BACKGROUND: Platinum-etoposide combined with a PD-L1 inhibitor (atezolizumab or durvalumab) is the standard first-line treatment for extensive-stage small cell lung cancer (ES-SCLC). Although phase 3 trials have demonstrated similar efficacy, no direct comparison exists, and differences in treatment cost and resource utilization may influence clinical decision-making. METHODS: In this multicenter retrospective study, real-world data from eight Japanese institutions were analyzed. Patients with ES-SCLC treated with platinum-etoposide plus atezolizumab or durvalumab between August 2018 and December 2022 were included. Individual-level medical costs were calculated from health insurance claims linked to electronic medical records. After propensity score matching and exclusion of cisplatin-treated patients, 128 patients were analyzed. The primary outcome was mean monthly medical cost during immunotherapy. Secondary outcomes included overall survival (OS), immune-related adverse events (irAEs), and prognostic factors. RESULTS: Among 128 patients (mean age, 74 years; 85% male), mean monthly medical cost was significantly lower with atezolizumab than durvalumab (¥1 003 922 [$7183] vs ¥1 596 511 [$11 422]; P < .001). Median OS was comparable (13.9 months [95% CI, 11.7-17.5] vs 14.8 months [95% CI, 10.5-not reached]; P = .92). Grade ≥2 irAEs (11% vs 31%; P = .009) and interstitial lung disease (3% vs 20%; P = .004) were less frequent with atezolizumab. Poor performance status was associated with worse OS, whereas treatment type was not. CONCLUSIONS: Atezolizumab was associated with lower medical costs and similar survival outcomes compared with durvalumab in ES-SCLC, suggesting its use as a clinically comparable option with lower associated costs in Japanese real-world practice.

Robotic surgery has transformed head and neck cancer (HNC) treatment. This scoping review synthesizes evidence on transoral robotic surgery (TORS), focusing on applications, limitations, and future directions. Following PRISMA-ScR guidelines, this review used the PCC framework (Population: HNC patients; Concept: technological advancements; Context: any clinical setting). A systematic search of five databases and gray literature was conducted. Two independent reviewers screened records and extracted data from clinical trials and reviews. From 5411 records, 21 studies were included. Evidence confirms TORS provides excellent local disease control and functional benefits (e.g., shorter hospitalization, improved swallowing) over open surgery, albeit with a distinct complication profile (e.g., hemorrhage). A significant finding is the scarcity of high-quality randomized trials comparing TORS to radiotherapy or open surgery. Technologically, evolution from multiport to single-port and flexible systems has improved access, though limitations like absent haptic feedback persist. Emerging trends focus on AI integration for precision and developing smaller instruments. Robotic surgery is a viable, evolving approach for HNC with demonstrable functional advantages. Its future depends on overcoming technological limits, establishing cost-effectiveness, and validating efficacy through robust comparative studies. AI integration is a promising frontier for enhancing surgical precision and personalization.

BACKGROUND: ACS-NSQIP began capturing operative approach in 2022. With increased adoption of minimally invasive (MIS) techniques for malignancy, a contemporary review of benchmark outcomes for open, laparoscopic and robotic gastrectomy is warranted. METHODS: We performed a retrospective cohort study of adults in ACS-NSQIP (2022-2024) undergoing partial or total gastrectomy (CPT 43631-4 and 43620-2) for cancer. Outcomes included operative time, length of stay (LOS), unplanned conversion-to-open, and 30-day morbidity, mortality, and readmission. Multivariable logistic regression evaluated patient and operative factors associated with morbidity. RESULTS: Among 1,459 patients (median age 66, 60.4% male), 66.8% underwent partial gastrectomy and 33.2% total gastrectomy. Approaches were 61.2% open, 19.5% laparoscopic, and 19.3% robotic. Thirty-day mortality (1.8%), major complications (18.2%), and readmissions (10.3%) did not differ by approach. Unplanned conversion-to-open occurred in 14.0% of MIS. Robotic had longer median operative time of +1.2 and +1.7 h than laparoscopic and open and median -1 and -2 days shorter LOS respectively (p < 0.001). Hypoalbuminemia (OR 3.10), CKD ≥ 3 (OR 1.75), and anemia (OR 1.48) were independently associated with major complications (p < 0.05). CONCLUSION: Operative approach influences operative time and LOS but not short-term morbidity and mortality. The newly available ACS-NSQIP operative approach variable enables approach-specific benchmarks for cancer-related gastrectomy.

INTRODUCTION: Randomized controlled trials have demonstrated substantial benefit of perioperative chemotherapy (PC) and surgery for locally advanced gastric adenocarcinoma. Patients with clinical T2N0 (cT2N0) gastric adenocarcinoma were included in these trials, but the benefit of PC remains unclear in this intermediate-stage disease due to the small number of patients included. The goal of this study was to determine the role and sequencing of chemotherapy for resected cT2N0 gastric adenocarcinoma. METHODS: The National Cancer Database from 2004 to 2020 was used to identify patients with cT2N0 gastric adenocarcinoma who underwent surgical resection. Patients were stratified by receipt of chemotherapy into three groups: (1) no chemotherapy, (2) perioperative chemotherapy (PC), and (3) adjuvant chemotherapy (AT). The primary outcome was overall survival. RESULTS: Of 3676 patients with cT2N0 gastric adenocarcinoma, 61.3% received no chemotherapy, 19.4% received PC, and 19.2% received AT. Of the 2961 patients who underwent upfront surgical resection, 28.8% (854) were upstaged on final pathology. Multivariable survival analysis revealed that both PC and AT were associated with a decreased mortality compared to no chemotherapy (0.64 and 0.68, respectively, p < 0.001). AT was associated with a 21% decrease in mortality compared to PC (HR 0.79, p = 0.015). CONCLUSION: Patients presenting with cT2N0 gastric adenocarcinoma benefit from chemotherapy in addition to surgery, although a minority of patients received guideline concordant care. Patients who received adjuvant chemotherapy had superior outcomes compared to those who received perioperative chemotherapy. The optimal treatment for cT2N0 gastric cancer should include surgery and chemotherapy, and consideration should be given to a strategy of upfront surgical resection and adjuvant therapy rather than perioperative chemotherapy.

Chimeric antigen receptor T-cell therapy (CART) has changed treatment for relapsed/refractory diffuse large B-cell lymphoma (r/r DLBCL), but most patients still die of their disease and may benefit from palliative care (PC) or hospice services. Whether CART availability has affected PC or hospice referral patterns and end-of-life outcomes remains unclear. We conducted a single-center retrospective study for deceased patients with r/r DLBCL to evaluate PC and hospice utilization before and after CART introduction (87 pre-CART, 95 post-CART). PC referral rates were similar between eras (57.5% vs 70.5%,  = 0.39), as were hospice referrals (79.3% vs 83.2%,  = 0.78). However, patients in the post-CART era had shorter time from last treatment to death (95 vs 51 days,  = 0.001), higher hospitalization rates in the last 30 days of life (57.5% vs 72.6%,  = 0.03), and more in-hospital deaths (19.5% vs 33.7%,  = 0.045). Overall, 20-30% of patients were never referred to PC or hospice.

Overall survival (OS) has improved in unresectable/metastatic pancreatic adenocarcinoma (mPDAC) patients. However, it is unclear who should be offered further treatment, and how to assess the response in unmeasurable disease. The study aims to evaluate the role of 6-month progression-free survival (PFS) and the corresponding tumor growth rate after first-line chemotherapy (G). After identifying 15 randomized trials (19 cohorts, 4,725 patients), 6-month PFS were extracted from curves and expressed as G. Median G was higher after polychemotherapy and was significantly associated with OS (β = 0.168; p-value <0.001). The number of drugs and female sex correlated with a slower tumor growth rate. Since it was calculated directly from PFS in this study, it is not surprising that G exhibits a similar behavior. However, it can be derived by imaging or other markers, therefore representing a variable distinct from PFS, and as such warrants further evaluation in future studies.

Pancreatic ductal adenocarcinoma (PDAC) remains one of the most lethal malignancies, characterized by the limited efficacy of current therapies and an urgent need for novel treatment strategies. Targeted radionuclide therapy (TRT) enables the selective delivery of radionuclides to tumor sites via specific ligands, integrating molecular targeting with cytotoxic radiation. Among these radionuclides, Lu, a β-emitter with moderate energy and suitable tissue penetration, offers a distinct advantage in theranostics, whereas Ac, an α-emitter with high linear energy transfer (LET) and an ultrashort path length, demonstrates superior efficacy against hypoxic and treatment-resistant tumor cells. Although no TRT agents have yet been approved for PDAC, multiple emerging targets are under active investigation, with several candidates entering early-phase clinical trials. This review systematically summarizes recent advances in Lu- and Ac-labeled radiopharmaceuticals for PDAC, comparing their physicochemical properties, biological effects, and translational potential. Future perspectives for TRT development are also discussed to facilitate its clinical application in PDAC.

BACKGROUND: The differential diagnosis of tuberculous pleural effusion (TPE) and lung adenocarcinoma-associated malignant pleural effusion (LA-MPE) remains challenging. This study aimed to measure interleukin‑9 (IL‑9) levels in pleural fluid and evaluate its diagnostic utility in distinguishing between these two conditions. METHODS: The study enrolled 105 patients with PE (51 TPE and 54 LA-MPE). IL-9 levels in pleural fluid were measured by enzyme-linked immunosorbent assay (ELISA). Receiver operating characteristic (ROC) curve analysis was employed to identify the optimal cutoff value and assess diagnostic performance, including area under the curve (AUC), sensitivity, and specificity, with adenosine deaminase (ADA) and carcinoembryonic antigen (CEA) as comparators. Internal cross-validation was conducted to examine model robustness, and decision curve analysis was used to evaluate the clinical net benefit of IL-9 alone and in combination with ADA and CEA. RESULTS: IL-9 levels were significantly elevated in TPE compared with LA-MPE (2828.13 vs. 310.55 ng/L, P < 0.001). At a cutoff of 748.47 ng/L, IL-9 distinguished TPE from LA-MPE with a sensitivity of 98.0% and specificity of 92.59%, and an AUC of 0.987 (P < 0.001), exceeding both ADA and CEA. Decision curve analysis showed that, within a threshold probability range of 0.10-0.40, the IL‑9‑based model consistently yielded greater net clinical benefit than conventional markers. Cross-validation further confirmed the robustness of IL-9 for distinguishing TPE from LA-MPE. CONCLUSION: IL-9 demonstrates promising diagnostic performance in differentiating TPE from LA-MPE, with favorable accuracy relative to ADA. It merits further investigation as a potential adjunctive diagnostic tool for pleural effusion.

BACKGROUND: We aimed to systematically summarize data on efficacy of local salvage therapies for local recurrence of renal cell carcinoma (RCC). METHODS: We searched MEDLINE, Embase, Web of Science, CENTRAL, and Google Scholar through 05/08/2026, for studies on local salvage therapies for local recurrence of RCC following radical nephrectomy, partial nephrectomy, or ablation (PROSPERO: CRD42024623099). Meta-analyses were conducted using random-effects models. Risk of bias (RoB) was assessed using ROBINS-I. RESULTS: Forty-seven studies comprising 2039 patients were included (45 retrospective). Patients recurring after primary ablation predominantly presented with new renal masses, and were managed with repeat ablation (6 studies, n = 193) or salvage surgery (3 studies, n = 48), both yielding low recurrence rates. Local recurrences (M0) after primary partial nephrectomy (PN), most often in patients with pT1 disease, were treated with repeat PN, radical nephrectomy (RN), or ablation (15 studies, n = 562), with heterogeneous outcomes across modalities, ranging from low recurrence rates to predominantly distant metastatic failure. In contrast, recurrences after primary RN (12 studies, n = 564) occurred in a population with primarily locally advanced disease (pT3-4) and outcomes were notably worse, driven by distant progression. Four studies used radiotherapy in salvage setting, with heterogeneous methods and outcomes. Majority of studies were assessed moderate RoB, 16 studies assessed as serious, predominantly due to bias in participant selection. CONCLUSION: Efficacy of local salvage therapies for RCC recurrence is influenced by the primary treatment and histopathological advancement of primary disease. Repeat ablation provides favorable outcomes, while recurrences after PN can be managed with repeat surgery or ablation, with heterogeneous results (from low recurrence rates to frequent distant metastases). Post-RN patients, often with initially advanced disease, have worse prognosis with approximately two-thirds experiencing progression by three years, primarily due to distant metastases. Overall, quality of evidence remains low. There is critical need for expert consensus on quality indicators for locally recurrent RCC care and for prospective registries with standardized outcome reporting.

PURPOSE: Fatigue is a common symptom in lymphangioleiomyomatosis (LAM) and is associated with reduced physical activity and quality of life. Coexistent skeletal muscle dysfunction has been reported for other chronic lung diseases but has not been investigated in LAM. METHODS: Fifteen patients with LAM and 15 matched individuals without LAM (NL) underwent computerized lower extremity dynamometry, standardized functional tests, and fatigue surveys. Immunohistochemistry to detect LAM+ cells and to characterize fiber-type distribution was performed on vastus lateralis (VL) samples of LAM and NL. Maximal cardiopulmonary exercise test (CPET) and six-minute walk test (6MWT) were additionally conducted for LAM. Welch's t-testing compared measures between LAM and NL. Pearson correlation tested relationships between variables. Data are mean ± SD. RESULTS: LAM exhibited lower (p < 0.05) muscular force (by 220 ± 89 N), power (by 312 ± 129 W), and endurance (by 4674 ± 1974 N*sec) in dynamometry and functional tests (by 119 ± 45s in wall squat test), and worse fatigue survey scores (p = 0.02 to 0.0004). Poorer muscular endurance in LAM was associated with less distance achieved in 6MWT (r = 0.68), lower VOmax (r = 0.58), and worse fatigue (r = 0.56). LAM with worse fatigue also exhibited lower relative fat utilization in CPET (r = 0.75, p = 0.005). No LAM+ cells were detected in VL samples, nor between-group differences in fiber type distribution. CONCLUSION: Muscular endurance and strength is lower in LAM, coincident with greater self-reported fatigue. Fiber type shift reported for skeletal muscle in other chronic lung disease is not observed in LAM. Further work is needed to elucidate peripheral muscle mechanisms for fatigue and exercise intolerance in LAM.

Gastric cancer remains a major cause of cancer mortality in Vietnam and illustrates how social conditions shape cancer trajectories. This narrative review synthesizes Vietnam-relevant evidence across infection, diet, tobacco and alcohol exposure, early detection, treatment, financial protection, survivorship, and palliative care. Helicobacter pylori acquisition is socially patterned by household and hygiene conditions; salt intake remains above recommended levels; and early gastric cancer represents about 4% of cases in available tertiary and multicenter studies. Broader Vietnamese health-system evidence suggests geographic concentration of specialist services and persistent out-of-pocket spending despite high insurance enrollment; these are contextual inferences rather than gastric-cancer-specific estimates. Cancer-wide studies from 2012 to 2014 document substantial financial catastrophe, but contemporary gastric-cancer-specific cost data are lacking. We propose an equity-oriented agenda combining representative surveillance, population prevention, quality-assured risk-stratified detection, regional care networks, patient navigation, and deeper financial protection, with routine socioeconomic, geographic, and patient-reported outcome monitoring.

Immunotherapy holds promise for gastric cancer, but its efficacy is constrained by primary and acquired resistance. Resistance mechanisms are complex, stemming from tumor features-such as the tumor microenvironment (TME). The TME is a dynamic ecosystem where tumor-immune-stromal interactions shape antitumor responses. Existing prognostic markers have clinical value, yet their insufficiency reflects the multidimensional nature of tumor-immune crosstalk. Emerging evidence indicates that immunotherapy response is a systems-level phenomenon. This review synthesizes current data on cellular, molecular, and systemic predictors, focusing on immune cell phenotypes, protein biomarkers, gene signatures, and metabolic factors. Integrative models capturing the functional state of the TME consistently outperform single biomarkers. Nevertheless, significant challenges remain, including a lack of standardization, limited prospective validation, and TME temporal plasticity, which complicates static biomarker assessments. Ultimately, predicting response requires understanding the tumor-immune ecosystem as an integrated, dynamic system to improve patient stratification and outcomes.

PURPOSE: Chronic inflammation is an important contributor to the development of oral cancer, particularly in Oral Potentially Malignant Disorders (OPMDs) progressing to Oral Squamous Cell Carcinoma (OSCC). PELP1 is an inflammation-responsive nuclear coregulator identified in multiple cancers; however, its role in oral cancer remains unclear. This study evaluates the expression of PELP1 and determines its clinical significance in inflammation-associated oral tumorigenesis. METHODS: PELP1 transcript levels were examined in the TCGA-HNSC dataset using different online tools. Immune infiltration analysis using TIMER and Kaplan-Meier survival analysis plots was also performed. Protein expression was validated by immunohistochemistry (IHC) in human normal oral mucosa, OPMDs, and OSCC tissues and in chemically induced murine OSMF models. Functional validation was performed by shRNA-mediated PELP1 knockdown in SCC131 cells, followed by western blot analysis of Cyclin B1 and NF-κB signaling. RESULTS: PELP1 expression was significantly upregulated in TCGA-HNSC tumors compared to normal tissues (p < 0.05) and was associated with advanced stage, higher grade, and nodal metastasis (p < 0.05). A positive correlation and a significant association between PELP1 expression and the abundance of immune cell infiltrates were observed (p < 0.05). In addition, high PELP1 expression was associated with markers of oral epithelial transformation (p < 0.05). Survival analysis showed a trend toward reduced overall survival (p = 0.24). IHC analysis showed a stepwise increase in nuclear PELP1 expression from normal mucosa to OPMDs; and OSCC (p < 0.05); along with elevated expression in fibrotic murine models (p < 0.05) compared to saline-treated control models. Functional validation demonstrated that PELP1 knockdown reduced Cyclin B1 expression, reduced total NF-κB p65 protein levels, and suppressed NF-κB signalling in SCC131 cells. CONCLUSION: PELP1 is significantly upregulated during oral cancer development and correlates with adverse clinicopathological features, supporting its potential role as a biomarker associated with inflammation-driven oral cancer progression.

This study presents an application of delocalized hydrocarbon neutral monoradical, an olympicenyl radical (OR6), as a high-performance organic photothermal agent (PTA) for targeted photothermal therapy (PTT). By encapsulating OR6 into functionalized nanoparticles (dOR6-NPs), a remarkable near-infrared-II (NIR-II) absorption at 1056 nm and photothermal conversion efficiency (PCE) of 84.66% are achieved. To overcome the limitations of passive tumor targeting, a bioorthogonal "tag-and-target" strategy is developed using metabolic glycan labeling and copper-free click reaction. This approach significantly enhanced photothermal therapeutic efficacy both in vitro and in vivo. The dOR6-NPs induce significant cytotoxicity of cancer cells under 1064 nm laser irradiation, leading to nearly complete tumor suppression in a xenograft model while maintaining excellent biocompatibility and systemic safety. This work not only highlights olympicenyl radicals as a new class of PTAs but also establishes a robust click-reaction-based platform for precision cancer therapy.

BACKGROUND: Pharmacogenomics (PGx) is increasingly recognised as a cornerstone of personalised medicine, with established recommendations for many commonly prescribed medicines. Despite this, translation into real-world clinical practice remains inconsistent, reflecting persistent implementation and health-system gaps. OBJECTIVE: To provide a multidisciplinary perspective on the system-level conditions required to normalise PGx within contemporary hospital care, drawing on structured knowledge exchange and priority-setting across clinical, digital and governance domains. METHODS: A multidisciplinary knowledge exchange program convened clinicians, pharmacists, genetic services, informatics teams, researchers and health-service leaders across oncology, transplantation, peri-operative care and palliative care. Knowledge was exchanged through presentations, informing the generation and ranking of shared priorities in groups and individually using the Nominal Group Technique. Aggregate scores were calculated, and priorities further refined. Presentation insights were synthesised using a narrative, interpretive approach, to identify cross-cutting translational themes. RESULTS: Eleven shared priorities were identified across four broad critical levers for sustainable integration: (1) computable, reusable PGx data embedded within electronic medical records (EMR); (2) coordinated and equitable testing and prescribing pathways; (3) workforce capability and stewardship; and (4) governance. Equity, access and data sovereignty were highlighted as foundational to responsible scale-up, particularly for First Nations peoples and under-represented communities. CONCLUSION: Insights from this knowledge-exchange program highlight the feasibility and clinical relevance of PGx, and identify workforce capability, EMR integration, and system-level governance as critical implementation levers of adoption. Coordinated national investment and policy alignment will be central to realising the full value of PGx.

Orthopedic diseases are referred to as a series of conditions affecting the normal structure and function of the skeletal system. With a wide variety of types and a year-by-year increasing incidence, they have a severe impact on patients' quality of life. Traditional research has made relatively significant progress in understanding the pathogenesis and treating orthopedic diseases, however, it remains constrained by limitations such as low-throughput experimentation, and difficulty in mimicking the complex bone microenvironment. In recent years, high-throughput screening (HTS) technology has been combined with experimental techniques and models (such as microfluidics, omics technologies, 3D bioprinting, artificial intelligence, and organoid models), which can be used to better simulate the real bone microenvironment and predict molecular activity. This combined approach has not only deepened our understanding of the mechanisms of orthopedic diseases, but also broken through the limitations of traditional drug development, which further accelerates drug discovery and clinical translation. This review aims to systematically summarize the research progress and applications of HTS in typical orthopedic diseases, including osteoporosis, osteoarthritis, bone defects, and bone tumors, to promote the development and clinical translation of novel therapeutic strategies for orthopedic disorders, and to provide references and guidance for researchers in orthopedic basic research, drug development, regenerative medicine, and clinical orthopedic practice. Accordingly, this review is intended for orthopedic researchers, clinicians and biomaterial scientists focusing on high-throughput screening and orthopedic therapeutic development.

OBJECTIVE: Obstructive sleep apnea (OSA) is associated with chronic low-grade systemic inflammation. In cases of continuous positive airway pressure (PAP) failure, hypoglossal nerve stimulation (HNS) is a treatment option for OSA but its impact on systemic inflammation to date is unknown. Herein, we investigated changes in cytokines and endothelial markers before and after HNS. METHODS: Eighteen adults with moderate or severe OSA underwent fasting blood sample collection before and 6-8 months after HNS implantation. Plasma levels of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), vascular endothelial growth factor (VEGF), angiopoietin-2 (Ang2), C-reactive protein (CRP), and E-selectin were measured using ELISA. Clinical metrics, including apnea-hypopnea index (AHI) and Epworth Sleepiness Scale (ESS), were assessed. RESULTS: HNS significantly reduced AHI (from 25.9 ± 13.4 to 14.2 ± 10.5) and ESS scores (from 12.6 ± 5.0 to 7.1 ± 4.0). There were significant decreases in VEGF ( = 0.033) and TNF-α ( = 0.0013) with HNS. CRP levels were elevated among OSA patients when compared with healthy donors and did not change after HNS. IL-6 levels did not change with HNS, but were low in both healthy and OSA patients. No significant overall changes were observed in Ang2 or E-selectin. Obese participants exhibited higher baseline inflammatory profiles compared with non-obese participants. CONCLUSIONS: In this small cohort, HNS improved OSA severity and was associated with decreases in VEGF and TNF-α while other inflammatory markers were unchanged. Larger, long-term studies are needed to understand the potential of HNS to confer cardiometabolic benefits through reduction of systemic inflammation in OSA.

OBJECTIVE: This study aimed to evaluate the association between coexisting adenomyosis and clinicopathological features in endometrial cancer (EC) patients and to develop an exploratory decision tree model for survival prediction. METHODS: A retrospective analysis was conducted on 400 patients who underwent primary surgery for histologically confirmed EC between 2008 and 2018 at a tertiary academic center. Patients stratified by histopathologically verified adenomyosis status. Clinical and pathological features were compared. Overall survival (OS) and disease-free survival (DFS) were assessed using Kaplan-Meier estimation and multivariable Cox proportional hazards regression, with formal testing of the proportional hazards assumption. As an exploratory adjunct, we trained an interpretable decision tree classifier for vital-status prediction using clinically established prognostic variables. RESULTS: Among 400 women, 69 (17.3%) had adenomyosis and more often presented with early stage disease (97.1% vs 88.5%; OR 0.23, 95% CI 0.05-0.98), less LVSI (10.1% vs 26.3%; OR 0.31, 95% CI 0.13-0.71), and shallower myometrial invasion (OR 2.04, 95% CI 1.15-3.62). In multivariable Cox models, adenomyosis was not independently associated with OS (HR 0.62, 95% CI 0.32-1.20, p=0.153) or DFS (HR 0.78, 95% CI 0.43-1.40). Older age, CA-125 > 35 U/mL, and non-endometrioid histology were independent predictors. The decision tree selected age, LVSI, and deep myometrial invasion ≥50% as primary splitters; adenomyosis was not selected. Test-set performance: accuracy 0.81, balanced accuracy 0.72, AUC 0.76. CONCLUSION: Coexisting adenomyosis in EC is associated with favorable clinicopathological features but does not independently predict OS or DFS after adjustment for established prognostic factors. The exploratory decision tree model identified age, LVSI, and deep myometrial invasion as the primary determinants of survival, while adenomyosis was not selected as a discriminating variable. These findings suggest that adenomyosis reflects a less aggressive disease phenotype but should not serve as a standalone prognostic marker. External validation of the decision tree model on independent cohorts is warranted before clinical application.

PURPOSE: To evaluate whether transpupillary thermal therapy and cryotherapy could improve control of small choroidal melanoma and reduce scleral extension risk. METHODS: A retrospective review identified 30 patients with clinically diagnosed unilateral choroidal melanoma treated sequentially with transpupillary thermal therapy and cryotherapy between 2001 and 2025. Data collected included demographics, tumor characteristics, treatment response, complications, visual acuity, metastasis, and mortality. Treatment failure was defined as the need for brachytherapy or enucleation. An exploratory comparison with a 2008 study of transpupillary thermal monotherapy was performed. RESULTS: All tumors (100%) showed growth prior to treatment. Mean tumor thickness was 1.63 mm (range, 0.50-2.80 mm), and maximum basal linear diameter was 7.80 mm (range, 5.00-12.00 mm). The mean follow-up was 5.80 years. Tumor regression was achieved posttreatment in 97% of cases; 1 patient required brachytherapy. All-cause mortality was 10%, with 1 patient experiencing death from metastatic melanoma. Compared with the 2008 transpupillary thermal monotherapy study (24% treatment failure rate, 32% complication rate, 8% extraocular extension), the current series demonstrated a 3% treatment failure rate, 53% complication rate, and no intrascleral or extrascleral extension. Macular pucker was the most common complication, occurring in 53%. CONCLUSIONS: Sequential transpupillary thermal therapy and cryotherapy may provide effective tumor control for small choroidal melanoma. Sequential transpupillary thermal therapy with cryotherapy was associated with low rates of treatment failure and scleral extension. However, the cohort also had relatively high complication rates for conditions such as macular pucker, vascular occlusion, and refractory cystoid macular edema. Further investigations with larger sample sizes and longer follow-up are warranted to assess the safety and efficacy of sequential transpupillary thermal therapy with cryotherapy.

Pancreatic cancer is one of the most malignant solid tumors, with a five-year survival rate of less than 10%. The therapeutic challenges primarily stem from difficulties in early diagnosis, high heterogeneity, and extensive resistance to chemotherapy, targeted therapy, and immunotherapy. Recent studies have revealed that metabolic reprogramming, a core hallmark of cancer, is a key mechanism driving the malignant phenotype of pancreatic cancer, persisting throughout its initiation, progression, and development of treatment resistance. This article systematically reviews the molecular mechanisms underlying the dysregulation of three major nutrient metabolic pathways-glucose, lipid, and amino acid metabolism-and their interconnected regulatory networks. Regarding glucose metabolism, enhanced aerobic glycolysis and PPP activation collectively support tumor growth, redox maintenance, and microenvironmental remodeling, whereas lactate accumulation further contributes to immune evasion. Lipid metabolic reprogramming is characterized by coordinated alterations in de novo synthesis, fatty acid oxidation, and cholesterol homeostasis, which collectively regulate membrane remodeling, stemness maintenance, and therapeutic resistance. Amino acid metabolism is characterized by glutamine dependency and branched-chain amino acid metabolic reprogramming, which collectively support biosynthesis, redox homeostasis, and tumor adaptation. These three major metabolic pathways do not operate in isolation but form a dynamic, interconnected network. This network confers robust metabolic plasticity and adaptability to the tumor, constituting a fundamental basis for treatment resistance. Concurrently, stromal cells and immune cells within the tumor microenvironment also undergo metabolic reprogramming, forming a metabolic symbiotic system with cancer cells that further exacerbates treatment resistance. Although combination strategies targeting metabolic pathways-such as glycolysis inhibitors combined with gemcitabine, statins synergizing with chemotherapy, or metabolic interventions combined with immunotherapy-have shown promise in preclinical models, clinical translation remains challenging. These challenges arise from multiple factors, including tumor heterogeneity, metabolic compensation, drug delivery limitations, and the complexity of the tumor microenvironment. Future efforts should integrate single-cell metabolomics, organoid models, and multimodal imaging technologies to advance precision therapy based on metabolic subtyping. Additionally, the development of novel nanodelivery systems and multi-target combination regimens is needed to bridge the gap from mechanistic understanding to clinical application. Metabolic intervention holds potential not only for advanced-stage treatment but also for chemoprevention at the precancerous lesion stage, offering a novel approach to improving the prognosis of pancreatic cancer.

OBJECTIVES: To evaluate the prognostic value of peripheral immune markers and their static and dynamic changes during different treatment stages in patients with hepatitis B virus (HBV)-related unresectable hepatocellula carcinoma (uHCC) receiving transarterial chemoembolisation (TACE) combined with immune checkpoint inhibitors (ICIs) and anti-vascular endothelial growth factor (anti-VEGF) antibodies or tyrosine kinase inhibitors (TKIs). METHODS: This single-centre retrospective study included patients with HBV-related uHCC treated with TACE combined with ICls and anti-VEGF antibodies or TKIs between July 2019 and July 2024. Peripheral blood immune indicators were collected at baseline (Cycle 0), the second treatment cycle (Cycle 2) and the fourth treatment cycle (Cycle 4). The primary outcome was overall survival (OS), while secondary outcomes included progression-free survival (PFS), objective response rate (ORR) and disease control rate (DCR), with tumour response assessed at the first treatment evaluation (at the end of the fourth treatment cycle) based on mRECIST criteria. Longitudinal changes between adjacent time points were calculated (Δ: Cycle 2 - Cycle 0; Δ2: Cycle 4 - Cycle 2). Both static values and dynamic changes in immune markers were subjected to LASSO-Cox and stepwise multivariate Cox regression analyses to identify independent predictors of OS. Based on the significant variables, a prognostic nomogram and an immune-based risk score model were developed. To further assess prognostic heterogeneity, patients were stratified by K-means clustering according to the temporal patterns of the most predictive immune marker, and survival outcomes were compared across the resulting subgroups. RESULTS: A total of 67 HBV-related uHCC patients treated with TACE plus ICIs and anti-VEGF antibodies/TKIs were included. The cohort had a median follow-up of 18.2 months, with a median overall survival (mOS) of 30.4 months and a median progression-free survival (mPFS) of 11.0 months. At the first evaluation, the objective response rate (ORR) was 53.7%, and the disease control rate (DCR) was 86.6%. LASSO-Cox regression identified several static and dynamic immune markers associated with OS. Ultimately, CD4⁺/CD8⁺ ratio at Cycle 4 (HR = 0.58,  = 0.035), Δ2 NLR (HR = 1.66,  = 0.014), and Δ2 CD3⁺CD4⁺ (HR = 0.04,  = 0.007) were confirmed by stepwise multivariate Cox regression. A prognostic nomogram incorporating these variables demonstrated favourable predictive performance (C-index = 0.72; AUCs = 0.750, 0.722 and 0.854 for 1-, 2- and 3-year OS, respectively). The derived immune-based risk score effectively stratified patients into high- and low-risk groups with significantly different OS (11.5 vs. 34.0 months,  < 0.001) and PFS (7.5 vs. 13.8 months,  = 0.006). The risk score showed a positive correlation with Δ2 NLR ( = 0.50) and negative correlations with CD4⁺/CD8⁺ ratio ( = -0.64) and Δ2 CD3⁺CD4⁺ ( = -0.45). Based on CD3⁺CD4⁺ trajectory clustering, three distinct immune dynamic subtypes were identified, among which the continuous decline group exhibited the poorest prognosis ( = 0.042). CONCLUSION: This study demonstrates the prognostic relevance of peripheral immune markers in patients with HBV-related uHCC receiving combination therapy. Immune dynamics observed during later treatment stages, rather than baseline measurements, were more strongly associated with overall survival. A risk model based on the CD4⁺/CD8⁺ ratio at Cycle 4, Δ2 NLR and Δ2 CD3⁺CD4⁺ enabled effective prognostic stratification and may provide a useful framework for risk assessment in this patient population.

BACKGROUND: Childhood cancer deaths may be associated with persistent parental grief. Evidence on grief symptoms beyond ten years post-loss remains limited. AIMS: We described grief symptoms, identified grief profiles, and examined associations between grief intensity and sociodemographic, cancer-related characteristics, and time since death. DESIGN: This multicenter cross-sectional survey was conducted in Switzerland (July 2022-July 2023). We used PG-13. Items were rated on a 5-point scale (1-5). We calculated the sum score to assess grief intensity (range 11-55). We employed descriptive statistics, latent profile analysis, and linear regression analyses. SETTING/PARTICIPANTS: Eligible parents had a child diagnosed with cancer (⩽18 years), who had received treatment at one of three participating Swiss pediatric oncology centers and had died ⩾1 year prior to study participation. Participants were identified via the Swiss Childhood Cancer Registry and invited by the child's former treatment facility. RESULTS: Of 388 identified cases, 103 parents of 81 deceased children participated. Mean grief intensity was 23.3 (SD = 9.0); represented the most prominent symptom (mean = 3.2), while was least prominent (mean = 1.3). Latent profile analysis revealed three grief profiles: low (56%), moderate (32%), and high grief (12%). High poverty risk (β = 11.04, p<0.001) and death in healthcare facility (β = 3.82,  = 0.024) were associated with higher grief intensity, while longer time since death was associated with lower grief intensity (β = -5.46,  = 0.041). CONCLUSIONS: Parental grief symptoms can persist long after the death of a child to cancer. Integrated palliative care, anticipatory guidance, and multidisciplinary collaboration may identify at-risk parents early, and ensure sustained support within the community.

The clinical efficacy of photodynamic therapy (PDT) is fundamentally limited by the scarcity of efficient photosensitizers (PSs) and the oxygen dependence of singlet-oxygen-mediated cytotoxicity. Here we report pentaperylene decaimide selenide (PPD-Se), a nanographene-derived photoelectronic material that functions as a high-performance Type-II photosensitizer. PPD-Se exhibits broadband absorption (300-650 nm), enhanced intersystem crossing enabled by a selenium-induced heavy-atom effect, a small ΔE (0.50 eV), and a high O quantum yield (Φ = 0.40). To address hypoxia-limited PDT, PPD-Se nanoparticles were covalently integrated with microalgae to construct an algae@PPD-Se biohybrid, in which PPD-Se is shielded from premature activation yet undergoes glutathione (GSH)-triggered release in the tumor microenvironment. Cleavage of disulfide linkages restores the photosynthetic activity of algae, enabling light-driven O production that alleviates local hypoxia and simultaneously boosts PPD-Se-mediated ROS generation. The biohybrid exhibits enhanced intracellular uptake, amplified ROS production, and potent apoptosis induction under white light-emitting diode (LED) irradiation (400-700 nm, 1 mW·cm). In vivo, algae@PPD-Se significantly downregulates HIF-1α, restores intra-tumoral oxygenation, and achieves marked tumor growth inhibition without observable systemic toxicity. This study introduces a dual-functional optoelectronic-biological PDT platform that couples a newly designed nanographene photosensitizer with photosynthetic oxygenation, offering a mechanistically driven strategy to overcome the oxygen dependency of PDT.

BACKGROUND: Although salvage surgery after photon-based chemoradiotherapy for esophageal squamous cell carcinoma (ESCC) is high risk, the safety of salvage surgery after proton beam-based chemoradiotherapy (PBC) remains unclear. This study aimed to evaluate the short- and long-term outcomes of salvage surgery after PBC. METHODS: This single-arm retrospective case series included patients who underwent curative-intent salvage surgery for residual or recurrent ESCC after PBC between June 2009 and February 2020. Salvage surgery included esophagectomy with lymph node dissection or resection of recurrent lymph nodes. The primary outcome was major morbidity (Clavien-Dindo grade ≥III). RESULTS: The study enrolled 19 patients with a median age was 64 years. Of the 19 patients, 12 underwent esophagectomy, and 7 underwent lymph node resection. Major morbidity occurred for 9 patients (47.3%). No operative mortality occurred. The median overall survival was 16.2 months. The 1-, 3-, and 5-year overall survival rates were 68.0%, 43.1%, and 35.9%, respectively. CONCLUSION: Salvage surgery after PBC for ESCC remains a high-risk procedure, and its feasibility should be carefully assessed on a case-by-case basis.