Search Results (5,463)

Background/Objectives: We aimed to evaluate temporal changes in patient selection, surgical practice, and postoperative outcomes of radical prostatectomy in Switzerland (2020–2025) using a national registry. Methods: Data from 7687 patients undergoing radical prostatectomy were extracted from a prospective national registry (January 2020–March 2025). Preoperative, operative, and postoperative variables were compared descriptively using the Mann–Whitney U test for continuous variables and the chi-square test for categorical variables. Temporal trends were assessed using locally estimated scatterplot smoothing. Multivariable logistic regression analyses were performed for positive surgical margins and PSA persistence. Results: Baseline patient characteristics remained stable over time. The use of MRI-targeted biopsy increased from 46% to 84% (p < 0.001). The proportion of low-risk diseases being treated decreased from 7.1% to 4.0% (p = 0.040). Minimally invasive surgery increased from 81% to 95% (p < 0.001); pelvic lymph node dissection declined from 83% to 63% (p < 0.001). Operative time (205 vs. 185 min, p = 0.002) and blood loss (300 vs. 200 mL, p < 0.001) decreased over time. Lymph node invasion decreased from 11% to 6.0% (p = 0.001), positive surgical margins from 27% to 22% (p = 0.044), and prostate-specific antigen persistence from 18.5% to 11.3% (p = 0.001). Severe postoperative complications decreased from 2.5% to 0.8% (p = 0.014). After multivariable adjustment, surgery performed in 2024 remained independently associated with lower rates of positive surgical margins (OR 0.73, 95% CI 0.57–0.93) and PSA persistence (OR 0.26, 95% CI 0.19–0.37) compared with 2020. Conclusions: Using the Swiss national registry, we demonstrate that radical prostatectomy has evolved toward more risk-adapted patient selection, near-universal minimally invasive surgery, and more selective pelvic lymph node dissection. Despite a shift away from low-risk disease, perioperative and early oncological outcomes improved, likely reflecting a combination of evolving diagnostic pathways, increasing surgical experience, and broader changes in perioperative management. Full article

Hashimoto thyroiditis (HT) coexists with differentiated thyroid carcinoma (DTC), particularly papillary thyroid carcinoma, in approximately 25% of cases. However, the impact of this association on DTC outcomes remains controversial. The aim of this study was to analyze the influence of Hashimoto thyroiditis on disease-specific survival (DSS) and recurrence-free survival (RFS) in DTC patients. Methods: A retrospective study conducted at our institution between 2007 and 2020 analyzed 707 DTC patients treated with surgery and/or I-131 therapy. Cox proportional hazards regression was used to identify independent predictors, including sex, age, tumor histology, HT status, and initial TNM stage. Results: Among 707 DTC patients, 628 (88.8%) had papillary cancer, 582 (82.3%) were female, 395 (55.9%) were <55 years old; HT coexisted in 137 (19.4%) patients. During follow-up, 23 (3.25%) developed recurrent disease; at last follow-up, 638 (90.2%) were alive. Initial distant metastases (p < 0.001) and higher T stage (p = 0.002) independently predicted worse DSS. For RFS, male sex (p = 0.015), higher T stage (p = 0.018), and lymph node involvement (p = 0.023) independently predicted an increased risk of recurrence. HT was not an independent predictor of DSS (HR 0.97, 95% CI 0.21–4.52; p = 0.964) or recurrence (HR 0.36, 95% CI 0.05–2.73; p = 0.322). Conclusions: Although Hashimoto thyroiditis was associated with favorable clinicopathological features, it was not independently associated with disease-specific or recurrence-free survival. Conventional staging parameters, particularly tumor stage, remain the principal determinants of prognosis in differentiated thyroid cancer. Full article

Introduction: Lymph nodes (LN) in the anterior periprostatic fat (APPF) may harbour metastatic disease in patients with Prostate Cancer (PCa). We investigated the incidence and significance of LN in APPF tissue removed during robotic and laparoscopic radical prostatectomy (RP). Patients and Methods: We retrospectively analysed RP performed by a single surgeon from 2013 to 2023. A total of 670 patients underwent RP, with 407 procedures conducted laparoscopically and 263 robotically. Histological results were available for 509 patients, who were examined for the presence of LN and any evidence of metastatic involvement. Results: LN were detected in the periprostatic fat of eighty patients; however, only twelve had lymph node metastasis. Seven of the twelve patients presented with prostate-specific antigen (PSA) levels greater than 10 ug/L. All LN-positive patients had a Gleason score of seven or higher. On MRI, all patients had a PIRADS score of four or higher, and eleven were staged at T3 or higher. Additionally, all twelve patients had a Briganti score exceeding twenty. Conclusions: Our series indicates that the APPF contains LN that can harbour metastatic disease. Patients can have LN involved in APPF without the involvement of pelvic LN. Therefore, our study suggests that routine excision of APPF should be considered for appropriate LN staging and to avoid missing any metastasis, and that scoring systems like Briganti should be used to help identify this high-risk group. Full article

Artificial intelligence (AI) is reshaping ultrasound diagnosis by converting operator-dependent grayscale, Doppler, elastography, contrast-enhanced, automated-volume, and video data into reproducible decision support. In breast ultrasound, the most mature evidence involves benign–malignant lesion classification, BI-RADS risk stratification, reduction in unnecessary biopsy in selected low-risk lesions, assistance for less experienced readers, automated breast volume scanning, video-based assessment, axillary staging, and prediction of biologic markers such as molecular subtype, HER2 status, Ki-67 expression, lymphovascular invasion, and nodal metastasis. AI does not replace sonographers, radiologists, pathologists, or clinical judgment; rather, it can standardize feature extraction, prompt second-reader review, quantify uncertainty, and integrate imaging with clinical context. This review summarizes current clinical applications of AI in ultrasound diagnosis, which has a strong recent multicenter evidence base. It also discusses implementation requirements, including standardized acquisition, external validation, calibration, imaging–pathology concordance, workflow integration, data security, and equity across scanners and patient populations. Full article

The diversity and abundance of the brain virome is an active field of investigation. However, how the brain virome relates to the presence of viruses outside of the nervous system remains unclear. The rationale for this study is that analyses across multiple biologically linked compartments within the same individuals provide an important opportunity to evaluate virome discordance and viral burden. To characterize viral prevalence and burden across anatomical compartments, we applied the targeted viral enrichment method ViroFind to matched postmortem brain (n = 66), cerebrospinal fluid (CSF; n = 24), and peripheral samples (spleen, peripheral blood mononuclear cells, and lymph nodes; n = 66) from individuals with and without human immunodeficiency virus (HIV) infection and substance use disorder (SUD) in the National NeuroAIDS Tissue Consortium. We detected nucleic acids from 27 viruses representing 12 taxa. Several viruses, including adenovirus, torque teno virus, Epstein–Barr virus, human herpesvirus 6 and 7, cytomegalovirus, parvovirus, and JC polyomavirus, showed significant inter-compartment differences in prevalence or burden. CSF exhibited lower overall viral diversity than brain or peripheral samples, whereas peripheral samples showed the highest viral burden. CNS viral detection was more likely when the same virus was also detected in the periphery. We also detected HBV and HCV in CNS samples despite them not being classically regarded as neurotropic. Broader virome profiling showed greater peripheral viral burden and diversity in HIV-positive than HIV-negative individuals, whereas SUD was not associated with overall viral burden differences. These findings highlight important cross-compartment differences in viral detection, including occurrence of occult HBV infection within the CNS, and support the value of CNS–periphery comparisons in virome studies. These findings can contribute to improved diagnosis and management of viral infections. Full article

Lymph nodes are central hubs of immune regulation and coordination, serving as primary sites for antigen presentation, lymphocyte activation, and the orchestration of adaptive immune responses. The composition and activation state of lymph node-resident immune cells critically shape both local and systemic immunity. Comprehensive immunophenotyping of these populations is therefore essential for understanding immune organization and functional heterogeneity. Here, we present an optimized protocol for the characterization of mouse lymph node-associated immune populations using 14-color multiparametric flow cytometry. The method combines lymph node isolation based on anatomical landmarks with mechanical dissociation and enzymatic digestion to generate high-quality single-cell suspensions suitable for downstream analysis. Furthermore, the described flow cytometry panel and gating strategy enable reliable identification and quantification of major lymphoid subsets, including helper CD4⁺ and cytotoxic CD8⁺ T cells with their differentiation states, as well as natural killer (NK) cells across distinct maturation stages. Although optimized for assessing lymphocyte maturation after lipopolysaccharide (LPS) challenge, the protocol serves as a reproducible platform for broad immunophenotyping of T and NK cell subsets in mouse lymphoid tissues under experimental conditions. Full article

Objectives: Endocrine neoplasms, as a general rule, show systemic, neuro-inflammatory and metabolic consequences, known as paraneoplastic syndrome. The comorbidity of thyroid tumors with neurological and autoimmune diseases prompt looking for common neuro-immuno-endocrine mechanisms of these disorders. While most TCs are well described, there is a gap in the literature after the isolation of oncocytic/Hürthle cell carcinoma (HCC), as a unique type due to immunoendocrine and metabolic features (low TSH-receptor expression and radioiodine avidity). The aim of this study was to collect clearly defined reports of HCC (as a separate entity) and to attempt determining common clinical symptoms and the usefulness of various diagnostic techniques (comprehensive critical review). This may be an introduction to modern treatment (patient-centered care) since the main cause of mortality is not local progression or metastases. Results: Until now, due to misnomenclature and data misinterpretation, HCC has been treated according to general standards (with overuse of TSH-ST and RIA). High thyroglobulin level, decreased total thyroxin (with normal FT3 and spontaneous decrease in TSH), hypercalcemia, as well as the “reverse flip-flop” phenomenon, as common symptoms, indicate the neuroendocrine origin of HCC. Sparse, well-documented lymph node metastases are another feature, although from few studies. Most studies omit the N stage. Whole-body ¹³¹iodine and ¹⁸F-fluorodeoxyglucose scintigraphy may be useful before FNAB. Fine-needle aspiration biopsy (FNAB), as a “gold standard” in early diagnosis of thyroid nodules, delays HCC diagnosis because of the inability to determine a benign/malignant nature. Conclusions: Final HCC outcome may be affected by various overlapping immunoendocrine factors (paraneoplastic effects). Due to very few thyroid function tests performed in HCC, we have proposed a set of basic laboratory analyses, core biopsy in HCC differentiation, and diagnostic chain for standardization. According to the review, adaptation and treatment of HCC based on existing standards for other thyroid cancers seem to be insufficient, and the risks outweigh the benefits. The key recommendations resulting from the 5th edition of the WHO Classification of Endocrine Neoplasms are only the beginning of refuting many myths and biases. Full article

The electrophilic allergen screening assay (EASA) uses small-molecule probes as surrogates for skin proteins to measure hapten protein carrier complex formation, Key Event (KE) 1 in the adverse outcome pathway for skin sensitization. Although multiple assays are accepted for this purpose, the EASA has higher throughput and needs less specialized equipment than other commonly used KE1 assays. This validation study assessed transferability of the EASA to naïve laboratories and within- and between-laboratory reproducibility. The predictive capacity of the assay in relation to reference data both from the murine local lymph node assay (LLNA) and, where available, human predictive patch tests, was estimated. The validation study was conducted using performance standards developed for methods that are under evaluation for inclusion in relevant test guidelines. The within- and between-laboratory reproducibility were cumulatively 96% and 85%, respectively. These scores exceeded the performance standard thresholds of 80%. Compared to reference LLNA data, the cumulative EASA results from the four laboratories had an overall sensitivity of 87%, specificity of 76%, and accuracy of 83%. The consensus results among the four laboratories had an overall sensitivity of 85%, specificity of 80%, and accuracy of 83%. For human reference data, the cumulative EASA results had an overall sensitivity of 81%, specificity of 76%, and accuracy of 70%. The EASA predicted sensitizers very well, although it had a slightly higher rate of misclassifying some negative test chemicals as positive with a specificity below the performance standards criterion of 80%. Our findings support further exploring use of the EASA in defined approaches to identify potential skin sensitizers. Full article

Background/Objectives: Differentiating mediastinal lymphadenopathy associated with lung cancer from sarcoidosis remains a clinical challenge because of overlapping imaging findings. This study evaluated whether CT-derived radiomic features, alone and in combination with clinical variables, could support the non-invasive differentiation of these two entities. Methods: In this retrospective single-center study, 204 histopathologically confirmed mediastinal lymph nodes were analyzed. A total of 107 radiomic features were extracted from manually segmented contrast-enhanced thoracic CT images. Multiple feature selection methods, dimensionality reduction techniques, and machine learning classifiers were evaluated using patient-level five-fold cross-validation. Additional clinical-only, combined clinical–radiomic, one-node-per-patient sensitivity, and exploratory interobserver feature stability analyses were performed. Results: Among radiomics-only models, LASSO achieved the highest ROC–AUC of 0.9108, whereas ElasticNet achieved the highest accuracy of 81.20%. The clinical-only ensemble model using age, sex, and smoking status showed strong performance, with an accuracy of 94.92% and an ROC–AUC of 0.9733. Selected combined clinical–radiomic models showed numerically higher performance; the combined correlation-filtered ensemble model achieved the highest accuracy of 97.78% and an ROC–AUC of 1.0000. Clinical integration also yielded more compact feature subsets in some methods, as combined LASSO selected 9.6 variables while improving ROC–AUC from 0.9108 to 0.9667 compared with radiomics-only LASSO. In the one-node-per-patient sensitivity analysis, clinical-only and combined models retained high performance, whereas radiomics-only LASSO showed reduced performance. Exploratory interobserver analysis showed moderate reproducibility for only a subset of radiomic features. Conclusions: CT-derived radiomic features may provide complementary information for differentiating mediastinal lymphadenopathy associated with lung cancer from that associated with sarcoidosis. However, clinical variables were highly informative, and the incremental value of radiomics should be interpreted cautiously. Further multicenter studies with external validation, standardized segmentation protocols, and clinically balanced cohorts are required before routine clinical implementation can be recommended. Full article

Background/Objectives: Robotic gastrectomy (RG) for gastric cancer requires structured implementation to ensure oncological safety, particularly in Western centers with lower case volumes. Indocyanine green (ICG)-guided near-infrared lymphography may facilitate adequate lymphadenectomy and reliable tumor localization. We report our stepwise institutional introduction of RG and evaluate the perioperative outcomes and diagnostic accuracy of ICG-guided lymphography. Methods: All consecutive patients who underwent curative-intent RG at the University Medical Center Ljubljana between June 2022 and September 2025 were retrospectively analyzed. The implementation followed a structured stepwise approach, beginning with subtotal gastrectomy and progressing to total gastrectomy after formal training at Severance Hospital, Yonsei University Health System, under the mentorship of Prof. Woo Jin Hyung. ICG was administered endoscopically the day before surgery for tumor localization and intraoperative lymphatic mapping. The operative learning curve was assessed by CUSUM analysis, segmented regression, and bootstrapped plateau estimation. Results: Thirty-eight patients underwent RG (17 subtotal and 21 total). R0 resection was achieved in 100% of cases. The conversion rate was 2.6%. Major complications (Clavien–Dindo ≥ IIIb) occurred in six patients (15.8%). The 30-day mortality rate was 0%, and the 90-day mortality rate was 2.6%. Bootstrapped plateau operative times were 321.2 min (95% Bias-corrected and accelerated confidence interval (BCa CI): 278.4–344.1) for subtotal and 413.5 min (95% BCa CI: 378.1–476.1) for total gastrectomy, with the steepest learning phase confined to the first 2–4 cases. ICG was used in 23 patients. In a validation subset of five patients (259 lymph node stations), the sensitivity and negative predictive value were both 100%, with zero false negatives in 57 ICG-negative stations. Conclusions: RG can be safely introduced using a structured, stepwise strategy supported by training at a high-volume expert center. ICG-guided lymphography demonstrated 100% sensitivity for tumor-draining nodal basins in a small validation cohort (n = 5), supporting the feasibility of the technique during program introduction and warranting prospective evaluation in larger series. Full article

Head and neck lymphedema (HNL) is a common complication of head and neck cancer (HNC) treatment. Surgery and radiation, the backbones of HNC treatment, disrupt lymphatic networks through direct injury and fibrosis, leading to accumulation of lymphatic fluid in interstitial spaces. This causes swelling of external and internal structures, leading to decreased quality of life, cosmetic distress, social withdrawal, and functional deficits such as dysphagia, dysphonia, and reduced cervical mobility. In this narrative review, we provide a broad overview of the pathophysiology, assessment, and prevention of HNL. Key surgical factors include the extent of neck dissection, including specific levels removed. Radiation compounds surgical injury through lymphatic fibrosis in a dose-dependent manner. Emerging radiation de-escalation strategies may reduce HNL, though lymphedema is rarely studied as a trial endpoint. Moreover, assessment of HNL remains challenging due to the absence of a gold standard—patient-reported outcome measures, clinician-reported scales, and instrumental tests each capture distinct components of external and internal HNL. Currently, the cornerstone of HNL treatment is conservative management with complete decongestive therapy, which shows mixed efficacy and does not address internal HNL. Surgical options including lymphovenous anastomosis and vascularized lymph node transfer show early promise but remain limited to case reports and small series. Lymphatic imaging, particularly indocyanine green lymphography, represents a promising emerging modality for guiding personalized treatment planning, though application to the head and neck remains challenging. Ultimately, current management of HNL remains largely reactive, with a noticeable lack of preventative therapies. Future research may benefit from better defining surgical options, including HNL as an endpoint in radiation de-escalation trials, and validate emerging lymphatic imaging techniques in order to improve outcomes for HNC survivors. Full article

Background/Objectives: Colorectal cancer (CRC) is relatively uncommon in individuals under 40 years of age; however, its rising incidence is a growing concern. This study aimed to investigate clinicopathologic features, genetic alterations, and protein expression patterns in early-onset colorectal cancer (EOCRC) to better understand the underlying mechanisms and prognostic factors. Methods: We retrospectively analyzed 18 patients diagnosed with EOCRC (<40 years) at our institution between 2018 and 2023. Next-generation sequencing (NGS) and immunohistochemistry (IHC) were used to assess genomic alterations and protein expression profiles. Clinicopathologic data were correlated with molecular findings and outcomes. Results: The cohort included ten females and eight males (mean age, 32.7 years; range, 17–38 years). Tumors most frequently arose in the rectum (56%) and were predominantly high stage (T3–T4, 67%) and moderately differentiated (78%). Lymphovascular invasion occurred in 50% of cases, and lymph node metastasis in 39%. Most tumors were microsatellite stable (MSS, 89%) and mismatch repair–proficient; two cases (11%) were MSI-high with germline MMR mutations. Among 17 patients who underwent NGS, the most frequent mutations involved KRAS (35%), APC (24%), TP53 (18%), and SMAD4 (18%). Notably, SMAD4 protein downregulation by IHC was observed in 67% of cases, including 60% of SMAD4 wild-type tumors. Loss of SMAD4 expression was significantly associated with lymph node metastasis (p = 0.037) and poor survival (p = 0.045). Conclusions: SMAD4 alteration—on both the genetic and protein levels—is common in EOCRC and is significantly correlated with aggressive clinicopathologic features and worse prognosis. Full article

There are a few molecules that are regularly used as markers for lymphatic endothelial cells (LECs) such as the adhesion molecule CD31/PEACAM1, the transcription factor PROX1, the Vascular Endothelial Growth Factor Receptor-3 (VEGFR3/FLT4), the glycoprotein podoplanin, and the hyaluronan receptor LYVE1. However, none of the molecules are exclusively expressed in LECs, and there is molecular and functional heterogeneity of LECs in initial lymphatics, lymphatic collectors and lymph nodes. Therefore, a combination of markers must be applied to identify lymphatics. This is particularly true for the characterization of conditions such as lymphatic malformations or cancers, in which the molecular profile of vessels may be variable or abnormal. Here we present two molecules that can help distinguish between endothelial cells of blood and lymphatic vessels: the scaffold protein liprin β-1 (PPFIBP1) and the intermediate filament synemin. We collected own data on the RNA and protein expression of the two molecules in humans, and studied publicly available databases. PPFIBP1 appears to be a suitable marker of LECs in initial lymphatics, collectors and lymph nodes, while synemin appears to be more restricted to initial lymphatics. We hope this will stimulate monoclonal antibody development and help expand the range of LEC markers in health and disease. Full article

Melanoma is a highly aggressive and invasive form of skin cancer that arises from the uncontrolled growth of melanocytes. It is characterized by early spread through the lymphatic system and metastasis. The success of metastasis is linked to the ability of melanoma and other cancer cells to resist anoikis, a type of cell death that occurs when cells lose their adhesion to the extracellular matrix. Redox signaling plays an essential role in anoikis resistance. The balance between intracellular levels of nitric oxide (NO) and the reactive oxygen species (ROS) O₂⁻ and H₂O₂ stimulate signaling pathways related to proliferation and survival or cell death. A375 and SK-MEL-28 human melanomas cell lines, representing primary melanoma and lymph node metastatic melanoma cells, respectively, under suspension and adherent culture conditions were used to investigate the redox regulation of anoikis resistance. Both cell lines express the three isoforms of nitric oxide synthases (NOS) and NADPH oxidase 4 (NOX4) as endogenous sources of NO and ROS, respectively. When A375 cells in suspension were treated with the pan-NOS inhibitor L-NAME, their viability decreased. The treatment resulted in a decrease in FAK phosphorylation at Tyr397 and in ERK 1/2 phosphorylation. The expression of FAK, ERK 1/2, β-actin, and α-tubulin were significantly reduced. Treatment with L-NAME led to an increase in the expression of the metalloprotease MMP-9. SK-MEL-28 cells in suspension and treated with the NOX4 inhibitor, GKT36901, exhibited reduced viability. This was accompanied by the inhibition of FAK phosphorylation at Tyr397, ERK 1/2 phosphorylation, and a reduction in the expression of FAK, ERK 1/2, β-actin, and α-tubulin, with a slight elevation in the expression of MMP-9. Migration and invasion were strongly inhibited in A375 cells upon treatment with L-NAME, while treatment with GKT36901 had a marginal effect on the migration and invasion capacities of SK-MEL-28 cells. In summary, melanoma cells employ nitrosative and oxidative stress to shield themselves from anoikis. Nitric oxide was essential for melanoma cells at the primary site for resisting anoikis, while H₂O₂ contributed to anoikis resistance in metastatic melanoma cells. Full article

Background and Clinical Significance: Torsion of the vermiform appendix is a rare condition with a clinical presentation closely resembling acute appendicitis, while preoperative investigations are of limited value in distinguishing between the two entities. In most cases, the definitive diagnosis is made incidentally during surgery. Case Presentation: The authors present the case of an 18-day-old female neonate who presented with marked abdominal distension, diffuse spontaneous and palpation-induced abdominal pain, guarding, and signs of peritoneal irritation. The clinical manifestations and paraclinical findings mimicked a neonatal intestinal obstruction; however, intraoperative exploration revealed a gangrenous vermiform appendix twisted 240° anticlockwise, associated with a fibrinous pseudomembrane and multiple enlarged mesenteric lymph nodes. Although the initial therapeutic strategy was to perform a laparoscopy, severe abdominal distension caused by marked aerocolia necessitated conversion to a supra- and infraumbilical midline laparotomy. We thus describe, to the best of our knowledge, one of the youngest neonatal cases of appendiceal torsion reported in the literature. Conclusions: Although rare, appendiceal torsion should be considered in the differential diagnosis of neonatal acute abdomen, and timely surgical exploration is key to achieving a favorable outcome. Full article