Oncology Reviews最新文献

Constitutional mismatch repair deficiency (CMMRD) is a rare pediatric cancer predisposition syndrome primarily characterised by central nervous system (CNS), gastro-intestinal (GI) tumours and hematological malignancies, along with NF1-like cutaneous features. The PMS2-related subtype (PMS2-CMMRD) is the most common molecular form of CMMRD, exhibiting variable severity and both early and late-onset clinical presentations. Although pathogenic and likely pathogenic PMS2 heterozygous variants are relatively frequent in healthy population, CMMRD incidence is generally rare in humans and genotype-phenotype correlations are still limited. To better characterise PMS2-CMMRD group, we collected clinical cases described in literature, using three alternative methods (VarChat, VarSome and LitVar2), starting from 102 pathogenic/likely pathogenic PMS2 variants (<50 bp) reported in ClinVar by clinical and research laboratories. PMS2-CMMRD cases were split into two distinct groups based on tumour onset age: early (diagnosis under 10 years) and later-onset (diagnosis after 10 years). Significant differences in tumour distribution were observed, with CNS tumours being most prevalent in the early-onset group, while GI tumours were more common in the later-onset group. Six PMS2 variants were associated with either early or later-onset CMMRD. Future validation through larger prospective cohort studies is necessary to confirm our findings and better understand the natural history of PMS2-CMMRD to inform clinical decision-making in PMS2-Lynch syndrome (PMS2-LS).

Gastric cancer (GC) remains a major global health challenge due to its high incidence and mortality. Emerging evidence underscores the critical role of RNA methylation, a key layer of epigenetic regulation, in GC pathogenesis. This review synthesizes current knowledge on various RNA modifications, including m⁶A, m⁵C, m¹A, and m⁷G, in GC. We critically evaluate the functions of their regulatory proteins (writers, erasers, readers) in modulating oncogenic signaling, metastasis, and tumor immunity. Among these, m⁶A and m⁵C modifications currently present the most compelling evidence, demonstrating significant correlations with patient prognosis and therapy resistance. Furthermore, we explore the translational potential of targeting the RNA methylation machinery, discussing both promising avenues and existing challenges in drug development. This comprehensive analysis aims to provide deeper mechanistic insights and highlight novel therapeutic opportunities for GC.

Introduction: Osteosarcoma is the most common malignant tumor of bone tissue in adolescents, and precise pathological diagnosis is the primary foundation for establishing the most effective treatment plan. The pathological evaluation of tumor necrosis after chemotherapy is crucial for assessing therapeutic efficacy in osteosarcoma patients. However, pathologists often face several challenges during the diagnosis and evaluation process.

Methods: To address these needs, we designed and developed a multi-model cascaded deep learning framework utilizing an advanced Vision Mamba (ViM) model as the core network architecture. The study employed one of the most comprehensive osteosarcoma datasets, sourced from: (1) real-world data from 68 osteosarcoma patients collected at Chongqing General Hospital, and (2) publicly available osteosarcoma assessment data from the University of Texas Southwestern/UT Dallas. Pathological images were annotated using the Palgo pathology image artificial intelligence self-training platform according to algorithm requirements. A triple verification mechanism of annotation, review, and archiving was implemented, and Palgo's integrated interactive algorithm correction mechanism was used to continuously refine the data annotation process.

Results and discussion: The model demonstrated Dice coefficient values of 0.83 or higher in tumor segmentation, osteosarcoma osteoid matrix segmentation, necrotic area segmentation, lung metastatic tumor segmentation, and lung metastatic osteoid matrix segmentation. For necrosis classification, overall osteosarcoma subtypes, and localized osteosarcoma subtypes, the area under the receiver operating characteristics curve (AUC), sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) all exceeded 90%. The proposed model exhibited excellent performance, indicating high potential for future clinical application in osteosarcoma patients. This framework shows promise for enhancing the precision and efficiency of pathological diagnosis and evaluation in osteosarcoma management.

Objective: To Compare the effects between thulium laser en bloc resection of bladder tumor (ERBT) and conventional transurethral resection of bladder tumor (TURBT) on catheter-related bladder discomfort (CRBD) in patients with bladder cancer.

Methods: Between January 2022 and December 2024, we retrospectively collected the demographic and clinical data for patients with bladder cancer. A total of 79 patients in the conventional TURBT group and 58 patients in the thulium laser ERBT group completed the study. Both demographic and outcome variables were recorded; and we compared the incidence and severity of CRBD at 1, 6 and 24 h postoperatively, score of postoperative pain at 1, 6 and 24 h and patient satisfaction at 24 h following the surgery.

Results: There were no significant differences in age, gender proportion, tumor multiplicity, tumor size and location, and duration of surgery between the two groups (P > 0.05). Pathological examination revealed that the ERBT had a higher rate of detrusor presence than TURBT (P = 0.04). The incidence and severity of postoperative CRBD were lower in ERBT group than TURBT group at 1 and 6h (P < 0.001), while there were no statistically significant difference between the two groups (P = 0.17) at 24 h. The VAS scores of postoperative pain were significantly lower in ERBT group than in TURBT group at 1 and 6 h postoperatively (P = 0.001 and P = 0.02, respectively). But at 24 h, there was no statistically significant difference (P = 0.08). As to postoperative patient satisfaction at 24 h, the result of ERBT group was significantly lower than TURBT group (P = 0.02). Additionally, the ERBT group had significantly less intraoperative blood loss and shorter postoperative irrigation duration (P = 0.001). No significant difference was found in the duration of indwelling catheter between the two groups (P = 0.07).

Conclusion: The results suggest that compared to conventional TURBT, thulium laser ERBT significantly reduce CRBD incidence and severity, lower postoperative pain, and improve postoperative patient satisfaction. However, as a single-center retrospective study, these findings require further validation by large-scale, prospective, multicenter trials.

Colorectal cancer (CRC) progresses through defined stages, from localized carcinoma in situ (Stage 0) to metastatic disease (Stage IV), with treatment strategies evolving from surgery in early stages to systemic therapies in advanced stages. Advances in biomarkers and genomic profiling have enabled personalized approaches, enhancing precision medicine. Nitric oxide (NO) plays a multifaceted role in CRC, acting as both a promoter and an inhibitor of cancer progression depending on its concentration, timing, and cellular context. At low concentrations, NO promotes angiogenesis, enabling tumor growth and metastasis. Conversely, high concentrations can exert anti-tumor effects, including the induction of cell death. Notably, its role in ferroptosis is biphasic: while high, exogenously delivered concentrations of NO can induce this iron-dependent cell death, lower, endogenously regulated levels can be protective by terminating lipid peroxidation. NO influences CRC by modulating the tumor microenvironment, mechanostress responses during metastasis, and signaling through extracellular vesicles (EVs), thereby aiding immune evasion. It also reprograms CRC cell metabolism, enhancing glucose utilization and mitochondrial activity to support growth in hypoxic conditions. The three nitric oxide synthases (NOS)-inducible NOS (iNOS), endothelial NOS (eNOS), and neuronal NOS (nNOS)-interact with hydrogen sulfide (H₂S) to regulate oxidative stress and tumor growth. Targeting NO-related processes, such as ferroptosis, metabolic adaptations, and immune modulation, offers promising therapeutic advances to improve CRC treatment outcomes. This review highlights the dual role of NO in CRC, with particular focus on its novel mechanisms in ferroptosis, metabolism, immune modulation, and tumor-microenvironment interactions.

The tumour-stroma ratio (TSR), which refers to the composition of stromal tissue and tumour epithelium of a malignant lesion, is gaining recognition as a promising biomarker in pathology. In 2018, recommendations for quantifying TSR in colorectal carcinoma were published, yet diverse quantification methods are still in use today. To assess the prognostic value of TSR, evaluate the impact of scoring variations, and explore efforts to automate TSR quantification, a scoping review was conducted. A total of 950 articles were identified through PubMed and Scopus, of which 76 met the inclusion criteria for this review. Of these, 56 employed manual scoring methods, while 20 utilised semi-automated or fully automated TSR quantification techniques. The TSR has been consistently identified as a strong prognostic indicator for disease-free survival. Its association with poor prognosis may be linked to its correlation with metastatic status, perineural invasion, and vascular invasion in stroma-high lesions. Variability in TSR scoring protocols was most evident in the selection of the region of interest and the type of histological specimen, both of which had a direct impact on final TSR scores. Moreover, significant inter-observer variability was observed in manual semi-quantitative TSR assessments, with Kappa scores ranging from 0.42 to 0.88. Automated TSR scoring pipelines have been proposed to standardise scoring protocols and reduce inter-observer variability. Deep learning models have demonstrated promising results, with pixel-wise and patch-wise accuracies exceeding 95%. Even though deep learning approaches have shown high performance, discrepancies remain, as evidenced by Kappa scores ranging from 0.239 to 0.472. In conclusion, the variation in TSR scoring protocols, along with a wide range of inter-observer variability, limits the broader clinical application of TSR. While automated TSR quantification methods show promise, they are still in the early stages, particularly in relation to region of interest selection and stratifying patients into risk categories. As these methods evolve, adjustments to TSR scoring cut-off values may be necessary to improve consistency. This scoping review highlights the prognostic significance of TSR in colorectal carcinoma while emphasizing the challenges posed by variability in scoring methods and the need for further advancements in automated quantification.

The colorectal cancer (CRC) screening landscape has rapidly evolved, introducing new technologies alongside established methods. The lack of head-to-head observational studies comparing these diverse options impairs clinicians' and patients' ability to make informed choices in CRC screening test selection. This manuscript aims to provide a comprehensive review of existing and emerging CRC screening technologies and develop a practical framework for informed decision-making. We conducted a systematic review of current literature on CRC screening methods, including colonoscopy, fecal immunochemical test (FIT), multi-target stool DNA test (mt-sDNA), the next-generation multi-target stool DNA test, multi-target stool RNA test (mt-sRNA), and blood-based tests. We summarized performance characteristics, adherence rates, follow-up colonoscopy rates, accessibility, and costs for each method. Our review revealed significant variations in test performance, patient adherence, and implementation factors across screening modalities. Blood-based tests showed promise in terms of patient acceptance but currently have lower sensitivity for early-stage cancers with a higher participant adherence when screening navigation is provided. Our review led to the development of a comprehensive framework for evaluating CRC screening options, addressing the critical need for informed decision-making in this area. The framework encompasses five key dimensions: test performance (sensitivity and specificity for CRC and precancerous lesions), patient considerations (invasiveness, preparation, and location preferences), adherence and follow-up (real-world rates and diagnostic colonoscopy completion rates), accessibility and cost (insurance coverage, out-of-pocket expenses, and system integration), and screening interval (recommended frequency and long-term impact). By synthesizing data, the framework enables healthcare providers and patients to navigate the complex landscape of screening options, facilitating personalized recommendations tailored to individual risk factors, preferences, and healthcare system constraints. Future research should validate this framework in diverse clinical settings and update it as new technologies emerge, ensuring continued improvement in CRC screening participation, effectiveness, and outcomes.

Background and aims: Liquid biopsy offers a minimally invasive tool to detect actionable mutations, monitor minimal residual disease (MRD), and guide therapy in gastrointestinal (GI) cancers. We critically review the clinical utility of circulating tumor DNA (ctDNA), circulating tumor cells (CTCs), and small extracellular vesicles (sEVs) across GI malignancies and propose a framework for their integration into clinical practice.

Methods: We synthesized evidence from over 200 studies, including prospective trials and translational research, to assess diagnostic accuracy, prognostic value, and clinical actionability of each biomarker type in esophageal, gastric, colorectal, pancreatic, hepatocellular, and biliary cancers.

Results: ctDNA has shown strong potential for MRD detection and treatment monitoring, particularly in colorectal and pancreatic cancer. CTCs offer insights into metastatic risk and therapeutic resistance, while sEVs provide molecular cargo relevant to immunomodulation and disease progression. Emerging microfluidics and AI-driven multi-omics approaches may overcome current limitations.

Conclusion: The integration of liquid biopsy technologies into GI oncology holds promise for early detection and precision therapy. We propose a five-phase clinical roadmap and outine the key research gaps that need to be addressed before widespread implementation in routine care.