MED15-TFE3 rearranged renal cell carcinoma (MED15-TFE3 rRCC) is a rare subtype of TFE3-rearranged renal cell carcinoma (TFE3 rRCC). To date, only 47 cases of MED15-TFE3 rRCC (including 2 cases from our institution) have been reported worldwide.

Using immunohistochemistry (IHC), fluorescence in situ hybridization (FISH), and RNA sequencing, we aimed to identify whether TFE3 rRCC patients at our institution harbor the MED15-TFE3 gene fusion. We will perform a statistical analysis of the pathological features, imaging findings, and clinical outcomes of all published cases of MED 15-TFE rRCC.

MED15-TFE3 rRCC typically has a cystic and solid (predominantly cystic) architecture. The tumor cells feature round nuclei with inconspicuous nucleoli, abundant cytoplasm, and clear to eosinophilic staining. Immunohistochemically, 38 of 39 patients had positive nuclear staining for TFE3, and 37 of 38 patients were positive for PAX8. The FISH assay was positive for rearrangement (red-green signal separation). RNA sequencing identified the MED15-TFE3 fusion gene. One pediatric patient presented with preoperative hilar lymph node metastasis. During follow-up, only one patient developed metastatic disease.

In contrast to traditional TFE3 rRCCs, MED15-TFE3 rRCCs may have distinctive clinicopathological features and a better prognosis. These findings enhance our understanding of the heterogeneity of TFE3 rRCCs.

Aging is a major risk factor for cancer, but the landscape of biological aging across different cancer types and its interplay with genetic risk remains unclear. This study aims to depict the biological aging profiles in specific cancers across diverse populations and investigate the bidirectional relationship between aging and cancer.

This study included 414,599 participants from the UK Biobank (UKB) and 83,788 participants from the electronic health record database of Hong Kong Hospital Authority (EHR-HK). Multivariable Cox and logistic regression models were used to evaluate associations between biological age acceleration (BioAgeAccel) and site-specific cancers in the UKB and EHR-HK, respectively. In the UKB cohort (n = 387,066), we further computed cancer-specific polygenic risk scores (PRSs) and calculated population attributable fractions (PAFs) to quantify the relative contributions of aging and genetics to cancer incidence and mortality. A nested two-sample bidirectional Mendelian randomization (MR) analysis within one-sample setting was employed to explore the reciprocal causality between aging and cancer.

Compared to cancer-free individuals, the most pronounced BioAgeAccel disparities were observed in liver cancer (mean difference (MD): 5.9 years) within the UKB, and oesophageal cancer (MD = 18.4 years) within the EHR-HK. A 5-year increment in BioAgeAccel was associated with elevated overall cancer risk, with leukaemia demonstrating the highest hazard ratio in the UKB (HR = 1.13, 95% CI: 1.11-1.15) and oesophageal cancer exhibiting the highest odds ratio in the EHR-HK (OR = 1.55, 95% CI: 1.33-1.81). PAF analyses revealed that BioAgeAccel contributed to 47% of lung cancer incidence and 60% of lung cancer-specific mortality, exceeding contributions from genetic risk. Significant interactions between genetics and aging were identified for colorectal, lung and non-melanoma skin cancer. Bidirectional MR analyses demonstrated the reciprocal relationship between BioAgeAccel and lung cancer (aging-to-cancer nexus: OR = 1.30, 95% CI: 1.11-1.51; cancer-to-aging nexus: 1.05 (1.02-1.08)), female breast cancer (aging-to-cancer nexus: 1.09 (1.02-1.15); cancer-to-aging nexus: 1.05 (1.03-1.07)), and prostate cancer (aging-to-cancer nexus: 1.08 (1.01-1.16); cancer-to-aging nexus: 1.02 (1.00-1.03)).

This pan-cancer study reveals intricate interrelationships between biological aging and cancer, particularly in lung, prostate, and female breast cancer, with population-specific patterns and synergistic genetic interactions. Findings underscore the potential for aging-targeted strategies in cancer prevention and treatment.

Simple bone cysts are benign, fluid-filled lesions commonly affecting the metaphyseal regions of long bones in children and adolescents. While often asymptomatic, they may present clinically when complicated by pathological fractures. Diagnosis is primarily radiographic, and management ranges from observation to surgery. This report highlights a rare femoral neck simple bone cyst with fracture, focusing on the technical nuances of definitive surgical treatment in a weight-bearing location.

A 14-year-old Arab female with no prior medical history presented with acute left hip pain after a minor fall. Radiographs revealed a displaced sub-capital femoral neck fracture overlying a well-defined cystic lesion. Surgical management included dynamic hip screw-guided cortical windowing, meticulous curettage, alcohol irrigation, tightly packed cancellous grafting from the iliac crest, and structural fibular strut grafts placed above and below the screw path. Internal fixation was achieved with a femoral head screw and dynamic hip screw plate. Histopathology confirmed a simple bone cyst.

This case underscores the value of a tailored, multi-component surgical technique in managing simple bone cyst-associated pathological fractures in pediatric weight-bearing bones. The approach resulted in excellent structural stability and functional recovery, with the patient regaining independent, unrestricted ambulation by 10 weeks postoperatively and no complications observed.

Schwannomas are benign, slow-growing tumors, primarily affecting the cervical and lumbar spine. When large, they may extend over multiple vertebral levels, posing surgical challenges. Spinal schwannomas are commonly encapsulated and extramedullary intradural tumors that rarely exhibit invasive characteristics.

A 13-year-old Ugandan Munyankore female patient, presented with a 6-year history of nontraumatic progressive quadriparesis, particularly in the lower limbs. Clinical examination showed power of 1/5 in the lower limbs, 4/5 in the upper limbs, hypertonia and hyperreflexia, with intact sensation, and no stigmata of neurofibromatosis. Magnetic resonance imaging revealed two "kissing" schwannomas extending from C2 to T2 in the cervical spine. Decompressive surgery was performed through laminoplasty and partial lesion resection, and histology confirmed schwannoma. Follow up of the patient showed stabilizing neurological status with noted improvement in lower limb strength.

"Kissing" schwannomas are most frequently documented in the cerebellopontine angle, rarely in the spine, and even more rarely in children. While multiple schwannomas are often associated with Neurofibromatosis type 2, this case had no family history or clinical signs of the disorder and no genetic testing were done. Giant invasive spinal schwannomas (GISS) that span multiple vertebrae demand intricate surgical approaches owing to their proximity to neurovascular structures, though such procedure may require advanced technology, which is not available in low income countries.

This is one of the rarest reported cases of kissing cervical schwannomas in a young patient from a low-to-middle-income country. Surgical decompression, though challenging, is critical for neurological recovery in such advanced cases.

Current guidelines recommend routine lymph node dissection (LND) for intrahepatic cholangiocarcinoma (iCCA) to achieve adequate staging; however, real-world compliance remains suboptimal. This study evaluated whether, compared with routine approaches, selective lymphadenectomy, on the basis of clinical judgment, compromises oncological outcomes in patients with iCCA.

A retrospective analysis of 179 patients who underwent curative hepatectomy for iCCA between 2014 and 2024 was performed. The cohort included pure cholangiocarcinoma (CCA, n = 102) and combined hepatocellular-cholangiocarcinoma (HCC-CCA, n = 77) patients. Patients were categorized by pathological nodal status: pN0 (LND performed, negative nodes), pN1 (LND performed, positive nodes), and pNx (no LND performed). Logistic regression identified factors influencing LND decisions. Survival outcomes were analyzed via the Kaplan‒Meier method and Cox proportional hazards modeling. Subgroup analysis was performed to explore the outcomes in CCA and HCC-CCA separately.

LND was performed in 54 patients (30%), with significant variation based on tumor characteristics. Preoperative cholangiocarcinoma diagnosis was the primary factor influencing LND decisions (OR 3.33, 95% CI 1.54-7.34; p = 0.002). The median overall survival (OS) was 30.5, 17.4, and 59.1 months (p = 0.007), and median progression-free survival (PFS) was 21.2, 8.4, and 16.6 months (p = 0.042) for pN0, pN1, and pNx, respectively. Subgroup analysis for CCA and HCC-CCA separately showed a similar Kaplan-Meier curve pattern, but the differences were not statistically significant because of the uneven distribution between groups. After adjusting for age, tumor stage, and histology, no significant difference in survival was detected between the pNx and pN0 groups (HR 0.78, 95% CI 0.46-1.30; p = 0.34). Patients with pure CCA had worse survival than those with HCC-CCA (HR 1.68, 95% CI 1.03-2.75; p = 0.040). Adequate lymphadenectomy (≥ 6 nodes) was achieved in only 26% of patients who underwent LND.

This study highlights the low compliance with the guidelines regarding lymph node dissection for intrahepatic cholangiocarcinoma in real-world settings. However, compared to lymphadenectomy with negative nodes, selective lymph node dissection based on clinical suspicion does not compromise the overall survival. These findings support individualized surgical approaches rather than universal lymphadenectomy protocols and challenge current guidelines mandating routine LND for all iCCA patients. Future guidelines should incorporate risk-stratified decision-making in lymph node management.

Malignant pleural mesothelioma (MPM) responds poorly to chemotherapy and is a highly progressive malignancy with a median survival time of only 6-9 months. Therefore, the development of anti-MPM tumor agents with high efficacy and low toxicity is urgent and addresses an unmet need for MPM patients.

Medicinal chemistry synthesis of small molecules based on the FL118 drug platform were further comparatively investigated using multiple MPM and osteosarcoma cell/tumor in vitro and/or in vivo models. The method includes cell viability assay, Western blot analysis, colony formation assay, immunocytochemical staining, β-galactosidase senescence staining, flow cytometry, DNA fragmentation cell death detection, vector-free CRISPR-Cas9-mediated gene knockout, bioinformatic analysis, FL496 efficacy determination using severe combined immunodeficiency (SCID) mice with human MPM tumor, and immunohistochemistry (IHC) analysis of MPM tumors.

Here, we report that we identified a novel FL118-derived small molecule (FL496). FL496 appears to be strikingly more effective in inhibiting MPM tumor growth in MPM tumor animal models than the currently most prevalent pemetrexed-cisplatin combination in the clinic. The treatment of MPM cells with FL496 rapidly induced p53 and p21 accumulation, and Rb and p-Rb inhibition, which were associated with MPM cell senescence and G₁/G₀ arrest and apoptosis. Knockout (KO) of the TP53/p53 gene decreased the ability of FL496 to inhibit MPM cell growth (i.e., increase FL496 IC₅₀ values) and colony formation. FL496-treated MPM cells resulted in strong inhibition of the expression of survivin, Mcl-1, Bcl-2, Bcl-XL, and the induction of active caspase-3, cleaved PARP, and PUMA, which were further confirmed using MPM tumor tissues via IHC analysis. High survivin in MPM patients' tumors is associated with poor patient survival. Similar to FL118, FL496 treatment reduces DDX5 expression in MPM cells, but FL496 is more potent than FL118 in inhibiting MPM cell growth. Therefore, the mechanism of action (MOA) of FL496 overlaps with, but is likely beyond the scope of FL118 MOA, which needs further investigation.

Together, these results indicate that FL496 is a promising anti-MPM small molecule, and its high anti-MPM potential is worthy of being further explored as a monotherapeutic agent to treat MPM patients in clinical trials.

The objective of this study is to assess the predictive significance of lactate dehydrogenase-to-albumin ratio (LAR) in patients with upper tract urothelial carcinoma (UTUC) who have undergone radical nephroureterectomy (RNU).

We performed a retrospective analysis on patients with UTUC at West China Hospital, covering the period from May 2003 to June 2019. The optimal cut point of LAR was determined using the X-Tile program. Relevant statistical methods included the utilization of Kaplan-Meier curves for survival estimation and the application of Cox proportional hazard model for risk evaluation. A nomogram was constructed to predict the 3-year and 5-year CSS and the predictive performance was also evaluated.

A cohort of 577 patients with UTUC who underwent RNU were included in the study, and the threshold value of LAR was 5.07. LAR ≥ 5.07 was associated with worse CSS [hazard ratio (HR) = 1.72; 95% confidence interval (95%CI): 1.18-2.50; P = 0.005] in fully adjusted Cox regression analysis. In addition, the nomogram utilizing the LAR exhibited excellent prognostic performance in predicting CSS, with time-dependent areas under the curve (tAUC) values of 0.814 and 0.781 for 3-year and 5-year CSS, respectively.

Preoperative LAR could be regarded as a valuable individualized tool for clinical decision-making, as it independently predicts CSS in UTUC patients undergoing RNU.

Nanoliposomal irinotecan plus fluorouracil with leucovorin (NFF) is the standard treatment regimen after gemcitabine-based therapy in patients with unresectable pancreatic cancer. However, data on the efficacy and safety of NFF in terms of the presence or absence of biliary drainage (BD) or serum bilirubin levels prior to NFF are limited. Therefore, we analyzed whether these factors affect the efficacy and safety of NFF in the real world.

The NAPOLEON-2 study consisted of a retrospective and a prospective phase. As the retrospective phase, we retrospectively evaluated 161 consecutive patients who received NFF as second- or later line treatment. The primary endpoint was overall survival (OS); other endpoints included progression-free survival, response rate, disease control rate, dose intensity, and adverse events (AEs). We compared the endpoints between the non-BD group and BD group first, and then between the serum total bilirubin ≥ 1.0 mg/dL group and < 1.0 mg/dL group.

All patients received gemcitabine prior to NFF. No significant difference in OS was observed between the non-BD and BD groups (9.1 vs 7.6 months; hazard ratio (HR), 1.09; 95% confidence interval (CI), 0.72-1.66; P = 0.69). The rates of severe hematological AEs and biliary tract infections were higher in the BD group than in the non-BD group. A significant difference in OS was noted between the bilirubin ≥ 1.0 mg/dL and < 1.0 mg/dL group (5.4 vs 8.9 months; HR, 2.13; 95%CI, 1.18-3.84; P = 0.01). In addition, the rate of severe hematological AE was higher in the high bilirubin group (56% vs. 26%).

BD had minimal impact on the efficacy of NFF in daily practice. Patients with total bilirubin ≥ 1.0 mg/dL had shorter OS than those with total bilirubin < 1.0 mg/dL.

The associations between excess adiposity and endometrial cancer (EC) risk may be mediated by altered metabolic profiles. Here, we triangulated evidence from observational and Mendelian randomisation (MR) analyses to investigate the relationship between adiposity traits, circulating metabolites, and their effects on endometrial cancer.

Observational analyses were performed in UK Biobank (N cases and controls = 1,005 and 215,339, respectively). Univariable and multivariable MR analyses were performed using female-specific summary statistics for adiposity traits (GIANT consortium; N BMI and WHR = 434,793 and 281,153, respectively), circulating metabolites (UK Biobank; N = 140,768) and EC (Endometrial Cancer Association Consortium; N cases and controls = 12,906 and 108,979, respectively).

Higher body mass index (BMI) was associated with increased odds of overall EC, endometrioid EC, and non-endometrioid EC in both observational and MR analyses; however, there was weaker evidence for waist-hip-ratio (WHR). BMI was associated with 165 metabolites, 25 of which were associated with EC risk. Multivariable MR analyses suggest that several lipid metabolites and ratios may mediate the association between BMI and non-endometrioid EC, although analyses using Phenoscanner suggest that alternative pathways such as height and blood cell traits could influence the EC risk.

Evidence here suggests that higher BMI causes a higher risk of overall and all histological subtypes of EC and variation in numerous circulating metabolites. Several of these metabolites showed relationships consistent with an intermediate role between BMI and non-endometrioid EC, however, further analyses highlighted other potential shared mechanisms that could influence the risk of EC.

This study aimed to assess the comparative effectiveness of indocyanine green and methylene blue in the marking and identification of sentinel lymph nodes during sentinel lymph node biopsy procedures in patients diagnosed with endometrial cancer undergoing staging surgery through vaginal natural-orifice transluminal endoscopic surgery.

In this retrospective cohort study conducted at a tertiary center, we analyzed 80 patients with endometrial cancer who underwent vaginal natural orifice transluminal endoscopic staging surgery. Patients were classified into two cohorts based on the tracer used for sentinel lymph node sentinel lymph node mapping: indocyanine green (n = 40) or methylene blue (n = 40). The primary endpoints, including sentinel lymph node detection rates (overall and bilateral) and number of nodes retrieved, along with surgical outcomes, were compared between the groups.

Eighty patients (indocyanine green group, n = 40; methylene blue group, n = 40) were included in the study. The vaginal natural orifice transluminal endoscopic surgery identification rate was significantly higher in the indocyanine green group (95%) than in the methylene blue group (82.5%) (p = 0.045). The mean number of sentinel lymph nodes identified in the indocyanine green group (3.2 ± 1.1) was significantly higher than that in the methylene blue group (2.5 ± 0.9) (p = 0.021). The rate of bilateral vaginal natural orifice transluminal endoscopic surgery identification was higher in the indocyanine green group (80%) than in the methylene blue group (65%); however, the difference was not statistically significant (p = 0.112). Surgical time, blood loss, and complication rates were similar between the two groups. Histopathological examination revealed a similar number of positive sentinel lymph nodes in both the groups.

In the context of sentinel lymph node biopsy for staging surgery and natural orifice transluminal endoscopic surgery for endometrial cancer, indocyanine green has demonstrated a superior sentinel lymph node identification rate and a higher yield of sentinel lymph nodes compared to methylene blue. Given the advantage of real-time imaging, indocyanine green has emerged as a promising agent for sentinel lymph node biopsy in minimally invasive approaches, such as vaginal natural orifice transluminal endoscopic surgery.