Safety of Combined Yttrium-90 Radioembolization and Immune Checkpoint Inhibitor Immunotherapy for Hepatocellular Carcinoma

PurposeTo investigate the safety of yttrium-90 radioembolization in combination with checkpoint inhibitor immunotherapy for the treatment of hepatocellular carcinoma (HCC).Materials and MethodsThis single-center retrospective study included 26 consecutive patients with HCC who received checkpoint inhibitor immunotherapy within 90 days of radioembolization from April 2015 to May 2018. Patients had preserved liver function (Child-Pugh scores A–B7) and either advanced HCC due to macrovascular invasion or limited extrahepatic disease (21 patients) or aggressive intermediate stage HCC that resulted in earlier incorporation of systemic immunotherapy (5 patients). Clinical documentation, laboratory results, and imaging results at 1- and 3-month follow-up intervals were reviewed to assess treatment-related adverse events and treatment responses.ResultsThe median follow-up period after radioembolization was 7.8 months (95% confidence interval [CI], 5.6–11.8). There were no early (30-day) mortality or grades 3/4 hepatobiliary or immunotherapy-related toxicities. Delayed grades 3/4 hepatobiliary toxicities (1–3 months) occurred in 2 patients in the setting of HCC disease progression. One patient developed pneumonitis. The median overall survival from first immunotherapy was 17.2 months (95% CI, 10.9–23.4). The median overall survival from first radioembolization was 16.5 months (95% CI, 6.6–26.4). From first radioembolization, time to tumor progression was 5.7 months (95% CI, 4.2–7.2), and progression-free survival was 5.7 months (95% CI, 4.3–7.1).ConclusionsRadioembolization combined with checkpoint inhibitor immunotherapy in cases of HCC appears to be safe and causes limited treatment-related toxicity. Future prospective studies are needed to identify the optimal combination treatment protocols and evaluate the efficacy of combination therapy.     

Role of optical coherence tomography angiography in the characterization of vascular network patterns of ocular surface squamous neoplasia

PurposeTo visualize and quantify vascular networks in individuals with ocular surface squamous neoplasia (OSSN) through optical coherence tomography angiography (OCTA).MethodCross-sectional study of OSSN patients. Vascular networks were measured by OCTA in the epithelium and sub-epithelial space in the tumors, adjacent tissue, and in the contralateral eye. Vessel area density (VAD, percent of blood vessels within 2.14 mm²), was calculated for each location. Total tumor density (TTD, percent of blood vessels within the entire tumor) was calculated. VAD was assessed separately for corneal and conjunctival locations and compared.ResultsFifteen patients with OSSN were included. The mean age was 61 ± 12 years and the majority were male (80%). The mean tumor area, volume, depth, and TTD were 28.0 ± 9.0 mm² (range, 10.9–39.7), 9.1 ± 4.1 mm³ (range, 3.4–18.8), 334 ± 125 μm (range, 177–571), and 33.2% ± 11.0% (range, 18.7–58.8), respectively. The VAD was highest within the tumor (28.9% ± 8.7%) followed by the adjacent sub-epithelial tissue and the tissue underneath the conjunctival component of tumor. These densities were higher than the VAD in the tissues of the non-involved eye (all P < 0.05). The VAD within conjunctival component of tumor was significantly higher than those with corneal component (29.8% ± 9.5% vs. 21.1% ± 5.5%, p = 0.006). The VAD under conjunctival tumor was also significantly higher than under corneal component (24.1% ± 7.8% vs. 17.0% ± 6.1%, p = 0.024).ConclusionsOCTA imaging allowed for visualization and quantification of vessel structure and density within, under, and surrounding OSSN.     

The respiratory syncytial virus fusion protein-specific B cell receptor repertoire reshaped by post-fusion subunit vaccination

Respiratory syncytial virus (RSV) is the major cause of acute lower respiratory illness in children of less than 5 years of age which usually results in hospitalization or even in death. Vaccine development is hampered in consequence of a failed vaccine trial with fatalities in the 1960s. Even though research has been more focused on the RSV fusion protein in its pre-fusion conformation, maternal vaccination with post-fusion protein (post F) was considered as a promising vaccine strategy for passive immunization of babies, because post F preserves very potent neutralizing epitopes. We extensively analyzed post F-binding B cell receptor (BCR) repertoires of three vaccinees who received a post F-subunit vaccine in the context of a first-in-human, Phase 1, randomized, observer-blind, placebo-controlled clinical trial (ClinicalTrials.gov Identifier: NCT02298179). In order to compare the vaccine-induced BCR repertoires with BCR repertoires induced by natural infection, we also analyzed pre F- and post F-binding BCRs isolated from a healthy blood donor with relatively high F-binding memory B cell (MBC) frequencies. Analysis of the vaccine-induced repertoires revealed that preferentially V_H4-encoded BCRs were expanded in response to vaccination. Estimation of antigen-driven selection further demonstrated that expanded BCRs accumulated positively selected replacement mutations which substantiated the hypothesis that post F-vaccination induces diversification of V_H4-encoded BCRs in germinal centers. Comparison of the vaccine-induced BCR repertoires with clonally related pre and post F-binding BCRs of the healthy blood donor suggested that the vaccine expanded pre/post F cross-reactive MBCs. Interestingly, several vaccine-induced BCRs shared stereotypic VDJ gene junctions with known neutralizing Abs. Once expressed for functional characterization, the selected monoclonal Abs demonstrated the predicted neutralization activities in plaque reduction neutralization assays indicating that the post F-vaccine induced expansion of neutralizing BCRs.     

A novel procedure combining transoral resection and set-back tongue flap for oropharyngeal cancer

Seven patients with advanced lateral oropharyngeal cancer (T3N2bM0, or T4N2bM0) underwent transoral lateral oropharyngectomy (TLO) with reconstruction performed through set-back tongue flap and polyglycolic acid (PGA) sheet. TLO was performed following en bloc resection of tumors using endoscopy. To cover the resulting defect in the lateral oropharyngeal wall, the set-back tongue flap was moved posteriorly and laterally to the area of the tongue base and lateral pharyngeal wall. The tip of the set-back tongue flap was sutured to the lateral pharynx to reconstruct the elevated tongue base and altered anterior pillar. The defect on the floor of the mouth was reconstructed using a PGA sheet. Following surgery, the mean observation period was 24 months. The mean operating time was 4 h and 2 min, with an average blood loss of 68.1 ml. All oral intake resumed on the first postoperative day via gastric tube. The mean gastric tube removal time was 1.6 postoperative days as a result of sufficient oral intake. None of the patients received postoperative radiotherapy or displayed evidence of tumor recurrence. We conclude that this novel procedure is highly effective for treating advanced oropharyngeal cancer as it demonstrates good prognostic and functional outcomes.     

肝癌患者行肝动脉化疗栓塞术前营养风险筛查的应用研究

目的 探讨肝癌患者行肝动脉化疗栓塞术前营养风险筛查的应用及对手术疗效、生活质量和生存预后的影响。方法 选取2013年1月至2018年12月首都医科大学附属北京世纪坛医院介入治疗科收治的行肝动脉化疗栓塞术治疗的中晚期肝癌患者180例，根据营养风险筛查2002（NRS 2002）将研究人群分为有营养风险组（NRS 2002≥3分）和无营养风险组（NRS 2002<3分），比较两组患者的临床基线特征、反映营养状况的物理和生化指标以及行肝动脉化疗栓塞术（TACE）手术疗效及并发症和生活质量评分，采用Kaplan-Meier方法对两组患者进行生存分析，比较上消化道出血、肝性脑病等临床终点事件的发生率。结果 纳入标准的180例患者中，无营养风险患者有85例，有营养风险患者有95例，营养风险发生率52.8%。两组患者的肱三头肌皮褶厚度、上臂肌围、体质指数、白蛋白之间存在统计学差异（P<0.05）；两组患者的总蛋白和前蛋白之间没有显著的统计学差异（P>0.05）。两组患者的TACE治疗肿瘤的临床有效率和术后并发症没有显著的差异（P>0.05）。无营养风险患者生活质量评分比有营养风险患者评分高（P<0.05）。有营养风险患者3年生存率为54.74%；无营养风险患者3年生存率为68.24%，存在统计学意义（HR=0.61，P=0.05， 95%CI=0.38~0.98）。肝性脑病、低蛋白血症和贫血的发生率两组之间有统计学差异（P<0.05）。上消化道出血和门脉癌栓堵塞的发生率之间没有统计学差异（P>0.05）。结论 营养风险筛查对于行TACE手术患者具有重要意义，营养风险与临床结局密切相关。     

基因间长链非编码RNA152靶向微小RNA?103a?3p对非小细胞肺癌细胞增殖和侵袭迁移的影响

目的探讨基因间长链非编码RNA 152(LINC00152)靶向调控微小RNA-103a-3p(miR-103a-3p)表达及对非小细胞肺癌(NSCLC)细胞增殖和侵袭迁移的影响。方法采用实时定量PCR(QPCR)检测正常肺上皮细胞BEAS-2B及NSCLC细胞(ANIP-973、NCI-H157、A549和NCI-H1975)的LINC00152水平。选取LINC00152水平最高的细胞分别转染LINC00152特异性小干扰RNA(si-LINC00152组)或无关序列(si-NC组),另设未转染细胞为对照组。QPCR检测LINC00152水平,活细胞计数CCK-8法、Transwell小室和划痕实验测定细胞增殖、侵袭和迁移能力,Western blotting检测基质金属蛋白酶(MMP)-2、MMP-9和第10号染色体缺失的磷酸酶及张力蛋白同源基因(PTEN)的水平;荧光素酶报告实验验证LINC00152靶向结合miR-103a-3p的能力。结果NSCLC细胞的LINC00152水平均高于BEAS-2B细胞(P<0.05),尤其是NCI-H1975细胞的最高。si-LINC00152组的LINC00152水平为0.352±0.087,低于对照组的1.058±0.219和si-NC组的1.126±0.139(P<0.05)。与si-NC组和对照组相比,si-LINC00152组NCI-H1975细胞转染48、72 h的增殖活力下降(P<0.05);si-LINC00152组的划痕愈合率和穿膜细胞数分别为(27.386±2.428)%和(78.840±5.031)个,低于si-NC组的(77.675±4.803)%和(179.208±13.264)个及对照组的(76.371±5.385)%和(174.003±15.678)个(P<0.05);与si-NC组和对照组相比,si-LINC00152组的MMP-2和MMP-9水平均降低,而PTEN水平升高(P<0.05)。对照组和si-NC组上述指标的差异无统计学意义(P>0.05)。双荧光素酶报告分析证实,miR-103a-3p模拟物降低了野生型LINC00152的荧光素酶活性(P<0.05),但对突变型无影响(P>0.05)。结论LINC00152在NSCLC细胞中高表达并发挥促癌作用,与NSCLC的迁移侵袭密切相关,LINC00152与miR-103a-3p间的相互作用在NSCLC靶向治疗中有一定潜能。     

Insight towards Nucleation Mechanism and Change in Morphology for Nanostructured Platinum Thin Film Directly Grown on Carbon Substrate via Electrochemical Deposition

Nanocrystalline platinum with different morphologies is synthesized via electrochemical deposition technique. The nucleation mechanism and its structural effect over the electrodeposited Pt on carbon electrodes have been systematically studied. Powder X-ray diffraction, X-ray photoelectron spectroscopy, and field-emission scanning electron microscopy are employed to study nucleation, oxidation states, and Pt structure growth on a carbon electrode. This study reports significant development of Pt metal nanoparticles with different morphologies such as a sphere, flower, core-flower, and rod-like structure directly fabricated on carbon electrode while tuning the deposition parameters such as current density, time, temperature, pH during the deposition process. The proposed electrochemical route represents a superior fabrication procedure for large-scale electrode fabrication compared to a conventional method for preparing membrane electrode assemblies for fuel cell stacks.