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Anterior gradient 2 is overexpressed in extramammary Paget's disease and involved in cell survival.6 days agoExtramammary Paget's disease (EMPD) is a rare skin cancer whose etiology and pathogenesis remain unclear. Because of limited treatment options, patients with advanced stages have a poor prognosis; therefore, identifying novel biomarkers for early detection and evaluation of therapeutic efficacy is necessary.
To investigate the association between anterior gradient 2 (AGR2) expression and clinical features in patients with EMPD and the potential involvement of AGR2 in the pathogenesis of EMPD.
Sixty-two tissue samples and 60 serum samples were evaluated using immunohistochemistry and enzyme-linked immunosorbent assay. In vitro experiments were performed using the EMPD cell line, KS-EMPD-1, to assess the effects of silencing AGR2 on cell growth, invasion, and migration.
Patients with AGR2 overexpression in tumor tissues tended to have a poor prognosis; however, the difference was not statistically significant. Serum AGR2 concentrations were significantly higher in patients with EMPD with or without metastasis than in healthy controls and decreased after treatment. AGR2 knockdown decreased cell number and induced apoptosis in EMPD cells, suggesting that AGR2 may influence the viability of EMPD cells via apoptosis.
AGR2 is overexpressed in patients with EMPD and plays an important role in the pathogenesis of EMPD.CancerCare/Management -
Chimeric Antigen Receptor T Cell Therapy for Glioblastoma: Clinical Advances and Emerging Strategies.6 days agoChimeric antigen receptor (CAR) T cell therapy is a promising investigational modality for glioblastoma (GBM), but durable disease control has been limited by antigen heterogeneity, adaptive resistance, and an immunosuppressive tumor microenvironment. Early phase I studies targeting IL-13Rα2, HER2, EGFRvIII, EphA2, B7-H3, and GD2 established proof-of-concept for CAR T cell therapy in recurrent GBM and provided important clinical insights regarding feasibility, safety, and resistance mechanisms. More recent approaches, including multi-antigen targeting and locoregional delivery, aim to address these limitations, and ongoing trials evaluating new antigens and engineered platforms may further expand the clinical potential of CAR T cells in GBM.CancerCare/Management
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Clinical translation of gut microbiome biomarkers and host immune dysregulation in colorectal neoplasia: a systematic review with Clinical and Molecular Pathology Prioritisation.6 days agoGut microbiome signatures are promising non-invasive biomarkers for colorectal neoplasia, but clinical translation is limited by heterogeneity in populations, platforms, validation and comparator tests. We evaluated microbiome-based biomarkers and microbiome-host immune associations, emphasising applicability.
We systematically reviewed human studies published from 1 January 2020 to 15 July 2026 evaluating gut microbiome-associated biomarkers in colorectal adenoma or colorectal cancer. Diagnostic studies were summarised by biomarker, target lesion, comparator, validation and performance, with Quality Assessment of Diagnostic Accuracy Studies-2 appraisal. A predefined seven-domain framework provided secondary translational prioritisation. Mechanistic and prognostic microbiome-immune studies were synthesised separately.
Recurrent signals included Fusobacterium nucleatum, multispecies panels, microbial gene and single-nucleotide-variant classifiers, multikingdom signatures and metabolite profiles. Some integrated models combining microbial biomarkers with faecal immunochemical testing, methylated DNA, clinical variables or metabolomics showed improved performance measures, but benefits were inconsistent. External validation was limited. Microbiome-immune studies linked microbial profiles with immune-related expression, immune-cell infiltration and treatment-response phenotypes without establishing improved screening accuracy.
Microbiome biomarkers show promise for colorectal neoplasia detection, but evidence does not establish universal multimodal superiority. Routine translation requires prospective validation, analytical standardisation, reproducibility, cost-effectiveness and demonstrated incremental utility.
CRD420261457983.CancerCare/Management -
Deep learning-based dose prediction for stereotactic prostate cancer radiotherapy with CyberKnife.6 days agoDeep learning-based (DL) approaches have gained interest in predicting dose distributions in radiotherapy of prostate cancer treated with volumetric modulated arc therapy and intensity-modulated radiation therapy. Meanwhile, research on predicting dose distributions in high-precision stereotactic radiotherapy treatments has remained relatively underrepresented.
We aimed to expand the previous studies by developing a DL-based framework for predicting dose distributions for robotic, stereotactic prostate cancer radiotherapy.
We harnessed a U-Net-based convolutional neural network for predicting clinically achievable dose distributions based on CT images, delineated structures, and distance information from the planning target volume. A dataset of 462 patients treated with CyberKnife (Accuray Inc.) utilizing an Iris collimator was divided into training (70%, n = 323), validation (10%, n = 46), and test (20%, n = 93) sets.
In the independent test set, the mean absolute error between the mean doses of predictions and clinical plans was 0.63 Gy for the rectum and 1.04 Gy for the bladder.
The proposed U-Net-based model demonstrated the ability to learn and reproduce characteristic dose distributions in CyberKnife prostate cancer radiotherapy. The model may provide patient-specific dose estimates for setting initial planning objectives to assist in automating treatment planning and improving inter-planner consistency.CancerCare/Management -
Acute variceal bleeding in a patient with phaeochromocytoma: the critical choice of vasoactive therapy.6 days agoA woman in her late 70s with known left-sided phaeochromocytoma presented with acute variceal bleeding secondary to suspected cirrhosis. Terlipressin, a standard first-line vasoactive agent, was contraindicated due to the risk of precipitating hypertensive crisis. Octreotide was successfully used as the preferred alternative, combined with careful alpha-blockade optimisation and endoscopic variceal ligation, achieving complete haemorrhage control without cardiovascular complications. This case highlights the need to recognise contraindications in patients with rare comorbidities and offers guidance on selecting vasoactive agents when standard treatments pose risks.CancerCare/Management
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Marjolin's ulcer developing in a post-traumatic scar: management with negative pressure wound therapy and split-thickness skin grafting.6 days agoMarjolin's ulcer is a rare but aggressive malignant transformation arising in chronic wounds or scars. We report the case of a man in his 60s who developed a large, non-healing ulcer at the site of a previous traumatic injury and reconstructive surgery performed three decades earlier. Clinical suspicion of malignancy led to wide local excision with sentinel lymph node biopsy, followed by staged reconstruction. Negative pressure wound therapy (NPWT) was used to optimise the wound bed, which was complicated by a local infection requiring targeted antibiotic therapy. Subsequent split-thickness skin grafting achieved complete graft take and satisfactory functional outcome. Histopathology confirmed well-differentiated squamous cell carcinoma with clear surgical margins. This case highlights the importance of early biopsy of chronic ulcers, multidisciplinary management and the role of NPWT in facilitating successful reconstruction after oncological resection.CancerCare/Management
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Implementing a medical opinion leader-led management model to promote timely treatment initiation among screen-positive patients with upper gastrointestinal cancer in rural China: a cluster randomised controlled trial protocol.6 days agoUpper gastrointestinal cancer (UGC), including oesophageal and gastric cancers, imposes a substantial health burden, particularly in China. Timely treatment after a positive screening result is critical, as treatment delays may contribute to disease progression and poorer outcomes. This study aims to evaluate the effectiveness of a management model led by medical opinion leaders (MOLs) in shortening the time to treatment initiation among screen-positive patients with UGC.
This multicentre, cluster randomised controlled trial will be conducted at 16 secondary hospitals in Shandong province, China. The participating hospitals will be randomly assigned to the intervention or control group in a 1:1 ratio. Screen-positive patients aged 18-80 years whose UGC diagnosis is confirmed by endoscopy and pathological examination will be recruited. At least 372 participants will be enrolled. The intervention group will receive an MOL-led management intervention comprising WeChat-based health education and face-to-face consultations. The primary outcome is the 30-day timely treatment rate, defined as the proportion of participants who initiate treatment within 30 days after pathological diagnosis. Secondary outcomes are the cumulative treatment initiation rates within 60, 90 and 180 days. Baseline information will be collected at enrolment, and treatment status will be assessed at 30, 60, 90 and 180 days.
The study protocol was reviewed and approved by the Science and Technology Ethics Committee of the School of Public Health, Shandong University (No. STEC-SPH-SDU-20250703). Written informed consent will be obtained from all participants. The study findings will be disseminated through publications in peer-reviewed journals, presentations at national and international academic conferences and communication with participating medical institutions and study participants.
ChiCTR2500109389.CancerCare/Management -
Rare Malignant Tumors of the Eyelid: A Comprehensive Clinicopathologic, Molecular, and Management Review of Adnexal and Neuroendocrine Neoplasms.6 days agoAlthough basal cell carcinoma, squamous cell carcinoma, and melanoma represent the most frequent malignant tumors of the eyelids, a diverse group of rarer adnexal and neuroendocrine neoplasms also demonstrates a strong predilection for this anatomic site. These tumors, including sebaceous carcinoma, Merkel cell carcinoma, primary cutaneous mucinous carcinoma, endocrine-mucin-producing eccrine gland carcinoma (EMPSGC), primary apocrine adenocarcinoma, and primary signet ring (histiocytoid) carcinoma, are characterized by unique epidemiologic patterns, biologic behavior, and histopathologic features. The specialized microanatomy of the eyelid-with a dense concentration of meibomian (sebaceous), apocrine (Moll), and eccrine glands-combined with thin tissue planes, rich lymphovascular networks, and chronic ultraviolet exposure, contributes to their development, patterns of local invasion, and potential for metastasis. Accurate diagnosis often requires careful clinicopathologic correlation, incorporating immunohistochemical and molecular studies to distinguish primary lesions from eyelid metastases and identify syndromic associations. This review provides a comprehensive synthesis of the epidemiology, pathogenesis, clinical presentation, detailed histopathology, genetic alterations, differential diagnosis, management, and prognosis of these rare malignant eyelid tumors, with emphasis on early recognition and multidisciplinary care.CancerCare/Management
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Nutritional status and survival outcomes in patients with cancer treated with immune checkpoint inhibitors: The ARON-MOUSEION-20 systematic review and meta-analysis.6 days agoThe prevalence of malnutrition in cancer patients is already high at diagnosis, reaching up to 40%, and tends to increase during treatment, affecting up to 75-80% of patients. To investigate the relationship between nutritional status and clinical outcomes, Progression-Free Survival (PFS) and Overall Survival (OS), in patients treated with Immune Checkpoint Inhibitors (ICIs).
The present systematic review and meta-analysis was registered in PROSPERO with id no. CRD420261356035. Embase, PubMed, Scopus and Web of Science databases were consulted by combining Boolean terms and keywords, specifically: "immune checkpoint inhibitors", "neoplasms", "nutrition assessment", "'overall survival" and "progression-free survival".
We pooled data from 19 studies reporting multivariable-adjusted hazard ratios (HR) for the association between Prognostic Nutritional Index (PNI) and PFS. The pooled analysis did not demonstrate a statistically significant association between PNI and PFS (HR = 0.85; 95% CI = [0.59; 1.23]; Z = -0.87; P = 0.385). The pooled estimate indicated no statistically significant effect of PNI on overall survival (OS), (HR = 1.23; 95% CI = [0.82; 1.84]; Z = 0.997; P = 0.319). While not statistically significant, the point estimate suggested a trend toward slightly poorer survival in patients with higher PNI values. For the association between PNI assessed by CONUT and PFS, the pooled analysis did not demonstrate a statistically significant association between PNI and PFS (HR = 1.01; 95% CI = [0.69; 1.48]; Z = 0.03; P = 0.972), and no clear trend toward improved or worse PFS was observed among patients with higher PNI values.
Despite the increasing attention to the role of nutrition in oncology, the available literature still included relatively few studies that comprehensively assessed nutritional status during the pre-treatment, treatment, and post-treatment phases. Longitudinal investigations describing changes in nutritional status throughout the therapeutic pathway remained poor. Adequate nutritional support could contribute to improving patients' overall health status, optimizing treatment tolerability, and potentially enhancing clinical outcomes associated with anticancer therapies.CancerCare/Management -
Clinical outcomes of endoscopic submucosal dissection for previously treated superficial non-ampullary duodenal epithelial tumors.6 days agoEndoscopic submucosal dissection (ESD) is increasingly used for superficial non-ampullary duodenal epithelial tumors (SNADETs). However, evidence from the United States (US) is limited. Moreover, the effectiveness and safety of ESD for previously treated SNADETs remain unclear. This study aimed to evaluate the outcomes of ESD for previously treated SNADETs.
This single-center retrospective cohort study included patients undergoing ESD for SNADETs at a US tertiary center between October 2018 and February 2025. Short-term outcomes (en bloc/R0 resection and adverse events) were compared between treatment-naïve and previously treated groups. Long-term outcomes were assessed by the presence of residual lesions after a single procedure.
A total of 45 ESDs in 37 patients were analyzed (29 treatment-naïve and 16 previously treated). En bloc (65.5% vs. 50.0%, p = 0.354) and R0 resection rates (48.3% vs. 37.5%, p = 0.544) did not differ between the groups, with comparable adverse events. Residual lesions after a single ESD tended to be more frequent in the previously treated group (6.9% vs. 31.3%, p = 0.079). Sensitivity analysis including all 47 endoscopic resections (ERs) supported this finding (6.9% vs. 33.3%, p = 0.041). In the primary analysis, all residual lesions were treated with repeat ER, and all patients achieved complete tumor eradication by ER alone (21-month median follow-up).
Despite a relatively high rate of residual lesions following ESD for previously treated SNADETs, ESD was feasible, and all patients ultimately achieved clinical success. ESD for previously treated SNADETs may represent a reasonable treatment option.CancerCare/Management