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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: Tramadol, a centrally acting analgesic, is widely used in postoperative pain management. This study investigates the relationship between CYP2D6 gene polymorphisms and the efficacy of tramadol in patients undergoing total knee arthroplasty.

Patients and methods: A total of 210 participants, including 110 TKA patients and 100 healthy controls, were enrolled. CYP2D6 genotyping was performed using PCR amplification and DNA sequencing. TKA patients received standard postoperative intravenous tramadol (100 mg), and pain intensity was assessed using the visual analogue scale (VAS) at 0, 15, 30, 45, and 60 minutes. Genotype-phenotype distributions and VAS time-course changes were statistically compared.

Results: The extensive metabolizer (EM) phenotype was the most common in the patient group (78.2%). Significant correlations were observed between VAS score changes and CYP2D6*3 and *4 alleles. EM patients demonstrated superior analgesic response to tramadol compared to intermediate metabolizers. Docking results revealed strong binding affinities for tramadol and its metabolites to CYP2D6, ranging from -6.0 to -8.0 kcal/mol.

Conclusion: The CYP2D6 genotype influences tramadol efficacy and side-effect profiles, suggesting that pharmacogenetic testing should guide postoperative pain therapy.

Background/aim: Immune checkpoint inhibitors (ICI), including nivolumab, have become the cornerstone of systemic treatment in metastatic renal cell carcinoma (mRCC). Blood-derived biomarkers including neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and lymphocyte-to-monocyte ratio (LMR) have emerged as important indicators of systemic inflammatory and immune status. The aim of this study was to evaluate the prognostic and predictive value of NLR, PLR, and LMR at baseline and their early dynamics during nivolumab monotherapy in mRCC patients.

Patients and methods: The associations of baseline NLR, PLR, LMR and their changes (Δ) after one month of nivolumab therapy with patient outcomes including progression-free survival (PFS), overall survival (OS) and objective response rate (ORR) were retrospectively analyzed.

Results: In total, 310 patients were included. Baseline NLR ≥4 (PFS: HR=2.136, p<0.001; OS: HR=2.442, p<0.001), PLR ≥310 (PFS: HR=2.383, p<0.001; HR=3.604, p<0.001), and LMR <1.5 (PFS: HR=1.802, p=0.002; OS: HR=2.273, p<0.001) were independent factors for inferior PFS and OS. Regarding early changes, ΔNLR ≥2 (PFS: HR=3.019, p<0.001; OS: HR=3.095, p<0.001) and ΔPLR ≥20 (PFS: HR=1.436, p=0.024; OS: HR=1.719, p=0.006) were independent factors for inferior PFS and OS, while ΔLMR <0 was independent factor for inferior PFS (HR=1.458, p=0.030). Lower ORR was associated with baseline NLR ≥4 (p=0.020), ΔNLR ≥2 (p=0.010), and ΔPLR ≥20 (p=0.019).

Conclusion: The results of the present study suggest a prognostic role for baseline NLR, PLR and LMR. In addition, an early change in NLR and PLR is associated with patient outcome and represents a candidate surrogate biomarker for monitoring the immunotherapy response.

Background/aim: Geotrichosis caused by Geotrichum candidum (G. candidum) is a rarely reported opportunistic infection. Immunocompromised hosts are particularly susceptible to this fungal strain. To shed more light on this opportunistic pathogen and its significance in human disease, we analyzed publicly available data and discussed potential therapies for this fungal strain.

Patients and methods: A systematic online search was conducted, and suitable case reports were retrieved for subsequent retrospective analysis. We eventually selected data on 22 cases for final analysis according to the PRISMA guidelines. To summarize the demographic and clinical variables, descriptive statistical measures were applied. Besides, we contributed one additional case of a leukemia patient with catastrophic G. candidum sepsis from our institution to the data pool.

Results: G. candidum mycosis is frequently deadly for patients with cancer. Leukopenia contributes to higher mortality rates in this vulnerable population. Cancer itself as well as hematological malignancies are more common among non-survivors in this explorative analysis [patients with cancer (n=11) vs. others (n=12), p<0.01; blood cancer (n=8) vs. others (n=15), p<0.05]. We did not detect a consistent association regarding differences in the choice of antifungal compounds for treatment (e.g., amphotericin B/liposomal amphotericin B vs. others) or whether monotherapy or sequential therapy was administered. One patient with acute myeloid leukemia from our center eventually died due to a mixed fungal pneumonia including G. candidum despite broad antifungal treatment.

Conclusion: Although deemed a yeast of low virulence, G. candidum can turn into a deadly germ for immunocompromised hosts. Leukopenia probably aggravates the course of the disease in these patients.