• Association of Neuronal Autoantibodies with Overall Survival in Patients with Gastric Cancer.
    3 weeks ago
    Neuronal autoantibodies have been identified in immune-mediated encephalitis, most of which are related to paraneoplastic neurologic syndromes (PNS). We detected neuronal autoantibodies in patients with gastric cancer without PNS and illustrated their correlation with clinical prognosis. All serum samples were tested by the mouse brain tissue-based assay (TBA) using immunofluorescence for screening neuronal autoantibodies. Known PNS-related neuronal autoantibodies were detected by cell-based assay. A single-center cohort has been started in Nanfang Hospital. The T-cell status of the tumor microenvironment was assessed. Single-cell sequencing was performed with limited tumor samples. Patients were grouped into TBA-positive (n = 144) and TBA-negative (n = 179) groups by the TBA status. Further screening of TBA+ specimens using the cell-based assay method revealed known PNS-related autoantibodies in 13.2% (19/144) of cases. Additionally, TBA-positive patients with gastric cancer exhibited lower CD8+ T-cell infiltration in the tumor tissue. The survival analysis show that neuronal autoantibodies in patients (TBA-positive) were associated with shorter overall survival (OS; P = 0.014). In the multivariate survival analysis, TBA positivity was still associated with shortened OS after adjusting the major covariates (HR = 2.28; 95% confidence interval, 1.31-3.97; P = 0.004). Meanwhile, single-cell sequencing indicates that cell junction assembly and synapse organization may play important roles in biological process. In this cohort study, neuronal autoantibodies were highly prevalent among patients with gastric cancer and were associated with shortened OS and features of immunosuppression within the tumor microenvironment, suggesting a candidate for exploring therapeutic relevance, with further mechanistic studies needed for validation.

    Neuronal autoantibodies are prevalent in patients with gastric cancer, and patients without neurologic symptoms are linked to shorter survival and immunosuppression. These results provide a new direction for prognostic biomarkers and targeted therapy exploration.
    Cancer
    Care/Management
  • What is in the Neuromuscular Junction Literature?
    3 weeks ago
    The review begins with epidemiology studies that show an increased incidence of later onset myasthenia gravis (MG) and higher short-term mortality rates, especially in females, compared with the general population in Denmark. In the United States, a study showed increased mortality especially in older patients, and there was racial disparity. In France, a study showed higher mortality with male gender, older age, and higher comorbidities. Economic burden is addressed in another article. Regarding clinical features, light sensitivity in MG is discussed along with differentiating thyroid eye disease symptoms and signs from those of ocular MG. MG-specific measures are highlighted with consensus recommendations for their use. Several articles contain data regarding diagnostic laboratory assays and test sensitivity and specificity among other measures. The role of thymectomy in older patients with MG is considered. The medical treatment section addresses corticosteroid regimens, intravenous immunoglobulin as maintenance therapy, a phase 3 study of the recently approved neonatal Fc receptor (FcRN) blocker nipocalimab, use of complement inhibitors and FcRN blockers in general, regimens for efgartigimod, and positive studies on the interleukin-16 receptor monoclonal antibody (Ab) satralizumab and the CD19 B-cell-depleting monoclonal Ab inebilizumab.
    Cancer
    Care/Management
  • Eco-Friendly Influence of Gamma-Irradiation on (Acrylamide/Carbon Disulfide) as a Potential Anticancer Agent Induced Apoptotic Cell Death in Pancreatic Carcinoma Cell Line.
    3 weeks ago
    Polyacrylamide (PAAm) was made from acrylamide (AAm), polycarbondisulfide (PCS2) from carbon disulfide (CS2), and their copolymer P(AAm/CS2) at a fixed equal ratio using gamma irradiation. The polymers were characterized using Fourier-transform infrared spectroscopy (FTIR), CHNS/O elemental microanalysis, x-ray diffraction (XRD), scanning electron microscopy (SEM), thermogravimetric analysis (TGA), and gel permeation chromatography (GPC). The results demonstrated the effective synthesis of PAAm, PCS2, and P(AAm/CS2), with the copolymer having an average molecular weight of 187,673 Da. The produced polymers were tested for their cytotoxic and pro-apoptotic effects on human pancreatic carcinoma (PANC-1) cells in light of the urgent need for efficient treatments against this aggressive cancer with a poor prognosis. With half-maximal inhibitory concentrations (IC50) of > 500 μg/mL for PAAm, 156 μg/mL for PCS2, and 99.2 μg/mL for P(AAm/CS2), the copolymer demonstrated superior cytotoxic potential. Flow cytometric analysis provided additional support for these findings. Treatment with 125 μg/mL of PAAm resulted in 4.8% early and 13.3% late apoptosis, whereas PCS2 at the same concentration caused 30.8% early and 18.5% late apoptosis. Notably, 125 μg/mL of P(AAm/CS2) caused a significant increase in apoptosis, resulting in 39.3% of early apoptotic cell populations and 28.6% of late apoptotic cell populations. According to gene expression analysis, P53, Caspase-3, Caspase-7, and Bax genes were upregulated and Bcl-2 was downregulated after treatment with 125 μg/mL of PCS2 or P(AAm/CS2). However, PAAm had no significant impact on these apoptotic markers. In comparison to untreated PANC-1 cells, P(AAm/CS2) showed the strongest response, resulting in significant (p ≤ 0.05) increases in P53 (4.4-fold), Caspase-3 (2.9-fold), Caspase-7 (8.3-fold), and Bax (5.5-fold) expression levels, while Bcl-2 expression was significantly reduced (0.09-fold). In conclusion, the produced copolymer P(AAm/CS2) exhibits a strong anticancer effect on pancreatic carcinoma cells by inducing apoptosis, thereby supporting its potential as a promising polymer-based therapeutic agent.
    Cancer
    Care/Management
  • Case Report: Novel likely pathogenic MEN1 mosaic mutation in the family with MEN-1 syndrome.
    3 weeks ago
    Multiple endocrine neoplasia type 1 (MEN-1; OMIM 131100) is a rare, autosomal dominant syndrome caused by heterozygous inactivating mutations in the MEN1 tumor suppressor gene (11q13; OMIM 613733). MEN-1 is characterized by polyglandular pathology, which typically involves the parathyroid glands (90%), pancreas (30-80%) and anterior pituitary (15-50%). To date, over 1,600 pathogenic MEN1 variants have been documented, including nonsense, frameshift, and splice-site mutations, as well as rare large deletions. While germline mutation detection rates reach 70-90% in clinically diagnosed probands, approximately 10-30% of phenotypically confirmed MEN-1 families test negative by conventional sequencing, suggesting possible regulatory region defects, deep intronic mutations, or mosaic variants. In cases where MEN1 germline testing is negative despite a clinical MEN-1 phenotype, somatic mosaicism should be considered. We investigated a familial cohort presenting with primary hyperparathyroidism, multifocal pancreatic and pituitary neuroendocrine neoplasms - a triad strongly suggestive of MEN-1. Using a multi-tissue sequencing approach, we analyzed DNA extracted from peripheral blood leukocytes and parathyroid adenomas tissue via both Sanger sequencing and next-generation sequencing (NGS) with high coverage. While conventional Sanger analysis failed to detect a mutation, targeted NGS revealed a novel, likely pathogenic MEN1 variant present at low allele frequency (5-15%), consistent with postzygotic mosaicism. The variant was classified as pathogenic per ACMG/AMP guidelines and correlated with disease manifestations in affected tissues. These findings demonstrate that high-coverage NGS of multiple tissues is critical for identifying low-level mosaic MEN1 mutations missed by standard testing. Alternative screening methods are required for patients with strong clinical indications of MEN-1 and/or a family history, but negative germline test results, one such method is NGS with high coverage.
    Cancer
    Care/Management
  • A case-based review of urachal carcinoma with mixed small cell neuroendocrine and adenocarcinoma components, with one new case report and analysis of nine published cases.
    3 weeks ago
    Urachal carcinoma (UrC) is an uncommon malignant neoplasm arising from urachal remnants and represents only 0.01%-0.7% of bladder cancers. Adenocarcinoma-usually of the intestinal type-accounts for over 80% of cases, whereas neuroendocrine carcinoma (NEC) is exceedingly rare. Fewer than ten cases of urachal NEC have been documented in the English-language literature, most diagnosed at advanced stages with poor outcomes. We report an additional case and review published data to enhance clinical recognition and management of this ultra-rare tumor.

    A 43-year-old woman presented to Shandong Provincial Hospital, Shandong First Medical University, after a urachal midline mass was incidentally detected on routine health examination. Preoperative tests showed a CEA level of 7.28 ng/mL. CTU revealed a 3.9 × 2.7 × 2.4 cm cystic-solid lesion at the anterior bladder wall, suspicious for urachal malignancy. Cystoscopic biopsy confirmed small-cell NEC. The patient underwent laparoscopic urachal resection with umbilicus preservation, extended partial cystectomy, and bilateral pelvic lymphadenectomy. Postoperative pathology showed a mixed urachal carcinoma composed of ~80% small-cell NEC and ~20% adenocarcinoma, forming a 4.5 × 3 × 1.5 cm cystic-solid mass. Margins and lymph nodes were negative. Immunohistochemical analysis showed a high Ki-67 labeling index (80%) and positive staining for synaptophysin (Syn), chromogranin A (CgA), insulinoma-associated protein 1 (INSM1), cytokeratin 20 (CK20), and mutant-pattern p53. Retinoblastoma protein (RB) and GATA-3 were negative. The patient received four cycles of adjuvant etoposide-cisplatin (EP) chemotherapy. Surveillance with tumor markers and whole-abdominal CT every three months showed no evidence of recurrence at the 8-month follow-up.

    Urachal NEC with mixed small-cell and adenocarcinoma components is an exceptionally rare and highly aggressive malignancy lacking standardized diagnostic or therapeutic guidelines. Complete surgical excision with negative margins remains the mainstay of treatment, while adjuvant regimens are typically adapted from small-cell carcinoma protocols of the lung or urinary tract. We report a case managed with umbilicus-sparing urachectomy and extended partial cystectomy followed by EP chemotherapy, together with a review of nine previously published cases. These findings provide literature-based evidence to guide individualized management and inform future multidisciplinary research.
    Cancer
    Care/Management
  • Biological poisons targeting the pituitary gland: insights across the five kingdoms.
    3 weeks ago
    The pituitary gland, as a central regulator of endocrine function, may be affected by a wide range of biologically derived harmful substances present in nature. While most available literature focuses on neoplasms, trauma or autoimmune disorders, the potential impact of natural toxins and poisons on pituitary function remains underexplored. This narrative review addresses the effects of acute or chronic exposure to harmful agents originating from the five biological kingdoms-Animalia, Plantae, Fungi, Monera, and Protista-on the hypothalamic-pituitary axis. Drawing on clinical reports, experimental data, and physiological insights, we describe how various biological substances may alter hormonal regulation, leading to temporary or persistent dysfunction. Importantly, this review does not cover direct infectious involvement of the pituitary, such as pituitary abscess, but focuses instead on biologically active compounds produced by living organisms. The review highlights a dispersed body of knowledge with implications not only for endocrinologists and pituitary specialists, but also for clinicians in toxicology, emergency medicine, infectious diseases, and global health. Recognizing the pituitary as a vulnerable target in diverse environmental and ecological contexts may aid in the early diagnosis and management of otherwise unexpected endocrine disorders.
    Cancer
    Care/Management
    Policy
  • Validation of WHO 2017 Classification and Identification of Prognostic Factors in Patients with Pancreatic Neuroendocrine Neoplasms: A Real-World Experience in Taiwan.
    3 weeks ago
    Background: Pancreatic neuroendocrine tumors (PanNETs) are rare neoplasms with an increasing incidence. This study aims to validate the clinical relevance of the WHO 2017 classification system in the Taiwanese population and identify independent prognostic factors for patients with PanNETs. Materials and methods: We conducted a retrospective analysis of 176 patients with PanNETs from the Chang Gung Medical Hospital at Linkou in Taiwan, spanning the years 2009 to 2022. Pathology reports were reassessed according to the WHO 2017 classification. Clinical characteristics, treatment patterns, and survival outcomes were documented, with subgroup analyses to compare grade 3 (G3) neuroendocrine tumors and neuroendocrine carcinomas (NEC). Results: The overall 5-year survival rate was 58.7%, with median survival of 107.6 months. Survival rates showed clear stratification across WHO 2017 classifications: G1 (83.1%, median 141.0 months), G2 (55.0%, median 105.2 months), G3 (14.6%, median 21.5 months), and NEC (9.4%, median 19.6 months). Multivariate analysis identified five independent prognostic factors: age over 60 years (HR 1.70), tumor size >2cm (HR 1.893), lymph node involvement (HR 1.801), distant metastasis (HR 3.042), and NEC classification (HR 2.382). NEC demonstrated significantly higher lymph node involvement (81% vs 48%, p=0.026), higher Ki-67 index (69 vs 43.8, p<0.001), and higher rates of metastases compared with G3 NET. Conclusions: Our findings validate the prognostic utility of the WHO 2017 classification, particularly in differentiating NET G3 from NEC. This refined classification system, combined with identified prognostic factors, provides valuable guidance for clinical decision-making and treatment selection in patients with PanNETs.
    Cancer
    Care/Management
  • Evidence-based modelling and taxonomy of hospital-based cancer care coordination nurses' roles and boundaries: an iterative multiphase convergent mixed study.
    3 weeks ago
    To develop an evidence-based reference model defining the exact boundaries of the missions and activities of the hospital-based cancer care coordination nurses, to clarify their roles and standardise practices for impact evaluation.

    Design: A multiphase, mixed-methods modelling study was conducted. First, we collected qualitative and quantitative data on cancer coordination nursing practices through a multicentre cross-sectional study. Mixed data were mapped to a previously developed reference framework to derive the reference model. Setting: 10 French hospitals, varying in size and status, over 20 months (2018-2019). Participants: Thirty-six hospital-based cancer coordination nurses, 162 patients, 142 caregivers and 352 healthcare professionals from both hospital and primary care settings. Main outcome measures: Qualitative data on roles, activities and experiences were collected through observations, interviews and focus groups. Quantitative data on role perceptions and organisational context were gathered using standardised questionnaires assessing support, commitment, role conflict, patient quality of life, precariousness and caregiver burden.

    We identified core missions such as active listening, clinical needs assessment and internal coordination, but also differences leading to a nurse typology into three groups: 'complex pathway coordinators', 'treatment specialists' and 'polyvalent nurses'. Only 'complex pathway coordinators', fully aligned with the reference framework, performed complete care coordination and correspond to the reference model.

    The modelling provides a foundation for standardising cancer care coordination practices, improving training and establishing a standard intervention for evaluating cancer care navigation which the authors are still calling for.

    NCT03350776.
    Cancer
    Care/Management
  • Extragonadal yolk sac tumor of the ureter with neuroendocrine differentiation: A case report.
    3 weeks ago
    Extragonadal germ cell tumors in the urinary tract are exceptionally rare, with only a small number of cases documented in the literature. Although these neoplasms exhibit considerable histologic heterogeneity, neuroendocrine differentiation within these tumor types have only been reported in isolated number of instances. Here, we report a unique case of a ureteral extragonadal germ cell tumor demonstrating yolk sac tumor-like histologic features with concomitant neuroendocrine differentiation with remarkably rapid progression. Given the aggressive clinical behavior observed, immediate surgical resection was imperative. Furthermore, in cases with neuroendocrine differentiation, adjuvant platinum-based chemotherapy should be strongly considered to optimize postoperative outcomes.
    Cancer
    Care/Management
  • Yttrium-90 radioembolization for treatment of anaplastic meningioma liver metastases.
    3 weeks ago
    Meningiomas are the most common primary intracranial neoplasm. The WHO classification, focusing on histomorphologic and molecular features, distinguishes WHO grade -1, -2, and -3 tumors. WHO-3 meningiomas are exceedingly rare, comprising 1%-3% of cases, and have the propensity to metastasize to the lungs, followed by bone and liver. Due to their rare occurence, there are no consensus guidelines on metastatic meningioma management. External beam radiation therapy is often the treatment of choice, therefore transarterial radioembolization is a reasonable option for meningioma metastases to the liver. In this case report, we describe the clinical course and outcomes of a patient with WHO-3 meningioma and extensive hepatic metastases which were initially detected during workup for possible renal transplant, confirmed with DOTATATE PET/CT, and successfully treated with Yttrium-90 radioembolization and ablation.
    Cancer
    Care/Management