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Background/aim: Although prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) is recommended for staging high risk prostate cancer (PCa), recently, it has demonstrated a good accuracy to guide targeted biopsy for the diagnosis of PCa. In this study we evaluated the cost-effectiveness of PSMA PET/CT as single procedure for diagnosis and staging high grade PCa.

Patients and methods: From June 2022 to June 2025 300 men (median age=65 years) underwent transperineal prostate biopsy at Cannizzaro Hospital (Catania, Italy) for suspicion of high grade PCa (PSA ≥20 ng/ml) and/or suspicious digital rectal examination (DRE). All the patients underwent PSMA PET/CT and intraprostatic lesions with a standard uptake value (SUV_max) ≥8 were submitted to targeted biopsies plus extended prostate biopsy. The overall cost of prostate biopsy was calculated using the Italian National Public Health System "Day Service" and "out of pocket" by market research to evaluate the cost of PSMA PET/CT, multiparametric magnetic resonance image (mpMRI), lung and abdominal CT and bone scan.

Results: Median PSA was 29.6 ng/ml (range=20-785 ng/ml) and 135/300 (45%) had positive DRE; a clinically significant PCa was found in 295/300 (98.3%) patients and 270/295 (91.5%) had a Gleason score ≥8/ISUP Grade Group ≥4. Clinical staging by PSMA PET/CT demonstrated: 125 (42.3%) cT2PCa vs. 170 (57.3%) cT3PCa cases; in detail, 86/295 (29.1%) had positive nodes, 42 (14.2%) bone metastases and 29 (9.8%) multiple metastases. The overall cost of the 300 prostate biopsies calculated using the Day Service model was 57,120€; conversely, the cost "out of pocket" of PSMA PET/CT would have been equal to 300,000/450,000€ and its exclusive use would have spared 103,000/300,000€ (25.5-40%) equal to the cost of mpMRI, bone scan, CT and staff trained to perform procedures reducing time of diagnosis and staging from a median of 90 to 45 days.

Conclusion: PSMA PET/CT for diagnosis and staging as a single imaging procedure in men with suspicion high grade PCa, improved cost-effectiveness by reducing cost (25.5-40%), time to the diagnosis and staging, whilst allowing for timely therapy initiation in men with high risk of metastases.

Background/aim: The impact of neoadjuvant chemohormonal therapy (NCHT) on biochemical recurrence-free survival (BRFS) in patients with very-high risk localized prostate cancer remains uncertain, particularly because previous studies have included heterogeneous populations with locally advanced disease. This retrospective study evaluated the clinical significance of NCHT in patients with strictly defined T2-T3a very-high risk disease.

Patients and methods: A total of 49 patients treated between 2017 and 2024 were analyzed; 25 received NCHT consisting of androgen deprivation therapy and estramustine phosphate, while 24 underwent radical prostatectomy without NCHT. All patients received robot-assisted radical prostatectomy with extended lymph node dissection.

Results: Baseline characteristics and pathological outcomes were comparable between the two groups, with a median follow-up period of 19 months in the NCHT group and 29 months in the non-NCHT group. Kaplan-Meier analysis demonstrated no significant difference in BRFS between the groups (p=0.397). In multivariable Cox analysis, primary Gleason pattern 5 was the only independent predictor of BRFS (hazard ratio=3.72; 95% confidence interval=1.19-11.58), whereas NCHT did not confer an oncological benefit.

Conclusion: These findings suggest that for patients with very-high risk prostate cancer limited to T2-T3a disease, NCHT does not improve biochemical recurrence outcomes, and tumor biology-particularly primary Gleason pattern 5-plays a more decisive role in prognosis than neoadjuvant systemic intensification. While cytotoxic therapy combined with androgen deprivation remains of investigational interest, its utility in organ-confined but biologically aggressive prostate cancer appears limited based on current evidence. Further large-scale, prospective studies are warranted to clarify the optimal patient selection for neoadjuvant approaches.

Background/aim: To determine whether methionine restriction using recombinant methioninase (rMETase) enhances the efficacy of ultra-low-dose cisplatinum against lung cancer cells in vitro, and whether combining a methionine-restricted (MR) diet with low-dose cisplatinum can inhibit lung cancer growth in vivo with reduced toxicity.

Materials and methods: Human A549 lung adenocarcinoma cells were treated with rMETase and cisplatinum in vitro. Cell viability was assessed after 72 hours using the WST-8 reagent. The IC₅₀ value of rMETase was determined, and synergy was evaluated by combining rMETase at its IC₅₀ with cisplatinum at its determined IC₁₀-IC₅₀. For in vivo analysis, A549 xenografts were established in nude mice and assigned to four groups: control: standard-dose cisplatinum [6 mg/kg, intraperitoneally (i.p.), weekly]; low-dose cisplatinum (3 mg/kg, i.p., weekly) + a methionine-restricted (MR) diet; or the MR diet alone. Treatments were administered for two weeks, with tumor size and body weight were monitored.

Results: For A549 lung-cancer cells the IC₅₀ value of rMETase was 0.64 U/ml. Combination treatment with rMETase (IC₅₀) and cisplatinum (IC₁₀-IC₅₀) synergistically reduced cell viability compared with either agent alone, even at the IC₁₀ of cisplatinum. In vivo, A549 tumor eradication was observed only in the low-dose cisplatinum + MR diet group. Standard-dose cisplatinum alone and MR-alone showed delayed or limited efficacy. Body-weight loss was minimal in the low-dose cisplatinum + MR group compared with the standard-dose cisplatinum group, indicating reduced systemic toxicity.

Conclusion: Methionine restriction enhances the efficacy of ultra-low-dose cisplatinum on lung cancer cells in vitro. Low-dose cisplatinum in combination with an MR diet prevented lung-cancer growth in nude mice. The present approach of cancer therapy may help reduce platinum-related toxicity and improve treatment outcomes, suggesting further investigation for clinical translation.

Background/aim: In patients with cirrhosis, decreased immune function is observed and is considered to lead to various unfavorable clinical events. Although it is not easy to clinically evaluate the immune status of patients, the Liver Immune Status Index (LISI) was recently proposed as an indicator to estimate the immune status of patients after hepatectomy for hepatocellular carcinoma. We investigated the relationship between the LISI and liver function, nutritional status, and prognosis of patients with cirrhosis.

Patients and methods: The present study analyzed 319 patients with cirrhosis who underwent nutritional assessment using indirect calorimetry at our institution. Associations between LISI values and liver functional parameters, nutritional status, and the prognosis of patients with cirrhosis were assessed.

Results: LISI values increased in line with disease severity and positively correlated with the Child-Pugh and albumin-bilirubin (ALBI) scores. The LISI was inversely associated with the geriatric nutritional risk index (GNRI) value, and the LISI values in patients with protein malnutrition were higher than in those without protein malnutrition. In addition, LISI values were higher in patients with energy malnutrition than in those without. When we classified the patients into two groups according to the median LISI, patients with a high LISI had a poorer prognosis than those with a low LISI.

Conclusion: The LISI was associated with the severity of liver fibrosis, decreased liver function, and malnutrition. In addition, the LISI value was related to a poor prognosis.

Background/aim: Accurate hip-knee-ankle (HKA) alignment plays a crucial role in the success of total knee replacement (TKR). Kinematic alignment (KA) aims to restore the patient's natural joint anatomy to improve postoperative function and satisfaction. Ultrasound, a noninvasive and real-time imaging technique, can identify the center of the femoral head (COFH) and enhance surgical alignment accuracy. This study aimed to evaluate whether ultrasound-guided COFH identification improves postoperative HKA alignment accuracy in KA-based TKR.

Patients and methods: A retrospective analysis of 217 patients who underwent primary TKR at Show Chwan Memorial Hospital (2020-2022) was performed. Patients were divided into a calipered group (without ultrasound) and an ultrasound-guided group. Postoperative alignment and HKA angles were compared between the groups using radiographic measurements and statistical analysis.

Results: The ultrasound-guided group demonstrated significantly improved alignment, with 91.6% of patients achieving postoperative HKA within the safe range (-4° valgus to +5° varus) compared to 81.1% in the calipered group (p=0.029). Moreover, the ultrasound-guided technique reduced the risk of postoperative varus cross-over to valgus by 59%.

Conclusion: Ultrasound-guided COFH identification significantly enhances the accuracy of KA-based TKR, particularly in neutral-type osteoarthritis knees. This noninvasive and real-time approach serves as a valuable adjunct for improving alignment precision and clinical outcomes.

Background/aim: The global COVID-19 vaccination campaign has raised concerns about potential side effects, including cardiac involvement or axillary lymphadenopathy. This study investigated the relationship between COVID-19 vaccination and thallium-201 myocardial perfusion imaging (Tl-201 MPI) findings, aiming to elucidate the impact of the vaccine impact on cardiac health.

Patients and methods: This retrospective analysis enrolled patients referred for MPI examination post-COVID-19 vaccination between June 2021 and January 2022. Eligible participants included symptomatic individuals without prior coronary artery disease (CAD) or with stable CAD, experiencing symptoms within one-month post-vaccination. MPI was conducted post dipyridamole-stress testing, and positive stress test results were further evaluated by cardiac catheterization. The association between vaccination and MPI results, including axillary lymphadenopathy presence, was assessed.

Results: Sixty-four patients were included, with a mean age of 54.7 years, and a predominance of males (64.3%). A notable incidence of positive MPI findings and axillary lymphadenopathy was observed, particularly in patients vaccinated with mRNA vaccines. Among the 15 patients with positive MPI, visible axillary lymphadenopathy was observed in 4 cases (26.7%), compared with 6 of 49 patients (12.2%) with negative MPI. Although this difference was not statistically significant, it suggests a possible trend toward a higher prevalence in the MPI-positive subgroup. Most patients with positive MPI findings had received the Moderna vaccine.

Conclusion: Our findings indicate a potential link between mRNA COVID-19 vaccination and cardiac issues detected via MPI, as well as an increase in axillary lymphadenopathy. Although further prospective studies are warranted to establish causality, our findings underscore the importance of post-vaccination monitoring, particularly in symptomatic patients, and the need of continued efforts to comprehensively assess vaccine safety to help reduce mortality rates.

Background/aim: Oral squamous cell carcinoma (OSCC) has a nearly 50% global mortality. Physalin A (PA) shows anti-cancer activities, but its role in metastasis remains unclear in OSCC cells. This study intended to determine whether PA inhibits OSCC cell migration and invasion and to clarify the underlying mechanisms.

Materials and methods: HSC-3 OSCC cells were analyzed using wound-healing, migration, and invasion assays. Atomic force microscopy (AFM) was used to assess morphological changes. Western blotting examined E-cadherin (E-cad), matrix metalloproteinases (MMPs), and urokinase plasminogen activator (uPA). A Ras^V12/scrib^-/- Drosophila model evaluated in vivo tumor suppression.

Results: PA significantly reduced wound closure, migration, and invasion in HSC-3 cells. AFM showed decreased cancer-related morphological alterations. PA increased E-cadherin and reduced MMPs and uPA. PA also inhibited growth factor receptor-bound protein 2 (Grb2)/Ras and phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)/nuclear factor-kappa B (NF-kB) signaling. In vivo, PA suppressed tumor formation and metastasis in Ras^V12/scrib^-/- genotype Drosophila.

Conclusion: PA attenuates HSC-3 OSCC cell migration and invasion by regulating Grb2/Ras, PI3K/Akt/NF-kB, and MMP/uPA pathways, suggesting its potential as an anti-metastatic agent for OSCC.

Background/aim: Allogeneic (allo-) hematopoietic cell transplantation (HCT) may confer a survival advantage in a selected population of patients with relapsed and refractory multiple myeloma (R/R MM), however, additional data are needed to identify the patients who will benefit the most.

Patients and methods: Between January 2000 and December 2024, 32 patients with R/R MM underwent allo-HCT at the Asan Medical Center, Seoul, Korea, and were included in this retrospective study.

Results: Before allo-HCT, complete remission (CR) achievement tended to be associated with better overall survival (OS) compared to partial response and refractory status (67.7% vs. 31.7% and 16.7% at 5 years, respectively, p=0.079). The OS rate was significantly higher in patients who underwent prior autologous (auto-) HCT compared to upfront allo-HCT (47.3% vs. 0% at 5 years, p=0.016). In multivariate analysis, upfront allo-HCT without previous auto-HCT was a significant adverse factor for OS [hazard ratio (HR)=6.248, 95% confidence interval (CI)=1.541-25.330, p=0.010]. In addition, the number of chemotherapy (≥3) before allo-HCT was a significantly independent adverse factor for OS (HR=2.854; 95%CI=1.071-7.602; p=0.035).

Conclusion: In R/R MM after auto-HCT, allo-HCT for patients who attained CR following less than three lines of chemotherapy can still be a promising treatment option with long-term survival.

Background/aim: This study aimed to investigate the effect of sex-related differences on surgical outcomes, postoperative complications, and prognosis in patients undergoing minimally invasive distal gastrectomy (MIDG) for gastric cancer (GC).

Patients and methods: We retrospectively analyzed 988 patients who underwent MIDG for GC at five institutions between January 2018 and December 2024. The patients were categorized according to sex (male or female). To minimize selection bias, propensity score matching (PSM) was performed using the following covariates: age, body mass index, the American Society of Anesthesiologists physical status classification, surgical approach (laparoscopic or robotic), reconstruction method, adjuvant chemotherapy, clinical stage, postoperative complications (Clavien-Dindo classification: CD), and prognoses, including overall survival (OS), relapse-free survival (RFS), and Cancer-Specific Survival (CSS).

Results: Even after the PSM, male patients demonstrated significantly worse outcomes in surgical and long-term settings. Compared with the females, males had a longer median operation time (293 min vs. 274 min, p<0.001) and greater blood loss (median 5 ml vs. 0 ml, p<0.001). Incidence of postoperative complications (CD II) was significantly higher in the male group (15.4% vs. 9.5%, p=0.037) than that in the female group. Multivariate logistic regression analysis identified male sex as an independent risk factor for postoperative complications (odds ratio: 1.727; 95% confidence interval=1.032-2.939; p=0.037). In a multivariate Cox regression analysis, male sex was as an independent risk factor for poorer RFS.

Conclusion: Male patients undergoing MIDG face significantly higher risks of postoperative complications and cancer recurrence than female patients, independent of baseline clinical and pathological factors.

Background/aim: Rheumatoid arthritis (RA) is an autoimmune disease, with synovial inflammation as an important symptom. However, the pathogenesis of RA has not been fully elucidated. Long noncoding RNAs play a role in various biological and pathological situations, and negative regulators of interferon response (NRIR) are long noncoding RNAs that regulate immune reactions. However, the role of NRIR in rheumatoid synovial inflammation remains unclear.

Materials and methods: Cultured human rheumatoid fibroblast-like synoviocytes (RFLS) were treated with a synthetic Toll-like receptor 3 (TLR3) ligand, polyinosinic:polycytidylic acid (poly I:C). Expression of NRIR was examined using reverse transcription-quantitative polymerase chain reaction. RNA interference against interferon-b (IFNB), nuclear factor-kappa B (NFKB) p65, and NRIR was performed by transfecting the cells with specific small interfering RNAs. Interleukin-6 (IL-6) protein levels in the culture medium were measured using an enzyme-linked immunosorbent assay kit. Phosphorylation of NF-kB p65 protein was determined using western blotting.

Results: Treatment of cultured RFLS with poly I:C induced the expression of NRIR. Poly I:C-induced expression of NRIR was decreased by the knockdown of IFNB or NFKB p65. IL-6 induction by poly I:C was reduced by knockdown of NFKB p65 or NRIR, but not of IFNB. Knockdown of NRIR did not affect NF-kB p65 phosphorylation.

Conclusion: NRIR is induced by TLR3 signaling in RFLS. IFN-b and NF-kB are involved in NRIR induction via TLR3 signaling. NRIR is at least partially implicated in TLR3-mediated IL-6 expression in RFLS. NRIR may play a role in TLR3/IL-6-mediated inflammatory reactions in RFLS and may be a potential target for new therapeutic strategies against RA.