Microwave ablation versus laparoscopic resection as first-line therapy for solitary 3-5-cm HCC.

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.

Inhibitory effect of 5-FU loaded ultrasound microbubbles on tumor growth and angiogenesis.

The anti-neovascularization treatment is one of the effective strategies for tumor molecular target therapy. At present, the target and effect of the anti-neovascularization treatment is limited, and it is urgent to establish a new vascular targeting strategy to effectively treat tumors. In this work, we used high intensity focused ultrasound (HIFU) combined with targeted microbubbles to establish a molecular targeted ultrasound response microbubble for neovascular cells. Furthermore, the effects of drug loaded microbubbles on neovascularization and tumor cells were studied. The tumor vascular targeted and ultrasound-responsive microbubbles of 5-FU@DLL4-MBs were prepared by the thin-film dispersion method. The size and zeta potential of 5-FU@DLL4-MBs was about 1248 nm and -9.1 mV. 5-FU@DLL4-MBs released 5-FU showed an ultrasound-responsive manner, and had better vascular-targeting ability. Furthermore, the 5-FU@DLL4-MBs showed the strongest cytotoxic effect on HUVECs or HepG-2 cells and can be effectively internalized into the HUVECs cells. Thus, 5-FU@DLL4-MBs combined with HIFU can be considered as a potential method for antitumor angiogenesis in the future.

Percutaneous Intramyocardial Septal Radiofrequency Ablation for Interventricular Septal Reduction: An Ovine Model with 1-Year Outcomes.

BACKGROUND: Percutaneous intramyocardial (PIM) septal radiofrequency ablation (SRA) is a novel treatment approach for hypertrophic obstructive cardiomyopathy patients, but there has been lack of a large animal model to study PIM-SRA. We aimed to validate the long-term safety and efficacy of PIM-SRA and to observe pathological changes of the ablated interventricular septum (IVS) in a healthy sheep model. METHODS AND RESULTS: Twelve sheep were randomized to the PIM-SRA group (n = 6) and the sham group (n = 6). In the PIM-SRA group, a radiofrequency (RF) electrode was inserted into the IVS with a maximum power of 80 W for 5 min. In the sham group, the RF electrode tip was positioned in the IVS segment but without RF power delivery. Septal hypokinesis was seen in all PIM-SRA group animals immediately after the procedure; the systolic wall thickening rate and motion amplitude of the ablated region decreased (p < 0.01), and the diastolic IVS thickness also decreased significantly over time (p < 0.01). ECG showed that all the sheep had normal sinus rhythm during the follow-up. Pathological examinations revealed scar tissue in the ablated region as expected. CONCLUSIONS: PIM-SRA produced precisely ablated myocardial tissue, reduced the IVS thickness significantly, preserved the global LV function, and avoided the incidence of conduction system damage in the long term. PIM-SRA was found to be a safe and effective minimally invasive septal reduction therapy.

Transmembrane protein 215 promotes angiogenesis by maintaining endothelial cell survival.

Sprouting angiogenesis is a major form of neovascularization of tissues suffering from hypoxia and other related stress. Endothelial cells (ECs) undergo proliferation, differentiation, programmed death, and migration during angiogenic sprouting, but the underlying molecular mechanisms regulating ECs in angiogenesis have been incompletely elucidated. Here we report that the transmembrane protein 215 (TMEM215) is involved in angiogenesis by regulating EC survival. The murine TMEM215 gene, which possesses two transcriptional starting sites as determined by 5'-rapid amplification of complementary DNA (cDNA) ends (RACE), encodes a two-pass TMEM. The TMEM215 transcripts were detected in ECs in addition to other tissues by quantitative reverse transcription-polymerase chain reaction. Immunofluorescence showed that TMEM215 was expressed in the vasculature in retina, liver, and tumor, and colocalized with EC markers. We show that knockdown of TMEM215 in ECs induced strong cell death of ECs in vitro without affecting cell proliferation and migration, suggesting that TMEM215 was required for EC survival. Downregulation of TMEM215 expression compromised lumen formation and sprouting capacities of ECs in vitro. Moreover, intravitreous injection of TMEM215 small interfering RNA resulted in delayed and abnormal development of retinal vasculature with poor perfusion. These results identified TMEM215 as a novel molecule involved in angiogenesis by regulating the survival of ECs.

Ultrasound-Guided Intratumoral Radiofrequency Ablation Coagulation to Facilitate Meningioma Resection: Preliminary Experience.

OBJECTIVES: This study aimed to explore the feasibility and safety of intratumoral radiofrequency ablation (RFA) in meningioma resection. METHODS: This study was approved by the Xijing Ethics Committee, and informed consent was obtained from all of the patients. Thirteen patients with meningiomas were recruited in the Neurosurgery Department of Xijing Hospital. These patients were treated with intratumoral RFA and surgery. We also chose 13 patients with meningiomas treated with traditional surgery as the control group. Two-dimensional ultrasound, color Doppler flow imaging, contrast-enhanced ultrasound, and magnetic resonance imaging were used to identify the location, border, and blood supply of the meningiomas preoperatively and to assess the therapeutic effect intraoperatively. Finally, the meningiomas were dissected and removed by surgery. RESULTS: All procedures were technically successful without serious complications. Intraoperative ultrasound was able to provide a clear display of the location, shape, size, and boundary of the tumor and its relationship with other tissues and reveal the vascular distribution in and around the tumors. With intratumoral RFA, coagulative necrosis was induced, and the meningiomas became hard in texture with a decreased blood supply. Blood loss was significantly lower in the RFA group versus control group (320.0 ± 24.8 versus 390.4 ± 36.8 mL; P < .001). The RFA group spent fewer days in the hospital (6.0 ± 0.9 versus 7.0 ± 1.2 days; P = .022). However, the surgical time of the RFA group was relatively longer (3.5 ± 0.5 versus 3.0 ± 0.3 hours, P = .007). CONCLUSIONS: The application of intratumoral RFA in meningioma resection is effective and safe. It may be a useful adjunct for meningioma treatment.

Effects of radiofrequency ablation versus other ablating techniques on hepatocellular carcinomas: a systematic review and meta-analysis.

BACKGROUND: Percutaneous ablation has quickly arisen as one of the important alternative treatments for hepatocellular carcinoma (HCC). We aimed to compare the therapeutic effects of radiofrequency ablation (RFA) and other ablative techniques on HCCs. METHODS: Databases were searched to identify literature on complete tumor ablation (CTA), overall survival (OS), local tumor recurrence (LTR), and complications of RFA in the treatment of HCC, compared with those of microwave ablation (MWA), percutaneous ethanol injection (PEI), PEI plus RFA, cryoablation (CRA), laser ablation (LSA), and high-intensity focused ultrasound. Randomized controlled trials and high-quality cohort studies were included in the assessment. RESULTS: The effects of MWA and CRA appeared to be similar to those of RFA, but lower rates of LTR and higher rates of CTA in large tumors compared with RFA were reported (P < 0.05). CTA rates were lower in patients treated with PEI (odds ratio [OR] 0.16, 95% confidence interval [CI] 0.06-0.42), and higher in those treated with PEI plus RFA (OR 2.28, 95% CI 1.19-3.60), with an increased incidence of fever (P < 0.05). LSA resulted in lower CTA rates (OR 0.32, 95% CI 0.13-0.81) and OS (hazard ratio 1.47, 95% CI 1.01-2.15), with a lower incidence of complications. CONCLUSIONS: Compared with RFA, identical effects were found in MWA and CRA groups. Fewer complications were observed in PEI and LSA group. PEI plus RFA appeared more effective, with a higher rate of complications. Well-designed randomized controlled trials are further needed to confirm above results.

Echocardiography-guided percutaneous per-ventricular laser ablation of ventricular septum: in vivo study in a canine model.

Surgical myectomy and ethanol ablation are established intervention strategies for left ventricular outflow obstruction in hypertrophic cardiomyopathy. Safety and efficacy limitations of these interventions call for a minimally invasive, potentially safer, and more efficacious strategy. In this study, we aimed to evaluate the feasibility of echocardiography-guided percutaneous per-ventricular laser ablation of a ventricular septum in a canine model. Six domestic dogs were chosen for the study. A 21G needle was inserted into the right ventricle with its tip reaching the targeted basal to mid-septum, after which laser ablation was performed as follows: 1-W laser for 3 min (180 J) at the basal segment and 5 min (300 J) at middle segment of the septum, respectively. Echocardiography, blood chemistry tests, and pathology examination were performed to assess the results of laser ablation. No death or major complications, i.e., tamponade, pericardial effusion, or ventricular fibrillation, occurred. The laser-ablated areas were well demarcated in the results of the pathological examination. The diameters of the ablated regions were 4.42 ± 0.57 and 5.28 ± 0.83 mm for 3 and 5 min ablation, respectively. Pre-ablation and post-ablation, cardiac enzymes were found to increase significantly while no significant differences were found among M-mode, 2D (LVEF), pulsed-wave (PW) Doppler, and tissue Doppler imaging (TDI) measurements. Contrast echocardiography confirmed the perfusion defects in the ablated regions. Microscopically, the ablated myocardium showed coagulative changes and a sparse distribution of disappearing nuclei and an increase in eosinophil number were observed. Our study suggests that percutaneous and per-ventricular laser ablation of the septum is feasible, potentially safe and efficacious, and warrants further investigation and validation.

Prediction Model and Nomogram of Early Recurrence of Hepatocellular Carcinoma after Ultrasound-guided Microwave Ablation.

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.

Thermal ablation with and without adjuvant systemic therapy: a nationwide multicenter observational cohort study of solitary colorectal liver metastases.

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.

Microwave ablation versus liver resection for primary intrahepatic cholangiocarcinoma within Milan criteria: a long-term multicenter cohort study.

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. Funding: National Natural Science Foundation of China.

A multicenter case-controlled study on laparoscopic hepatectomy versus microwave ablation as first-line therapy for 3-5 cm hepatocellular carcinoma in patients aged 60 and older.

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.

Ultrasound-guided percutaneous laser and ethanol ablation of rabbit VX2 liver tumors.

BACKGROUND: Only a small percentage of patients with hepatocellular carcinoma (HCC) may benefit out of surgical resection. Thus, lots of these patients are in need of local control, such as percutaneous ethanol injection (PEI), percutaneous laser ablation (PLA), or radiofrequency thermal ablation (RF). PURPOSE: To investigate the effects of ultrasound-guided PLA combined with PEI on rabbit VX2 liver tumors, using conventional gray-scale ultrasonography (US), color/power Doppler (CD/PD)US, contrast-enhanced (CE) US, and histologic examination. MATERIAL AND METHODS: VX2 tumors were implanted in the livers of 80 rabbits. Fourteen days after implantation, animals were randomly separated into four groups of 20 rabbits. Treatment of the four groups was with: (i) PLA; (ii) PEI; (iii) combined therapy of PLA immediately followed by PEI; and (iv) combined therapy of PEI immediately followed by PLA. Conventional gray-scale US, CD US, PD US, and CE US were performed before and after ablation. The effects on ablated areas were assessed by histologic examination. RESULTS: Conventional gray-scale US showed a clear boundary around the ablated area in groups 1, 3, and 4. An isoechoic treated region with an irregular boundary was seen in group 2. On CE US, coagulated areas demonstrated a perfusion defect. Both conventional gray-scale US and CE US showed that the ablated volume in group 4 was larger than that in groups 1, 2, and 3. CD US and PD US demonstrated residual tumor in the periphery of ablated areas in groups 1 and 2, but not in groups 3 and 4. CE US demonstrated no residual tumor in group 4, unlike in groups 1, 2, and 3. Examination of treated tumors demonstrated necrosis in the ablated zones and increasing surrounding fibrous bands in the four treatment groups. Residual viable tissue in group 4 was less than that in groups 1, 2, and 3. CONCLUSION: Combined therapy of PEI immediately followed by PLA can coagulate significantly larger volumes of tumor and reduce residual tumor.

PLEKHA4 promotes glioblastoma progression through apoptosis inhibition, tumor cell migration, and macrophage infiltration.

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.

Flexible nano-liposomes-based transdermal hydrogel for targeted delivery of dexamethasone for rheumatoid arthritis therapy.

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 value of contrast-enhanced ultrasound quantitative parameters in the prognosis prediction of hepatocellular carcinoma after thermal ablation: a retrospective cohort study.

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.

Case report: Long response to PD-1 blockade after failure of trastuzumab plus chemotherapy in advanced Epstein-Barr virus-associated gastric cancer.

Background: Trastuzumab-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 Presentation: We 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. Summary: We 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.

Role of sonography for implantation and sequential evaluation of a VX2 rabbit liver tumor model.

OBJECTIVE: We investigated the role of sonography in the implantation process of a VX2 rabbit liver tumor model and sequential evaluation. METHODS: Fifty rabbits were divided into 2 groups. Animals in group I underwent surgical implantation, whereas those in group II received percutaneous sonographically guided implantation. At 7, 14, 21, and 28 days after implantation, respectively, 5 rabbits in each group were examined with conventional, color Doppler (CD), contrast-enhanced (CE) pulse inversion harmonic (PIH), and CE CD sonography. Pathologic examination was performed with hematoxylin-eosin, nicotinamide adenine dinucleotide phosphate-diaphorase, and succinic dehydrogenase stains. RESULTS: Twenty-one rabbits with tumors survived in group I, and 22 with tumors survived in group II. The mean duration of implantation +/- SD in group II was 16.9 +/- 3.4 minutes, whereas that in group I was 21.5 +/- 4.1 minutes (P < .05). The tumor volume measured by conventional sonography increased from 0.28 +/- 0.14 cm(3) at 7 days to 16.49 +/- 5.50 cm(3) at 28 days in group I and from 0.31 +/- 0.19 to 19.79 +/- 4.70 cm(3) in group II, whereas no significant difference existed between the groups. On CD, CE PIH, and CE CD sonography, most tumors were hypervascular before 14 days and after 14 days had peripheral vessels and central hypovascular areas, which were shown as necrotic areas by pathologic examination. CONCLUSIONS: Sonographically guided implantation achieved a good success rate with convenient inoculation performance. Conventional gray scale, CD, CE PIH, and CE CD sonography were useful in sequential evaluation of tumor growth and characteristic vascularity.

Clinical application of contrast-enhanced ultrasonography in diagnosis of superficial lymphadenopathy.

OBJECTIVE: The purpose of this study was to evaluate the value of contrast-enhanced ultrasonography (CEUS) in differential diagnosis of superficial lymphadenopathy. METHODS: Ninety-four superficial enlarged lymph nodes in 94 patients were studied by conventional ultrasonography (gray scale and color Doppler) and CEUS. Contrast-enhanced sonograms were analyzed using contrast-specific quantification software. All of the results were compared with pathologic diagnoses. RESULTS: Of the 94 lymph nodes examined, 44 were benign and 50 were malignant (33 metastases and 17 lymphomas). The sensitivity, specificity, and accuracy of conventional ultrasonography in differential diagnosis between benign and malignant nodes were 51%, 47%, and 55%, respectively. Contrast-enhanced ultrasonography showed intense homogeneous enhancement in 39 of 44 benign lymph nodes, inhomogeneous enhancement in 32 of 33 metastases, and intense homogeneous enhancement and absence of perfusion in 9 of 17 and 6 of 17 lymphomas, respectively. The sensitivity specificity, and accuracy of CEUS were 84%, 79%, and 80%. After time-intensity curve gamma variates were calculated, the area under the curve of the benign lymph nodes was greater than those of the metastatic lymph nodes and lymphomas (P < .01). CONCLUSIONS: These results indicate that the use of CEUS and contrast-specific software has a higher degree of diagnostic accuracy than conventional ultrasonography for evaluations of superficial lymphadenopathy. The contrast enhancement patterns and time-intensity curves provide valuable diagnostic information for differential diagnosis of benign and malignant lymph nodes.

Establishment and Evaluation of a Monkey Acute Cerebral Ischemia Model.

OBJECTIVES: Cerebral ischemia seriously threatens human health and is characterized by high rates of incidence, disability and death. Developing an ideal animal model of cerebral ischemia that reflects the human clinical features is critical for pathological studies and clinical research. The goal of this study is to establish a local cerebral ischemia model in rhesus macaque, thereby providing an optimal animal model to study cerebral ischemia. METHODS: Eight healthy rhesus monkeys were selected for this study. CT scans were performed before the operation to exclude cerebral vascular and intracranial lesions. Under guidance and monitoring with digital subtraction angiography (DSA), a microcatheter was inserted into the M1 segment of the middle cerebral artery (MCA) via the femoral artery. Then, autologous white thrombi were introduced to block blood flow. Immediately following embolization, multisequence MRI was used to monitor cerebrovascular and brain parenchymal conditions. Twenty-four hours after embolization, 2 monkeys were sacrificed and subjected to perfusion, fixation and pathological examination. RESULTS: The cerebral ischemia model was established in 7 rhesus monkeys; one animal died during intubation. DSA and magnetic resonance angiography (MRA) indicated the presence of an arterial occlusion. MRI showed acute local cerebral ischemia. HE staining revealed infarct lesions formed in the brain tissues, and thrombi were present in the cerebral artery. CONCLUSION: We established a rhesus macaque model of local cerebral ischemia by autologous thrombus placement. This model has important implications for basic and clinical research on cerebral ischemia. MRI and DSA can evaluate the models to ensure accuracy and effectiveness.

Ablation of high-intensity focused ultrasound assisted with SonoVue on Rabbit VX2 liver tumors: sequential findings with histopathology, immunohistochemistry, and enzyme histochemistry.

BACKGROUND: We investigated sequential effects of HIFU ablation combined with contrast agent SonoVue by using histopathology examination, immunohistochemistry, and enzyme histochemistry. MATERIALS AND METHODS: Forty rabbits with VX2 liver tumors were subjected to HIFU ablation. Before ablation, a bolus injection of 0.2 mL SonoVue was administrated in group II (n = 20), and normal saline solution was injected in group I (n = 20). On day 0, 3, 7, and 14 after ablation, 5 animals in each group were sacrificed. The tissue in ablated zone, transient zone (within 3 mm around ablated area), and surrounding zone (beyond 3 mm around ablated area) were collected. Coagulated volume measurement, hematoxylin-eosin staining, immunohistochemistry of Ki 67, Bcl-2, CD54, and MMP-2 to determine cell proliferation and tissue repair, and nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-d) and succinic dehydrogenase (SDH) staining to evaluate tissue viability were performed. RESULTS: The coagulated volume in group II at each time point was larger than that in group I (P < .05). After day 3, hematoxylin-eosin staining demonstrated necrosis in ablated zones and increasing surrounding fibra bands in group I and group II, while increasing expression of Ki 67, Bcl-2, CD54, and MMP-2 in transient zones was detected using immunohistochemistry in both groups (P > .05). NADPH-d and SDH staining showed dramatic decrease of enzyme activities in ablated zones immediately after ablation, while residual viable tissues in ablated zones of group II were less than those of group I (P < .05). CONCLUSION: Contrast agent SonoVue enables improvement of HIFU ablation on rabbit VX2 liver tumors.