The MITF E318K variant has been associated with melanoma risk, while risk associated with other variants or of other cancers remains uncertain. We performed a systematic review with meta-analysis of 11 retrospective case-control studies to evaluate cancer risks associated with germline MITF variants. Across 8,606 melanoma patients and 17,953 controls, the E318K variant was detected in 2.1% and 0.8% of individuals, respectively, corresponding to a significantly increased melanoma risk (OR 2.55, 95% CI 1.90-3.43). The association was stronger in patients with multiple primary melanomas, with carrier frequencies up to 2.6% compared to 1.0% in single melanoma cases and ORs reaching 4.45 in individual studies. Phenotypic analyses showed enrichment of high nevus burden (> 200 nevi), with ORs up to 12.4 in multiple melanoma cohorts. No consistent association with age at onset or pigmentary traits was observed. Evidence for non-melanoma cancers was limited and heterogeneous: a single study reported increased renal cancer risk (OR 7.64), whereas larger cohorts failed to replicate this finding; an association with pheochromocytoma/paraganglioma was observed (OR 3.19) but lacks confirmation. No other MITF variants demonstrated significant cancer risk. These findings support MITF E318K as a moderate-penetrance melanoma susceptibility allele, particularly associated with multiple primary melanomas.

This cross-sectional study examined whether parental distress is associated with treatment adherence in children with neuroblastoma and identified specific parental psychological factors as independent risk markers for non-adherence.

Three hundred fifty families from four tertiary medical centers in China were enrolled. Parents completed the Parenting Stress Index-Short Form (PSI-SF), Medication Adherence Rating Scale (MARS-5), Beck Depression Inventory-II (BDI-II), and Family Assessment Device-General Functioning (FAD-GF). Path analysis examined associations between parental distress, family functioning, disease risk, and treatment adherence. Common method bias was assessed using Harman's single-factor test. Sensitivity analyses examined MARS-5 cutoff robustness using median split and MARS-5 < 18 thresholds.

Parental distress was significantly associated with lower treatment adherence (beta = -0.35, p = 0.002). Family functioning was statistically consistent with partial mediation (indirect beta = -0.12, p = 0.003), though causal interpretation is precluded by the cross-sectional design. Paternal depressive symptoms emerged as the strongest independent risk marker for non-adherence (OR = 2.2, 95% CI 1.18-4.09, p = 0.013). Mothers reported significantly higher parenting stress than fathers (Bonferroni-corrected p < 0.008; Cohen's d = 0.37-0.62). Families with poor functioning were 2.8 times more likely to exhibit suboptimal adherence. Harman's single-factor test yielded 8 factors with eigenvalues > 1.0, with the first factor explaining 28.4% of total variance-below the 40% threshold indicative of substantial common method bias. Sensitivity analyses using alternative MARS-5 cutoffs confirmed the robustness of paternal depression and family functioning as predictors.

Parental distress, particularly paternal depressive symptoms, represents a modifiable risk marker associated with treatment non-adherence. Screening for paternal psychological distress and family dysfunction may support treatment adherence in pediatric neuroblastoma. Given the cross-sectional design, these associations should be interpreted as concurrent rather than causal.

Spheno-orbital meningiomas (SOMs) are surgically challenging lesions characterized by tumor infiltration and hyperostosis of the sphenoid wing and orbit. Surgical treatment requires tumor resection, drilling of hyperostotic bone, orbital decompression and skull base reconstruction. Traditionally, reconstruction has been performed either free hand or as a delayed second-stage procedure, often resulting in suboptimal skull and facial symmetry. Single-stage resection with immediate CAD/CAM-assisted reconstruction offers a feasible alternative but requires meticulous preoperative planning and a standardized surgical workflow.

In this retrospective study of 34 patients with SOMs, we present our institutional standardized protocol for preoperative CAD/CAM planning and single-stage tumor resection with immediate skull reconstruction technique. Clinical, functional and radiological outcomes were also assessed.

Exopthalmos was the predominant presenting symptom. Gross-total resection was achieved in 73.5% of cases, resulting in a reduction of exophthalmos in 85% of patients and improvement of visual acuity in approximately 70%. However, postoperative amaurosis occurred in 8.8% and transient diplopia in 55.9%. CAD/CAM implants demonstrated appropriate intraoperative fit without major implant-related complications and with preservation of orbital and facial symmetry.

Single-stage resection with immediate CAD/CAM-assisted skull reconstruction for SOMs is feasible, safe and reproducible. The standardized workflow by combining tumor resection and patient-specific reconstruction within a single-stage procedure may offer practical advantages in the overall surgical pathway.

This study aimed to compare the efficacy and safety of transoral robotic surgery (TORS) versus radical radiotherapy (RT) following neoadjuvant therapy in patients with oropharyngeal carcinoma (OPC). OPC patients who received neoadjuvant therapy followed by either transoral robotic surgery(TORS) or radiotherapy (RT) between 2018 and 2024 across two centers were included in this study. To address potential confounding and ensure comparability, the overlap weighting (OW) method was employed. Progression-free survival (PFS), overall survival (OS), locoregional relapse-free survival (LRRFS), distant metastasis-free survival (DMFS), and adverse events were evaluated. A total of 367 eligible patients were included (264 in the RT group and 103 in the TORS group). Over a median follow-up of 41 months in the OW-adjusted cohort, no significant differences were observed between TORS and RT groups in 3-year PFS (75.6% vs. 74.4%, p = 0.834), OS (80.5% vs. 84.8%, p = 0.703), LRRFS (76.1% vs. 75.0%, p = 0.909), or DMFS (80.0% vs. 82.0%, p = 0.941). Subgroup analyses demonstrated that the treatment effect remained highly consistent across all subgroups, without significant statistical interactions (all P for interaction > 0.05). Toxicity patterns differed: the RT group had higher rates of xerostomia, mucositis, and leukopenia, while the TORS group had more hemorrhage (including one fatal case) and infection. Following neoadjuvant therapy, survival outcomes were comparable between TORS and RT in the OW-adjusted cohort. Toxicity patterns differ between the groups, underscoring the importance of personalized, multidisciplinary treatment decisions.

Synovial sarcoma is a rare, late-relapsing soft-tissue sarcoma of the extremities. Whether anatomical location shapes the surgical treatment pathway, rather than prognosis alone, is unclear. We compared upper-extremity (UE) and lower-extremity (LE) tumors with respect to margin status, re-excision, reconstruction, morbidity and long-term oncological events.

Retrospective single-center cohort of 59 consecutive patients with histologically confirmed extremity synovial sarcoma treated between 2000 and 2023. Co-primary endpoints were a microscopically positive margin (R1) at the index resection and any postoperative complication within 8 weeks (Clavien-Dindo). Metastasis-free survival (MFS) and overall survival were exploratory. Fisher exact, Mann-Whitney U, Kaplan-Meier and log-rank methods were used; odds ratios (OR) are UE relative to LE.

Twenty-three tumors were UE and 36 LE. R1 at the index resection was more frequent in UE tumors (14/23 [61%] vs. 5/36 [14%]; OR 9.64, 95% CI 2.73-34.1; P < 0.001), as was neoadjuvant therapy (39% vs. 8%; P = 0.007). Definitive R0 was achieved in all patients. Any postoperative complication (13% vs. 53%; OR 0.13, 95% CI 0.03-0.53; P = 0.002) and major complications (9% vs. 39%; P = 0.015) were more frequent after LE surgery. Seven of nine distant metastases occurred in LE tumors, several beyond six years; ten-year MFS was 90% versus 56% (log-rank P = 0.095).

Upper- and lower-extremity synovial sarcomas followed distinct surgical pathways and carried distinct morbidity profiles, whereas definitive R0 resection was attained in both. The time-to-event findings are exploratory and require multicenter validation.

To test for differences in overall survival (OS) according to cytoreductive nephrectomy (CN) in medullary metastatic renal cell carcinoma (med-mRCC) relative to most comparable clear cell metastatic RCC (cc-mRCC) patients.

Within the Surveillance, Epidemiology and End Results (SEER) database (2000-2021), we identified 62 patients with med-mRCC vs. 10,372 with cc-mRCC. Propensity score matching (PSM, ratio 1:3), Kaplan-Meier plots and multivariable Cox regression analyses addressed were used.

Of 10,434 patients, 62 (0.6%) harbored med-mRCC vs. 10,372 (99.4%) cc-mRCC. Med-mRCC patients were younger (27 vs. 63 years, p < 0.001), more frequently African American (74 vs. 6%, p < 0.001) and more frequently harbored N1 stages (52 vs. 28%, p < 0.001). After 1:3 PSM for age, race/ethnicity, T-stage and N-stage, 62 of 62 (100%) med-mRCC (median OS 4 months) and 186 of 10,372 (2%) cc-mRCC patients (median OS 10 months) remained for further analyses. In med-mRCC, median OS was 9 months with CN vs. 3 months without CN (p = 0.01). In cc-mRCC, median OS was 28 months with CN vs. 5 months without CN (p < 0.001). In med-mRCC, CN independently predicted better OS (Hazard's Ratio [HR] 0.5, p = 0.005), as well as in cc-mRCC (HR 0.4, p < 0.001).

Med-mRCC patients exhibit a drastically different phenotype relative to their cc-mRCC counterparts. Despite this difference, med-mRCC exposed to CN harbor a similar relative protective survival effect compared to their cc-mRCC counterparts with most comparable age, race/ethnicity and tumor characteristics.

Active surveillance (AS) is an established management strategy for men with low- and favorable intermediate-risk prostate cancer (PCa). Nevertheless, a substantial proportion of patients ultimately undergo radical prostatectomy (RP), and the impact of prior AS on subsequent outcomes remains uncertain. We therefore compared surgical methods, adverse pathological findings and post-RP PCa-treatment among men undergoing deferred RP after AS with those of comparable men treated with immediate RP.

Using nationwide data from the Norwegian Prostate Cancer Registry, we identified men diagnosed between 2009 and 2022 with low- or intermediate-risk PCa who underwent deferred RP following AS or immediate RP. Descriptive statistics summarized clinical characteristics and surgical methods. Multivariable logistic regression evaluated adverse pathological findings in the surgical specimen, and Cox proportional hazards models analyzed post-RP PCa-treatment. Kaplan-Meier analyses with log-rank test assessed 10-year PCa-specific survival.

Compared with immediate RP (n = 5767), the deferred RP (n = 1839) group had more unfavorable preoperative tumor characteristics, fewer nerve-sparing procedures and more frequent lymph node dissection. Deferred RP after AS was associated with higher risk of adverse pathological findings (OR 1.99, 95% CI 1.8-2.3) and post-RP PCa-treatment (HR 1.52, 95% CI 1.3-1.8). Ten-year PCa-specific survival did not differ between groups. Limitations include incomplete data on surveillance intensity.

Deferred RP after AS was associated with more extensive surgery, adverse pathological findings and post-RP PCa-treatment, but similar ten-year PCa-specific survival, compared to immediate RP. These findings emphasize the need for surveillance strategies that ensure timely detection of disease progression and transition to radical treatment.

Spinal metastases impose urgent diagnostic and therapeutic demands; however, evidence from low- and middle-income countries (LMICs) in Latin America is sparse. We aimed to characterize real-world practices, access gaps, and priorities to in-form context-adapted guidelines. We conducted a multinational, cross-sectional online survey (September-October 2025) of licensed clinicians managing spinal metastases across 20 Latin American countries. A validated multilingual instrument (60 items; Cronbach's α = 0.87) assessed practice patterns, diagnostic and therapeutic resources, perceived complications and outcomes, and barriers to care. Because this was a clinician-reported survey rather than a patient-level registry, estimates of survival, complications, neurological or ambulatory recovery, length of stay, and reintervention were considered perceptions of local practice and were not interpreted as objective clinical outcomes or measures of treatment effectiveness. A total of 1,318 complete responses were analyzed using descriptive and nonparametric comparative statistics. Respondents were predominantly neurosurgeons (63.4%) and orthopedic spine surgeons (34.3%); most practiced in tertiary centers (88.0%) and managed 10-50 spinal metastasis cases annually (76.6%). Diagnostic capacity was uneven: MRI was the preferred initial study (69.9%), yet round-the-clock availability existed in only 40.5%; advanced imaging was routine in 20.9% and unavailable in 30.1%. Symptom-to-diagnosis intervals were 1-3 months in 56.9% and > 6 months in 13.7%, with longer delays in public and lower-middle-income settings (p ≤ 0.041). Biopsy access was present in 90.9%, but pathology turnaround exceeded two weeks in 26.1%. Surgical access was always selected in 86.3%; open surgery predominated (56.9%), combined approaches 29.4%, and minimally invasive surgery 8.5%. Time-to-surgery exceeded two weeks for 26.8% of cases. Stereotactic body radiotherapy was available in 14.4%, and initiation of radiotherapy occurred > 1 month after indication in 62.7%. Economic cost (46.7%), limited instrumentation (19.7%), and delayed diagnosis (19.1%) were leading barriers. Multidisciplinary tumor boards were routine in 35.3%. Reported survival exceeded one year in 59.3% of practices; common complications included infection (33.8%), implant failure (25.0%), and pulmonary events (22.3%). Standardized outcome scales were used routinely by 79.6%. In Latin America, clinicians demonstrate broad expertise but face systemic constraints (diagnostic delays, restricted advanced imaging/navigation, limited SBRT, and high out-of-pocket costs), that blunt timely, integrated care. Priority actions include accelerating diagnostic pipelines, expanding radiotherapy and navigation assisted capacity, strengthening multidisciplinary pathways, and implementing financial protection. Regionally coordinated registries and targeted training are essential to narrow equity gaps in metastatic spine care.

Accurate diagnosis of acute leukemia (AL) is essential for management. Morphological assessment is used in resource-limited settings, but interpretation can be challenging in ambiguous cases. Flow cytometric immunophenotyping provides diagnostic precision, yet its utility in Yemen remains underreported. This study aimed to assess the concordance between morphological diagnosis and flow cytometric immunophenotyping in newly diagnosed patients at the National Oncology Center, Sana'a, Yemen, and describe discordant cases and antigen-expression patterns. An exploratory prospective cross-sectional diagnostic-agreement study was conducted in July-August 2024. Seventy-five newly diagnosed patients were evaluated using morphology and immunophenotyping. Concordance, antigen expression patterns, discordant cases, and hematological parameters were assessed. By immunophenotyping, 42 patients (56.0%) had precursor acute lymphoblastic leukemia (ALL), 32 (42.7%) had acute myeloid leukemia (AML), and 1 (1.3%) had Burkitt lymphoma/leukemia. For comparative analyses, the Burkitt case was included in the ALL analytical group. The participants included 40 males (53.3%) and 35 females (46.7%), with ages ranging from 8 months to 75 years (mean 24.5 ± 21.2 years). In the analytical groups, children accounted for 69.8% of ALL-group cases, whereas 81.3% of AML cases were adults. The concordance between morphology and immunophenotyping was 89.3%, with κ = 0.79 (95% CI: 0.65-0.93, p < 0.001). Eight cases (10.7%) were discordant, including reclassification of ALL to AML and vice versa. Aberrant antigen expression contributed to misclassification, with examples of CD19 positivity in AML and CD2/CD7 co-expression in AML profiles. Hematological parameters did not differ significantly between AML and ALL, including platelet count (p = 0.084). Morphology demonstrates high agreement with immunophenotyping in the diagnosis of acute leukemia. Flow cytometry supports more precise lineage assignment, particularly in ambiguous cases and those with aberrant markers. Expanding the diagnostic infrastructure and improving access to immunophenotyping may strengthen leukemia diagnosis and care in Yemen, particularly when used as part of an integrated diagnostic approach.

Colorectal cancer (CRC) remains a major cause of cancer incidence and mortality worldwide. Because colonoscopy is resource-intensive and participation is incomplete, non-invasive screening tests are central to population-level prevention. This review synthesizes recent evidence on fecal immunochemical testing (FIT), multi-omics stool DNA-FIT (mt-sDNA-FIT), multi-omics stool RNA-FIT (mt-sRNA-FIT), and blood-based assays, with emphasis on screening of asymptomatic individuals at average risk, the distinction between cancer detection and advanced precancerous lesion detection, and the operational requirements needed to translate test performance into public health benefit. FIT remains the most scalable first-line option in many programs because it is inexpensive, repeatable, and supported by evidence from organized screening. Its performance depends on hemoglobin threshold, sampling and handling, lesion biology, repeated adherence, and colonoscopy completion after a positive result. Molecular stool assays generally improve single-application sensitivity for CRC and advanced precancerous lesions but reduce specificity and increase costs and demand for colonoscopy. Blood-based assays may improve acceptability among people who decline stool testing or colonoscopy; however, current evidence indicates reduced detection of advanced precancerous lesions, limiting their preventive value when used as direct replacements for stool-based strategies. Implementation barriers occur across the screening pathway, including invitation, test access, sample return, laboratory processing, result communication, diagnostic colonoscopy, pathology, treatment access, and registry tracking. Future progress should prioritize risk-adapted screening, validated molecular and multiomics biomarkers, and artificial intelligence-assisted triage, and equitable program design. The most defensible strategy is not universal adoption of a single assay but a resource-stratified pathway that matches screening modality to population risk, patient acceptability, and system capacity.