BACKGROUND: To evaluate whether quantitative craniospinal MRI assessment of baseline tumor burden provides prognostic value in patients with recurrent, previously irradiated medulloblastoma undergoing MEMMAT (Metronomic Antiangiogenic) therapy. METHODS: We analyzed craniospinal MRI of 40 patients with recurrent, previously irradiated medulloblastoma enrolled in the MEMMAT trial (April 1, 2014, and March 31, 2021). Ependymal, leptomeningeal, and local relapse lesions were retrospectively manually segmented on T1-contrast-enhanced (T1CE) and diffusion-weighted imaging (DWI) at baseline and follow-up (best response). Lesion count and volume were quantified. Bland-Altman analyses and intraclass correlation coefficients (ICC) assessed inter-sequence agreement., logistic regression evaluated associations between baseline tumor burden and progressive disease. RESULTS: Patients achieving Complete Response (n = 6/40) showed mean monthly decreases of - 12.7% in T1CE lesion count and - 12.9% in volume. Partial Response patients (n = 9/40) showed similar declines (-10.3% and - 13.0%). Stable Disease patients (n = 5/40) demonstrated minimal decreases (-0.8% and - 2.3%). Progressive Disease patients (n = 16/40) showed increases of 33.7% in lesion count and 56.2% in volume. Logistic regression indicated trends toward higher baseline tumor burden predicting PD (volume OR 1.18, p = 0.08; lesion count OR 1.05, p = 0.075). Agreement between T1CE and DWI was limited (ICC 0.35 for lesion count, 0.47 for volume), with 23% of patients misclassified using either modality alone. Survival analyses demonstrated significantly shorter overall survival in patients with baseline lesion volumes ≥ 5.5 ml (log-rank p = 0.003), while a similar association for progression-free survival did not reach statistical significance (p = 0.053). CONCLUSIONS: Combined intracranial and intraspinal T1CE and intracranial DWI assessment improves response evaluation. Exploratory analyses suggested that higher baseline tumor burden may be associated with progression, although the observed associations were of borderline statistical significance and require validation in larger cohorts.

Radiotherapy (RT) is frequently compromised by radioresistance and insufficient immunogenicity. Multiomics analysis here identifies a significant association between glycolysis and DNA damage repair, linking them to RT resistance and poor patient survival. To address this, we develop a mild thermia-guided radiosensitizer, GQD@PDA/Au, which reprograms glycolytic metabolism upon photothermal stimulation to inhibit lactate accumulation. Reduced lactate levels aggravate DNA damage and dsDNA breaks, thereby enhancing tumor radio-immunogenicity by activating the cGAS-STING pathway, inducing tumor ICD, and facilitating dendritic cell maturation. This work develops a clinically translatable platform that overcomes RT resistance and augments antitumor immunity via mild thermia-responsive radiosensitization.

BACKGROUND: Palliative-intent therapies are a key component in the management of metastatic rectal cancer; however, contemporary national trends and disparities in their utilization remain incompletely characterized. METHODS: A retrospective cohort study was conducted using the National Cancer Database (NCDB) from 2012 to 2023. Adult patients with stage IV rectal adenocarcinoma were included. Palliative therapy was defined using the NCDB variable indicating treatment administered with non-curative intent. Temporal trends were evaluated overall and stratified by facility type and median household income. Multivariable logistic regression was performed to identify independent predictors of palliative therapy utilization. RESULTS: A total of 43 443 patients were included, of whom 8931 (20.6%) received palliative-intent therapy. Utilization increased significantly over time, from 16.2% in 2012 to 25.6% in 2023 (p < 0.001). Systemic therapy was the most frequently used modality and increased over time, while surgical palliation declined substantially. Immunotherapy use rose markedly in later years. Palliative therapy utilization increased across all facility types. Across all income strata, utilization also increased, with the most pronounced rise among patients from lower-income areas. On multivariable analysis, lower income (OR 1.82, 95% CI 1.21-2.74), brain metastases (OR 5.75, 95% CI 1.76-18.70), and immunotherapy use (OR 1.65, 95% CI 1.24-2.21) were independently associated with increased odds of receiving palliative therapy, whereas primary tumor resection was associated with reduced utilization (OR 0.45, 95% CI 0.32-0.61). CONCLUSION: In this large national cohort, palliative therapy utilization increased modestly over time, with a shift from surgical to systemic approaches. These patterns, observed across diverse healthcare settings and socioeconomic groups, reflect the evolving integration of palliative-intent treatment in the modern management of metastatic rectal cancer.

BACKGROUND: Retroperitoneal sarcoma (RPS) requires complex surgery with high post-operative morbidity. Prehabilitation aims to optimize the physical, psychological, and nutritional status of high-risk patients before surgery. This study outlines our experience with a multimodal prehabilitation program for RPS patients. METHODS: We retrospectively analyzed 41 patients who underwent RPS resection and participated in prehabilitation (2020-2023) at a tertiary center, describing assessment findings and peri-operative outcomes. RESULTS: A total of 41 patients were included in the analysis out of 132 patients who had surgery for RPS during the specified time period. All participated in a multimodal prehabilitation program, including physical, nutritional, and psychological support. The average program duration was 57 days (range, 42-132). Among 36 (88%) who completed cardiopulmonary exercise testing, the mean respiratory exchange ratio was 1.15 (±0.2), and peak vO2 was 14.9 (±4.1) mls/kg/min. Mean Australia-modified Karnofsky Performance Status (AKPS) was 85 (±10). Seventeen (41%) had an MST score ≥2, indicating malnutrition risk. Mean operative time was 5.7 (±2.4) hours; hospital and ICU stays averaged 12.5 (±8.1) and 1.3 (±1.6) days. Major post-operative complications (Clavien-Dindo ≥ 3) occurred in 9 patients (21%), with 2 (4%) requiring re-operation. CONCLUSIONS: A Multimodal prehabililtation program in retroperitoneal sarcoma is feasible and may be worthwhile for patients at high-risk of perioperative complications.

Talimogene laherparepvec (T-VEC), an intralesional therapy designed to elicit an immunogenic anti-tumor response, has a favorable safety profile in phase II trial and may be an effective second-line therapeutic in sarcoma; however, there is a paucity of data on its therapeutic efficacy. We present a case series of patients who received T-VEC for sarcoma at a high-volume sarcoma center. A total of four patients who had prior progression of disease on immune checkpoint inhibitors (ICI) received a median of 9.5 (range, 4-15) doses of T-VEC over 26.5 (range, 10-49) weeks with a median progression free-survival of 9 weeks (range, 9-10). Only one patient experienced toxicity, which presented as mild flu-like symptoms. This case series of patients receiving T-VEC for sarcoma adds to the literature of intralesional therapies for this rare disease. Our experience suggests that T-VEC may be administered safely and may provide local tumor control in select patients with sarcoma who have failed prior therapy with ICI.

Malignant transformation of a perianal fistula is rare, predominantly associated with chronic fistula. Carcinogenesis is presumably initiated by chronic inflammation, and its mechanism is not clearly understood. We aimed to study the clinicopathologic characteristics and treatment outcomes of patients with malignant perianal fistula. A systematic literature search was performed on the electronic databases of PubMed, Scopus, and Web of Knowledge. A single-arm meta-analysis of non-comparative studies was performed using OpenMeta[Analyst] software. Eleven retrospective studies, including 172 patients (M: 135/F: 37), were included. The mean age of the patients was 56.89 years, and the most frequent presenting complaint was pain. The estimated mean duration of Crohn's disease (CD) was 30.61 years, and the mean duration of fistula before diagnosis was 17.92 years. The most commonly performed procedure was abdominoperineal resection (APR) and the most common histopathological subtype was adenocarcinoma. During the mean follow-up time of 40.56 months, 20.16% of patients had recurrence, and 35.62% of patients died. The pathophysiology of fistula-associated cancer is not well known, has diagnostic challenges, and the literature is sparse in predicting prognosis.

BACKGROUND: Current staging systems for head and neck cutaneous squamous cell carcinoma (HNCSCC), such as AJCC8 and BWH, often fail to adequately stratify high-risk patients, particularly due to the exclusion of important biological and host factors. This study aimed to identify independent prognostic factors for HNCSCC outcomes in the largest multi-institutional retrospective series to date. METHODS: De-identified data from 8,610 primary HNCSCC tumors, treated with curative intent surgery across multiple international centers, were analyzed. Outcomes included local recurrence (LR), locoregional metastasis (LM), distant metastasis (DM), and disease-specific death (DSD). Multivariable Fine-Gray subdistribution hazard regression models with robust standard errors clustered at the patient level were fitted to generate exploratory hypotheses regarding independent hazard determinants. RESULTS: During a median follow-up of 31.4 months (IQR 14.2-52.8), the cumulative incidence was 3.3% for LR, 2.7% for LM, 0.5% for DM, and 1.2% for DSD. Multivariable analysis confirmed that tumor diameter, poor differentiation, deep invasion, and large-caliber perineural invasion (LCPNI) were the strongest predictors, being significantly associated with at least three of the four outcomes. Notably, factors currently excluded from or weighted differently in staging systems also proved critical: Immunosuppression was significantly associated with LR (SHR 2.03) and DSD (SHR 1.70); and lymphovascular invasion (LVI) was independently associated with LM (SHR 3.00). Poor differentiation demonstrated high prognostic impact, being a significant predictor for all four endpoints. CONCLUSION: Tumor diameter, poor differentiation, deep invasion, LCPNI, immunosuppression status, and LVI are the most critical independent factors for HNCSCC prognosis. Our multi-institutional data provide a robust framework for hypothesis generation, highlighting that incorporating host biological features and non-anatomic variables could significantly refine future staging system discussions.

INTRODUCTION: The Brazilian Society of Surgical Oncology (SBCO) developed national guidelines for the rational use of blood concentrates in surgical procedures. METHODS: Between June and December 2024, a multidisciplinary team of 42 experts formulated 48 key questions on the rational use of blood concentrates in surgery. The guidelines were structured in three phases: preoperative, intraoperative, and postoperative. Expert groups performed literature reviews and proposed preliminary recommendations, which were later refined by the coordinators. An adapted grading system was used to assess the level of evidence, and an online voting process determined consensus among experts. CONCLUSION: Implementing a bloodless surgery protocol requires a meticulous and coordinated approach across multiple medical disciplines. Essential elements for success include patient and staff education, comprehensive preparation, and the use of advanced surgical techniques and technologies to optimize outcomes.

BACKGROUND: Rates and predictors of open conversion at robotic adrenalectomy (rRA) are unknown. METHODS: We identified patients treated with rRA (National Inpatient Sample 2009-2019). First, temporal trends in open conversion were assessed using Estimated Annual Percentage Changes (EAPC). Second, multivariable logistic regression models were used to identify predictors of open conversion during rRA. RESULTS: Of 2,292 rRA patients, 286 (12.0%) underwent open conversion. The rates of open conversion decreased over time from 39.2% to 10.2% over the study span (EAPC -15.9%; p = 0.0003). Open conversion patients during rRA were more frequently male (59.0 vs. 53.0%; p = 0.04) and had more comorbidities (Charlson Comorbidity Index [CCI] ≥ 4: 28.0 vs. 17.0%; p < 0.001). In multivariable logistic regression models predicting open conversion, CCI ≥ 4 versus 0-3 (OR: 2.0; p < 0.001) and low versus medium-high surgical volume hospital (OR: 2.0; p < 0.001) were independent predictors. A dose-response effect was observed when CCI and hospital volume were combined. Specifically, the rates of open conversion were respectively 13.9 versus 25.9% in patient with CCI 0-3 versus CCI ≥ 4 at low surgical volume hospitals (p < 0.001). Conversely, the rates of open conversion were respectively 7.7 versus 13.4% in patient with CCI 0-3 versus CCI ≥ 4 at medium-high surgical volume hospitals (p < 0.001). CONCLUSION: The rate of open conversion at rRA significantly decreased over time from 39.2% to 10.2%. Individuals at particularly elevated risk consisted of patients with CCI ≥ 4 in whom rRA is contemplated at low-volume hospitals (25.9%). Relegation of such individuals to medium-high surgical volume hospitals may reduce the conversion rate by half (13.4%).

Bilateral prophylactic mastectomy (BPM) or contralateral risk-reducing mastectomy (CRRM) are considered in CDH1 carriers as a strategy to reduce lobular breast cancer (LBC) risk in women. In this study we aimed to evaluate the overall number of these procedures reported in literature. We conducted a literature search and a scoping review through the PUBMED database. We identified eleven studies eligible for our interest. Overall numbers, frequencies, geographic distribution, family history, and post-operative histopathological findings of BPM or CRRM were the main outcomes considered. Articles reporting information about BPM or CRRM were reported only in Europe and North America. A total of 75 (32.1%) women were treated with any mastectomy (BPM or CRRM), from a population of 234 positive at CDH1 genetic testing; 81.3% of these women, were treated in North America and 18.7% in Europe. In total, 69.3% of surgical procedures were BPM and 30.7% were CRRM; 76.9% of BPMs were performed in North America, and 23.1% in Europe. Instead, 91.3% of CRRMs were reported in North America, and 8.7% in Europe, respectively. A positive family history for BC was documented in 81.8% and post-operative histopathological findings described at least one in situ LBC in nearly all breast specimens. In conclusion, BPM or CRRM were performed in about 1/3 of women with germline CDH1 pathogenic or likely pathogenic variants; studies were reported only in Western countries. Family history for BC in CDH1 carriers and detection of LCIS in post-operative specimens were also frequently described.

For adults with newly diagnosed acute myeloid leukemia (AML) aged ≥ 75 years or considered unfit for intensive induction therapy, the combination of venetoclax (VEN) and hypomethylating agents (HMAs) has become the standard of care. However, real-world data on demographic disparities in treatment uptake among Medicare beneficiaries remain limited. We conducted a retrospective cohort analysis using Medicaire fee-for-service claims to identify factors influencing the receipt of AML-directed therapy. The study included 12,154 patients with newly diagnosed AML who were either ≥ 75 years and/or unfit for intensive induction chemotherapy. Overall, 5,647 patients received treatment, while 6,507 remained untreated. Treatment utilization increased over time. Untreated patients were older than treated patients (81.2 vs 77.9 years). Females were more likely to be untreated than males. Patients diagnosed in 2019 or later were more likely to receive therapy, and among those, 67.3% received VEN-based therapy. No significant differences in treatment receipt were observed by race or geographic residence. These findings suggest that factors extending beyond disease biology, such as age and sex, influence AML treatment uptake in the Medicare population. Management of AML demands a conscious effort to ensure equitable access to treatment and fair representation in clinical trials.

AIM: To synthesise relevant theories and empirical evidence on telehome-based palliative care, with a focus on care delivery, caregiver involvement and service coordination in nursing practice. DESIGN: Integrative review. METHODS: Peer-reviewed studies of telehome-based palliative care for adults with life-limiting illnesses were included if they reported evidence relating to healthcare providers, patients, or family caregivers. Methodological quality was appraised using the Mixed Methods Appraisal Tool. Data were synthesised using thematic synthesis informed by Normalisation Process Theory and a dual supply-demand framework. DATA SOURCES: Eleven electronic databases were searched from database inception to 3 March 2026: PubMed, Web of Science, Embase, Scopus, the Cochrane Library, Ovid, China National Knowledge Infrastructure, Wanfang Data, VIP, Duxiu and Chinese Biomedical Literature Database. RESULTS: Thirty-three studies were included. Telehealth-supported palliative care improved access to specialist support, enabled more proactive symptom management and strengthened continuity of care at home. Implementation, however, depended on the interaction between service design and user capability, with digital literacy, language barriers, caregiver burden and organisational readiness shaping engagement. CONCLUSION: Telehome-based palliative care is a socio-technical and relational care model rather than an isolated digital intervention. Its implementation and sustainability rely on effective alignment between service structures and patient-caregiver needs and capacities. IMPLICATIONS FOR THE PROFESSION AND PATIENT CARE: Nursing leaders and organisations should prioritise workforce digital competence, interdisciplinary coordination, and caregiver-inclusive telehealth design. IMPACT: This review provides an equity-focused framework for developing and implementing telehome-based palliative care. REPORTING METHOD: The review was reported in accordance with PRISMA 2020 and SWiM where applicable. PATIENT OR PUBLIC CONTRIBUTION: No patient or public contribution was involved because this was a review of published literature. REVIEW REGISTRATION: The review protocol was prospectively registered in PROSPERO (CRD420261303371).

Ablation therapy offers a minimally invasive alternative for selected paediatric solid tumour lesions but published outcomes are inconsistently reported. We Performed a scoping review of the literature from 2000 to 2024, including studies reporting ablation in children aged under 18 years with solid tumours. Data on tumour type, anatomical site, ablation modality, treatment indication, reported oncological outcomes, recurrence, and complications were extracted. Thirty-three studies reported 202 children with 304 treated lesions across various anatomical locations. Radiofrequency ablation was the most frequently reported technique, followed by microwave ablation. The liver and lung were the commonest sites treated, and hepatoblastoma and osteosarcoma were the most frequently reported tumour types. Reported local tumour control was generally favourable in selected patients, although definitions of response and recurrence vary substantially between studies. Major complications were uncommon. Ablation appears technically feasible and generally safe in selected children with solid tumours, but the available evidence is limited by small cohorts, retrospective design and marked heterogeneity in case mix and outcome reporting. Prospective multicentre studies with standardised outcome definitions are needed to better define indications, assess safety and clarify how ablation compares with surgical resection in selected patients.

Breast cancer remains a significant clinical challenge, with treatment failure and patient mortality primarily attributable to tumor metastasis. Daucosterol linoleate (DL) was previously isolated from sweet potato (Ipomoea batatas). Using HPLC analysis of ten commercial dried sweet potato products from different regions of China, DL was detected in all samples, with concentrations ranging from 1.24 mg to 6.05 mg per 100 g, confirming its widespread presence in commercially processed sweet potato products. Pharmacokinetic analysis showed that DL exhibited a peak plasma concentration (C) of 1452.28 ng/mL, an elimination half-life (t) of 11.14 h, and a mean residence time (MRT) of 9.62 h, supporting its potential for oral administration. DL significantly suppressed proliferation and migration of MCF-7, 4T1, and MDA-MB-231 cells in vitro and reduced lung metastasis in vivo. Proteomic analysis identified SCD1 as a key molecule mediating the effects of DL. Mechanistically, DL downregulated SCD1 to inhibit epithelial-mesenchymal transition (EMT), as evidenced by decreased expression of N-Cadherin, MMP2, Vimentin, and Snail, alongside increased E-Cadherin expression. Collectively, DL inhibits breast cancer metastasis by downregulating SCD1 and suppressing EMT, supporting its dual potential as a functional food ingredient and adjuvant therapeutic.

BACKGROUND: Accurate assessment of treatment response after neoadjuvant therapy is crucial to select patients with rectal cancer for organ-preserving strategies. Digital rectal examination (DRE) remains a key component of response assessment, but its precise clinical role and the lack of standardized reporting limit its utility. This study aimed to assess variability in DRE reporting and to explore the association between DRE findings at first reassessment and subsequent local oncological outcome within a watch-and-wait pathway, rather than to evaluate DRE as a stand-alone diagnostic test. METHODS: In this retrospective cohort study at a Belgian tertiary referral center, all patients with rectal cancer considered for active surveillance between January 2018 and January 2023 were reviewed. DREs at diagnosis and first post-treatment reassessment were classified as normal or abnormal. Clinical outcomes during surveillance, including sustained clinical complete response (cCR), local regrowth, and salvage surgery, were recorded. For the primary analysis, histopathologically confirmed viable tumor at salvage surgery was classified as residual tumor, whereas sustained cCR for at least 2 years or salvage surgery without viable tumor was classified as no residual tumor. Sensitivity, specificity, positive predictive value, and negative predictive value were calculated descriptively as exploratory estimates of clinical performance within this multimodal surveillance pathway. RESULTS: Among 105 eligible patients, 20 (19.0%) had abnormal DRE findings at first reassessment. Of these, 19 underwent salvage surgery due to clinical suspicion of local regrowth, and 17 (85.0%) had viable tumor confirmed histopathologically. Among the 85 patients with a normal DRE at reassessment, 24 (28.2%) later underwent salvage surgery for suspicion of local regrowth during follow-up, and all had histologically confirmed viable tumor, while 61 (71.8%) maintained a sustained cCR. At the time of later local regrowth or clinical suspicion, 35 of 39 available DRE reports (89.7%) were abnormal. DRE documentation was brief and heterogeneous, typically consisting of one to two free-text sentences. CONCLUSIONS: Within a multimodal watch-and-wait pathway, DRE at first reassessment appears to function primarily as a clinical warning-sign examination rather than as an isolated diagnostic test. A normal DRE does not exclude future residual disease or regrowth, whereas an abnormal DRE should be considered a relevant warning sign within multimodal reassessment. These findings are hypothesis-generating. The marked variability in reporting underscores the need for standardized terminology and structured documentation in rectal cancer response assessment.

BACKGROUND: New long field-of-view (FOV) PET scanners using bismuth germanate (BGO) detectors without time-of-flight (TOF) capability are now available. These systems incorporate deep learning-based TOF (DLb-TOF) models to compensate for the absence of TOF. There is a lack of studies systematically investigating the optimal balance between signal to noise ratio and lesion detectability across a broader range of acquisition times and β-values for these DLb-TOF models. This study aims to evaluate the trade-off between acquisition time, signal-to-noise ratio (SNR) and lesion detectability to guide optimization of clinical protocol. MATERIALS AND METHODS: Twenty patients referred for a clinical [F]fluorodeoxyglucose (FDG) PET scan were included. Each patient received 3.5 MBq/kg of [F]FDG and underwent a whole-body PET acquisition (120 s/bed) on a digital BGO PET/CT (32 cm FOV) 60 min post-injection. Data were reconstructed into images (384 × 384 matrix) representing different acquisition times (120 s, 90 s, 60 s, 45 s, 30 s and 15 s) using BSREM with β-values ranging from 50 to 1100. Three DLb-TOF models (Low, Medium, High) were applied. Volumes of interest were placed in the liver and two avid lesions per patient. SNR were calculated as SUVmean/SD and detectability were calculated as SUVpeak/SUVpeak. RESULTS: SNR increased with longer acquisition times and higher β-values. DLb-TOF models improved SNR across all settings, with the Low DLb-TOF model producing the largest increase. Lesion detectability depended on the acquisition time and β-value. At longer acquisition times (120 s, 90 s), β100 provided the highest detectability, while shorter times (60-15 s) required higher β-value (β300) for optimal detectability. Among DLb-TOF models, the High model gave the best detectability overall, though the Low model performed better at lower β-values. CONCLUSION: SNR increased with higher β-values, longer acquisition times, and DLb-TOF application. Lesion detectability, defined as the ratio of SUV in the lesion to SUV in the liver, depended on the β-value, acquisition time, and the DLb-TOF model used. The Low DLb-TOF model had the best SNR but at the expense of detectability. The optimal parameters for the evaluated BGO PET/CT system, balancing SNR and lesion detectability within a clinical reasonable acquisition time, were 60-90 s with β-values of 500-300, in combination with the Medium DLb-TOF model, when 3.5 MBq/kg [F]FDG was administered.

INTRODUCTION: Enfortumab vedotin plus pembrolizumab (EVP) is the standard first-line treatment for metastatic or locally advanced urothelial carcinoma (m/laUC). Real-world patients frequently present with unfavorable clinical characteristics, raising uncertainty about whether outcomes mirror those of the pivotal EV-302/KEYNOTE-A39 trial. This study assessed effectiveness and safety of EVP in a real-world cohort of patients with m/laUC. MATERIALS AND METHODS: Retrospective multicenter study including patients treated with EVP across 25 German hospitals (between 03/2022 and 08/2025). Treatment delivery and monitoring followed local clinical standards. Adverse events (AEs) were documented per CTCAE v5.0. Responses were assessed locally using RECIST v1.1. Progression-free survival (PFS) and overall survival (OS) were analyzed using Kaplan-Meier methodology. RESULTS: A total of 468 patients (median age = 69 years) were included. The overall response rate (ORR) was 50.2% (partial response:37.4%, complete response:12.8%). Median PFS was 10.2 months (95%CI,8.0-12.7). 12-month and 24-month OS rates were 71.9% and 60.6%, respectively. ECOG PS 0-1 and occurrence of skin toxicity were associated with improved outcomes. Any-grade AEs occurred in 81.8% and grade ≥ 3 AEs in 35.8%. Peripheral sensory neuropathy and skin toxicity were the most common AEs. Ten treatment-related fatal events were recorded. CONCLUSIONS: EVP demonstrated robust effectiveness and manageable toxicity in a large and diverse real-world cohort including patients with divergent histology. Skin toxicity was associated with superior ORR, PFS, and OS. Our findings support EVP as an effective first-line option for patients with m/laUC treated outside clinical trials.

Breast carcinoma is the most prevalent and lethal malignancy affecting females, and it always presents an essential healthcare problem. Doxorubicin (DOX) is a common chemotherapy utilized in treating breast carcinoma, but it also has dangerous side effects. Hence, searching for potent and safe anticancer compounds is urgent. An alkaloid, piperine, mostly found in pepper species, is a naturally occurring substance with anticancer properties. This work aims to assess the anticancer impact of piperine on breast carcinoma cells by potentially inhibiting the γ-secretase/Notch pathway, and to compare its impacts with those of DOX. The anti-proliferative effects of piperine and DOX were evaluated on various human breast carcinoma cell lines (MCF-7, T47D, and MDA-MB-231). Additionally, a flow cytometric analysis was carried out to identify the cell cycle arrest. Moreover, the protein expression levels of Notch-1, γ-secretase components, NICD, c-myc, p21, Bax, and Bcl-2 were assessed. The results demonstrated that among the tested cell lines, MDA-MB-231 cells exhibited the highest sensitivity to piperine treatment, with the lowest IC value (32.37 ± 2.5 µM). At the G2/M phase, piperine and DOX both stopped the cell cycle. Furthermore, piperine and DOX inhibited the Notch signaling by reducing Notch-1, γ-secretase components, and NICD expression. Piperine and DOX also reduced the levels of Notch target proteins, namely, p21 and c-myc. Lastly, both drugs induced apoptosis by elevating Bax and reducing Bcl-2 expression in malignant breast cells. The promise of piperine as a targeted therapy candidate for the treatment of breast cancer is substantially supported by this research.

OBJECTIVES/HYPOTHESIS: Concurrent chemoradiotherapy (CCRT) is an effective treatment for various head and neck cancers; however, CCRT can result in significant swallowing impairment, presumably due largely to dysfunction of the muscles of swallowing, which are within the field of radiation. This translational study examines the mechanisms underlying CCRT-induced muscle dysfunction using (1) a rat model of CCRT and (2) analysis of archival human specimens. METHODS: 131 Sprague Dawley rats were divided into experimental and control groups. Experimental rats received cisplatin and 5-fluorouracil intravenously, followed by 7 Gray radiation daily for 5 days. Rats were further split into three time points: acute (2 weeks), intermediate (5 months), and long-term (10 months), at which time tissue was harvested for analysis. Human samples included preexisting CCRT-treated and age- and sex-matched control muscle samples from head and neck cancer patients. Quantitative analyses of Paired Box Homeotic Gene 7-positive cells (Pax7 in rats; PAX7 in humans), fibrosis, muscle fiber size, and neuromuscular junctions were conducted and compared between groups in both rats and humans. RESULTS: Analysis demonstrated a significant decline in the percent of Pax7/PAX7-positive cells (a marker of muscle stem cells) after CCRT in both rats and humans, increased collagen percent, and decreased muscle percent in rats at 10 months. CCRT was associated with significantly reduced muscle fiber size in human specimens. Neuromuscular junction presence and morphology in rats were not affected. CONCLUSION: This translational study demonstrates significant alterations in head and neck muscles in both a rat model and human specimens from subjects exposed to CCRT. LEVEL OF EVIDENCE: NA.

PURPOSE: Acute portal vein thrombosis (PVT) poses a significant threat to life, with mortality rates ranging from 20% to 50%. However, a clear consensus on the management of acute PVT in children is lacking, and treatment strategies often rely on protocols established for adults. This study summarizes our experience and results in treating acute PVT with heparin combined with urokinase, providing reference data for the diagnosis and treatment of pediatric acute PVT. METHODS: From November 2017 to February 2026, 5 children (2 males and 3 females) experienced acute PVT after surgery in our hospital. The ages of these children ranged from 2 to 14 years (median: 13 years). Among the 5 patients, one had hereditary spherocytosis (HS), one had total splenic infarction caused by myeloproliferative neoplasms (MPNs), and three had Abernethy malformation. Splenectomy was performed in two patients with HS and MPN, and ligation of the portosystemic shunt was performed in the other three patients with Abernethy malformation. Abdominal ultrasound (US) and enhanced computed tomography (CT) were routinely performed at postoperative days 1-7 to detect PVT. An anticoagulant and thrombolytic treatment protocol involving the combined use of heparin and urokinase is implemented in cases of PVT involving the main portal vein and/or superior mesenteric vein (SMV); in this, intravenous heparin is administered continuously at an initial dosage of 20 U/kg per hour with an increased infusion rate to achieve APTT of 60-85 s, and intravenous urokinase is continuously administered at a dosage of 4400 U/kg per hour for 2-6 h every day. After the stabilization or disappearance of the PVT, oral medications, including aspirin and dipyridamole or rivaroxaban, were used for 6 months. The routine follow-up was performed after 1, 3, and 6 months, and every 6 months thereafter. RESULTS: The acute PVT was detected by US and CT in all patients at postoperative days 1-7 (median: 3 days). The thrombus was located in the main portal vein in 3 patients, in the SMV in 4 patients, in the IMV in 3 patients, and in the splenic vein in 4 patients. PVT occurred simultaneously in three or more branches of the portal vein system in 4 patients. One patient experienced severe abdominal pain caused by PVT, and there were no symptoms, including abdominal pain, hematochezia, nausea, or vomiting in the other 4 patients. When portal vein thrombosis is detected, there is a notable elevation in D-dimer levels. The level of D-dimer was gradually reduced, followed by the reduction of PVT after the anti-coagulation and thrombolysis therapy. The usage of heparin combined with urokinase therapy was successful in all patients; one patient developed CTPV but exhibited no symptoms of portal hypertension, whereas the PVT completely resolved in the remaining four patients between after 19 days to 6 months. There was no bleeding caused by anticoagulation or thrombolysis during therapy. The duration of hospitalization after surgery ranged from 15 to 34 days (median: 20 days). The duration of follow-up ranged from 2 months to 4 years (median: 1 year). There was no recurrence of PVT in all patients. CONCLUSIONS: The use of heparin combined with urokinase for the treatment of pediatric PVT is feasible and effective under the premise of ensuring safety. Nevertheless, further verification of its safety and effectiveness is still needed through increased sample size.

Glioblastoma multiforme (GBM) remains a lethal and aggressive malignancy with limited response to standard therapies. This study hypothesized that artesunate, a ferroptosis inducer, enhances the cytotoxic and immunomodulatory efficacy of standard anticancer agents through mechanisms involving oxidative stress-mediated ferroptotic cell death and lipid peroxidation, influencing hypoxia-inducible factor-1α, insulin-like growth factor-1 (IGF-1), and leptin pathways. These pathways collectively regulate tumor proliferation, angiogenesis, and immune evasion; hence, their modulation may sensitize GBM to therapy. The study evaluated the therapeutic potential of artesunate in combination with anticancer drugs using in vitro GL261 glioblastoma cells and in vivo subcutaneous GL261 models. Clinically relevant agents representing distinct mechanisms, temozolomide, cyclophosphamide, paclitaxel, imatinib, and thymoquinone, were tested. Tumor volume, body weight, and serum biochemical parameters (IL-6, IGF-1, HIF-1α, and leptin) were analyzed, along with CD3 + T cell infiltration by immunohistochemistry. Combination treatments, particularly artesunate with temozolomide or paclitaxel, produced marked tumor regression compared with controls. Serum biomarker modulation and enhanced infiltration of CD3 + T cells indicated activation of ferroptotic and immune-mediated anti-tumor mechanisms, with minimal systemic toxicity. Artesunate potentiates the antitumor efficacy of standard chemotherapeutic agents through mechanisms involving ferroptosis and immune modulation, promoting a tumor-suppressive microenvironment. These findings support further mechanistic and translational studies toward developing ferroptosis-driven multimodal therapies for resistant glioblastomas.

PURPOSE: A comprehensive geriatric assessment (CGA) followed by geriatric assessment-guided interventions was demonstrated to reduce treatment-related toxicities CTCAE III°-V° in older adults with cancer undergoing systemic cancer treatments, but implementation remains insufficient. Thus, we aimed to evaluate the feasibility of implementing CGA into routine care and multidisciplinary tumor boards (MDTs) in Germany within a bicentric feasibility trial (DRKS00035569; 19.12.2024). METHODS: Patients ≥ 65 years with positive geriatric screening (G8 < 15 points) and all patients ≥ 70 years received CGA as part of their routine care. Results were presented during MDT discussions to derive treatment recommendations. After CGA, patients were asked for trial participation which included data analysis and a telephone follow-up after 3 months. Clinicians participating in the MDT were asked about the added value of CGA presentation. Primary endpoint was the estimation of patient's willingness to participate with an accuracy of ± 7.5% to inform design for a later (cost) effectiveness trial. RESULTS: 75 patients received CGA (62.5% females). Of those, 72 (96%) agreed to participate (95% confidence interval, [0.8875; 0.9917]). With an accuracy of estimating the willingness to participate of < |7.5%|, the primary endpoint was reached. The median age was 76.7 years (range 69-92 years). A member of the geriatric team attended 2/3 of MDT meetings. Clinicians rated the integration of CGA results predominantly as useful. CONCLUSION: Integration of CGA into routine care of older cancer patients is feasible but will likely require adequate geriatric staffing per center. A larger implementation study, evaluating efficacy and cost-effectiveness in the German healthcare system, is necessary.

PURPOSE: Pediatric colorectal malignancies are rare, with lymphomas- predominantly non- Hodgkin's lymphoma (NHL) representing the most common type, accounting to 0.5-2% of large bowel malignancies. Colorectal NHL can be primary or secondary. This study analyzes the rare manifestations of pediatric colorectal lymphoma and examines their diagnostic challenges and surgical implications. METHOD: A Pubmed search was done with search words "lymphoma of colon pediatric" with filter of last 5 years on 12 Feb 2026. The search comprised of 47 articles, among which 10 relevant articles were selected. After going through the articles, one article was excluded. 9 articles were finally included in the study. RESULTS: Colorectal lymphoma can be a primary malignancy or it can arise in the background of inflammatory bowel disease. It can also be a secondary extension from bulky intra- abdominal lymphoma. Clinical manifestations can present either as flare up of inflammatory bowel disease or colorectal carcinoma or bowel obstruction or acute abdomen. This can lead to potential diagnostic delay and inappropriate escalation of medical therapy, unless early biopsy is performed. The routine use of broad spectrum anti-infectives in lymphoma decreased the gastrointestinal integrity and increased opportunistic infections in the gut, complicating the clinical assessment. Imaging aids in differentiation from epithelial malignancies. It also guides in staging, treatment and operative planning. Rare presentations of colonic lymphoma were its appearance in a child (below five years) on medical management for ulcerative colitis, and in another patient on Vedolizumab for Crohn's disease. Another rare presentation recorded occurrence of primary rectal lymphoma in an eleven year old child. Early presentation (below 10 years) with synchronous colorectal carcinoma and family history of malignancy, suggested an underlying genetic cancer predisposition syndrome. Surgery plays a crucial role in managing complications like perforation, obstruction and intussusception when lymphoma is the lead point. Laparoscopy assisted en-bloc resection is feasible in selected cases. CONCLUSION: Pediatric colorectal lymphomas represent a clinically significant and occasionally misleading entity. While systemic chemotherapy remains the cornerstone of treatment, surgical intervention has a defined role in tissue diagnosis and management of complications. Early recognition and coordinated multidisciplinary care are essential to optimize outcomes.

Acidic extracellular pH (pHe), a hallmark of the solid tumor microenvironment, is closely associated with increased tumor malignancy and therapy resistance. However, the real-time, noninvasive visualization of dynamic pHe changes in vivo remains a formidable technical challenge. In this study, we developed a novel small-molecule ratiometric near-infrared fluorescent probe PSMA-ratio-pH targeting the prostate-specific membrane antigen (PSMA), designed to enable rapid and precise imaging of prostate cancer acidity in living mice. This probe exhibits a pK of 6.4, a value well-suitable for tumor acidity detection, along with dual near-infrared emission, high sensitivity (1250-fold activation), good reversibility, concentration-independent response, robust photostability, and high selectivity. Cellular experiments confirmed its specific anchoring to PSMA on the cell membrane and reliable sensing of pHe. In mouse models of prostate cancer, the probe achieved rapid tumor targeting and ratiometric acidity imaging within 15 min post intravenous injection owing to favorable pharmacokinetics and high PSMA affinity, and was capable of monitoring dynamic pH changes in tumor acidosis. This research provides a powerful molecular tool for the real-time and precise visualization of tumor microenvironment acidity, holding broad application prospects in cancer diagnosis and treatment evaluation.

Interprofessional primary care providers play a central role in delivering palliative care, although it remains challenging to implement. We evaluated a virtual interprofessional education program called CAPACITI, aiming to increase early identification of palliative care needs in the context of interprofessional primary care teams. A three-module two-arm version of CAPACITI was delivered in a randomized controlled trial, with teams assigned to either a self-directed or facilitated learning arm. Participants completed surveys before and after each module, including the Assessment of Interprofessional Team Collaboration Scale-II (AITCS-II). The pre-intervention survey also included the Organizational Readiness to Change Assessment (ORCA) measure. Descriptive statistics, paired -tests, and generalized linear models were conducted. Of the 566 enrolled, 380 (67.1%) completed Module 1, 274 (48.4%) completed Module 2, 202 (35.7%) completed Module 3, and 192 (33.9%) completed all three modules. AITCS-II scores improved significantly ( < .001) following CAPACTI, with no difference between self-directed and facilitated groups for any module. Participants with lower ORCA scores at baseline experienced greatest improvement in team collaboration. CAPACITI demonstrates promise as an effective and scalable intervention to enhance interprofessional collaboration in palliative primary care. These findings support the integration of virtual team-based training as a strategy to strengthen collaborative care across primary care settings.