To develop expert consensus recommendations in Spain for the management of biochemical recurrence (BCR) in prostate cancer across different clinical scenarios using a modified Delphi methodology, and to provide a multidisciplinary, evidence-based framework to inform clinical decision-making regarding definition, risk stratification, imaging, and treatment after radical prostatectomy (RP), radiotherapy (RT), and RP followed by salvage RT.

A multidisciplinary scientific committee formulated 51 clinical statements based on a narrative literature review and expert experience. A panel of 49 specialists, including urologists, radiation oncologists, and nuclear medicine physicians, independently rated these statements through two rounds of an online Delphi survey.

Forty-two Spanish panelists completed both rounds. Consensus was reached for 38 of 51 statements (75%): 33 in the first round and 5 in the second. Key agreements included defining BCR after RP as a confirmed PSA rise ≥ 0.2 ng/mL; strong endorsement of next-generation imaging (NGI) for disease assessment, particularly in high-risk patients; and recommending salvage RT with or without androgen deprivation therapy (ADT) as the standard, reserving systemic therapy including androgen receptor pathway inhibitors (ARPI) for patients unsuitable for local salvage. The panel emphasized individualized ADT duration and risk-adapted imaging and treatment approaches. Additional areas of ongoing debate and future research needs were identified.

These expert-driven recommendations provide a structured clinical framework integrating current evidence and consensus guidance to optimize BCR management in prostate cancer. The findings support personalized decision-making and highlight areas requiring further prospective validation.

Triple-negative breast cancer (TNBC), characterized by the absence of ER, PR, and HER2 expression, is associated with aggressive clinical behavior and limited treatment options. Hypoxia in the tumor microenvironment (TME) may influence intercellular communication through exosomes. In this study, we investigated whether hypoxia-derived exosomes regulate malignant phenotypes of TNBC cells through exosomal miRNAs. Exosomes derived from hypoxic TNBC cells increased proliferation, migration, and invasion of recipient TNBC cells compared with normoxia-derived exosomes. Small RNA sequencing and RT-qPCR validation showed enrichment of miR-4791 in hypoxia-derived exosomes. Functional assays indicated that miR-4791 overexpression promoted TNBC cell proliferation, whereas miR-4791 inhibition reduced proliferative capacity. Mechanistically, miR-4791 directly targeted the 3'UTR of CTCFL and was associated with reduced PTEN expression. Rescue experiments suggested that restoration of CTCFL or PTEN partially attenuated miR-4791-associated malignant phenotypes in vitro and in vivo. Analysis of GSE19536 showed higher miR-4791 expression in breast cancer tissues than in normal tissues; however, the number of normal samples was limited. Survival analysis using GSE19783 indicated that higher miR-4791 expression was associated with poorer survival, although the prognostic ROC performance was weak-to-modest. Overall, these findings suggest that hypoxia-derived exosomal miR-4791 may contribute to TNBC progression, at least in part, through a CTCFL/PTEN-related mechanism.

Sarcomas with MEIS1 fusions represent a rare, recently recognized group of mesenchymal neoplasms with a predilection for genitourinary and gynecologic sites. A subset exhibits skeletal muscle differentiation resembling spindle cell rhabdomyosarcoma. Existing literature is limited to case reports and small series, with scant comprehensive clinicopathologic, molecular, and outcome data. In this study, we analyzed a multi-institutional cohort of 20 MEIS1-rearranged sarcomas using integrated clinicopathologic review, genomic profiling, and DNA methylation analysis. The tumors occurred in 17 females and 3 males (median age 41 years, range 6-58), arising mainly in the uterus/vagina (n=12), vulva/perineum (n=4), bone (n=2), and kidney (n=2), with a median size of 9 cm (range 2.5-20 cm). Histology showed mostly bland spindle cells in fascicles/storiform patterns, alternating cellularity, fibromyxoid stroma, prominent vascularity, and adipose metaplasia (45%). A subset of cases featured high-grade morphology with epithelioid cells and increased mitotic activity. Skeletal muscle markers were variably positive in 9 cases. Fusions involved MEIS1 with NCOA2 (16/20), NCOA1 (3/20), or FOXO1 (1/20). Recurrent additional genomic alterations included CTNNB1 mutations (31.6%) and MDM2 amplification (15%). DNA methylation profiling showed that MEIS1-rearranged sarcomas formed a unifying cluster comprising two subgroups, regardless of rhabdomyosarcomatous phenotype, clearly separated from other mesenchymal neoplasms, including various rhabdomyosarcoma subtypes and uterine sarcomas. The two DNA methylation subgroups correlated with differences in genome-wide copy-number variation status (Meth-CNVh vs Meth-CNVl), with Meth-CNVh tumors characterized by high mitotic rate, frequent tumor necrosis, recurrent co-occurring CTNNB1 and MDM2 alterations, and recurrent chromosomal arm-level changes. Most importantly, this subgroup exhibited significantly worse overall survival (median 25 vs 44.5 months; p=0.027) and disease-free survival (5 vs 28 months; p=0.017). This study establishes MEIS1-rearranged sarcoma as a distinct entity with generally indolent but potentially aggressive behavior. The two methylation/CNV subgroups provide potential utility for prognostic stratification and highlight actionable molecular targets in high-risk cases.

Tumor next-generation sequencing (NGS) is widely used to refine diagnosis and identify therapy targets. However, reporting criteria, schemas, and formats vary greatly which can affect uniformity of clinical cancer care. With the aim of promoting harmonization, the current state of NGS reporting practices was profiled across Genomics Organization for Academic Laboratories (GOAL) members. The assessment included a group landscape analysis to refine topics followed by a survey of member laboratories and post-survey discussions. A total of 28 surveys covering hematology and/or solid tumor panels from 21 academic laboratories were analyzed. A majority of responses indicated use of one or more variant tiering systems and reporting of all presumed somatic variants of uncertain significance. Most indicated significant manual effort by directors in generating final reports related to variant annotation using multiple external and internal laboratory databases, evaluation for potential germline variants, and correlation with prior NGS studies and clinical context. Report differences by indication related to more frequent inclusion of longitudinal comparisons for hematologic neoplasms and potential therapies for solid tumor reports. Based on areas of strong consensus among survey participants, considerations for best practices are presented along with opportunities for future harmonization, which may require improvements in classification schemas or better software tools.

Myasthenia gravis (MG) is a complex autoimmune neuromuscular disorder, and the role of lipid metabolism dysregulation in MG pathogenesis remains unclear. This study aimed to investigate the molecular mechanisms of lipid metabolism regulation in myasthenia gravis development by integrating single-cell and bulk transcriptomic data. This study analyzed bulk RNA sequencing data from the GSE85452 dataset (13 MG patients and 12 healthy controls) and single-cell RNA sequencing data from the GSE227835 dataset (10 MG patients and 10 healthy controls). Differential expression analysis was performed, and weighted gene co-expression network analysis (WGCNA) was conducted to identify disease-related modules. Key genes were screened through the intersection of differentially expressed genes (DEGs), WGCNA hub genes, and lipid metabolism-related genes. Functional enrichment analysis, protein‒protein interaction (PPI) network construction, immune infiltration analysis, and regulatory network analysis were performed. Single-cell analysis was used to characterize cellular heterogeneity and intercellular communication features. A nomogram prediction model was constructed and internally validated using leave-one-out cross-validation (LOOCV). Potential therapeutic compounds were identified through drug prediction and molecular docking analysis. Furthermore, key genes were validated by RT-qPCR in an independent cohort of 5 MG patients and 5 healthy controls. A total of 823 DEGs and 13 co-expression modules were identified, of which 4 modules were significantly associated with MG. Twenty-one candidate genes were screened, and 2 key genes (IRS2 and ALDH2) were ultimately determined. IRS2 was significantly downregulated while ALDH2 was significantly upregulated in MG patients. The nomogram model based on key genes demonstrated excellent predictive performance (AUC = 0.897). Immune infiltration analysis showed increased regulatory T cells (Tregs) and decreased CD4+ memory activated T cells in MG patients. Single-cell analysis identified 10 major cell types. Cell‒cell communication analysis revealed dense interactions among CD4+ T cells, B cells, and CD14+ monocytes. Drug prediction identified metformin and cyclophosphamide as potential therapeutic candidates, and molecular docking confirmed favorable binding affinities. This integrative study generated the hypothesis that lipid metabolism dysregulation, potentially mediated by IRS2 and ALDH2, may contribute to immune dysfunction in MG pathogenesis. These findings provide preliminary insights into the molecular mechanisms underlying MG development and suggest potential diagnostic biomarkers and therapeutic targets. However, these results are hypothesis-generating, and clinical translation is contingent upon rigorous mechanistic validation through functional experiments, animal models, and larger multicenter clinical cohorts.

SLFN11, highly expressed in SCLC, predicts sensitivity to DNA-damaging agents. Its role in other lung neuroendocrine neoplasms (NENs) (typical/atypical carcinoids - TC/AC and large cell neuroendocrine carcinoma- LCNEC) is unknown. This multicentre study assessed SLFN11 across lung NENs exploring its clinical-molecular associations.

SLFN11 immunohistochemistry (H-score 0-300) was assessed in 361 tumours (127 TC, 35 AC, 152 LCNEC, 47 SCLC). Ki67, pRb, cMYC, DLL3, ASCL1, HNF1a, OTP and NEUROD1, ASCL1, POU2F3, and YAP1 (NAPY; H-score > 50 as dominant subgroup) staining were integrated with clinicopathologic data and survival. Median SLFN11_expression (_exp) was used for survival analysis.

SLFN11_exp varied across histologies (p < 0.001), with median values of 0 in TC (range 0-20) and AC (0-40), 2.49 (0-250) in LCNEC, 35 (0-240) in SCLC. SLFN11 showed a positive correlation with Ki67 (R² = 0.187) across all histologies. In TC/AC, SLFN11_exp was enriched in A1 subgroup tumours (known for ASCL1_exp) (p = 0.035) and not correlated with OTP, HNF1A, CD44 and SSTR2A_exp. In LCNEC, SLFN11_exp was higher in ASCL1_high tumors (median 17.2; 0-162.5, p = 0.003) and correlated with cMYC_exp (p = 0.024), but not with pRB and DLL3 status. In SCLC, a trend toward higher SLFN11_exp in ASCL1_high tumours was observed. SLFN11_exp was not prognostic in TC/AC or LCNEC. In SCLC, SLFN11_exp ≥ median value was associated with improved OS (13.9 vs 6.8 months; HR = 0.48, 95%CI 0.26-0.90, p = 0.020).

SLFN11_exp in lung NENs is higher in SCLC > LCNEC > TC/AC, and correlated with Ki67. SLFN11_exp was associated with ASCL1_exp in all lung NENs. SLFN11 role in TC/AC and LCNEC remains to be defined.

Bladder cancer (BCa) is a highly prevalent urological malignancy and one of the most frequently occurring cancers worldwide, necessitating the development of diagnostic and therapeutic biomarkers. This study aimed to explore candidate genes that may be involved in the carcinogenesis of BCa.

BCa gene expression data from the Gene Expression Omnibus (GEO) database were analyzed. Both differential expression analysis and weighted gene co-expression network analysis (WGCNA) were performed on datasets (GSE236932, GSE133624) to identify the key modules and hub genes. We subsequently extracted genes from the top modules positively correlated with tumor traits identified via WGCNA and intersected them with differentially expressed genes (DEGs) in each dataset. Finally, the overlapping genes were screened for their therapeutic potential as biomarkers in bladder cancer, and quantitative Real-Time PCR (qRT-PCR) was executed to validate the expression patterns of the most promising candidate genes in clinical tissue samples.

Integrative analysis revealed a set of hub genes potentially involved in bladder cancer, including PSMG3, ESRP1, GRHL2, MAL2, CDH1, AP1M2, PAFAH1B3, PRKCZ, MAPK13, and RAB25. Among these, PAFAH1B3 and PSMG3 emerged as notable novel candidates. qRT-PCR validation further underscored the significant overexpression of these genes in BCa samples, with approximately two-fold changes relative to normal tissues.

This study suggests that PAFAH1B3 and PSMG3 may serve as valuable biomarkers and potential therapeutic targets in bladder cancer. However, further investigations are needed to establish their biological function and clinical relevance.

Epithelial-Mesenchymal Transition (EMT) is a critical driver of metastasis and drug resistance in breast cancer. Repurposing FDA-approved drugs offers a rapid strategy to target EMT pathways. This study evaluates Itraconazole, an antifungal agent with reported anti-cancer properties, as a potential multi-target inhibitor of the EMT signaling network. We investigated the binding mechanism and selectivity of Itraconazole against four key EMT regulators: Smoothened (SMO), TGF-βR1, EGFR, and GLI1. Our results identify SMO as the primary target, exhibiting high binding affinity and thermodynamic stability. Conversely, EGFR and GLI1 displayed significant structural instability, indicating a lack of direct inhibition. The study provides atomic-level structural evidence supporting the repurposing of Itraconazole as a selective, combinatorial therapeutic agent to target EMT-driven metastasis.

Induced Fit Docking (IFD) was performed using the Schrödinger IFD protocol and the Glide XP scoring function within the Schrödinger Maestro suite. The dynamic stability of the protein-ligand complexes was evaluated using 500 ns molecular dynamics (MD) simulations with the Desmond software and the OPLS4 force field. To differentiate false positives and assess pose stability under enhanced sampling, Binding Pose Metadynamics (BPMD) was utilized. Thermodynamic binding free energies were calculated using the Thermal MM/GBSA method. All simulations were analyzed using the Simulation Interaction Diagram and trajectory clustering tools within Schrödinger.

To evaluate whether adding milk of magnesia (MOM) to an enhanced recovery after surgery (ERAS) pathway prevents postoperative ileus (POI) and improves postoperative bowel function.

This randomized controlled trial at the Gynecology Unit, Siriraj Hospital (Bangkok, Thailand) enrolled patients undergoing hysterectomy for benign or malignant indications during September 2023 through February 2024. Participants were randomly assigned to ERAS alone (n = 80) or ERAS plus MOM (n = 80). The MOM group received 15 mL on postoperative day 0 and then 30 mL twice daily until first flatus or bowel movement. The primary outcome was the time from surgery to resumption of a well-tolerated solid diet. Secondary outcomes included POI incidence, time to first flatus, patient-reported outcomes, and MOM-related complications.

Among 160 patients, 60 (37.5%) had gynecologic malignancies: endometrial cancer (n = 34), ovarian cancer (n = 16), cervical cancer (n = 8), and leiomyosarcoma (n = 2). Time to well-tolerated solid diet was significantly shorter in the MOM group compared with the control group (20.6 ± 10.9 vs 28.8 ± 16.3 h; P < 0.001). The incidence of POI was also significantly lower (3.8% vs 27.5%; P < 0.001), and time to first flatus was shorter (17.1 ± 7.9 vs 22.3 ± 10.8 h; P < 0.001). Patient-reported outcomes favored the MOM group, with higher eating and daily activity satisfaction scores. No severe adverse events occurred in the MOM group.

Adding MOM to ERAS was associated with reduced POI incidence and faster recovery of bowel function in patients undergoing abdominal hysterectomy for benign or malignant conditions.

Thai Clinical Trials Registry (TCTR: TCTR20230816005), registered on 16 August 2023.

To identify the imaging features of pancreatic acinar cell carcinoma (PACC) and to classify them according to morphological subtypes.

This multicenter retrospective study included 36 patients with pathologically confirmed PACC who underwent CT/MRI from 2008 to 2024. Tumors were classified into three morphologic subtypes based on imaging features identified in this study: Type 1, well-demarcated solid mass; Type 2, predominantly intraductal mass; Type 3, indistinct infiltrative mass. Maximal tumor size, marked diffusion restriction, lobulated internal architecture, venous thrombosis, and proportion of intratumoral necrosis were evaluated. Differences among subtypes were analyzed using the Kruskal-Wallis test and Fisher's exact test. In 28 patients who underwent curative resection, Cox regression analysis was performed to identify predictors of recurrence.

PACC commonly showed marked diffusion restriction (76.7%), lobulated internal architecture (52.8%), and minimal intratumoral necrosis (80.6%). Nineteen tumors were classified as Type 1, eight as Type 2, and nine as Type 3. Type 1 tumors were larger than Type 2 and Type 3 (6.3 cm vs. 3.0 cm vs. 2.5 cm; p = 0.002) and more frequently showed venous thrombosis (31.6% vs. 0% vs. 0%; p = 0.040) and lobulated internal architecture (78.9% vs. 37.5% vs. 11.1%, p = 0.002). On multivariable analysis, maximal tumor size (hazard ratio (HR) 1.7, 95% confidence interval (CI) 1.2-2.3) and Type 3 tumor (HR 7.7, 95% CI 1.1-53.6) were independent predictors of recurrence.

PACC shows characteristic imaging features and distinct morphologic subtypes. Tumor size and the infiltrative subtype may predict postoperative recurrence.

Question Pancreatic acinar cell carcinoma (PACC) is a rare tumor with imaging features overlapping other pancreatic neoplasms, and imaging biomarkers for recurrence risk remain limited. Findings PACC showed three morphologic imaging phenotypes, and an indistinct infiltrative subtype and larger tumor size were independently associated with recurrence after curative resection. Clinical relevance Recognition of morphologic imaging phenotypes of PACC may help radiologists differentiate PACC from more common pancreatic tumors and identify patients at higher risk of postoperative recurrence.