Upper tract urothelial carcinoma (UTUC) presents distinct diagnostic and therapeutic challenges because of its rarity, anatomic constraints, frequent understaging at biopsy, and risk of systemic recurrence after radical nephroureterectomy. Current perioperative management is driven primarily by clinicopathologic risk factors, which may be insufficient to identify occult molecular residual disease (MRD) or to determine which patients are most likely to benefit from systemic therapy. This narrative review summarizes available evidence on circulating tumor DNA (ctDNA) in UTUC and related urothelial carcinoma settings, classifies the level of evidence supporting each application, and proposes a research framework for prospective evaluation. The strongest UTUC-specific evidence supports ctDNA as a prognostic biomarker associated with recurrence risk, whereas predictive validity for selecting chemotherapy, immune checkpoint inhibitors, antibody-drug conjugates, targeted therapy, or surveillance intensity remains unproven. Evidence from muscle-invasive bladder cancer, including ctDNA-correlative and ctDNA-guided perioperative trials, provides biologic rationale but should not be directly translated into routine UTUC care without disease-specific validation. We outline key implementation questions, including target population, assay selection, timing, false-positive and false-negative results, lead-time bias, and integration of plasma ctDNA with utDNA. Prospective UTUC-specific trials are needed to determine whether ctDNA-guided perioperative strategies improve survival, reduce unnecessary toxicity, and are cost-effective.

Background: Cervical esophagogastric anastomosis using a gastric conduit is commonly performed after esophagectomy for esophageal cancer, but anastomotic leakage remains a major postoperative complication. Totally mechanical Collard (TMC) anastomosis provides favorable stricture outcomes; however, leakage rates remain variable. The clinical benefit of staple-line oversewing in TMC anastomosis has not been fully clarified. Methods: This retrospective cohort study included consecutive patients who underwent esophagectomy with TMC cervical anastomosis between January 2017 and December 2024. Patients were divided into oversewing and non-oversewing groups according to whether staple-line oversewing was performed. The primary endpoint was anastomotic leakage. Secondary endpoints included leakage severity, timing of leakage onset, healing duration, anastomotic stricture, and postoperative complications. Multivariable logistic regression analysis was used to identify independent risk factors for leakage. Results: A total of 803 patients were included (oversewing: n = 313; non-oversewing: n = 490). Baseline characteristics were well balanced between the two groups. The incidence of anastomotic leakage was significantly lower in the oversewing group than in the non-oversewing group (4.4% vs. 8.1%, p = 0.043). Leakage severity was also reduced, with Grade I leakage occurring more frequently in the oversewing group (78.5% vs. 30%, p = 0.004). Leakage occurred later in the oversewing group (12.7 ± 7.6 vs. 8.9 ± 4.2 days, p = 0.01), whereas healing duration was comparable between groups. The incidence of anastomotic stricture did not differ significantly between the two groups (3.5% vs. 5.3%, p = 0.3). Multivariable analysis identified body mass index ≥25 kg/m2 (OR 2.37, 95% CI 1.08–4.93, p = 0.03) and the absence of staple-line oversewing (OR 2.15, 95% CI 1.03–4.82, p = 0.04) as independent risk factors for leakage. Conclusions: Staple-line oversewing of TMC cervical anastomosis was associated with a reduced incidence and milder severity of anastomotic leakage without increasing anastomotic stricture. This simple and reproducible technique may improve anastomotic stability after esophagectomy for esophageal cancer.

Following publication of this article [...].

Organ-preservation strategies are increasingly being incorporated into rectal cancer management, but the role of HDR endorectal/endoluminal brachytherapy boost remains less well defined than that of broader non-operative treatment pathways. Existing literature is frequently mixed with contact X-ray brachytherapy series, neoadjuvant protocols with planned surgery, or heterogeneous watch-and-wait cohorts, limiting the interpretation of this specific strategy. We performed a PROSPERO-registered systematic review and meta-analysis of studies evaluating definitive-intent external beam radiotherapy (EBRT), with or without chemotherapy, followed by HDR endorectal/endoluminal brachytherapy boost in histologically confirmed rectal adenocarcinoma managed without planned surgery. Pooled analyses were performed for clinical complete response (cCR) and late grade ≥3 gastrointestinal (GI) toxicity. Regrowth/local failure outcomes were synthesized descriptively because of heterogeneity in endpoint definitions, denominator selection, and follow-up structure. Six studies were included in the quantitative evidence base, with one additional small feasibility report summarized narratively. The pooled cCR proportion was 69.2% (95% confidence interval [CI], 43.7-86.6). The pooled proportion of late grade ≥3 GI toxicity was 18.1% (95% CI, 10.9-28.6). Reported regrowth/local failure outcomes were not suitable for formal pooling because of inconsistent definitions, differing denominator structures, and non-uniform follow-up frameworks across studies. Current evidence suggests that EBRT plus HDR endorectal/endoluminal brachytherapy boost may represent a selective organ-preservation strategy for carefully chosen patients with rectal adenocarcinoma, particularly where surgery is not feasible or not desired. Its broader clinical use remains limited not only by the small size of the evidence base, but also by fragmented endpoint definitions, inconsistent denominator reporting, and insufficiently standardized durable local-control outcomes. These findings support cautious interpretation of the current evidence and highlight priorities for future prospective studies in rectal cancer management.

Background: Accurate colposcopy assessment is essential for detection of cervical precancerous lesions. However, the diagnostic performance depends heavily on the examiner's experience and subjective interpretation. Recent advances in artificial intelligence offer new opportunities for automated image analysis. In particular, deep learning models have shown promise for colposcopy image analysis intended for precancer screening. However, their limited interpretability restricts their translational value in clinical gynecology. This study leverages a custom dataset of expert-annotated digital colposcopic images to quantify the diagnostic strengths of these architectures. Methods: A comparative analysis was provided of the well-established convolutional neural network YOLOv11 and the modern transformer-based RF-DETR architecture, both of which were trained for the segmentation of 10 distinct classes. Target objects included anatomical structures, medical instruments and colposcopic findings. Results: Our results demonstrate that the YOLO architecture provides better performance for anatomical structures, whereas the RF-DERT reaches higher scores for colposcopy findings. These findings demonstrate transformer architecture superiority in more nuanced segmentation of clinically relevant findings, providing an interesting framework for computer-aided decision support systems in colposcopy. Conclusions: Both YOLOv11 and RF-DETR enable effective segmentation of colposcopic images, with performance dependent on class size and characteristics. Best results were achieved for large anatomical structures, while small and underrepresented findings remained challenging due to class imbalance. YOLO offers greater stability and efficiency, whereas RF-DETR performs better on more complex cases. Limitations include data imbalance, variable image quality, and annotation inconsistencies; future work should address these issues to improve generalization.

Background: Given the higher incidence of adrenocortical carcinoma in peri-menopausal women, this study investigates the associations between sex, age, and ACC prognosis. Methods: We analyzed the National Cancer Database (NCDB) for adult patients with ACC (n = 2384) from 2004 to 2022. Overall survival (OS) was the primary endpoint. Patients were stratified by sex and menopausal status (pre- and post-menopausal age of ≤45 and ≥55, respectively). Data from The Cancer Genome Atlas (TCGA) cohort (n = 92) were analyzed to examine clinical characteristics, genetics, transcriptomics, and methylation profiles of primary ACC samples by age group. Results: The analysis of the NCDB cohort revealed that younger men and pre-menopausal women had significantly longer OS compared to older groups. However, age was the only independent variable associated with OS. Using 50 years as the optimal age cutoff, we found no differences in clinical characteristics, rates of pathogenic driver mutations, methylation or gene expression profiles, or enriched molecular pathways in the TCGA ACC cohort by age group. Conclusions: While age ≥50 years is an independent factor associated with shorter OS in ACC, no differences in clinical characteristics or multi-omic profiles were observed by age. These findings suggest that age-related prognosis may be influenced by other factors such as microenvironmental changes or epigenetics.

Pancreatic cancer is highly metastatic, and metastasis is the main cause of cancer-related deaths. Therefore, finding methods to inhibit pancreatic cancer metastasis has important clinical value. N-dihydrogalactochitosan (GC) is an immunostimulant that can enhance the anti-tumor immune response to inhibit metastasis in combination with photothermal therapy. Here, we found that GC can inhibit the migration of pancreatic cancer cells through interactions with caveolin-1 (Cav-1). The fluorescence of GC-FITC on the cell surface overlaps with Cav-1-Red, is enhanced by adCav-1, and is weakened by siCav-1, indicating that the localization of GC depends on Cav-1. GC inhibits the migration of malignant cells by blocking the signal transduction of Cav-1 and its downstream molecules. In an orthotopic pancreatic tumor model, GC can inhibit tumor metastasis in tumor-bearing mice. These results demonstrate GC's capacity to act as a partner in pancreatic cancer therapy and indicate future directions for metastatic cancer therapy.

Surgical resection remains the standard treatment for large brain metastases (LBMs), but many patients are not surgical candidates due to poor performance status or uncontrolled systemic disease. Gamma Knife-based hypofractionated stereotactic radiotherapy (GKRS) has emerged as a potential alternative; however, its clinical role in this population remains insufficiently defined. We evaluated whether a uniform daily 5-fraction GKRS provides effective and safe local treatment for surgery-ineligible LBMs. We retrospectively analyzed 100 patients with LBMs (>14 cm3) who underwent primary hypofractionated GKRS using a uniform daily 5-fraction schedule. Forty-six patients were male; the median age was 60 years. The median Karnofsky Performance Status (KPS) was 70 (60-100); a total of 47 patients (47%) had pre-GKRS neurological deficits. The most common primary sites were lung (41), breast (24), and kidney (14). The median tumor volume was 22.0 cm3 (14-70 cm3), and the marginal dose was 35.2 Gy (50% isodose line) in 5 fractions. The primary endpoints included local tumor control (LTC), intracranial progression-free survival (PFS), and overall survival (OS). Radiation necrosis (RN) was assessed as a key safety outcome. At a median follow-up of 18 months, the overall LTC rate was 74%, with 1-, 2-, and 3-year rates of 73%, 65%, and 60%, respectively. Median PFS and OS were 7.5 and 16.3 months. Higher pre-treatment KPS and absence of neurological deficits were independently associated with improved OS (p = 0.003 and 0.025, respectively). RN occurred in 16% of patients, with 9% developing symptoms; all symptomatic cases were effectively managed with corticosteroids or bevacizumab. Most tumors demonstrated substantial volumetric reduction, with a median decrease of 80% and 30% achieving near-complete response (>95%). A uniform daily 5-fraction hypofractionated GKRS provides effective local control with acceptable toxicity in patients with LBMs. These findings support its role as a feasible local treatment option in selected patients who are not candidates for surgery. Integration with systemic therapies and prospective validation are warranted to refine patient selection and optimize outcomes.

Background/Objectives: Pediatric cancers are disorders of dysregulated development driven largely by genomic and epigenetic alterations. Precisely modeling these developmental differences is essential for understanding the unique biology of childhood cancers. Patient-derived organoids (PDOs) offer a powerful in vitro platform that recapitulates tumor heterogeneity, plasticity, microenvironment (including immune cells) and disease-relevant features. Methods: Here, we describe a step-by-step protocol for the establishment of PDOs from cells derived from pediatric brain tumors and extracranial solid tumor biopsies and bone marrow aspirates, including tumor processing, organoid culture/subculture, and cryopreservation. Results: Furthermore, we present the use of PDOs for further experimental analysis such as fluorescence imaging, Western blotting, flow cytometry, and immunohistochemistry (IHC) to investigate the underlying pathophysiology of tumorigenesis. Conclusions: Expanding the application of organoids to childhood malignancies holds exceptional promise for elucidating pediatric tumor biology and advancing therapeutic strategies, representing the long-overdue convergence of technology and clinical need.

GBC is an aggressive biliary tract malignancy with limited survival. Although actionable genomic alterations (AGAs) are increasingly recognized in GBC, their prognostic association in real-world practice remains incompletely defined because genomic status is often confounded by stage at presentation and treatment selection. We evaluated the association between documented AGA status and overall survival (OS) using a tiered matching strategy to account for major clinical confounders. Using the TriNetX Global Collaborative Network, we identified adults with GBC and stratified them into patients with at least one documented AGA in KRAS, TP53, ERBB2, IDH1, FGFR1, PIK3CA, or ARID1A, and a comparison cohort with no documented AGA (representing a real-world population of untested and wild-type patients). Two 1:1 propensity score-matched models were constructed: Model 1 matched for age, sex, and race/ethnicity; Model 2 additionally matched for metastatic disease, surgical resection, and chemotherapy history. Outcomes were evaluated using risk analysis and Kaplan-Meier survival methods. A marked disparity in genomic documentation was observed before matching, with unknown race recorded in 51.0% of the comparison cohort versus 3.7% of the documented AGA cohort. In the demographic-matched analysis (Model 1), the documented AGA cohort had higher mortality (52.8% vs. 42.5%, p < 0.001) and shorter median OS (684 vs. 948 days; HR 1.23, p = 0.006). In the primary stage- and treatment-matched analysis (Model 2), mortality remained higher in the documented AGA cohort (56.2% vs. 43.0%), corresponding to an absolute risk difference of 13.2% (p < 0.001). Median OS was numerically shorter in the documented AGA cohort (750 vs. 784 days), although the proportional hazards assumption was violated, supporting interpretation based primarily on absolute risk measures. In exploratory subgroup analyses, KRAS alterations were associated with worse survival, whereas the TP53 subgroup was limited by small sample size. In this real-world matched analysis, the presence of documented AGAs in GBC were associated with higher mortality even after matching for major demographic, stage-related, and treatment-related variables. These findings support the prognostic relevance of genomic status in GBC and underscore the need to address disparities in access to genomic documentation and testing.