Intratumoral microbiota are essential components of tumours and are substantially involved in tumour initiation, progression, and treatment. However, owing to the vast diversity and abundance of microbial species, understanding their molecular mechanisms within tumours, particularly in pancreatic cancer (PC), remains challenging.

Microbiota composition was analysed in pancreatic cystic neoplasm (PCN) and pancreatic ductal adenocarcinoma (PDAC) tissues using 16S rRNA sequencing. Liquid chromatography-mass spectrometry (LC-MS) was employed in the same samples to quantify tissue metabolites. Subsequently, the association between intratumoral microbiota and metabolites was examined to investigate potential interactions. Western blotting, quantitative real-time polymerase chain reaction, and immunohistochemistry were used to detect the expression of 3-hydroxyacyl-CoA dehydrogenase (HADH), AMP-activated protein kinase (AMPK), and G protein-coupled receptor 43 (GPR43). The biological role of the intratumoral bacterial metabolite sodium acetate (NaAc) was determined through in vitro and in vivo experiments.

Certain bacterial taxa, including Muribaculaceae, Prevotella, Lachnospiraceae NK4A136 group, and Blautia, were significantly enriched in PDAC tissues and were associated with lipid molecules. Specific taxa exhibited positive correlations with lipid molecules in PDAC tissues. Low concentrations of NaAc promoted PC cell proliferation and migration in vitro and enhanced tumour growth in vivo. Mechanistically, NaAc activated the GPR43/AMPK/HADH signalling pathway in PC cells, leading to increased fatty acid oxidation.

Specific intratumoral microbiota contribute to the progression from PCN and PDAC by modulating lipid metabolism. These findings provide a theoretical framework for understanding the microbiota-driven mechanisms in PDAC and highlight their role in tumour growth.

Colorectal cancer (CRC) is a major cause of cancer-related death. Resveratrol (RES), despite its promising anti-inflammatory, antioxidant, and anticancer properties, suffers from poor solubility, low bioavailability, and limited tumor accumulation. Accordingly, eight RES-loaded bilosomes were prepared and characterized. Optimization was performed using a desirability study based on the observed colloidal properties. The selected formulation was radiolabeled with iodine-131 and assessed for radiolabeling efficiency and stability. In-vitro cytotoxicity was evaluated against HT- 29 and LS174T CRC cell lines. Biodistribution studies in tumor-bearing mice were also assessed. Bilosomes displayed PS (93.08 to 340.00 nm), negative charges (-27.50 to -51.80 mV), EE% (73.45-96.35%), and a sustained release over a 24-h period. Optimization revealed formulation with PS (163.8 nm), PDI (0.41), EE% (93.80%) and ZP (- 51.8 mV). Radiolabeling efficiency was 93.23 ± 2.15% and was stable for 2 h. In tumor-bearing mice, the tumor uptake of ¹³¹I-RES bilosomes was 4.34-fold compared to ¹³¹I-RES solution, indicating enhanced tumor accumulation and selectivity, likely driven by enhanced permeability and retention-mediated passive targeting. Bilosomes significantly enhanced cytotoxicity, reducing IC₅₀ values ~ fourfold in LS174T and ~ sixfold in HT-29 cells versus free RES. The pharmacokinetic behavior revealed a significantly higher C_max for bilosomes relative to the solution. This study marks the first integration of ¹³¹I-radiotracking with RES-loaded bilosomes, enabling precise measurement of biodistribution and tumor targeting. The approach established a theranostic framework that combined enhanced drug delivery with real-time tracking. Mechanistically, it improved RES accumulation in CRC, highlighting its potential but also underscoring the need for further preclinical research.

Primary gastrointestinal diffuse large B-cell lymphoma (PGI-DLBCL) constitutes 30%-40% of primary extranodal lymphomas. While rituximab has significantly improved survival in nodal DLBCL, its impact on the prognosis of PGI-DLBCL remains inadequately defined. This study aimed to compare the survival outcomes of PGI-DLBCL patients between the pre-rituximab and rituximab eras.

We identified all PGI-DLBCL cases from the Surveillance, Epidemiology, and End Results (SEER) registry (1975-2015). Patients were categorized into pre-rituximab (diagnosed before 2006) and rituximab-era (diagnosed in or after 2006) groups. Overall survival (OS) and lymphoma-specific survival (LSS) were compared between the two groups.

Among 2780 patients, median age was 68 years; 72.2% had stage I/II disease. The rituximab-era group showed significantly longer median OS (119 months vs. 43 months, p < 0.0001). Median LSS was not reached in the rituximab era versus 115 months in the pre-rituximab group (p < 0.0001), with an 11-year LSS rate of 58%. Multivariable analysis confirmed that the rituximab era, younger age, early stage, and chemotherapy were associated with better OS and LSS.

PGI-DLBCL represents a significant subset of non-Hodgkin lymphomas and is the most prevalent type within the gastrointestinal tract. Younger age, female, Asian, marital status, early-stage and with chemotherapy, as well as the period of lymphoma diagnosis (rituximab era), are associated with better prognosis.

Homeobox (HOX) genes are essential regulators of embryonic development and cellular differentiation under physiological conditions. Among this gene family, HOXA10 has emerged as a pivotal factor in gastrointestinal (GI) cancers, influencing tumor growth, metastasis, disease progression, and resistance to therapy. HOXA10 functions as a transcription factor and plays key roles not only in embryogenesis but also in immunomodulation. HOXA10 and its transcriptional targets play a crucial role in cancer development, promoting cell growth, invasion, migration, metastasis, and resistance to cell death. Recent studies have explored the influence of HOXA10 on the tumor immune microenvironment, particularly its role in modulating immune cell recruitment and signaling pathways that enable tumor immune evasion. Our recent research identified a HOXA10-regulated five-gene signature that distinguishes long-term from short-term survivors of pancreatic cancer, with HOXA10 expression correlating with increased regulatory T cell (T_reg) infiltration. HOXA10 impacts genes and pathways involving macrophages, Tregs, and other immune cells, potentially creating an immunosuppressive niche that promotes metastasis and diminishes the effectiveness of immunotherapies. In this review, we examine the diverse functions of HOXA10 in GI cancers, offering a comprehensive comparison with other HOX family proteins to elucidate their overlapping and distinct roles in malignancy. Our goal is to provide a thorough overview of how HOXA10 contributes to tumor development and its microenvironment. We highlight its critical role in facilitating cancer progression and metastasis, supported by data from cell lines, patient tumor samples, and clinical studies. Recognizing existing gaps in the understanding of HOXA10's role in cancer, we also explore potential strategies to target this gene, with an emphasis on synergistic approaches that combine HOXA10 inhibition and immunotherapy. Ultimately, these insights aim to identify vulnerabilities within GI cancers that could be exploited through novel therapeutic agents and combination treatments, paving the way for improved clinical outcomes.

Jejunal carcinoid tumors are rare neuroendocrine neoplasms that often present with nonspecific abdominal symptoms, resulting in delayed diagnosis. Intussusception is an uncommon complication in adults, and skeletal metastases at initial presentation are exceedingly rare. To our knowledge, this is the first reported case of a jejunal carcinoid tumor presenting simultaneously with jejuno-jejunal intussusception and skeletal metastases involving the axial skeleton.

A 48-year-old man presented with one week of recurrent colicky abdominal pain, bilious vomiting, and constipation. His medical history was significant for chronic low back pain progressing to paraplegia, with imaging evidence of vertebral metastases identified two years earlier. Contrast-enhanced computed tomography demonstrated jejuno-jejunal intussusception with proximal bowel dilatation and mixed sclerotic-lytic lesions of the axial skeleton. After preoperative stabilization, laparoscopic localization followed by laparotomy was performed, with resection of a 40-cm jejunal segment containing a circumferential mass acting as the lead point. A side-to-side stapled anastomosis was fashioned. The postoperative course was uneventful. Histopathological examination revealed a high-grade neuroendocrine neoplasm with a mitotic index >20 per high-power field. Postoperative PET imaging showed no residual disease at the primary site but confirmed skeletal metastases. Systemic therapy with somatostatin analogues and multidisciplinary oncologic follow-up were recommended.

This case illustrates an unusual presentation of a jejunal carcinoid tumor complicated by jejuno-jejunal intussusception and skeletal metastases. Recognition of such atypical metastatic patterns may facilitate earlier diagnosis and more appropriate management. Jejunal neuroendocrine tumors should be considered in the differential diagnosis of adult intussusception, particularly in the presence of unexplained skeletal lesions, with surgical resection remaining central to management.

To characterize the capabilities of CE-marked AI products for lung nodule analysis in lung cancer screening (LCS), quantify their coverage of tasks defined in nodule management recommendations, and assess their peer-reviewed evidence.

Six core tasks in LCS (nodule detection, classification, measurement, growth assessment, malignancy risk estimation, and structured management) were derived from 4 nodule management recommendations: Lung-RADS 2022, British Thoracic Society (BTS) guidelines, European Union Position Statement (EUPS), and European Society of Thoracic Imaging (ESTI). Products were identified through www.healthairegister.com . Vendors confirmed capabilities using a standardized questionnaire; public documentation supplemented non-responders. Task coverage was calculated as the percentage of functional overlap (0-100%) per recommendation. Peer-reviewed evidence was evaluated using a six-level efficacy framework and assessed for study characteristics.

In total, 16 products from 16 vendors were included; 10 vendors completed questionnaires. Analysis showed that 14 products detect and measure solid and subsolid nodules, 12 support growth assessment, and 9 provide malignancy risk estimation (PanCan in 5, AI-based scores in 4). No product provides support for endobronchial or cystic lesions. High task coverage (> 75%) was observed in 10 products for EUPS and 4 for BTS, whereas no product achieved high coverage for Lung-RADS or ESTI. Overall, 60 peer-reviewed studies were identified; 7% were prospective and evidence clustered at lower efficacy levels: 70% assessed diagnostic accuracy, while none reported patient outcomes or societal impact.

Numerous CE-certified AI products could support CT-based lung cancer screening, but gaps in task coverage and predominantly lower-level evidence necessitate cautious, monitored implementation.

Question Do commercially available AI products for lung nodule analysis functionally cover international nodule management recommendation-defined tasks, and what peer-reviewed clinical evidence supports them? Findings AI products support standard nodule detection and measurement in line with management recommendations but lack support for endobronchial or cystic lesions and high-level clinical evidence. Clinical relevance CE-marked AI products can assist radiologists with core lung cancer screening tasks, but capability gaps exist. Limited high-level clinical evidence complicates integrating AI into guidelines, securing reimbursement, and formulating recommendations for its use in lung cancer screening programs.

Pathogenic variants in Transcription Factor 12 (TCF12) have been identified as genetic causes of craniosynostosis. The phenotypic spectrum of TCF12-related craniosynostosis is broad and remains incompletely understood. Herein, we report a case of a 2-month old male with a heterozygous pathogenic variant of TCF12 (c.1267C > T; pArg423*) and bicoronal craniosynostosis. He underwent bicoronal suturectomy at 4 months of age, followed by post-operative molding helmet therapy. He returned at 2 years of age with developmental regression including loss of expressive language and fine motor skills. Shortly after he developed clinical findings of elevated intracranial pressure (ICP) and was found to have synostosis of the sagittal and bilateral lambdoid sutures, and a Galassi III left middle fossa arachnoid cyst with significant midline shift, requiring surgical fenestration. Post-operatively, the cyst decreased in size with resolution of midline shift. The patient did not regain any developmental milestones and continued to demonstrate deficits in language, social communication, and fine motor function despite resolution of other preoperative signs and symptoms of elevated ICP. To our knowledge, this is the first reported case of TCF12-associated craniosynostosis with a co-occurring arachnoid cyst. Furthermore, there is limited literature describing the long-term neurodevelopmental outcomes of children with TCF12 pathogenic variants. Thus, this case offers expanded insight into the broad phenotypic spectrum of TCF-12 related craniosynostosis and its potential clinical sequelae.

Pancreatic ductal adenocarcinoma remains one of the deadliest malignancies, characterized by late diagnosis, aggressive biology and limited therapeutic success. Advances in multiagent chemotherapy have improved outcomes across disease stages, whereas precision medicine approaches are reshaping treatment paradigms. Personalized RNA vaccines and oncogenic KRAS-directed agents represent emerging immunological and molecular frontiers. Multimodal treatment regimens and surgical innovations, including vessel-oriented and minimally invasive techniques, have enhanced complete resection rates and enabled conversion of initially unresectable locally advanced pancreatic cancer into resectable disease. Increasingly, multidisciplinary, biology-guided strategies define resectability and the sequence of systemic and local therapies. The tumour microenvironment's complex stromal and immune ecology remains central to therapeutic resistance but also offers opportunities for rational combination therapy. Early detection and risk-adapted surveillance for high-risk individuals are advancing, as are artificial intelligence-assisted imaging and liquid biopsy approaches. Despite persistent challenges, the convergence of mechanistic insights, precision therapeutics and supportive care provides a framework for transforming pancreatic ductal adenocarcinoma from an inevitably lethal disease towards a better manageable condition.

Left ventricular( LV) tamponade is rare and can occur in special circumstances like regional pericardial effusion overlying LV. The therapeutic approach of LV tamponade is different according to the causative factor and the place of loculated pericardial effusion. We report a case of neoplastic cardiac tamponade manifesting as left ventricular diastolic dysfunction. A 78-year-old man with a history of aortic arch surgery and lung cancer surgery presented with dyspnea. Echocardiogram showed posterior loculated pericardial effusion and LV diastolic dysfunction. Pericardial window operation was performed, then revealed bloody effusion and cytodiagnosis examination revealed class V( adenocarcinoma). Atypical forms of cardiac tamponade with varied clinical presentations may be seen in patients after cardiac surgery. It is important to accurately understand the pathological condition through clinical progress and echocardiography, and to select an appropriate approach and surgical procedure.

IntroductionUrological cancers, including prostate, renal, and bladder cancers, present significant challenges to human health, particularly for patients in advanced stages due to limited targeted therapy options, high drug resistance, and poor prognosis. This study seeks to systematically identify new therapeutic targets by integrating multi-omics data and elucidating their molecular mechanisms.MethodsOur methodology involved a multi-phase integrative approach to identify therapeutic targets in urological cancers. We conducted a transcriptome-wide Mendelian randomization (TWMR) analysis using the druggable genome. We used cis-expression quantitative trait loci (cis-eQTL) data from the eQTLGen consortium (N = 31,684) as exposures and GWAS summary statistics from FinnGen R11 and Open GWAS as outcomes. Significant genes were identified through Bonferroni correction, followed by colocalization analysis to assess shared genetic effects between risk SNPs and gene expression. Summary-data-based MR (SMR) analysis was carried out using eQTLGen data. Validation of potential targets included drug prediction using DSigDB and molecular docking with AutoDock Vina. Furthermore, we integrated DNA methylation quantitative trait loci (mQTL) data from GoDMC to explore methylation-mediated regulatory mechanisms through mediation MR analysis.ResultsOur transcriptome-wide MR analysis identified 11 high-confidence therapeutic targets in urological cancers: 4 in prostate cancer (BNIP2, KAT5, MMP24, SIK2), 2 in renal cancer (GRB10, GPR17), and 5 in bladder cancer (CELSR1, GPS1, PROC, GSTM1, KLC3). Molecular docking confirmed favorable interactions between these targets and existing drugs. Epigenetic analyses showed DNA methylation-mediated regulation of key targets: PROC (cg09747827) and CELSR1 (cg00784671) in bladder cancer, and SIK2 (cg11344533) in prostate cancer.ConclusionsThis study integrates multi-omics data to identify 11 high-confidence therapeutic targets in urological cancers and is the first to elucidate DNA methylation-mediated regulatory mechanisms for targets like PROC and SIK2. The findings introduce a "DNA methylation-gene expression" axis-based strategy for combined targeted-epigenetic therapy, providing crucial evidence for optimizing precision treatment in urological oncology.