly negatively correlated. Significantly more homogenous enhancement was seen in tumors with elevated TIL levels (p = 0.001). The ADC values and the enhancing characteristics were the most important factors in predicting TIL levels, according to logistic regression analysis, and when combined, they demonstrated the strongest ability to distinguish between the two groups (AUC = 0.744). Conclusions: MRI features, particularly ADC values and enhancement characteristics, may play a pivotal role in the assessment of TIL levels in BC before surgery. This could help patients to better customize treatments to the features of their tumors. Full article

Luminal B breast cancer (LBBC) represents an aggressive, high-grade ER+ disease, associated with a high proliferation rate, higher mutation burden, and higher probability of eliciting the immune response. Clinical and pathological data from 89 patients of stage II-III, triple-negative (TN), and luminal B-like BC (LB-like BC) were included in the analysis. All patients were submitted to neoadjuvant chemotherapy (NACT). Quantitative and qualitative evaluations of TILs (Tumor-Infiltrating Lymphocytes) were performed on tissue microarrays constructed from pretreatment core-needle biopsy tumor specimens. The proportion of stromal TILs, CD8, CD4, and PD-L1 positive (+) immune cells (IC), as well as the number of FOXP3, CTLA4, and HSP-70+ IC, was observed concerning tumor immunophenotype, traditional clinicopathological prognostic factors, and tumor response to NACT. There was no statistically significant difference in the proportion of stromal TILs between the LB-like and TNBC (p = 0.344) cohorts. However, a higher CD4/CD8 ratio was associated with the TNBC biology (p = 0.018) and within the LB-like BC cohort with a high proliferation index and metastatic nodal involvement (p = 0.045, p = 0.015). Within the LB-like BC cohort, a higher expression of PD-L1 and HSP70+ IC was associated with a high proliferation index of tumor cells (p = 0.018, p = 0.040), massive metastatic nodal involvement (p = 0.002, p = 0.026), and higher stages of disease (p = 0.004, p = 0.042). Better response to NACT was associated with higher numbers of HSP70+ IC and higher proportions of CD8+ cells within the LB-like BC cohort (p = 0.045, p = 0.012). Routine evaluation of immune markers and HSP70 may help identify high-risk patients of LB-like breast cancer who would have a better response to NACT. Full article

Background: Lung cancer remains the leading cause of cancer-related mortality, often diagnosed at advanced stages, where minimally invasive tissue sampling is essential for diagnosis and molecular profiling. Rapid On-Site Evaluation (ROSE) enhances the diagnostic yield of small biopsies, but is frequently limited by a shortage of pathologists and logistical constraints. Telepathology offers a potential solution by enabling remote real-time assessment. This study evaluates the feasibility, diagnostic accuracy, and efficiency of telecytology-assisted ROSE (TC-ROSE) using touch imprint cytology (TIC) during CT-guided transthoracic core needle biopsy (CNB) of pulmonary nodules. Methods: 50 patients underwent CNB. TIC samples were assessed and evaluated on-site or remotely via a fully remote-controlled microscope system (OCUS^®). TIC slide preparation was performed by pathologists (30 cases), radiologists (10), and trained assistants (10). The study analyzed diagnostic concordance between remote and on-site assessments, time efficiency, and the feasibility of involving non-pathologists in TIC preparation. Results: Diagnostic samples were obtained in 86% of TIC samples, with full concordance (100%) between TC-ROSE and traditional ROSE. The slides required approximately 140 s for scanning, and the overall evaluation time was around 3 min per case. Overall, 100% of TICs were adequately assessed by both pathologists and non-pathologists. No increased number of complications was recorded among patients with TCROSE, compared to those ROSE evaluated. The remote setup allowed pathologists to maintain routine workflows, improving time efficiency. Conclusions: The findings confirm that telecytology is a viable, accurate, and efficient approach to ROSE, offering a practical solution for overcoming workforce and logistical barriers, particularly in settings with limited pathology resources. Full article

Artificial intelligence (AI) is becoming an integral part of pathological assessment and diagnostic procedures in modern pathology. As most prostate cancers (PCa) arise from glandular epithelial tissue, an AI-based methodology has been developed to recognize glandular epithelial nuclei in prostate biopsy tissue. An integrated machine-learning network, named GlandNet, was developed to correctly recognize the epithelial cells within prostate glands using cell-centric patches selected from the core biopsy specimens. Feulgen-Thionin (a DNA stoichiometric label) was used to stain biopsy sections (4–7 µm in thickness) from 82 active surveillance patients diagnosed with PCa. Images of these sections were human-annotated, and the resultant dataset consisted of 1,264,772 segmented, cell-centric nuclei patches, of which 449,879 were centered on epithelial gland nuclei from 110 needle biopsies (training set: n = 66; validation set: n = 22; and test set: n = 22). The training of GlandNet used semi-supervised machine-learning knowledge of the training and validation cohorts and integrated both human and AI predictions to enhance its performance on the test cohort. The performance was evaluated against a consensus deliberation from three observers. The GlandNet demonstrated an average accuracy, sensitivity, specificity, and F1-score of 94.1%, 95.7%, 87.8%, and 95.2%, respectively, when tested on the 20,735 glandular cells found in the three needle biopsies with the visually best consensus predictions. Conversely, the average accuracy, sensitivity, specificity, and F1-score were 90.9%, 86.4%, 94.0%, and 89.7% when assessed on 57,217 cells found in the three needle biopsies with the visually worst consensus predictions. GlandNet is a first-generation AI with an excellent ability to differentiate between epithelial and stromal nuclei in core biopsies from patients with early prostate cancer. Full article

In triple-negative (TNBC) and human epidermal growth factor receptor 2-positive (HER2+) breast cancer patients, neoadjuvant systemic therapy is the standard recommendation for tumors larger than 2 cm. Monitoring the response to primary systemic therapy allows for the assessment of treatment effects, the need for breast-conserving surgery (BCS), and the achievement of pathological complete responses (pCRs). In estrogen receptor-positive/HER2-negative (ER+/HER2-) breast cancer, the benefit of neoadjuvant strategies is controversial, as they have shown lower tumor downstaging and pCR rates compared to other breast cancers. In recent decades, several gene expression assays have been developed to tailor adjuvant treatments in ER+/HER2- early breast cancer (EBC) to identify the patients that will benefit the most from adjuvant chemotherapy (CT) and those at low risk who could be spared from undergoing CT. It is still a challenge to identify patients who will benefit from neoadjuvant systemic treatment (CT or endocrine therapy (ET)). Here, we review the published data on the most common gene expression signatures (MammaPrint (MP), BluePrint (BP), Oncotype Dx, PAM50, the Breast Cancer Index (BCI), and EndoPredict (EP)) and their ability to predict the response to neoadjuvant treatment, as well as the possibility of using them on core needle biopsies. Additionally, we review the changes in the gene expression signatures after neoadjuvant treatment, and the ongoing clinical trials related to the utility of gene expression signatures in the neoadjuvant setting. Full article

Background: The use of dynamic magnetic resonance imaging (MRI) for the evaluation, detection, and characterization of ductal carcinoma in situ (DCIS) has been increasing; however, its application in this context remains controversial and uncertain. Materials: A retrospective study including women with pure DCIS, confirmed between January 2012 and December 2022 using ultrasound-guided core-needle biopsy (CNB) or stereotaxy-guided vacuum-assisted biopsy (VAB), was conducted. Mammography, ultrasound (US), and MRI of DCIS lesions were evaluated according to histological grade. The size of the DCIS, as assessed by mammography, US, MRI, and final surgical histopathology, was compared using Lin’s concordance correlation and Bland–Altman plots. Results: A total of 144 women (mean age 55.5 ± 10.3 years) with histopathological diagnoses of pure DCIS and no evidence of infiltration in the percutaneous biopsy were included in the study. Microcalcifications were the most prevalent feature observed in mammography (82.63%). Round/punctate morphology was more common in low-grade lesions, while fine pleomorphic morphology was more frequent in medium- and high-grade lesions. Lesions manifesting as microcalcifications only on mammography were significantly associated with intermediate and high-nuclear grade DCIS (p = 0.005). The most common MRI manifestation of DCIS was non-mass enhancement (86.11%). A total of 141 lesions showed enhancement with MRI (sensibility 97.92%). There were no significant differences (p = 0.29) between negative and positive enhancement with MRI and the histological grade of the lesions. There were no significant differences (p = 0.49) between the type of enhancement curve with MRI and the histological grade. Preoperative MRI detected additional malignancies (multifocal, multicentric, or bilateral) in 35 patients (24.31%). Conclusions: DCIS demonstrated enhancement with MRI regardless of histological grade but overestimated the size of the lesions in low-nuclear-grade DCIS. Preoperative MRI identified additional malignancies (multifocal, multicentric, and bilateral lesions) in 24 patients (16.67%), which were confirmed by histopathological examination. These malignancies were either undetected or not visible with mammography and ultrasound. However, MRI also overestimated the size of the DCIS, leading to three unnecessary mastectomies in our study. Full article

The kidneys are integral to homeostasis but are susceptible to nephrotoxic compounds. Proximal tubular epithelial cells (PTECs) mediate drug metabolism and transport and are widely used in preclinical studies. However, commercial PTECs are limited in availability and physiological relevance. This study aimed to develop a novel, reliable protocol for isolating and culturing PTECs from human kidney biopsies. Primary PTECs were isolated from kidney biopsies of two patients (MFUM-RPTEC-1 and MFUM-RPTEC-2). Their morphology, population doubling time, transepithelial electrical resistance (TEER), and phenotypic markers were evaluated. Polarization and transporter expression were analyzed using cells cultured on Transwell inserts. Colonies formed within 24–48 h, with confluence reached by 8–10 days and dome (hemicyst) formation by day 13. TEER values peaked at 190 Ω/cm² after 7–14 days, confirming tight junction formation. Immunostaining identified characteristic markers (e.g., SGLT2, OAT1/3, OCT2, P-gp, MRP4, MATE1, N-cadherin, ZO-1, CK-18). Cells cultured on Transwell plates exhibited native polarization, expressing transporters crucial for drug excretion on apical and basolateral surfaces. We present two robust protocols for isolating and characterizing PTECs, offering a scalable method to obtain functional, polarized cells from scarce biopsy material. The isolated PTECs, therefore, present a valuable platform for preclinical studies, especially for drug excretion testing through the expressed transporters. Drug competition for these transporters during tubular secretion is also a common cause of nephrotoxicity. Full article

Mammography is an essential tool in breast screening, often revealing lesions that appear as microcalcifications with or without an associated mass. Decisions about biopsy requirements are guided by the BI-RADS system, aiming to confirm the histopathology of suspicious lesions while avoiding unnecessary procedures. A vacuum-assisted breast biopsy (VABB) is a minimally invasive procedure for diagnosing breast abnormalities. Precise lesion targeting is ensured under stereotactic guidance, reducing the need for repeated procedures. Compared to traditional core needle biopsy (CNB) and fine-needle aspiration cytology (FNAC), it differs in using vacuum assistance to gather more tissue volume, increasing diagnostic accuracy and reducing the likelihood of histological underestimation. This is particularly crucial in cases where microcalcifications are the primary finding, as they are often the earliest signs of ductal carcinoma in situ (DCIS). Managing such findings requires precise diagnostic tools to differentiate benign from malignant lesions without subjecting patients to unnecessary surgical interventions. Building on several years of experience in our department, we have assembled a selection of ten interesting cases encountered in our clinical practice. Each case is documented with paired mammographic images and their corresponding image of histopathological findings, offering a comprehensive view of the diagnostic journey. These cases were selected for their educational value, highlighting the integration of imaging modalities, histopathological evaluation, and clinical decision-making. All cases underwent an extensive diagnostic workup at our facility. This compilation aims to provide valuable insights for both clinicians and researchers, offering a deeper understanding of advanced diagnostic techniques and their role in improving patient outcomes. Full article

Background and clinical significance: Phyllodes tumors (PTs) are rare stromal neoplasms originating in the connective tissue of the breast, distinct from carcinomas that arise from the ducts or lobules. These tumors exhibit a broad spectrum of morphologic features and are traditionally classified as benign, borderline, or malignant. Case presentation: We present the case of a 71-year-old female diagnosed with a malignant PT and treated at our hospital. The patient noticed a gradually enlarging lump in her right breast over several months. Mammography was inconclusive, but an ultrasound later revealed a lobulated, firm mass, classified as BIRADS 5. Physical examination identified a 20 cm mass, and core needle biopsy suggested a borderline PT. Following lumpectomy, pathology confirmed a malignant tumor with narrow surgical margins (0.1 cm). Although mastectomy was recommended to achieve wider margins, the patient opted for adjuvant radiotherapy. She received 50 Gy in 25 fractions to the whole breast, followed by a 16 Gy boost to the tumor bed in 8 fractions. The treatment was well tolerated and completed successfully. Initially, the patient’s therapeutic management was delayed due to a combination of personal and organizational factors. However, the process was later streamlined through the use of a novel digital tool developed to facilitate the entire patient journey within our hospital system. Conclusions: This case highlights the diagnostic complexities of PTs, the critical need for effective collaboration between specialties, and the importance of timely treatment planning for optimal patient outcomes. Full article

B3 breast lesions, classified as lesions of uncertain malignant potential, present a significant diagnostic and therapeutic challenge due to their heterogeneous nature and variable risk of progression to malignancy. These lesions, which include atypical ductal hyperplasia (ADH), papillary lesions (PLs), flat epithelial atypia (FEA), radial scars (RSs), lobular neoplasia (LN), and phyllodes tumors (PTs), occupy a “grey zone” between benign and malignant pathologies, making their management complex and often controversial. This article explores the diagnostic difficulties associated with B3 lesions, focusing on the limitations of current imaging techniques, including mammography, ultrasound, and magnetic resonance imaging (MRI), as well as the challenges in histopathological interpretation. Core needle biopsy (CNB) and vacuum-assisted biopsy (VAB) are widely used for diagnosis, but both methods have inherent limitations, including sampling errors and the inability to determine malignancy in some cases definitively. The therapeutic approach to B3 lesions is nuanced, with treatment decisions strongly influenced by factors such as the lesion size, radiological findings, histopathological characteristics, and patient factors. While some lesions can be safely monitored with watchful waiting, others may require vacuum-assisted excision (VAE) or surgical excision to rule out malignancy. The decision-making process is further complicated by the discordance between the BI-RADS score and biopsy results, as well as the presence of additional risk factors, such as microcalcifications. This review provides an in-depth analysis of the current diagnostic challenges and treatment strategies for B3 lesions, emphasizing the importance of a multidisciplinary approach to management. By synthesizing the most recent research, this article aims to provide clinicians with a clearer understanding of the complexities involved in diagnosing and treating B3 breast lesions while highlighting areas for future research, such as artificial intelligence and genomics, to improve the diagnostic accuracy and patient outcomes. Full article

Background: Breast cancer is a leading cause of cancer-related mortality among women worldwide. Accurate staging, including the detection of axillary metastases, is vital for treatment planning. This study evaluates the efficacy of MRI relaxometry as a diagnostic tool for axillary lymph node metastases in breast cancer patients. Methods: A prospective study was conducted on 67 consecutive breast cancer patients. Relaxometry parameters, including T2Max, T2Min, and 1HAv, were assessed using 1.5 Tesla MRI. All axillary metastases were histologically confirmed using core-needle biopsy or surgical specimens. Statistical analyses included ROC curves, chi-square tests, and multivariate analysis to determine correlations between imaging findings and pathological results. Results: Significant associations were found between T2Min-ipsilateral (p = 0.018), 1HAv-ipsilateral (p = 0.003), and axillary metastases. ROC analysis demonstrated that T2Min-ipsilateral and 1HAv-ipsilateral have modest to acceptable discriminatory abilities (AUC = 0.681 and AUC = 0.740, respectively). Combined clinical and imaging models enhanced diagnostic accuracy (AUC = 0.749). Conclusions: MRI relaxometry improves the detection of axillary metastases in breast cancer, particularly when integrated with clinical and pathological evaluations. Full article