Background The optimal sequencing of thermal ablation relative to systemic therapy for colorectal liver oligometastases (CLOM) remains controversial, with limited evidence to guide treatment planning. Purpose To compare the long-term survival outcomes of patients with CLOM receiving upfront ablation (UA) versus delayed ablation (DA) in combination with systemic therapies. Materials and Methods Patients with five or fewer CLOM (maximum lesion diameter, <5 cm) from 21 Chinese tertiary hospitals were included in this multicenter cohort study (October 2009 to March 2024). Patients were categorized into UA and DA groups based on the decisions of multidisciplinary teams. UA consisted of microwave ablation followed by adjuvant systemic therapy administered within 1 month. DA involved neoadjuvant systemic therapy (delivered over 2-3 months) combined with subsequent ablation. The primary outcome was progression-free survival (PFS), and a secondary outcome was overall survival (OS), both assessed using multivariable-adjusted Cox regression analysis and Kaplan-Meier survival curves. Procedure-related complication rates were analyzed. Sensitivity analyses, including propensity score matching, inverse probability treatment weighting, and overlap weighting, were performed to adjust for confounders. Results A total of 1047 patients were included (DA group [n = 536]: mean age, 57.53 years ± 10.99 [SD]; 381 male; UA group [n = 511]: mean age, 60.96 years ± 11.77; 356 male). The follow-up duration was 15 years. Median PFS (1.48 vs 0.98 years; hazard ratio [HR], 0.70 [95% CI: 0.61, 0.81]; P < .001) and OS (6.94 vs 4.74 years; HR, 0.70 [95% CI: 0.57, 0.87]; P = .001) were longer in the UA group compared with the DA group. Sensitivity analyses confirmed robustness (PFS HR, 0.67-0.80; OS HR, 0.73-0.77). UA benefits persisted across subgroups, including synchronous metastases (HR, 0.67 [95% CI: 0.55, 0.81]; P = .04) and lesions smaller than 3 cm (HR, 0.68 [95% CI: 0.58, 0.80]; P = .005). Elevated carcinoembryonic antigen levels (≥5 µg/L) and multiple metastases independently predicted worse survival (HR, 1.30 and 1.47, respectively; P < .001 for both). Conclusion UA combined with systemic therapy significantly improved long-term survival compared with DA, with similar complication rates. © RSNA, 2026 Supplemental material is available for this article. See also the editorial by Woodrum in this issue.
To investigate the long-term efficacy of percutaneous thermal ablation (PTA)-based locoregional treatment of patients with hepatocellular carcinoma (HCC) bearing tumors > 3 cm. In this single-center, retrospective study of 359 HCC patients with 587 tumors (5.1 ± 0.021 cm) treated with PTA-based locoregional treatment between 2011 and 2021 was performed. Radiological response was evaluated per lesion on enhanced computed tomography imaging one month after ablation. Local tumor progression (LTP), regional recurrence (RR), disease-free survival (DFS) and overall survival (OS) rates were assessed per patient in follow-up, while a Cox hazards regression analysis was used to determine significant factors associated with OS and DFS. Therapeutic outcomes were assessed in a subgroup analysis of tumor size, number, and the patients’ age after propensity score matching. The mean ± SD follow up duration was 30.0 ± 22.1 months. Complete Response was achieved in 87.7
No randomized trials or large-scale observational studies directly compared thermal ablation (TA) and hepatectomy (HT) for solitary colorectal liver metastases (SCLM) ≤ 5 cm with long-term follow-up. In this multicenter target trial emulation (2009–2024), 1,334 patients with SCLM ≤ 5 cm from 21 Chinese hospitals were enrolled. Propensity score matching (1:1) balanced baseline characteristics, yielding 437 matched pairs. Primary and secondary endpoints were progression-free survival (PFS) and overall survival (OS), respectively. Complications, hospital stay, and costs were analyzed. Sensitivity analyses were performed to evaluate the robustness of the results. After matching, median PFS was 1.81 years (95
Objective:Methotrexate (MTX) is widely used for rheumatoid arthritis (RA) but has poor targeting and significant side effects. This study developed MTX-loaded lipid nanoparticles modified with PVCAM-1 peptide (MTX@LNP-PVCAM-1) to enhance targeting and reduce toxicity. Methods:MTX@LNP-PVCAM-1 was prepared using the thin-film dispersion method. Particle size and morphology were assessed by dynamic light scattering (DLS) and transmission electron microscopy (TEM). Biocompatibility was tested using human umbilical vein endothelial cells (HUVEC) and hemolysis assays. Cellular uptake was examined via fluorescence microscopy, while cytotoxicity and cell migration inhibition were evaluated using CCK-8 and scratch assays. Inflammatory cytokines (IL-1β, IL-6) were measured by ELISA. Distribution in adjuvant-induced arthritis (AIA) rats was observed using in vivo imaging, and safety and anti-inflammatory effects were assessed through blood tests, paw volume, joint scores, and histology. Results:MTX@LNP-PVCAM-1 had an average particle size of 168.5 nm, PDI of 0.142, and zeta potential of -12.1 mV, with spherical morphology. It exhibited pH responsiveness and good biocompatibility. Compared with unmodified MTX@LNP, PVCAM-1 surface modification significantly increased cellular uptake efficiency (p<0.05) and more effectively inhibited the growth (p<0.05), migration (p<0.05), and secretion of inflammatory cytokines (significantly reduced levels of IL-1β and IL-6, p<0.05) of synovial fibroblasts. In animal experiments, the accumulation of MTX@LNP-PVCAM-1 in inflamed sites was significantly higher than that of MTX@LNP (p<0.05), demonstrating good targeting. Moreover, it enhanced the anti-inflammatory effects of methotrexate in AIA rats, significantly reducing paw swelling (p<0.05) and joint clinical scores (p<0.05). Importantly, it had no significant effect on the blood routine indicators of rats (p>0.05), indicating no obvious toxicity. Conclusion:MTX@LNP-PVCAM-1 combines passive and active targeting, delivering MTX efficiently to inflamed sites and reducing toxicity. This approach enhances anti-inflammatory effects in AIA rats, offering a potential strategy for low-toxicity RA treatment.
The Chinese guidelines for ultrasound-guided thermal ablation of thyroid nodules (2024 edition) were jointly initiated by the Ultrasound Committee of Chinese Medical Association, the Interventional Ultrasound Committee of Chinese Association of Ultrasound in Medicine and Engineering, the Ultrasonic Intervention Committee of Chinese Colleges of Interventionalists, and the Oncological Intervention Committee of Chinese Research Hospital Association; 37 multidisciplinary experts in interventional ultrasound, ultrasound medicine, endocrinology, and thyroid surgery participated in the compilation of this guide, which expanded the depth and breadth of the perspective and enhanced the authority of the guide. Based on the systematic review of literature related to ultrasound-guided thermal ablation of thyroid nodules and the professional opinions of experts, the guidelines define the indications and contraindications of thermal ablation, including pre-ablation evaluation and preparation, thermal ablation techniques and operational procedures, post-ablation follow-up, therapeutic effect evaluation, complication prevention and treatment, and the writing of medical documents for ablation. According to the Grading of Recommendations Assessment, Development, and Evaluation (GRADE), a total of 17 objective and comprehensive recommendations were given. The publication and promotion of this guideline will play a positive role in promoting the standardization of ultrasound-guided thermal ablation of thyroid nodules.
Background: There is currently a lack of convincing evidence for microwave ablation (MWA) and laparoscopic liver resection (LLR) for patients ≥60 years old with 3–5 cm hepatocellular carcinoma. Materials and methods: Patients were divided into three cohorts based on restricted cubic spline analysis: 60–64, 65–72, and ≥73 years. Propensity score matching (PSM) was performed to balance the baseline variables in a 1:1 ratio. Overall survival (OS) and disease-free survival (DFS) were assessed, followed by a comparison of complications, hospitalization, and cost. Results: Among 672 patients, the median age was 66 (IQR 62–71) years. After PSM, two groups of 210 patients each were selected. During the 36.0 (20.4–52.4) month follow-up period, the 1-year, 3-year, and 5-year OS rates in the MWA group were 97.6, 80.9, and 65.3% and 95.5, 78.7, and 60.4% in the LLR group (HR 0.98, P =0.900). The corresponding DFS rates were 78.6, 49.6, and 37.5% and 82.8, 67.8, and 52.9% (HR 1.52, P =0.007). The 60–64 age cohort involved 176 patients, with no a significant difference in OS between the MWA and LLR groups (HR 1.25, P =0.370), MWA was associated with a higher recurrence rate (HR 1.94, P =0.004). A total of 146 patients were matched in the 65–72 age cohort, with no significant differences in OS and DFS between the two groups (OS (HR 1.04, P =0.900), DFS (HR 1.56, P =0.110)). In 76 patients aged ≥73 years after PSM, MWA provided better OS for patients (HR 0.27, P =0.015), and there were no significant differences in DFS between the two groups (HR 1.41, P =0.380). Taken together, for patients older than 65 years, the recurrence rate of MWA was comparable with LLR. Safety analysis indicated that LLR was associated with more postoperative bleeding ( P =0.032) and hypoproteinemia ( P =0.024). Conclusions: MWA was comparable to LLR in patients aged 65 years and older. MWA could be an alternative for the oldest old or the ill patients who cannot afford LLR, while LLR is still the first option of treatments for early-stage 3–5 cm hepatocellular carcinoma in capable elderly’s.
BACKGROUND:Ultrasound-guided microwave ablation (MWA) is recommended as a first-line treatment for early liver cancer due to its minimally invasive, efficient, and cost-effective nature. It utilizes microwave radiation to heat and destroy tumor cells as a local thermal therapy and offers the benefits of being minimally invasive, repeatable, and applicable to tumors of various sizes and locations. However, despite the efficacy of MWA, early recurrence after treatment remains a challenge, particularly when it occurs within a year and has a significant impact on the prognosis of the patient. OBJECTIVE:This study aimed to identify the risk factors for early recurrence after MWA in patients with hepatocellular carcinoma (HCC) and establish a predictive model. METHODS:A total of 119 patients with hepatocellular carcinoma (HCC) treated in the Department of Ultrasound at the First Affiliated Hospital of the Air Force Medical University from January, 2020 to April, 2022 were included in this study. Patients were categorized into the early recurrence group and the non-early recurrence group based on whether recurrence occurred within 1 year. We conducted univariate analysis on 29 variables. A predictive model was developed using multiple-factor logistic regression analysis, and a risk column graph was created. RESULTS:A total of 28 patients were included in the early recurrence group, with an early recurrence rate of 23%. Tumor size ≥ 3cm, multiple tumors, AST > 35 U/L, low pathological differentiation, CD34 positive, Ki67 level, quantitative parameters mean transit time (mTT), and rise time (RT) were confirmed as risk factors affecting early recurrence after ablation (P < 0.05). Furthermore, the model constructed based on these 5 predictive factors, including tumor size, tumor number, pathological differentiation, CD34, and quantitative analysis parameter mTT, demonstrated good predictive ability, with an AUC of 0.93 in the training set and 0.86 in the validation set. CONCLUSION:Our research indicates that the risk column graph can be utilized to predict the risk of early postoperative recurrence in patients after MWA. This contributes to guiding personalized clinical treatment decisions and provides important references for improving the prognosis of patients.
BACKGROUND:Researches comparing laparoscopic liver resection (LLR) with microwave ablation (MWA) for 3-5 cm multifocal hepatocellular carcinoma (MFHCC) are rare. MATERIALS AND METHODS:From 2008 to 2019, 666 intrahepatic tumours in 289 patients from 12 tertiary medical centres in China were included in this retrospective study. Propensity score matching (PSM) was performed to balance variables between the two treatment groups over time frames 2008-2019 and 2013-2019 to observe the potential impact of advancements in intervention techniques on overall survival (OS), disease-free progression (DFS) of patients. complications, hospitalization, and cost were compared. RESULTS:Among 289 patients, the median age was 59 years [interquartile range (IQR) 52-66]. 2008-2019, after PSM, the median OS was 97.4 months in the LLR group and 75.2 months (95% CI 47.8-102.6) in the MWA group during a follow-up period of 39.0 months. The 1-year, 3-year and 5-year OS rates in the two groups were 91.8%, 72.6%, 60.7% and 96.5%, 72.8%, 62.5% [hazard ratio (HR) 1.03, 95% CI 0.62-1.69, P =0.920]; The corresponding DFS rates were 75.9%, 57.2%, 46.9%, and 53.1%, 17.5%, 6.2% (HR 0.35, 95% CI 0.23-0.54, P <0.001). 2013-2019, the median OS time was not reached in either group during the 34.0 months of follow-up, the 1-year, 3-year and 5-year OS rates in the two groups were 90.2%, 67.6%, 56.7% and 96.5%, 76.7%, 69.7% (HR 1.54, 95% CI 0.79-3.01, P =0.210); The corresponding DFS rates were 69.6%, 53.9%, 43.3%, and 70.4%, 32.1%, 16.5% (HR 0.68, 95% CI 0.41-1.11, P =0.120). The incidence of major complications was similar in both groups (all P> 0.05). MWA had shorter intervention times, hospitalization, and lower costs. CONCLUSIONS:For resectable MFHCC patients, LLR is preferable due to its lower recurrence rate. For patients who do not qualify for LLR, advances in ablation technology have promoted MWA as a promising alternative.
Background Ablation has been recommended by worldwide guidelines as first-line treatment for hepatocellular carcinoma (HCC), while evidence regarding its efficacy for primary intrahepatic cholangiocarcinoma (iCCA) is lacking. We aimed to study the efficacy of ablation in treating iCCA by comparing its prognosis with surgery. Methods In this real-world multicenter cohort study from January 2009 to June 2022, 10,441 iCCA patients from ten tertiary hospitals were identified. Patients who underwent curative-intent microwave ablation (MWA) or liver resection (LR) for tumors within Milan criteria were included. One-to-many propensity score matching (PSM) at variable ratios (1:n <= 4) was used to balance baseline characteristics. Mediation analysis was applied to identify potential mediators of the survival difference. Findings 944 patients were finally enrolled in this study, with 221 undergoing MWA and 723 undergoing LR. After PSM, 203 patients in the MWA group were matched with 588 patients in the LR group. The median follow-up time was 4.7 years. Compared with LR, MWA demonstrated similar overall survival (5-year 44.8% versus 40.4%; HR 0.96, 95% CI 0.71-1.29, P = .761). There was an improvement in the 5-year disease-free survival rate for MWA from 17.1% during the period of 2009-2016 to 37.3% during 2017-2022, becoming comparable to the 40.8% of LR (P = .129). The proportion of ablative margins >= 5 mm increased from 25% to 61% over the two periods, while this proportion of surgical margins was 62% and 77%, respectively. 34.5% of DFS disparity can be explained by the mediation effect of margins (P < .0001). Similar DFS was observed when both ablative and surgical margins exceeded 5 mm (HR 0.83, 95% CI 0.52-1.32, P = .41). Interpretation MWA may be considered as a viable alternative to LR for iCCA within Milan criteria when an adequate margin can be obtained.
BACKGROUND:Thermal ablation is routinely used for solitary colorectal liver metastases (SCLM), but the added value of adjuvant systemic therapy in SCLM remains unclear. This study aimed to compare the long-term outcomes for SCLM treated by ablation alone (AB) versus ablation plus systemic therapy (AS). METHODS:This multicenter retrospective study using nationwide data from fourteen institutions between October 2010 and May 2023, 369 patients with initial SCLM smaller than 5 cm, no extrahepatic metastases, and colorectal cancer R0 resection treated by thermal ablation were included. The crude analysis was used to analyze eligible cases between the two groups. The propensity score matching to control for potential confounders in each matched group. Subgroup analyses were performed to identify specific survival benefits. RESULTS:61.2% (226/369) of eligible patients were treated with AS and 38.8% (143/369) with AB. During the median follow-up period of 8.8 years, 1-/3-/5-year DFS/OS rates did not differ between the two groups, when analyzed via propensity score matching ( P =0.52/0.08). Subgroup analysis revealed that AS was significantly associated with better OS than AB in patients with plasma CEA >5 ug/l ( P =0.036), T (III-IV) category of primary cancer ( P =0.034), or clinical risk score (1-2) ( P =0.041). In each matched group, the authors did find a significant difference in drug-related adverse events ( P <0.001) between AS group (24.1%, 28/116) and AB group (0.0%, 0/116). CONCLUSIONS:For patients with plasma CEA >5 ug/l, T (III-IV) category of primary cancer, or clinical risk score (1-2), thermal ablation plus systemic therapy appeared to be associated with improved overall survival. Thermal ablation was equally effective in disease-free survival for treating SCLM, whether with or without adjuvant systemic therapy.
Background: Glioblastoma(GBM) has a profound impact on human health, making the identification of reliable prognostic biomarkers pivotal. While PLEKHA4 has been associated with tumor genesis and development, its role in gliomas is still uncertain.Methods: We analyzed PLEKHA4 expression in tumor tissues using the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Additionally, we utilized TCGA data to investigate its impact on prognosis, pathway enrichment, and immune infiltration. In vitro loss-of-function experiments were conducted to elucidate the effect of PLEKHA4 silencing on GBM cell behavior. Results: TCGA and GEO data sets revealed increased levels of PLEKHA4 expression in glioma tissues. Furthermore, we identified a correlation between PLEKHA4 expression and higher disease classification, pathological grading, and poorer prognosis. Silencing PLEKHA4 in vitro resulted in decreased glioma cell migration and increased apoptosis. It also reduced macrophage infiltration and hindered M2 polarization of macrophages.Conclusion: Our findings highlight the pivotal role of PLEKHA4 in GBM pathogenesis and suggest its potential as a diagnostic and therapeutic target for GBM.
Background and Aims The study objective was to compare the effectiveness of microwave ablation (MWA) and laparoscopic liver resection (LLR) on solitary 3-5-cm HCC over time. Approach and Results From 2008 to 2019, 1289 patients from 12 hospitals were enrolled in this retrospective study. Diagnosis of all lesions were based on histopathology. Propensity score matching was used to balance all baseline variables between the two groups in 2008-2019 (n = 335 in each group) and 2014-2019 (n = 257 in each group) cohorts, respectively. For cohort 2008-2019, during a median follow-up of 35.8 months, there were no differences in overall survival (OS) between MWA and LLR (HR: 0.88, 95% CI 0.65-1.19, p = 0.420), and MWA was inferior to LLR regarding disease-free survival (DFS) (HR 1.36, 95% CI 1.05-1.75, p = 0.017). For cohort 2014-2019, there was comparable OS (HR 0.85, 95% CI 0.56-1.30, p = 0.460) and approached statistical significance for DFS (HR 1.33, 95% CI 0.98-1.82, p = 0.071) between MWA and LLR. Subgroup analyses showed comparable OS in 3.1-4.0-cm HCCs (HR 0.88, 95% CI 0.53-1.47, p = 0.630) and 4.1-5.0-cm HCCs (HR 0.77, 95% CI 0.37-1.60, p = 0.483) between two modalities. For both cohorts, MWA shared comparable major complications (both p > 0.05), shorter hospitalization, and lower cost to LLR (all p < 0.001). Conclusions MWA might be a first-line alternative to LLR for solitary 3-5-cm HCC in selected patients with technical advances, especially for patients unsuitable for LLR.
Objective:To investigate the safety and efficacy of echocardiography-guided trans-right-ventricular percutaneous intramyocardial septal radiofrequency ablation (PIMSRA) in a healthy sheep model, and to observe the pathological changes of myocardium in ablation area one year later.Methods:Twelve sheep were divided into PIMSRA group ( n=6) and sham group ( n=6). In PIMSRA group, a radiofrequency (RF) electrode was inserted to the interventricular septum (IVS) with maximum power of 80 Watts for 5 minutes. In the sham group, RF electrode tip was positioned in IVS segment but without the RF power delivery. Electrocardiogram (ECG), echocardiography, myocardial contrast echocardiography(MCE) were performed to assess the efficacy of PIMSRA at postoperative immediately, 2-week, 1-month, 2-month, 3-month, 6-month and 12-month during the follow-up. The following parameters were recorded, including the thickness of ablation area, the systolic wall thickening rate and amplitude of movement of the ablated region, left ventricular outflow tract pressure gradient (LVOT PG), and left ventricular ejection fraction (LVEF), mitral valve early diastolic peak velocity(E), late diastolic peak velocity(A) and the E/A ratio, peak velocity of early diastolic mitral annular motion(E′), peak velocity of late diastolic mitral annular motion(A′), and the E′/A′ ratio.For both groups, the myocardial biomarkers of troponin I, myoglobin and isoenzymes of creatine kinase were tested before the ablation and 3 h after the ablation, and again after 2 weeks. Tissue pathology examinations were performed at the end of study. Results:None of the animals in both groups was observed to have pericardial tamponade during perioperative period.Immediately after the procedure, septal hypokinesis was seen in all PIMSRA group animals, the systolic wall thickening rate and amplitude of movement of the ablated region were significantly decreased ( P<0.001), which was sustained until 12 months.In Sham group, there were no significant differences in the wall thickening rate and amplitude of movement of the operated region(all P>0.05).The thickness of the ablation area in the PIMSRA group was significantly increased immediately after the procedure( P<0.001), decreased to baseline level at 1-week ( P=0.931), and significantly increased at 3-month ( P<0.001).In the Sham group, the IVS thickness was significantly increased immediately after the procedure( P=0.005), decreased to baseline level at 1-week ( P=0.027), then has no further significant changes.There were no significant differences in LVEF, E/A, E′/A′ between PIMSRA and Sham group(all P>0.05).MCE showed the thickness of the ablation area was significantly decreased in the PIMSRA group 12 months after the operation.In both groups, troponin I increased significantly 3 h after the operation(all P<0.005), which decreased to baseline level 2 weeks later(all P>0.05). ECG showed that all the sheep had normal sinus rhythm. Pathological examinations revealed the tissue in the ablation area was fibrotic, having clear boundary with the surrounding normal tissue and no carbonization was observed 1 year later. Conclusions:Echocardiography-guided trans-right-ventricular PIMSRA produced precisely ablated myocardial tissues, reduced the IVS thickness significantly, preserved the global left ventricular function. All the sheep had normal sinus rhythm and without pericardial tamponade in 1 year follow-ups. Echocardiography-guided trans-right-ventricular PIMSRA is a safe and effective minimally invasive treatment for septal reduction therapy.
Background: The postoperative recurrence rate is the main factor affecting the prognosis of hepatocellular carcinoma (HCC) patients, this study sought to investigate the value of contrast-enhanced ultrasound (CEUS) quantitative parameters in predicting the recurrence and the survival of HCC patients after thermal ablation. Methods: The data of 97 patients with pathologically diagnosed HCC who underwent thermal ablation were retrospectively included in this study. The patients had an average age of 46.6 years (range, 23–79 years), and 79 were male and 18 were female. CEUS follow-up was performed at 1- and 3-month after thermal ablation, then at 6-month intervals thereafter for 5 years. CEUS was performed before thermal ablation, and the results were analyzed quantitatively using CEUS perfusion software (VueBox®, Bracco, Italy). The ratios of the CEUS quantitative parameters between the HCC lesions and reference liver parenchyma were calculated. The parameters included the average contrast signal intensity (MeanLin), peak enhancement (PE), rising time (RT), fall time (FT), time to peak (TTP), mean transit time (mTT), perfusion index (PI), Wash-in Area Under the Curve (WiAUC), Wash-in Rate (WiR), Wash-in Perfusion Index (WiPI), Wash-out Area Under the Curve (WoAUC), Wash-out Rate (WoR), and WiAUC + WoAUC (WiWoAUC). The correlations between the preoperative CEUS quantitative parameter ratios, the blood laboratory indexes, postoperative recurrence, and survival were analyzed using log-rank tests and a Cox regression model. Results: The average follow-up duration period was 79 months (range, 5–145 months). The average recurrence time after ablation was 1–127 months, and the median disease-free survival time was 21 months. The 1-, 3- and 5-year survival rates were 96.9%, 92.3%, and 80.6%, respectively. The log-rank tests showed that tumor size, prothrombin time, and WiAUC, WoAUC, and WiWoAUC ratios were predictors of survival, and aspartate aminotransferase was a predictor of recurrence. The Cox regression analysis showed that tumor size [odds ratio (OR): 6.421; 95% CI: 1.434–28.761] and alanine transaminase (OR: 0.88; 95% CI: 0.010–0.742) were predictors of a poor prognosis. Conclusions: CEUS quantitative parameters before thermal ablation and blood laboratory indexes provide potential clinical value for predicting the postoperative recurrence and survival of HCC patients.
BackgroundTrastuzumab-containing chemotherapy is the first-line treatment for advanced gastric cancer (GC) with HER2 positive. Although PD-1 inhibitors significantly improved the outcome of GC patient’s refractory to previous chemotherapy regimens, few studies explore the role of anti-PD-1 therapy overcomes resistance to trastuzumab plus chemotherapy in advanced Epstein-Barr Virus-associated gastric cancer (EBVaGC) with PD-L1 and HER2 positive.Case PresentationWe report a case of advanced EBVaGC in a 45-year-old man presenting with fatigue, dysphagia, and weight loss for several months. Initial endoscopy revealed a large tumor at the gastroesophageal junction. Computed tomography revealed GC accompanied by multiple lymph nodes and hepatic and pulmonary metastases. The immunohistochemistry indicated that HER-2 and PD-L1 were overexpressed, and tumor cells were positive for EBV-encoded small RNA (EBER) by in situ hybridization. Trastuzumab plus DCS was started as first-line chemotherapy with a PFS of 4 months and shifted to trastuzumab plus FOLFIRI or gemcitabine as second-/third-line therapy. After five-cycle nivolumab monotherapy, the patient received partial response and was treated with total radical gastrectomy plus sequential radiotherapy. He continued the postoperative immunotherapy over 30 cycles with a PFS of 28 months. Due to a new abdominal lymph node metastasis confirmed by PET-CT, he received toripalimab as the next-line treatment and achieved complete remission as the best objective response.SummaryWe presented an advanced HER2-positive EBVaGC patient with PD-L1 high expression, refractory to trastuzumab plus chemotherapy, and had a durable clinical benefit sequence with a single dose of the PD-1 inhibitor.
Rheumatoid arthritis (RA) is an inflammatory immune-mediated disease that can lead to synovitis, cartilage destruction, and even joint damage. Dexamethasone (DEX) is a commonly used agent for RA therapy on inflammation manage. However, the traditional administering DEX is hampered by low efficiency and obvious adverse effects. Therefore, in order to efficiently deliver DEX to RA inflamed joints and overcome existing deficiencies, we developed transdermal formation dextran sulfate (DS) modified DEX-loaded flexible liposome hydrogel (DS-FLs/DEX hydrogel), validated their transdermal efficiency, evaluated its ability to target activated macrophages, and its anti-inflammatory effect. The DS-FLs/DEX exhibited excellent biocompatibility, sustainable drug release, and high uptake by lipopolysaccharide (LPS)-activated macrophages. Furthermore, the DS-FLs/DEX hydrogel showed desired skin permeation as compared with regular liposome hydrogel (DS-RLs/DEX hydrogel) due to its good deformability. In vivo, when used the AIA rats as RA model, the DS-FLs/DEX hydrogel can effectively penetrate and accumulate in inflamed joints, significantly improve joint swelling in RA rats, and reduce the destructive effect of RA on bone. Importantly, the expression of inflammatory cytokines in joints was inhibited and the system toxicity did not activate under DS-FLs/DEX hydrogel treatment. Overall, these data revealed that the dextran sulfate (DS) modified DEX-loaded flexible liposome hydrogel (DS-FLs/DEX hydrogel) can prove to be an excellent drug delivery vehicle against RA.
The study objective was to compare the effectiveness of microwave ablation (MWA) and laparoscopic liver resection (LLR) on solitary 3–5-cm HCC over time. From 2008 to 2019, 1289 patients from 12 hospitals were enrolled in this retrospective study. Diagnosis of all lesions were based on histopathology. Propensity score matching was used to balance all baseline variables between the two groups in 2008–2019 ( n = 335 in each group) and 2014–2019 ( n = 257 in each group) cohorts, respectively. For cohort 2008–2019, during a median follow-up of 35.8 months, there were no differences in overall survival (OS) between MWA and LLR (HR: 0.88, 95% CI 0.65–1.19, p = 0.420), and MWA was inferior to LLR regarding disease-free survival (DFS) (HR 1.36, 95% CI 1.05–1.75, p = 0.017). For cohort 2014–2019, there was comparable OS (HR 0.85, 95% CI 0.56–1.30, p = 0.460) and approached statistical significance for DFS (HR 1.33, 95% CI 0.98–1.82, p = 0.071) between MWA and LLR. Subgroup analyses showed comparable OS in 3.1–4.0-cm HCCs (HR 0.88, 95% CI 0.53–1.47, p = 0.630) and 4.1–5.0-cm HCCs (HR 0.77, 95% CI 0.37–1.60, p = 0.483) between two modalities. For both cohorts, MWA shared comparable major complications (both p > 0.05), shorter hospitalization, and lower cost to LLR (all p < 0.001). MWA might be a first-line alternative to LLR for solitary 3–5-cm HCC in selected patients with technical advances, especially for patients unsuitable for LLR.
目的 评价一种综合方案(简称TUDB方案)对接受胆肠吻合术肝肿瘤消融治疗患者预防肝脓肿形成的价值,验证该预防方案的安全性.方法 回顾性分析西京医院2017年1月至2020年7月曾接受过胆肠吻合术的肝肿瘤消融治疗患者(n=35)的资料,按是否采用TUDB方案分为两组,采用TUDB方案的患者为观察组(n=18),未采用TUDB方案的患者为对照组(n=17).根据患者消融术后的临床症状、实验室检查、影像学检查诊断是否有肝脓肿形成,观察使用相关药物的不良反应.记录两组患者消融治疗后肝脓肿的发生率,比较分析两组患者性别、年龄、术前白细胞水平、血清白蛋白水平、胆肠手术至消融术间隔时间、消融前2周内是否化疗、住院天数等.结果 两组患者性别、年龄、术前白细胞水平、血清白蛋白水平、胆肠手术至消融术间隔时间、消融前2周内是否化疗差异不显著(P>0.05).35例胆肠吻合术后患者肝肿瘤消融后脓肿发生率为31.4%(11/35);观察组肝脓肿发生率为0%(0/18),显著低于对照组的64.7%(11/17)(P<0.01).观察组住院天数[(3.28±0.45)d]明显低于对照组[(11.18±7.67)d](P<0.01).所有采用TUDB方案的患者均未出现药物相关的不良反应.结论 TUDB方案可以有效地预防曾接受过胆肠吻合术的肝脏消融治疗患者术后肝脓肿形成,该预防方案未出现药物相关不良事件,安全性得到了验证.
目的:制备载氟尿嘧啶(5-Fu)的新型内皮细胞靶向脂质微泡(5-Fu-LF9-MBs),对其合成、制备及体外稳定性进行研究,探索其作为一种新型内皮细胞靶向药物载体的可行性.方法:合成以Dll4-Notch通路特异性相关的结构域的活性片段LF9,进一步包载抗癌药5-Fu,制得载药脂质微泡5-Fu-LF9-MBs.以粒径、Zeta电位、包封率(EE)、载药量(DL)、PDI等评价指标筛选出脂质微泡最佳制备处方,并通过荧光显微镜考察5-Fu-MBs和5-Fu-LF9-MBs两种脂质微泡的形态和其在不同浓度浓度BSA溶液中的稳定性.结果:靶向脂质微泡(5-Fu-LF9-MBs)能高效负载5-Fu,包封率为86.9%,载药量为0.05%,且体外稳定性佳.结论:LF9修饰的新型脂质微泡能够高效负载5-Fu,有一定的临床应用潜力.
目的 研究超声衰减参数(UAP)诊断慢性肝病患者肝脏脂肪变性程度的临床价值.方法 采用回顾性分析方法,研究对象为2017年1月至2020年1月空军军医大学第一附属医院收治入院的126例存在肝脏脂肪变性的慢性肝病患者,均经肝穿刺活组织检查确诊.选取瞬时弹性成像技术(iLivTouch)检测UAP、肝脏硬度,计算体重指数,同时,基于肝组织病理学结果对肝脏脂肪变性程度与UAP相关性进行分析,并通过受试者工作特征(ROC)曲线分析慢性肝病患者肝脏脂肪变性程度诊断中UAP的准确性及特异度,并分析影响UAP值的相关因素.结果 经肝穿刺活组织学检查显示42例慢性肝病患者的肝脏脂肪变性程度为F1级,46例F2级,31例F3级,7例F4级;UAP与肝脏脂肪变性程度(r=0.379,P<0.01)、体重指数(r=0.362,P<0.01)呈正相关.UAP诊断肝脏脂肪变性程度F≥2、F≥3、F=4的截断点依次为275、287、292 dB/m,敏感度依次为0.378、0.500、0.750,特异度依次为0.929、0.921、0.835.结论 慢性肝病患者肝脏脂肪变性程度诊断中UAP具有重要的临床价值,可明确慢性肝病患者有无肝脏脂肪变性,还可评估肝脏脂肪变性程度.