Intraoperative thalamocortical tract monitoring via direct cortical recordings during craniotomy

ObjectiveNeuromonitoring of primary motor regions allows preservation of motor strength and is frequently employed during cranial procedures. Less is known about protection of sensory function and ability to modulate movements, both of which rely on integrity of thalamocortical afferents (TCA) to fronto-parietal regions. We describe our experience with TCA monitoring and their cortical relays during brain tumor surgery.MethodologyTo study its feasibility and usefulness, continuous somatosensory evoked potentials (SSEP) recording via a subdural electrode was attempted in 32 consecutive patients.ResultsMedian and posterior tibial SSEP were successfully monitored in 31 and 17 patients respectively. SSEP improved lesion localization and prevented unnecessary cortical stimulation in 9 and 16 cases respectively. A threshold of ≥30% SSEP amplitude decrease influenced management in 10 patients while a decrement of ≥50 % had a sensitivity of 0.89 and specificity of 1 in detecting worsening of sensory function. Simultaneous motor evoked potentials (MEP) and SSEP monitoring were performed in 10 cases, 9 of which showed short-lived fluctuations of the former.ConclusionDirect cortical SSEP monitoring is feasible, informs management and predicts outcome.SignificanceEarly intervention prevents sensory deficit. Concomitant MEP fluctuations may reflect modulation of motor activity by TCA.     

Diffusion-weighted MRI and PET/CT reproducibility in epithelial ovarian cancers during neoadjuvant chemotherapy

PurposeTo investigate the reproducibility of diffusion-weighted (DW) MRI and ¹⁸F-Fluorodeoxyglucose (¹⁸F-FDG)-Positron emission tomography/CT (PET/CT) in monitoring response to neoadjuvant chemotherapy in epithelial ovarian cancer.Materials and methodsTen women (median age, 67 years; range: 41.8–77.3 years) with stage IIIC-IV epithelial ovarian cancers were included in this prospective trial (NCT02792959) between 2014 and 2016. All underwent initial laparoscopic staging, four cycles of carboplatine-paclitaxel-based chemotherapy and interval debulking surgery. PET/CT and DW-MRI were performed at baseline (C0), after one cycle (C1) and before surgery (C4). Two nuclear physicians and two radiologists assessed five anatomic sites for the presence of ≥ 1 lesion. Target lesions in each site were defined and their apparent diffusion coefficient (ADC), maximal standardized uptake value (SUV-max), SUV-mean, SUL-peak, metabolic tumor volume (MTV) and total lesion glycolysis (TLG) were monitored (i.e., 10 patients × 5 sites × 3 time-points). Their relative early and late changes were calculated. Intra/inter-observer reproducibilities of qualitative and quantitative analysis were estimated with Kappa and intra-class correlation coefficients (ICCs).ResultsFor both modalities, inter- and intra-observer agreement percentages were excellent for initial staging but declined later for DW-MRI, leading to lower Kappa values for inter- and intra-observer variability (0.949 and 1 at C0, vs. 0.633 and 0.643 at C4, respectively) while Kappa values remained > 0.8 for PET/CT. Inter- and intra-observer ICCs were > 0.75 for SUV-max, SUL-peak, SUV-mean and their change regardless the time-point. ADC showed lower ICCs (range: 0.013–0.811). ANOVA found significant influences of the evaluation time, the measurement used (ADC, SUV-max, SUV-mean, SUV-max, SUL-peak, MTV or TLG) and their interaction on ICC values (P = 0.0023, P< 0.0001 and P =0.0028, respectively).ConclusionWhile both modalities demonstrated high reproducibility at baseline, only SUV-max, SUL-peak, SUV-mean and their changes maintained high reproducibility during chemotherapy.     

Predicting osimertinib‐treatment outcomes through EGFR mutant‐fraction monitoring in the circulating tumor DNA of EGFR T790M‐positive patients with non‐small cell lung cancer (WJOG8815L)

The WJOG8815L phase II clinical study involves patients with non‐small cell lung cancer (NSCLC) that harbored the EGFR T790M mutation, which confers resistance to EGFR tyrosine kinase inhibitors (TKIs). The purpose of this study was to assess the predictive value of monitoring EGFR genomic alterations in circulating tumor DNA (ctDNA) from patients with NSCLC that undergo treatment with the third‐generation EGFR‐TKI osimertinib. Plasma samples of 52 patients harboring the EGFR T790M mutation were obtained pretreatment (Pre), on day 1 of treatment cycle 4 (C4) or cycle 9 (C9), and at diagnosis of disease progression or treatment discontinuation (PD/stop). CtDNA was screened for EGFR‐TKI‐sensitizing mutations, the EGFR T790M mutation, and other genomic alterations using the cobas EGFR Mutation Test v2 (cobas), droplet digital PCR (ddPCR), and targeted deep sequencing. Analysis of the sensitizing—and T790M—EGFR mutant fractions (MFs) was used to determine tumor mutational burden. Both MFs were found to decrease during treatment, whereas rebound of the sensitizing EGFR MF was observed at PD/stop, suggesting that osimertinib targeted both T790M mutation‐positive tumors and tumors with sensitizing EGFR mutations. Significant differences in the response rates and progression‐free survival were observed between the sensitizing EGFR MF‐high and sensitizing EGFR MF‐low groups (cutoff: median) at C4. In conclusion, ctDNA monitoring for sensitizing EGFR mutations at C4 is suitable for predicting the treatment outcomes in NSCLC patients receiving osimertinib (Clinical Trial Registration No.: UMIN000022076).

Abbreviations

CIs

confidence intervals

ctDNA

circulating tumor DNA

ddPCR

droplet digital PCR

EGFR

epidermal growth factor receptor

MFs

mutant fractions

NGS

next‐generation sequencing

NSCLC

non‐small cell lung cancer

ORR

overall response rate

OS

overall survival

PD

progressive disease

PFS

progression‐free survival

PR

partial response

SD

stable disease

TKI

tyrosine kinase inhibitor

     

血清p53抗体异常高水平对消化道肿瘤的早期诊断价值分析

目的:探讨血清p53抗体异常高水平对消化道肿瘤的早期诊断的价值。方法:选取2016年3月至2019年3月来我院检查确诊为消化道肿瘤的患者80例为消化道肿瘤组,选取来我院健康体检的67例健康志愿者为健康对照组。通过酶联免疫吸附实验检测血清中人体抑癌基因p53及其抗体水平;通过RT-qPCR检测血清中细胞凋亡相关基因Bcl-2、Bax和Caspase-3蛋白表达量。采用Pearson相关性分析明确消化道肿瘤p53、p53抗体水平和Bcl-2、Bax、Caspase-3蛋白表达水平的关系。结果:消化道肿瘤组p53水平降低,p53抗体水平异常升高(P<0.05)。与健康对照组相比,消化道肿瘤组Bcl-2表达量增加,Bax和Caspase-3蛋白表达量降低(P<0.05)。消化道肿瘤p53水平与Bcl-2蛋白表达水平呈负相关关系,与Bax、Caspase-3蛋白表达水平均呈正相关关系;p53抗体水平和Bcl-2蛋白表达水平呈正相关关系,与Bax、Caspase-3蛋白表达水平均呈负相关关系(P<0.05)。结论:消化道肿瘤患者血清p53抗体异常高水平,可作为临床辅助诊断消化道肿瘤的可靠指标之一。     

腹腔镜低位直肠癌根治术中应用盆腔腹膜关闭技术的疗效研究

目的:探讨盆腔腹膜关闭技术在腹腔镜低位直肠癌根治术应用的疗效。方法:回顾性分析2012年1月至2016年5月我院54例腹腔镜低位直肠癌根治术中行盆底腹膜关闭患者和57例未行盆底腹膜关闭患者的临床资料。结果:盆腔腹膜关闭组与盆腔腹膜未关闭组在手术时间、术中出血量、肛门排气时间、术后进食时间以及盆腔引流管拔除时间等方面差异均无统计学意义(P>0.05)。盆腔腹膜关闭组中8例患者发生短期并发症;6例患者发生中期并发症;14例患者发生远期并发症,均为肠梗阻。盆腔腹膜未关闭组中31例患者发生短期并发症,28例患者发生中期并发症,36例患者发生远期并发症。所有患者均治疗好转。Coxs回归模型分析提示,盆腔腹膜是否关闭是腹腔镜低位直肠癌根治术患者术后生存的独立指标。结论:腹腔镜Miles术中行盆底腹膜关闭安全可行,具有临床实用价值。     

Thymic epithelial tumor with superior vena cava syndrome diagnosed by percutaneous endovascular tumor biopsy: A report of two cases

Thymic epithelial tumor is a rare, potentially progressive disease that commonly infiltrates mediastinal structures. In rare cases, it may cause superior vena cava syndrome. Pretreatment histopathological diagnosis is essential to determine the most effective treatment strategy. Percutaneous endovascular biopsy is a rarely reported non-surgical diagnostic option for large vessel tumoral involvement. We report two cases of thymic epithelial tumor with superior vena cava syndrome diagnosed by percutaneous endovascular biopsy. No procedural complications occurred, and subsequent systemic treatment was promptly administered. This procedure may have potential as a useful diagnostic method for patients with mediastinal tumors involving large vessels.     

Interactions between cancer cells and immune cells drive transitions to mesenchymal-like states in glioblastoma

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