In vivo最新文献

Background/aim: Esophageal cancer (EC) is a malignant tumor with poor prognosis. Prognostic factors that may be used in the treatment and management of EC are important. The purpose of this study was to evaluate the impact of the hemoglobin, albumin, lymphocyte, and platelet (HALP) score on the long-term oncological prognosis of patients with EC who have undergone curative treatment.

Patients and methods: Patients with EC who underwent curative resection at Yokohama City University between 2000 and 2020 were included. Clinical data were retrospectively retrieved from medical records and analyzed. The HALP score was determined as follows: HALP=[hemoglobin (g/l)×albumin (g/l)×lymphocytes (/l)]/platelets (/l). Kaplan-Meier method and Cox regression model were used to assess the overall (OS) and recurrence-free survival (RFS) and to evaluate the prognostic value of the HALP score.

Results: In total, 180 patients were included in this study. They were classified into the HALP-low (n=110) and HALP-high (n=70) groups using a cutoff value of 40. The 5-year OS rate was 46.9% in the HALP-low group and 66.0% in the HALP-high group (p=0.012). The 5-year RFS rate was 31.1% in the HALP-low group and 51.4% in the HALP-high group (p=0.006). The HALP score was found to be an independent prognostic factor for OS [odds ratio (OR)=1.954, 95% confidence interval (CI)=1.157-3.299, p=0.012] and RFS (OR=1.852, 95% CI=1.197-2.866, p=0.006).

Conclusion: The HALP score is a factor that predicts the oncological prognosis in patients with EC who have undergone radical resection.

Background/aim: Neoadjuvant chemoradiation therapy (nCRT) followed by surgery is recommended for patients with locally advanced rectal cancer (LARC). However, because 30%-40% of patients with LARC do not respond to nCRT, better prediction of treatment responses and survival outcomes is required. Therefore, this study aimed to identify apparent diffusion coefficient (ADC) values that predict survival outcomes after nCRT in patients with LARC.

Patients and methods: We analyzed data from 66 patients with LARC who underwent nCRT and evaluated the ADC values pre- and post-nCRT. Cox proportional hazard regression analyses were conducted to assess survival outcomes.

Results: There were no significant differences in disease-free survival (DFS) and overall survival (OS) between low and high ADC values pre-nCRT. However, patients classified as low ADC in post-nCRT had a significantly worse prognosis in OS and DFS (OS: p=0.01; DFS: p<0.01) than patients classified as high ADC. Moreover, an alteration in ADC values between pre- and post-nCRT was associated with poor OS [univariate, p<0.01; multivariate: p=0.01]. Finally, we identified ADC values that were significantly superior in predicting tumor regression grade, demonstrating remarkable diagnostic accuracy [post-nCRT: area under the curve (AUC)=0.79; alteration-nCRT: AUC=0.85].

Conclusion: We identified the clinical importance of changes in ADC values as a predictor of survival outcomes in patients with LARC. These results highlight the clinical importance of ADC values on improving the treatment strategies of patients.

Background/aim: This study aimed at evaluating the potential benefit of automatic non-coplanar volumetric arc therapy (VMAT) (hyperarc, HA) technique in treating glioblastoma multiforme (GBM).

Patients and methods: Twenty-seven patients with GBM who received coplanar VMAT (C-VMAT) were selected in this study. HA and non-coplanar VMAT (NC-VMAT) plans were generated with the same prescriptions and constraints. The Target coverage, organs at risk (OARs) dose, and dosimetric indexes were compared among three plans.

Results: The HA plan demonstrated a reduction in dose to normal tissues while maintaining target coverage, compared to C-VMAT and NC-VMAT. Additionally, HA plans demonstrated higher coverage of the GTV and PTV₆₀ as well as improved CI from PTV₆₀ and PTV₄₆ compared to the other plans. Regarding the dose gradient, HA plans showed a greater dose fall-off, resulting in reduced high-dose and intermediate-dose spillage at PTV₄₆ The HA also demonstrated a tighter gradient radius at PTV₆₀ and PTV₄₆ The HA plan requires fewer MUs than both C-VMAT and NC-VMAT.

Conclusion: The HA plan had better dosimetric results compared to C-VMAT and NC-VMAT. The HA with automatic planning module and auto-delivery treatment also provided high-quality planning and delivery efficacy. These advantages suggest that HA could potentially escalate tumor doses while minimizing toxicity, thereby improving outcomes in GBM patients.

Background/aim: There is insufficient evidence regarding the optimal treatment for squamous cell lung cancer patients with epidermal growth factor receptor (EGFR) mutations, and a standard treatment strategy has not been established.

Case report: A 60-year-old woman was diagnosed with advanced EGFR-mutant squamous cell lung cancer. She was treated with EGFR tyrosine kinase inhibitors and then received the combined therapy of cytotoxic agents plus immune checkpoint inhibitors as third-line therapy. She was then treated with the fourth-line combination therapy of cisplatin, gemcitabine, and necitumumab, which resulted in a progression-free survival of 5.0 months and shrinkage of the liver metastatic lesion.

Conclusion: The combination therapy of cisplatin, gemcitabine, and necitumumab was effective in treating pretreated EGFR-mutant squamous cell lung cancer in this case. It is necessary to accumulate more evidence to determine the most effective treatment for advanced EGFR-mutant squamous cell lung cancer.

Background/aim: Systemic lupus erythematosus-associated pulmonary arterial hypertension (SLE-PAH) is a severe complication marked by elevated pulmonary artery pressure, leading to exertional dyspnea and right-sided heart failure. Standard treatments frequently fall short in effectively controlling symptoms, highlighting the need for innovative therapeutic approaches. This aim of this study was to investigate the efficacy of molecular hydrogen therapy in a patient with SLE-PAH with decompensated right-side heart failure.

Case report: We present the case of a 51-year-old female diagnosed with SLE-PAH in 2012. Despite treatment with vasodilator agents, her condition worsened following an episode of sepsis, leading to severe dyspnea and oxygen desaturation since 2018. In March 2024, molecular hydrogen therapy was introduced as an adjuvant treatment. The patient received daily hydrogen capsules, which resulted in an increased percentage of Tr1 cells, and a decreased percentage of Treg cell subsets, B cell subsets, marginal cell, and plasma cell. Her clinical symptoms stabilized, and no adverse effects or complications were observed.

Conclusion: This case study highlights the potential efficacy of molecular hydrogen therapy in a patient with SLE-PAD and decompensated right-sided heart failure precipitated by sepsis. Further research is needed to confirm its therapeutic benefits, particularly its ability to modulate immune markers and improve clinical outcomes.

Background/aim: New generation androgen receptor-targeting agents (ARTA) have been in the spotlight for their efficacy in metastatic castration-resistant prostate cancer (mCRPC). Prostate-specific antigen (PSA) represents one of the most commonly used serum cancer biomarkers worldwide. The present retrospective study focused on the prognostic role of serum PSA isoforms and their early dynamics in mCRPC patients treated with abiraterone acetate (ABI) or enzalutamide (ENZ).

Patients and methods: The association between outcomes of 334 mCRPC patients treated with ABI or ENZ and the levels of serum total PSA (tPSA), free PSA (fPSA), [-2]proPSA and the Prostate Health Index (PHI) at baseline and one month after treatment initiation was analyzed retrospectively.

Results: In the multivariable Cox proportional hazards models, baseline tPSA>50 μg/l (p<0.001), and [-2]proPSA>300 ng/l (p=0.017) remained independent significant factors associated with inferior OS, while baseline fPSA>1.75 μg/l (p=0.050) and Δ [-2]proPSA >-50% approached statistical significance (p=0.062). The results of ROC analyses assessing the ability of baseline tPSA, fPSA, and [-2]proPSA to predict mortality within two years showed area under the curve (AUC) values of 0.709, 0.685, and 0.740, respectively. Among the subgroup with baseline tPSA≤20.0 μg/l, the results of ROC analyses for baseline tPSA, fPSA and [-2]proPSA showed AUC values of 0.441, 0.682, and 0.688, respectively.

Conclusion: Our results suggest a significant correlation between pretreatment serum levels of tPSA and [-2]proPSA with OS in mCRPC patients receiving ARTA.

Background/aim: Sepsis-induced acute kidney injury is a fatal, potentially reversible clinical condition. C5a receptor (C5aR) has been implied to play pivotal roles in both autophagy and sepsis-induced organ dysfunction. The aim of this study was to demonstrate the effects of intravenous immunoglobulin preparations on the expression of autophagy markers and investigate possible association between C5aR expression and autophagy in the kidney tissue of septic rats.

Materials and methods: Sepsis was induced by cecal ligation perforation (CLP) in rats, which were divided into control, sham, CLP+saline, CLP+IgG (250 mg/kg, iv), and CLP+immunoglobulins enriched with immunoglobulin M (IgGAM) (250 mg/kg, iv) groups. Kidney samples were obtained in two sets of experiments to examine the early (1 day) and late (10 days) effects of treatment. Renal expression levels of C5aR, LC3A/B, and beclin-1 were measured using immunoblotting.

Results: CLP did not enhance the renal expression of autophagy markers or C5aR. Contrariwise, IgG, and IgGAM administration reduced mortality caused by the CLP procedure and significantly increased C5aR, beclin-1, and LC3A/B expression levels in kidney samples of septic rats. Surviving rats had higher renal expression levels of C5aR, beclin-1, and LC3A/B than deceased rats. Expression levels of C5aR, beclin-1, and LC3A/B showed a strong correlation during the early stage of CLP-induced sepsis but not in the late stage.

Conclusion: Human-derived immunoglobulin preparations may ameliorate sepsis-related organ dysfunction partially through autophagy-related mechanisms. In the early stage of treatment, enhancement of autophagy in the kidney appears to be associated with C5aR expression.

Background/aim: This study aimed to identify the incidence and risk factors for leptomeningeal seeding (LMS) in patients with breast cancer following brain metastasis resection and radiotherapy (RT) and to determine potential candidates for preoperative stereotactic radiosurgery (SRS).

Patients and methods: Between 2012 and 2022, 33 patients with breast cancer underwent surgical resection and postoperative RT for newly detected brain metastases. Twenty-one patients received whole-brain RT, while 12 patients were treated with SRS. Survival and incidence of LMS development were retrospectively analyzed. Several risk factors for the development of LMS were identified.

Results: After a median follow-up of 25.3 months, the 1- and 3-year overall survival (OS) rates were 81.2% and 58.1%, respectively. Development of LMS was the only significant factor affecting OS in multivariate analysis (Hazard ratio=3.08). Significant risk factors for LMS included age ≤45 years, triple-negative breast cancer (TNBC), and piecemeal resection. The 1-year LMS risk was 85.7% for younger patients, 46.2% for those with TNBC or piecemeal resection, and 11.1% for older patients without TNBC undergoing en-bloc resection.

Conclusion: Patients with breast cancer brain metastases who were ≤45 years old, had TNBC, or underwent piecemeal resection were at high risk of developing LMS, regardless of the postoperative RT technique used. Patients with these risk factors are essential candidates for alternative treatment approaches, such as preoperative SRS.

Background/aim: Benign prostatic hyperplasia (BPH) is characterized by the abnormal proliferation of prostate stromal cells, resulting in the enlargement of the prostate gland and the manifestation of troublesome symptoms, such as nocturia, urinary retention, and urinary incontinence. Dihydrotestosterone (DHT) and interleukin-17 (IL-17) are known to be key factors in promoting the overproduction of transforming growth factor-beta (TGF-β) in prostate stromal cells, contributing to their excessive proliferation, leading to BPH.

Materials and methods: In this study, selected plant extracts traditionally used to alleviate urinary symptoms were subjected to primary screening for their anti-proliferative activity by evaluating DHT- and IL-17-induced proliferation in WPMY-1 prostate stromal cells. This was followed by a secondary screening using TGF-β induction.

Results: The extract that significantly inhibited cell proliferation was standardized and further investigated for its anti-proliferative effects through the TGF-β signaling pathway. Results showed that the leaf extract of P. indica significantly inhibited cell proliferation induced by DHT, IL-17, and TGF-β. It was demonstrated that P. indica has anti-proliferative properties via the TGF-β signaling pathways by inhibiting PCNA protein expression and inducing cell accumulation at the G₀/G₁ phase, while reducing the cell population at the S phase. Additionally, it down-regulated the expression of both canonical (p-SMAD2/3) and non-canonical (p-ERK1/2) proteins in TGF-β-induced WPMY-1 cells.

Conclusion: The standardized leaf extract of P. indica showed notable anti-proliferative activity against TGF-β-induced WPMY-1 cells by arresting the cell cycle at the G₀/G₁ phase through the SMAD2/3 and ERK1/2 signaling pathways.

Background/aim: The increased use of robotic rectal surgery has raised concerns regarding the increase in postoperative complications, e.g., compartment syndrome, associated with factors such as the Trendelenburg position, use of the adjustable lithotomy stirrup, and prolonged surgical duration. Therefore, in this study, we evaluated the utility of high-positioning pelvic pads during laparoscopic rectal and sigmoid colon surgeries, which is employed in our institution to maintain a stable body position with reduced head-down tilt.

Patients and methods: We included patients who underwent laparoscopic sigmoidectomy and rectal resection at Shinshu University Hospital between January 2016 and December 2021. We performed two studies: Study 1 compared the short-term treatment outcomes between patients who used high-positioning pelvic pads during surgery and those who did not, whereas Study 2 analyzed factors affecting the time to inferior mesenteric artery division using multivariate analysis.

Results: In Study 1, no significant differences in patient demographics were observed between the groups. The use of high-positioning pelvic pads significantly reduced the overall surgical time and number of gauzes used, with no significant differences in blood loss, complication rates, or duration of hospital stay. In Study 2, we identified intra-abdominal adhesions requiring adhesiolysis and use of high-positioning pelvic pads as factors influencing the time to inferior mesenteric artery division.

Conclusion: The use of high-positioning pelvic pads facilitated surgeries with a reduced head-down tilt, thereby contributing to shorter surgical times. This approach may help decrease the incidence of compartment syndrome, suggesting the need for further prospective trials and studies on robotic surgery.