Journal of the Chinese Medical Association : JCMA最新文献

Background: Boron neutron capture therapy (BNCT) is a targeted form of particle radiotherapy (RT) that better spares normal tissues than does conventional photon RT. We describe our experience with compassionate-use BNCT for locally recurrent nasopharyngeal cancer (rNPC) after prior RT.

Methods: Data from patients with rNPC who received BNCT outside of clinical trials at the Tsing-Hua Open-Pool Reactor between 2020 and 2024 were retrospectively analyzed.

Results: Ten patients (eight men and two women) with a median age of 54 years and recurrent stage T2-T4N0-N1 disease were included. The median radiation dose before BNCT was 70 (range: 70-124) Gy. For the initial BNCT session, the median average tumor dose was 16.4 (range: 11.7-25.1) Gy-Eq delivered in a single fraction. Two patients underwent a second BNCT session for residual or recurrent disease at 3 and 12 months after the first, respectively. The median follow-up period was 10.7 (range: 2.2-50.9) months. Overall, one complete response and one partial response were observed after one or two BNCT sessions among eight evaluable cases. The most common acute toxicities were low-grade mucositis and dermatitis. No cases of carotid blowout syndrome were reported. Temporal lobe necrosis occurred in one patient who received two BNCT sessions. The 1-year overall survival rate was 44.4%, and the 1-year progression-free survival rate was 33%. One patient survived for more than 4 years.

Conclusion: In this small cohort of patients with recurrent NPC, compassionate BNCT with moderate doses yielded a 25% response rate and one long-term survivor (4 years). Protocol modifications involving adjusted dose-fractionation schedules and combination with other treatment modalities in future prospective trials may improve the outcomes for recurrent NPC.

Background: The efficacy and safety of preservative-free timolol (PF-timolol) vs preserved timolol (P-timolol) have not been compared in patients with primary open-angle glaucoma (POAG) or ocular hypertension (OHT).

Methods: In this randomized, crossover, single-center study, patients received PF-timolol twice daily or P-timolol once daily for 6 weeks, followed by crossover to the alternate treatment for 6 weeks. The primary endpoint was the change in intraocular pressure (IOP) between treatment groups. Secondary endpoints were tear film breakup time (TBUT), superficial punctate keratopathy (SPK) score, conjunctival hyperemia, systemic vital signs, and patient-reported symptoms.

Results: Thirty-four patients (mean age 58.1 years; male 50%) were enrolled. At baseline, mean IOP was 13.6 ± 2.7 mmHg (right eye, OD) and 13.4 ± 2.7 mmHg (left eye, OS). At week 6, PF-timolol led to a greater reduction in IOP in the OD vs P-timolol (-1.3 ± 1.5 mmHg vs -0.2 ± 1.2 mmHg; p = 0.004), whereas no significant difference was observed in the OS ( p = 0.08). At week 12, the mean IOP did not differ between the two groups for both eyes. TBUT increased in the PF-timolol group but decreased in the P-timolol group ( p = 0.006), and the change from baseline favored PF-timolol ( p = 0.001). The SPK score decreased significantly more in the OD in the PF-timolol group than P-timolol group (-0.4 ± 0.8 4 vs 0.2 ± 1.1; p = 0.03). S ystemic vital signs remained stable throughout the study. Patient-reported symptoms were comparable between groups.

Conclusion: PF-timolol eye drops achieved a greater IOP reduction at week 6 but showed comparable efficacy to P-timolol by week 12, while providing additional advantages in ocular safety outcomes and subjective tolerability. PF-timolol offers an effective and safer option for glaucoma management, particularly in patients sensitive to preservatives.

Background: The role of adjuvant concurrent chemoradiotherapy (CCRT) in stage III gastric cancer remains unclear, particularly after D2 lymphadenectomy. While CCRT may benefit patients with residual disease, its value for patients with R0 resection remains uncertain. Accordingly, this study evaluated the survival effect of adjuvant CCRT in R0 and non-R0 resection groups.

Methods: We retrospectively reviewed the medical records of patients with stage III gastric adenocarcinoma who underwent gastrectomy with D2 lymphadenectomy between January 2011 and June 2024. Patients were stratified by resection margin (R0 vs non-R0) and receipt of adjuvant therapy. Propensity score matching (PSM) was performed to adjust for baseline imbalances. Overall survival (OS) was analyzed using Kaplan-Meier and Cox regression analyses.

Results: A total of 559 patients were included, of whom 483 (86.4%) underwent R0 resection and 76 (13.6%) underwent non-R0 resection. Overall, 78.9% received adjuvant therapy, with CCRT more frequently used in the non-R0 group (28.9% vs 4.6%; p < 0.001). In the non-R0 resection group, both adjuvant chemotherapy and CCRT were associated with significantly improved OS, with CCRT demonstrating additional benefits over chemotherapy ( p = 0.039). After PSM, CCRT was associated with a nonsignificant trend toward improved OS (34.2 vs 28.4 months, hazard ratio: 0.55, 95% confidence interval: 0.26-1.15; p = 0.096) compared with chemotherapy. In matched patients with R0 resection, no survival benefit was observed with CCRT (24.1 vs 36.0 months, hazard ratio: 1.29, 95% confidence interval: 0.56-2.98; p = 0.550).

Conclusion: Adjuvant CCRT was associated with a trend toward improved survival in patients with non-R0 resection. However, it was not associated with additional survival benefits compared with chemotherapy in patients undergoing R0 resection after D2 lymphadenectomy, indicating that systemic therapy alone may be sufficient. These findings support the selective use of CCRT and underscore the need for prospective studies to optimize adjuvant strategies.

Background: Sarcopenia, characterized by a progressive loss of muscle mass and strength, is increasingly recognized in aging populations. Although gut hormones may play a role in sarcopenia pathogenesis, their clinical relevance remains unclear. In this study, we investigated whether circulating cholecystokinin (CCK) is associated with sarcopenia and its effects on myogenesis.

Methods: From 2018 to 2022, 179 adults (aged ≥65 years) at the Taipei Veterans General Hospital were enrolled and classified as having sarcopenia or not based on the 2019 Asian Working Group for Sarcopenia criteria. Comprehensive geriatric assessments, including Mini-Nutritional Assessment Short-Form (MNA-SF), Instrumental Activities of Daily Living (IADL), and bioelectrical impedance analysis were performed. Circulating levels of CCK, ghrelin, glucagon-like peptide-1 (GLP-1), and peptide YY were measured from blood samples collected at enrollment. In the experimental arm, murine C2C12 myoblasts were cultured and exposed to different concentrations of CCK. Myogenic differentiation was assessed by western blotting of MYH1/2 expression, and myotube fusion was quantified using immunofluorescence-derived fusion indices.

Results: The enrolled participants comprised 84 non-sarcopenic and 95 sarcopenic subjects. Compared with the non-sarcopenic group, sarcopenic individuals had significantly higher serum levels of CCK and GLP-1, lower MNA-SF scores, Barthel Index, IADL scores, and higher frailty prevalence. In multivariate logistic regression analysis, age, BMI, and MNA-SF remained significant independent predictors of sarcopenia. However, after adjustment, CCK was not independently associated with sarcopenia. In vitro, CCK had no significant effects on early myoblast differentiation, although it significantly inhibited myotube fusion, indicating specific disruption of a key step in muscle development.

Conclusion: Although CCK was not independently associated with sarcopenia after adjustment, elevated serum CCK and its inhibitory effects on myotube fusion indicate a potential pathophysiological role in muscle degeneration.

Background: This study aimed to establish a targeted fetal next-generation sequencing (NGS) panel and evaluate its diagnostic yield in sonographically normal fetuses.

Methods: A retrospective analysis was conducted on 1,820 cases of sonographically normal fetuses who underwent fetal NGS targeted panel testing, based on parental requests, between June 2021 and June 2023.

Results: Among the 1,820 cases analyzed, 833 cases (45.8%) showed no anomalies, 893 cases (49.1%) were identified with abnormal carrier statuses, and 94 cases (5.2%) exhibited pathogenic condition. The most frequently identified condition was glucose-6-phosphate dehydrogenase (G6PD) deficiency, with hemizygous mutations observed in 35 cases. This was followed by homozygous pathogenic variants in the GJB2 gene, identified in 19 cases. Additionally, 83 cases exhibited G6PD gene mutations, and 344 cases were identified as carriers of GJB2 gene variants. Other notable findings included 15 cases of familial hypercholesterolemia, 5 cases of Noonan syndrome, and 2 cases of osteogenesis imperfecta. Rare disorders identified were Wilson's disease, cystic fibrosis, Cockayne syndrome, and ototoxic hearing loss, each occurring in a single case.

Conclusion: The study demonstrated that the fetal NGS targeted panel yielded critical findings in 5.16% of sonographically normal fetuses, emphasizing its potential in prenatal diagnostics. Effective screening requires careful variant selection and detailed pre- and post-test genetic counseling to ensure clinical relevance and informed decision-making for parents.

Background: The clinical significance of programmed death-ligand 1 (PD-L1) expression in epithelial ovarian cancer (EOC), particularly its association with platinum resistance (PR) and prognosis, remains unclear. This study aimed to evaluate the relationship between PD-L1 expression and PR in EOC and investigate cisplatin-induced PD-L1 modulation using in vitro and in vivo models.

Methods: We retrospectively analyzed 189 patients with EOC, treated between 2014 and 2020. Tumor PD-L1 expression was assessed by immunohistochemistry (IHC) using the combined positive score (CPS). Serum PD-L1 levels were measured using enzyme-linked immunosorbent assay (ELISA). Cisplatin-induced PD-L1 regulation was examined in paired platinum-sensitive (PS: A2780 and ES2) and PR (A2780R and ES2R) cell lines and xenograft models.

Results: High tumor PD-L1 expression (CPS ≥10) was more frequent in PR (38.5%) than in PS patients (19.0%, p < 0.01), and was associated with higher recurrence rates ( p < 0.001) and shorter overall survival ( p < 0.001). Serum PD-L1 concentrations were significantly elevated in patients with endometrioid and clear cell histologies compared with those in the control group ( p < 0.05). In vitro, PD-L1 expression was upregulated in PR cell lines compared with parental PS cell lines and was further increased following cisplatin exposure in a dose- and time-dependent manner. Xenograft models confirmed that cisplatin induces PD-L1 upregulation in both tumor tissue and serum, with more pronounced effects observed in PR tumors.

Conclusion: PD-L1 upregulation (CPS ≥10) is associated with PR, disease recurrence, and poor prognosis in EOC. Endometrioid and clear cell histologic subtypes demonstrated higher baseline PD-L1 expression in our cohort. Cisplatin-induced PD-L1 upregulation represents a tumor-intrinsic response, particularly in PR tumor cells, highlighting PD-L1 as a histology-specific marker of poor prognosis and a potential therapeutic target in platinum-resistant EOC.

Background: Single-large hepatocellular carcinoma (SLHCC) is defined as a solitary tumor that is >5 cm and lacks macrovascular invasion or extrahepatic spread. SLHCC is a distinct clinical subtype with considerable prognostic heterogeneity, and available staging systems offer limited predictive accuracy for this subgroup. Therefore, we aimed to develop a machine learning (ML)-based decision-tree model to improve individualized prognostic stratification of SLHCC.

Methods: This retrospective study included patients with SLHCC who were diagnosed at Taipei Veterans General Hospital between January 2012 and January 2023. The patients were randomly assigned to a training cohort and a validation cohort. Prognostic factors for overall survival (OS) were identified using multivariate Cox regression and incorporated into a decision-tree algorithm. The model performance was evaluated using accuracy and the area under the receiver operating characteristic curve (AUROC).

Results: Among the 477 patients, 307 (64.4%) received curative treatment, and 170 (35.6%) received non-curative therapy. The median age was 70 years, and 77.1% were male. After a median follow-up of 50 months, the 5-year OS rate was 42.0%. Six variables were independently associated with OS: tumor size >10 cm, serum creatinine >1 mg/dL, non-curative treatment, albumin-bilirubin (ALBI) grade 2, fibrosis-4 (FIB-4) score ≥2.67, and serum alpha-fetoprotein (AFP) >20 ng/mL. The decision-tree model incorporated four key variables: treatment modality, creatinine, tumor size, and FIB-4. The model stratified patients into five risk groups. The model's accuracy was 74.3% in the training cohort and 67.1% in the validation cohort, and the AUROCs were 0.756 and 0.706, respectively.

Conclusion: The clinically interpretable ML-based decision-tree model effectively stratifies patients with SLHCC according to prognosis using routine clinical and laboratory data. This model complements conventional staging systems and could support personalized treatment planning and patient counseling in real-world clinical practice.