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[HIFU: Best Practices for Optimal Performance].3 weeks agoHigh-intensity focused ultrasound (HIFU) is a minimally invasive treatment option for selected patients with localized prostate cancer. This article is not intended as an original outcome study but as a practice-oriented expert review and institutional experience report on focal and hemiablative HIFU.
We describe patient selection, preoperative diagnostic assessment and biopsy mapping, intraoperative planning, safety margins, HIFU ablation using EDAP/Focal One(R), the double tap strategy, documentation and follow-up. Institutional practice is explicitly distinguished from evidence-based standards and consensus recommendations.
Reproducible outcomes require concordance between imaging and histological findings, an adequate safety margin around the index lesion, structured intraoperative documentation and a follow-up strategy including PSA kinetics, mpMRI and biopsy when indicated. The double tap strategy is presented as an institutionally established technical modification, with a brief summary of the available group data.
HIFU can be performed safely when carried out in a standardized manner. Treatment quality depends substantially on patient selection, treatment planning, technical execution, and post-treatment follow-up.CancerCare/Management -
[Which Focal Therapy for Whom and When?].3 weeks agoFocal therapy (FT) is used to selectively ablate tumor-bearing regions while preserving as much healthy prostatic tissue as possible. This approach seeks to maintain the functional advantages over radical treatment options - such as radical prostatectomy or radiation therapy - without significantly compromising local tumor control. At present, FT is offered primarily to carefully selected patients with low-risk or early intermediate-risk prostate cancer who do not wish to undergo active surveillance or are considered unsuitable candidates for this approach. Reliable patient selection requires multiparametric magnetic resonance imaging, targeted and systematic biopsies, and a precise assessment of tumor location, tumor volume, and prostatic anatomy.FT procedures can be divided into thermal (e.g., high-intensity focused ultrasound (HIFU) or cryotherapy) and non-thermal ablation methods (vascular-targeted photo-dynamic therapy (VTP) or irreversible electroporation (IRE)). These procedures differ in terms of their mechanism of action, technical implementation, and suitability for specific tumor locations. Consequently, the choice of procedure must be made on a case-by-case basis, taking into account the anatomical characteristics and the physical limitations of the respective technology.The aim of this review is to present the currently available focal therapy techniques with regard to their indications, technical characteristics, limitations, and suitability for different tumor locations. Particular emphasis is placed on identifying the most appropriate treatment modality for a given tumor location. Precise diagnostic evaluation, consideration of tumor location, and the selection of an appropriate ablation technique are essential determinants of treatment success. Given the varying strengths and limitations of the available technologies, centers should offer several complementary techniques to enable individualized treatment tailored to the specific tumor.CancerCare/Management
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6-aminonicotinamide dismantles proliferative and migratory capacities of oral cancer cells via PPP blockade.3 weeks agoCancer cells frequently exploit the Pentose Phosphate Pathway (PPP) to fuel antioxidant defenses and the synthesis of essential biomolecular precursors. It is hypothesized that sustained upregulation of glucose flux through the PPP is crucial for meeting the anabolic demands of cancer cells and mitigating oxidative stress. We investigated whether pharmacological inhibition of the rate-limiting PPP enzyme, glucose 6-phosphate dehydrogenase (G6PD), could decrease proliferation, disrupt cell-cell interactions, and impede migration in oral squamous cell carcinoma (OSCC).
Non-tumorigenic keratinocytes (HaCaT), less invasive (CAL27) and highly invasive (SCC9) OSCC had the G6PD pathway inhibited using 6-aminonicotinamide (6-AN) and then submitted to proliferation, spheroid formation, and cell migration assays.
Inhibition of G6PD significantly decreased cell proliferation, disrupted spheroid integrity, and reduced migratory capacity across both OSCC cell lines, while exhibiting only moderate cytotoxicity towards non-tumorigenic keratinocytes, yielding Selectivity Index (SI) values of 1.47 for CAL27 and 3.39 for highly invasive SCC9 cells.
Given that cancer cells often detach and migrate within challenging microenvironments, the ability of 6-AN to induce metabolic stress and impede both cell-cell interactions and migration highlights its potential as an adjuvant therapeutic strategy against OSCC progression.CancerCare/Management -
Management of Enneking type III pelvic defects: A comprehensive review of biomechanics and reconstruction strategies.3 weeks agoResection of Enneking type III pelvic tumors and the subsequent reconstruction of the anterior pelvic ring pose significant challenges due to their deep anatomical location, limited bone stock, and close proximity to vital viscera and neurovascular bundles. The optimal surgical approach for these defects remains controversial. While non-reconstruction is widely practiced to minimize operative time and infection risks, it can disrupt the load-bridging function of the anterior ring, frequently leading to long-term biomechanical instability, compensatory stress fractures, and pelvic visceral herniation. Osseous reconstruction and three-dimensional (3D)-printed implants have markedly transformed type III pelvic reconstruction by offering precise anatomical matching, porous trabecular networks for biological integration, and restored structural continuity. Many orthopedic oncology centers have adopted osseous and prosthetic reconstruction strategies, leading to reduced visceral herniation and enhanced long-term biomechanical stability. However, most studies are limited to single centers with a small number of cases and short follow-up periods. Furthermore, current surgical decision-making relies heavily on subjective functional scores and personal experience, which provokes biomechanical controversies and highlights the urgent need for standardized, evidence-based guidelines. To provide a comprehensive assessment of this clinical domain, we conducted an analysis of existing literature, encompassing anatomical and biomechanical characteristics, the evolution of reconstruction strategies, and future precision reconstruction technologies.CancerCare/Management
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Older adults with resectable gastric cancer undergoing perioperative chemotherapy or preoperative chemoradiotherapy plus perioperative chemotherapy: A secondary analysis of the AGITG TOPGEAR phase III trial.3 weeks agoTo evaluate treatment adherence, adverse events, and survival in older (≥70 years) adults undergoing perioperative treatment for gastric cancer.
Patients with resectable gastric/gastro-esophageal junction adenocarcinoma (ECOG 0-1) enrolled in the phase III TOPGEAR trial were randomized to perioperative chemotherapy (ECF/ECX or FLOT) alone or perioperative chemotherapy plus preoperative chemoradiotherapy (45 Gy in 25 fractions with concurrent fluoropyrimidine). In this exploratory analysis, treatment completion, grade ≥ 3 adverse events (CTCAE v3.0), surgical outcomes, overall survival (OS) and progression-free survival (PFS) were compared between older and younger adults.
Of the 574 patients enrolled, 135 (24%) were ≥ 70 years. Older adults more frequently required preoperative chemotherapy dose reductions, omissions, or delays (chemoradiotherapy: 55% vs 35%, p = 0.004; chemotherapy: 60% vs 48%, p = 0.087). Rates of grade ≥ 3 adverse events were comparable between older and younger patients (chemoradiotherapy: 66% vs 67%, p = 0.874; chemotherapy: 68% vs 59%, p = 0.220), but older adults more often had hematologic toxicity and grade ≥ 3 diarrhea in the chemotherapy group (56% vs 37%, p = 0.006; 21% vs 6%, p < 0.001). Resection rates, grade 3/4 surgical complications, number of removed lymph nodes, and 30-/90-day mortality were similar by age. OS and PFS were comparable across age groups, with numerically favorable outcomes for older adults (OS: HR 0.86, 95% CI 0.58-1.26 [chemoradiotherapy]; HR 0.75, 95% CI 0.51-1.11 [chemotherapy]; PFS: HR 0.78, 95% CI 0.53-1.15 [chemoradiotherapy]; HR 0.70, 95% CI 0.47-1.03 [chemotherapy]).
Older adults with gastric cancer achieved comparable oncologic outcomes to younger patients, despite more frequent treatment modifications and higher hematologic toxicity.CancerCare/Management -
Effects of Auricular Acupressure Combined With Heat-Sensitive Moxibustion on Gastrointestinal Hormone Levels and Recovery of Gastrointestinal Function After Laparoscopic Colorectal Cancer Surgery.3 weeks agoThis single-center retrospective cohort study aimed to evaluate the efficacy of auricular acupressure combined with heat-sensitive moxibustion in promoting gastrointestinal functional recovery and regulating gastrointestinal hormone levels in patients who underwent laparoscopic colorectal cancer surgery.
A total of 68 patients with colorectal cancer who underwent laparoscopic radical resection at Ningde Municipal Hospital affiliated to Ningde Normal University from January to December 2022 were retrospectively enrolled. According to the postoperative intervention measures received, the patients were divided into an intervention group (n = 34, standard postoperative care plus auricular acupressure combined with heat-sensitive moxibustion) and a control group (n = 34, only standard postoperative care). The primary outcome indicators included the time to first flatus, time to recovery of bowel sounds, and time to first defecation after surgery. The secondary outcome indicators included the incidence and severity of postoperative abdominal distension, abdominal distension scores and bowel sound scores at 12, 24, 48 and 72 h after surgery, and the levels of gastrointestinal hormones (gastrin [GAS], motilin [MTL], gastric inhibitory polypeptide [GIP]) detected by radioimmunoassay before surgery and 5 days after surgery. The clinical data of the two groups were collected and statistically analyzed to compare the differences in each outcome indicator.
There were no statistically significant differences in baseline demographic data, clinical characteristics and operative variables between the two groups (p > 0.05), with good comparability. The time to first flatus, time to recovery of bowel sounds and time to first defecation in the intervention group were significantly shorter than those in the control group (all p < 0.05). At 72 h after surgery, the incidence of abdominal distension in the intervention group (67.65%) was significantly lower than that in the control group (88.24%), and the severity of abdominal distension in the intervention group was milder than that in the control group (p < 0.05). The abdominal distension scores and bowel sound scores of the intervention group at 12, 24, 48 and 72 h after surgery were significantly lower than those of the control group (all p < 0.05). There were no significant differences in the levels of GAS, MTL and GIP between the two groups before surgery (p > 0.05). At 5 days after surgery, the levels of the three gastrointestinal hormones in both groups were changed compared with those before surgery, and the levels of GAS, MTL and GIP in the intervention group were significantly higher than those in the control group (all p < 0.05).
Auricular acupressure combined with heat-sensitive moxibustion can effectively shorten the recovery time of gastrointestinal function, reduce the incidence and severity of postoperative abdominal distension, and effectively regulate the levels of gastrointestinal hormones in patients after laparoscopic colorectal cancer surgery. It is a safe and effective non-pharmacological adjuvant therapy for postoperative clinical management, and is worthy of clinical promotion and application.CancerCare/Management -
Interpreting vaccine-associated survival differences in immune checkpoint inhibitor therapy.3 weeks agoRecent studies proposed that SARS-CoV-2 mRNA vaccination may sensitize tumors to immune checkpoint inhibitor (ICI) therapy through immune modulation. Using 100% national Medicare fee-for-service claims data, we evaluated whether survival differences among vaccinated patients receiving ICIs were specific to mRNA vaccines. Among 121,676 beneficiaries initiating systemic anticancer therapy, including 10,824 initiating ICIs, vaccination near treatment initiation was associated with lower mortality across mRNA COVID-19, adenoviral COVID-19, and influenza vaccines. We found that survival associations and formal vaccine-ICI interaction effects were similar across vaccine platforms. These findings suggest that currently available population-level survival data do not isolate an mRNA-specific tumor-sensitization mechanism.CancerChronic respiratory diseaseCare/ManagementPolicyAdvocacy
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Computational identification and evaluation of Adenium obesum phytochemicals as potential EGFR inhibitors for targeted therapy against non-small-cell lung cancer.3 weeks agoNon-small-cell lung cancer (NSCLC) remains the leading cause of lung cancer-related mortality, largely driven by aberrant activation of the epidermal growth factor receptor (EGFR). Despite the clinical success of EGFR tyrosine kinase inhibitors (TKIs), intrinsic and acquired resistance, coupled with safety concerns, highlight the need for novel, safer inhibitors. Natural products represent an underexplored source of structurally diverse bioactive compounds with favorable biocompatibility. In this study, a comprehensive in silico approach is used to evaluate phytochemicals from Adenium obesum as potential candidate EGFR-targeting compound. Initially, sixteen phytochemicals were first assessed for predicted antineoplastic activity using PASS. High-scoring molecules were docked against the EGFR kinase domain (PDB ID: 1M17), besides performed detailed protein-ligand interaction analysis, drug-likeness and ADMET profiling, toxicity prediction and 100-ns molecular dynamics (MD) simulations. PASS-based bioactivity prediction revealed strong anticancer potential among the sixteen screened compounds, with consistently high antineoplastic and antiproliferative activity probabilities (Pa > 0.79) and low inactivity scores, supporting their selection for subsequent docking, ADMET, and molecular dynamics analyses. Next, several phytochemicals exhibited strong docking affinities, with Cardenolide achieving the highest binding score (-9.9 kcal/mol) and forming stable interactions with key catalytic residues. A 100-ns MD simulation confirmed the structural stability, persistent binding, and dynamic integrity of the EGFR-Cardenolide complex under physiological conditions. Importantly, interaction mapping revealed that Cardenolide engages conserved and functionally critical regions of the EGFR kinase domain associated with catalytic activity and structural stability, supporting its mechanistic relevance as an ATP-competitive scaffold. Additionally, predicted pharmacokinetic and toxicity profiles further supported Cardenolide's suitability as a drug-like candidate. Collectively, these results identify Cardenolide as a computationally prioritized candidate with favorable predicted EGFR-binding characteristics, structural stability, and physicochemical and toxicity profiles. However, as the present study is based entirely on computational analyses, these findings should be considered hypothesis-generating and do not establish EGFR inhibitory activity or therapeutic efficacy. Experimental validation, including biochemical kinase inhibition and cellular assays, is therefore required to determine the actual EGFR inhibitory potential and anticancer activity of Cardenolide. Nevertheless, the findings provide a rational basis for prioritizing Cardenolide for further experimental investigation and illustrate the potential of Adenium obesum phytochemicals as a source of candidate EGFR-targeting compounds for future NSCLC drug discovery.CancerChronic respiratory diseaseCare/Management
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Concordance of PD-1 expression on paired peripheral and bone marrow T cells: Surrogate potential and clinical implications in DLBCL.3 weeks agoBackgroundThe PD-1/PD-L1 axis represents a key mechanism of tumor immune evasion. However, its expression across different immune compartments and clinical implications in DLBCL patients remain unclear.MethodsThis study included 67 newly diagnosed DLBCL patients and 59 healthy controls. The levels of PD-1-positive T cells in the peripheral blood (PB) and bone marrow (BM) were assessed via flow cytometry. Furthermore, this study analyzed the correlation between PD-1 expression on PB and BM T-cell subsets and the clinicopathological features of DLBCL patients to elucidate their clinical implications.ResultsCompared with healthy controls, DLBCL patients presented significantly elevated PD-1 expression on T cells in both the PB and BM. Elevated PD-1 expression is significantly correlated with adverse clinical outcomes and poor prognostic factors, including advanced Ann Arbor stage (III-IV), a high International Prognostic Index (IPI 3-5), elevated lactate dehydrogenase (LDH>250 U/L) and the presence of B symptoms. A strong concordance in PD-1 levels was observed between paired PB and BM samples.ConclusionIncreased PD-1 expression in the peripheral blood of DLBCL patients is correlated with PD-1 expression in the bone marrow. Our results demonstrate that elevated circulating PD-1+T cells are associated with high-risk, aggressive disease features. Importantly, our data support the potential utility of peripheral blood PD-1+T cells as a minimally invasive surrogate biomarker to reflect intramedullary T cell exhaustion. DLBCL patients with abundant circulating PD-1+T cells may have greater potential to respond to PD-1/PD-L1 blockade immunotherapy, although this hypothesis requires prospective validation. These findings warrant further clinical investigation.CancerCare/Management
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PTPN11 variants in four Chinese patients: a case series and genotype-phenotype analysis.3 weeks agoNoonan syndrome (NS) and LEOPARD syndrome (LS) are well-characterized RAS/MAPK pathway-related disorders with strong genotype-phenotype correlations. Most cases of both syndromes are caused by variants in the PTPN11 gene, with specific sites predisposing to either NS or LS. The association between PTPN11 and granular cell tumours (GCTs) remains largely unexplored. To further investigate the phenotypic spectrum of patients with PTPN11 variants. We performed whole-exome sequencing on four Chinese children who presented with café-au-lait macules as the initial cutaneous manifestation. To confirm the mutation, Sanger sequencing was performed on DNA samples obtained from the patient and both parents. Histopathological examination and immunohistochemical staining were performed on a subcutaneous nodule from patient 1 to characterize the lesion. Three PTPN11 variants were identified: c.1391G>C (p. Gly464Ala), c.1403C>T (p. Thr468Met), and c.1493G>T (p. Arg498Leu). Notably, patient 1, who carried the PTPN11 c.1391G>C variant, presented with coexisting granular cell tumours -an association that has not previously been reported for this specific variant. The association with granular cell tumours highlights the clinical importance of long-term surveillance of neural crest-derived neoplasms in PTPN11 variant carriers and broadens our understanding of the diverse phenotypic outcomes associated with PTPN11 variants.CancerCare/Management