作者没有致谢。

本研究使用带有 BF-UC180F EBUS 内窥镜的 EVIS Exera II 内窥镜塔（图 1）来演示内窥镜和手术科学模拟器（ENDO 导师套件）和 Simbionix 的 GI-Bronch Mentor 软件，Essential EBUS Case 6，在基于模拟的设置中执行 EBUS 程序。研究中不包括任何患者，因为整个过程是在外科科学模拟器（ENDO 导师套件）上进行的。在EBUS手术之前，使用常规支气管镜进行完整的支气管镜检查，以确保支气管树已系统地可视化，并确定必须位于潜在淋巴结站的关键解剖位置（图2）。
1. 内窥镜的处理
注意： EBUS 内窥镜的处理方式与支气管镜类似。然而，需要注意的是，与支气管镜相反，EBUS内窥镜提供倾斜角度视图，因为超声换能器会降低能见度（图3）。
<ol><li>左手握住内窥镜，左手拇指放在转向杆上。</li>
	<li>右手握住内窥镜的远端，通过鼻腔或口腔进入气管。当声带在图片底部可视化时（图3B），通过按下屏幕上的相应按钮，通过模拟器施用2mL的2%利多卡因两次，并小心地通过声带。</li>
	<li>在气管以及右支气管和左主支气管中分别再施用 2 mL 的 2% 利多卡因。</li>
</ol>2. 解剖学
<ol><li>检查支气管树后，缩回支气管镜并更换为EBUS镜。打开超声换能器，按以下顺序找到六个解剖EBUS标志。<ol><li>定位地标 1 = 车站 4L<ol><li>将 4L 站定位在气管左侧，就在隆突的颅骨上。要找到4L站，请在气管中逆时针转动内窥镜，并将其定位在主动脉弓和左肺动脉之间，有时称为“米老鼠窗口”（图4）。</li>
		</ol></li>
		<li>定位地标 2 = 车站 7<ol><li>在右肺动脉和隆突下方的左心房之间找到第 7 站。将EBUS内窥镜放在右侧或左侧主支气管中，并将内窥镜朝内侧转动（图5）。</li>
		</ol></li>
		<li>定位地标 3 = 车站 10L<ol><li>定位工作站 10L，靠近左主支气管颅至左上叶。将内窥镜放在左主支气管或左上叶并向上看。左肺动脉的上边界形成4L和10L站之间的边界（图6）。</li>
		</ol></li>
		<li>定位地标 4 = 车站 10R<ol><li>将站 10R 定位在右主支气管的侧壁上，就在合子静脉下缘的尾部。上边界是合子静脉的下边界。将内窥镜放在右主支气管或右上叶支气管中并向上看（图7）。</li>
		</ol></li>
		<li>定位地标 5 = 合子矿脉<ol><li>要找到合子静脉，请稍微向颅内缩回内窥镜，然后在气管中顺时针转动换能器。逆时针转动换能器以可视化合子静脉流入上腔静脉（图8）。</li>
		</ol></li>
		<li>定位地标 6 = 车站 4R<ol><li>要找到工作站 4R，请将内窥镜从合子静脉进一步向颅缩回，并在气管中顺时针转动换能器。将工作站 4R 定位在合子静脉下边界上方的气管右侧或前方，这标志着工作站 10R 和 4R 之间的边界（图 9）。</li>
		</ol></li>
	</ol></li>
	<li>找到六个标志后，寻找其他淋巴结站，即站 2R、2L、11R 和 11L，以及其他具有临床重要性的结构。至少应对 4L、7 和 4R 站进行活检3.</li>
	<li>当相关淋巴结定位后，向助手索要活检设备。活检设备包括一个保护针头的护套，该护套连接到一个可以锁定在内窥镜上的手柄。护套内为针，针内为管心针。将针头插入工作通道时，请将转向杆保持在视频所示的中立位置，以免损坏内窥镜。 注意： 此处使用的针头随模拟器一起提供。但是，此手术的推荐针头尺寸为 21 G。</li>
	<li>调整护套，使其在内窥镜末端可见;但是，不超过 1-2 毫米。</li>
	<li>将换能器转向支气管壁，使淋巴结在超声图像的左侧可见。现在，进行活检。</li>
	<li>用针头刺穿淋巴结后，让助手取出管心针，然后按下屏幕上的相应按钮对针头进行抽吸。针头必须前后移动数次。</li>
	<li>在护套内取下吸力并缩回针尖。确保内窥镜远端不弯曲并保持中立位置，以防止损坏内窥镜。每个淋巴结必须至少穿刺三次10,11。</li>
	<li>最后一次活检后，检查是否有出血。用白光检查活检的地方，并停留几秒钟。如果没有观察到出血，请缩回内窥镜。</li>
</ol>

EBUS-TBNA 的基于仿真的训练

<ol>
	<li>WHO. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Cancer.">Cancer.</a> , (2022).</li><li>Kutob, L., Schneider, F. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Lung+cancer+staging.">Lung cancer staging.</a> Surgical Pathology Clinics. 13 (1), 57-71 (2020).</li><li>Vilmann, P., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Combined+endobronchial+and+esophageal+endosonography+for+the+diagnosis+and+staging+of+lung+cancer:+European+Society+of+Gastrointestinal+Endoscopy+(ESGE)+Guideline,+in+cooperation+with+the+European+Respiratory+Society+(ERS)+and+the+European+Society+of+Thoracic+Surgeons+(ESTS).">Combined endobronchial and esophageal endosonography for the diagnosis and staging of lung cancer: European Society of Gastrointestinal Endoscopy (ESGE) Guideline, in cooperation with the European Respiratory Society (ERS) and the European Society of Thoracic Surgeons (ESTS).</a> Endoscopy. 47 (6), 545-559 (2015).</li><li>Konge, L., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Simulator+training+for+endobronchial+ultrasound:+a+randomised+controlled+trial.">Simulator training for endobronchial ultrasound: a randomised controlled trial.</a> European Respiratory Journal. 46 (4), 1140-1149 (2015).</li><li>Liam, C. K., Lee, P., Yu, C. J., Bai, C., Yasufuku, K. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+diagnosis+of+lung+cancer+in+the+era+of+interventional+pulmonology.">The diagnosis of lung cancer in the era of interventional pulmonology.</a> International Journal of Tuberculosis and Lung Disease. 25 (1), 6-15 (2021).</li><li>Clementsen, P., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Diagnosis+and+staging+of+lung+cancer+with+the+use+of+one+single+echoendoscope+in+both+the+trachea+and+the+esophagus:+A+practical+guide.">Diagnosis and staging of lung cancer with the use of one single echoendoscope in both the trachea and the esophagus: A practical guide.</a> Journal of Endoscopic Ultrasound. 10 (5), 325-334 (2021).</li><li>Farr, A., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Endobronchial+ultrasound:+launch+of+an+ERS+structured+training+programme.">Endobronchial ultrasound: launch of an ERS structured training programme.</a> Breathe (Sheffield, England). 12 (3), 217-220 (2016).</li><li>Konge, L., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+Simulation+Centre+at+Rigshospitalet,+Copenhagen,+Denmark.">The Simulation Centre at Rigshospitalet, Copenhagen, Denmark.</a> Journal of Surgical Education. 72 (2), 362-365 (2015).</li><li>Jenssen, C., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Ultrasound+techniques+in+the+evaluation+of+the+mediastinum,+part+2:+mediastinal+lymph+node+anatomy+and+diagnostic+reach+of+ultrasound+techniques,+clinical+work+up+of+neoplastic+and+inflammatory+mediastinal+lymphadenopathy+using+ultrasound+techniques+and+how+to+learn+mediastinal+endosonography.">Ultrasound techniques in the evaluation of the mediastinum, part 2: mediastinal lymph node anatomy and diagnostic reach of ultrasound techniques, clinical work up of neoplastic and inflammatory mediastinal lymphadenopathy using ultrasound techniques and how to learn mediastinal endosonography.</a> Journal of Thoracic Diseases. 7 (10), 439-458 (2015).</li><li>Lee, H. S., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Real-time+endobronchial+ultrasound-guided+transbronchial+needle+aspiration+in+mediastinal+staging+of+non-small+cell+lung+cancer:+how+many+aspirations+per+target+lymph+node+station.">Real-time endobronchial ultrasound-guided transbronchial needle aspiration in mediastinal staging of non-small cell lung cancer: how many aspirations per target lymph node station.</a> Chest. 134 (2), 368-374 (2008).</li><li>Kinsey, C. M., Arenberg, D. A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Endobronchial+ultrasound-guided+transbronchial+needle+aspiration+for+non-small+cell+lung+cancer+staging.">Endobronchial ultrasound-guided transbronchial needle aspiration for non-small cell lung cancer staging.</a> American Journal of Respiratory and Critical Care Medicine. 189 (6), 640-649 (2014).</li><li>Sanz-Santos, J., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Systematic+compared+with+targeted+staging+with+endobronchial+ultrasound+in+patients+with+lung+cancer.">Systematic compared with targeted staging with endobronchial ultrasound in patients with lung cancer.</a> Annals of Thoracic Surgery. 106 (2), 398-403 (2018).</li><li>Crombag, L. M. M., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Systematic+and+combined+endosonographic+staging+of+lung+cancer+(SCORE+study).">Systematic and combined endosonographic staging of lung cancer (SCORE study).</a> The European Respiratory Journal. 53 (2), 1800800 (2019).</li><li>Andersen, A. G., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Preparing+for+reality:+A+randomized+trial+on+immersive+virtual+reality+for+bronchoscopy+training.">Preparing for reality: A randomized trial on immersive virtual reality for bronchoscopy training.</a> Respiration. 102 (4), 316-323 (2023).</li><li>Naur, T. M. H., Nilsson, P. M., Pietersen, P. I., Clementsen, P. F., Konge, L. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Simulation-based+training+in+flexible+bronchoscopy+and+endobronchial+ultrasound-guided+transbronchial+needle+aspiration+(EBUS-TBNA):+A+systematic+review.">Simulation-based training in flexible bronchoscopy and endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA): A systematic review.</a> Respiration. 93 (5), 355-362 (2017).</li><li>Konge, L., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Reliable+and+valid+assessment+of+clinical+bronchoscopy+performance.">Reliable and valid assessment of clinical bronchoscopy performance.</a> Respiration. 83 (1), 53-60 (2012).</li><li>Du Rand, I. A., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=British+Thoracic+Society+guideline+for+diagnostic+flexible+bronchoscopy+in+adults:+accredited+by+NICE.">British Thoracic Society guideline for diagnostic flexible bronchoscopy in adults: accredited by NICE.</a> Thorax. 68 (Suppl 1), 1-44 (2013).</li><li>Nilsson, P. M., Naur, T. M. H., Clementsen, P. F., Konge, L. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Simulation+in+bronchoscopy:+current+and+future+perspectives.">Simulation in bronchoscopy: current and future perspectives.</a> Advances in Medical Education and Practice. 8, 755-760 (2017).</li><li>Cold, K. M., Clementsen, P. F. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Diagnosis+and+staging+of+lung+cancer+using+transesophageal+ultrasound:+Training+and+assessment.">Diagnosis and staging of lung cancer using transesophageal ultrasound: Training and assessment.</a> Journal of Endoscopic Ultrasound. 11 (2), 92-94 (2022).</li><li>Korevaar, D. A., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Added+value+of+combined+endobronchial+and+oesophageal+endosonography+for+mediastinal+nodal+staging+in+lung+cancer:+a+systematic+review+and+meta-analysis.">Added value of combined endobronchial and oesophageal endosonography for mediastinal nodal staging in lung cancer: a systematic review and meta-analysis.</a> Lancet Respiratory Medicine. 4 (12), 960-968 (2016).</li></ol>

作者没有什么可透露的。

我们特此提出一种系统的 EBUS-TBNA 程序方法，将解剖结构分成六个标志，以帮助引导内窥镜医师穿过支气管迷宫。此外，我们还演示了如何以系统的方式进行针吸，每次都可以重复，以标准化程序。
尽管基于模拟的环境是一个安全的环境，但内窥镜医师应该了解手术中的一些关键步骤。最初，重要的是要知道EBUS示波器的倾斜角度，以便能够通过声带。随后，重要的是要知道?...

肺癌是全球最常见的癌症之一，2020 年有 221 万例，也是最常见的癌症死亡原因，2020 年有 180 万人死亡1。与大多数癌症一样，快速准确地诊断肺癌对于能够提供最佳治疗至关重要，在局部疾病没有或很少扩散到纵隔淋巴结的情况下，可以通过手术切除肿瘤。为了能够确认或否定恶性肿瘤的怀疑，并在确诊肺癌时确定肿瘤淋巴结转移 （TNM） 分类2，对疑似肿瘤或淋巴结进行良好且具有代表性的活检非常重要。
在侵入性技术中，纤维支气管镜检查联合支气管内超声引导下经支气管针吸 （EBUS-TBNA） 起关键作用3.然而，这是一个复杂的技术程序，成功取决于操作员的能力4.如果内窥镜医师不了解纵隔的解剖结构，则很容易失去解剖方向。因此，了解内超声解剖学及其与 TNM 肺癌分类系统的关系至关重要。在肺癌的情况下，如果在任何淋巴结站中没有发现肿瘤细胞，则该疾病被归类为 N0 疾病，并且通常是可手术的，因此可能治愈。在右侧肺肿瘤的情况下，如果肿瘤细胞仅在 10R 站中发现并且可以手术，因此可能治愈，则该疾病被归类为 N1 疾病。但是，如果在4R站中发现肿瘤细胞，则该疾病被归类为N2疾病，并且只能为患者提供延长生命的化疗5。因此，应记住三个边界，因为它们对治疗和预后很重要。
（一）气管的左边界是 4R 和 4L 站之间的边界。 （二）左肺动脉的上边界是 4L 和 10L 站之间的边界。 （三）合子静脉的下边界是站点 4R 和 10R6 之间的边界。
因此，为了有资格在可能的肺癌诊断过程中执行EBUS-TBNA，在对患者进行EBUS-TBNA之前，必须根据结构化的培训课程在基于模拟器的环境中进行全面培训。因此，欧洲呼吸学会 （ERS） 提供的 EBUS 认证培训计划采用了依赖于六个解剖标志的阶梯式方法7。
我们在丹麦哥本哈根医学教育与模拟学院 （CAMES） 的模拟环境中演示了逐步结构化指南8，关于如何使用 EBUS 内窥镜进行 EBUS-TBNA，依靠六个解剖标志9 作为指导。

<table><tbody><tr><td>EVIS Exera II endoscopy tower with a BF-UC180F EBUS endoscope</td><td>Olympus</td><td>https://medical.olympusamerica.com/products/bf-uc180f-ebus-bronchoscope</td><td></td></tr><tr><td>ENDO mentor suite</td><td>Surgical Science</td><td>https://simbionix.com/endo-mentor-suite/</td><td>Surgical Science Simulator</td></tr><tr><td>GI-Bronch Mentor software</td><td>Simbionix</td><td>https://simbionix.com/simulators/gi-mentor/</td><td></td></tr></tbody></table>

systematic endobronchial ultrasound - the six landmarks approach

肺癌是全球癌症死亡的主要原因。为确保与治疗方案相关的正确诊断和分期，从疑似肿瘤和纵隔淋巴结中获得有效的活检，并根据肿瘤淋巴结转移 （TNM） 分类准确识别纵隔淋巴结至关重要。纤维支气管镜检查联合支气管内超声引导下经支气管针吸 （EBUS-TBNA） 对于疑似肺癌患者的病情检查和诊断至关重要。来自纵隔淋巴结的 EBUS-TBNA 是一项技术上困难的手术，已被确定为最重要的手术之一，应整合到侵入性肺科医生基于模拟的培训计划中。为了满足这一需求，需要更具体的指南来管理EBUS-TBNA的培训。我们特此提出一种系统的、循序渐进的方法，特别注意在支气管迷宫中导航时支持内窥镜医师的六个标志。欧洲呼吸学会 （ERS） 提供的 EBUS 认证培训计划采用了依赖于六个里程碑的逐步方法。

自 2016 年以来，作为欧洲呼吸学会 （ERS） 提供的 EBUS 认证培训计划的一部分，CAMES 一直在教授上述 EBUS-TBNA 程序的结构化方法7。6 个里程碑方法基于经过验证的评估工具，用于测量 EBUS 引导的经支气管穿刺抽吸能力4。如上图所示，通过结构化的方式进行EBUS-TBNA，不会遗漏任何重要的淋巴结，诊断准确性将非常高。
如协议中所述和视频中所...

Watch this Scientific Journal Video about Demonstrating Systematic Endobronchial Ultrasound to New Endoscopists at JoVE.com

作者聚焦：向新内窥镜医师演示系统支气管内超声 

使用经支气管针吸的支气管内超声引导取样在肺癌的分期和诊断中起着关键作用。我们提出了一种系统的逐步方法，将程序分为六个里程碑，应该教给新的操作员。

系统性支气管内超声 - 六个里程碑方法

Lung cancer is the leading cause of cancer mortality globally. To ensure the correct diagnosis and staging in relation to treatment options, it is crucial ...

我们想展示一个逐步结构化的指南，介绍如何在基于模拟的环境中使用内窥镜执行 EBUS 程序，依赖于六个解剖标志方法。在医学和外科领域，基于模拟的环境中的侵入性手术培训已在全球范围内广泛增加，以确保专业人员在对患者进行侵入性手术之前在模拟器中进行练习。最重要的技术是我们在食道中使用EBUS内窥镜，即所谓的USB，因为我们知道EBUS和USB的组合比单独的EBUS要好得多。在基于模拟的环境中对侵入性手术进行培训应该是黄金标准。然而，许多专业人员无法使用这些培训设施，或者没有优先考虑培训。因此，我们目前的实验挑战是传播这些基于模拟的设置的知识，并促进尽可能多的培训。

systematic-endobronchial-ultrasound-the-six-landmarks-approach

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Cancer Research

Systematic Endobronchial Ultrasound - The Six Landmarks Approach

1.8K 次观看.  Rigshospitalet, University of Copenhagen. 我们想展示一个逐步结构化的指南，介绍如何在基于模拟的环境中使用内窥镜执行 EBUS 程序，依赖于六个解剖标志方法。在医学和外科领域，基于模拟的环境中的侵入性手术培训已在全球范围内广泛增加，以确保专业人员在对患者进行侵入性手术之前在模拟器中进行练习。最重要的技术是我们在食道中使用EBUS内窥镜，即所谓的USB，因为我们知道EBUS和USB的组合比单独的EBUS要?...

视频: 作者聚焦：向新内窥镜医师演示系统支气管内超声 

Endobronchial Ultrasound-guided Intratumoral Injection of Cisplatin for the Treatment of Isolated Mediastinal Recurrence of Lung Cancer

Isolated hilar and mediastinal recurrence (IMHR) following external beam radiation therapy (EBRT) in patients with lung cancer is common. These patients do not have many treatment options and are usually offered palliative chemotherapy or best supportive care. Endobronchial ultrasound (EBUS)-guided intratumoral injection of cisplatin (ITC) is a novel approach for these patients. The procedure is performed under conscious sedation. The lesion is located with a bronchoscopy using EBUS, and a 22-gauge EBUS needle is advanced through the working channel of the scope and locked in position. Under ultrasound guidance, the wall of the tracheobronchial tree is punctured and the needle is moved into the target lesion. The needle stylet is then removed and cisplatin (40 mg/40 mL) is injected into the lesion. One to two sites are treated per session. Details of the procedure are described in the protocol section of paper. At our center, 50 sites were treated in 36 patients (19 males, 17 females). The mean age of our cohort was 61.9 &#177;8.5 years. We performed final analyses on 35 patients and 41 sites. 24/35 (69%) had complete or partial response (responders), whereas 11/35 (31%) had stable or progressive disease (non-responders). Overall, survival in our group was 8 months (95% CI of 6-11 months), with patients who responded having significantly better survival than the ones who did not.

The management of isolated recurrent lung cancer in a previously-irradiated field is challenging. Here, we describe an endobronchial ultrasound (EBUS)-guided cisplatin injection for the management of patients with localized lung cancer recurrence in a previously-radiated field.

支气管内超声引导下顺铂瘤内注射对肺癌纵隔孤立复发的治疗

Isolated hilar and mediastinal recurrence (IMHR) following external beam radiation therapy (EBRT) in patients with lung cancer is common. These patients ...

科研

癌症研究

Utilizing High Resolution Ultrasound to Monitor Tumor Onset and Growth in Genetically Engineered Pancreatic Cancer Models

The LSL-KrasG12D/+; LSL-Trp53R172H/+; Pdx-1-Cre (KPC) mouse model represents an established and frequently used transgenic model to evaluate novel therapies in pancreatic cancer. Tumor onset is variable in the KPC model between 8 weeks and several months. Therefore, non-invasive imaging tools are required to screen for tumor onset and monitor for response to treatment. To address this issue, different approaches have emerged over the last years. High resolution ultrasound has major advantages such as non-invasiveness, fast session times and a high image resolution without radiation exposure. However, ultrasound in mice is not trivial and sufficient anatomical knowledge and practical skills are required to successfully perform high resolution ultrasound in preclinical pancreatic cancer models. With the following article, a detailed hands-on guide for abdominal ultrasound in murine models with a particular focus on endogenous pancreatic cancer models is presented. Furthermore, a summary of common mistakes and how to avoid them is provided.

This article describes the utilization of high-resolution ultrasound in genetically engineered pancreatic cancer mice. The primary aim is to provide a detailed instruction for detection and evaluation of endogenous pancreatic tumors.

应用高分辨率超声监测基因工程胰腺癌的肿瘤发病和生长

The LSL-KrasG12D/+; LSL-Trp53R172H/+; Pdx-1-Cre (KPC) mouse model represents an established and frequently used transgenic model to evaluate novel ...

Utilization of Ultrasound Guided Tissue-directed Cellular Implantation for the Establishment of Biologically Relevant Metastatic Tumor Xenografts

Preclinical testing of anticancer therapies relies on relevant xenograft models that mimic the innate tendencies of cancer. Advantages of standard subcutaneous flank models include procedural ease and the ability to monitor tumor progression and response without invasive imaging. Such models are often inconsistent in translational clinical trials and have limited biologically relevant characteristics with low proclivity to produce metastasis, as there is a lack of a native microenvironment. In comparison, orthotopic xenograft models at native tumor sites have been shown to mimic the tumor microenvironment and replicate important disease characteristics such as distant metastatic spread. These models often require tedious surgical procedures with prolonged anesthetic time and recovery periods. To address this, cancer researchers have recently utilized ultrasound-guided injection techniques to establish cancer xenograft models for preclinical experiments, which allows for rapid and reliable establishment of tissue-directed murine models. Ultrasound visualization also provides a noninvasive method for longitudinal assessment of tumor engraftment and growth. Here, we describe the method for ultrasound-guided injection of cancer cells, utilizing the adrenal gland for NB and renal sub capsule for ES. This minimally invasive approach overcomes tedious open surgery implantation of cancer cells in tissue-specific locations for growth and metastasis, and abates morbid recovery periods. We describe the utilization of both established cell lines and patient derived cell lines for orthotopic injection. Pre-made commercial kits are available for tumor dissociation and luciferase tagging of cells. Injection of cell suspension using image-guidance provides a minimally invasive and reproducible platform for the creation of preclinical models. This method is utilized to create reliable preclinical models for other cancers such as bladder, liver and pancreas exemplifying its untapped potential for numerous cancer models.

Here, we present a protocol to utilize ultrasound-guided injection of neuroblastoma (NB) and Ewing's sarcoma (ES) cells (established cell lines and patient-derived tumor cells) at biologically relevant sites to create reliable preclinical models for cancer research.

超声引导组织定向细胞植入术在生物学相关转移性肿瘤移植中的应用

Preclinical testing of anticancer therapies relies on relevant xenograft models that mimic the innate tendencies of cancer. Advantages of standard ...

Evaluation of the Feasibility, Safety, and Accuracy of an Intraoperative High-intensity Focused Ultrasound Device for Treating Liver Metastases

Today, the only potentially curative option in patients with colorectal liver metastases is surgery. However, liver resection is feasible in less than 20% of patients. Surgery has been widely used in association with radiofrequency, cryotherapy, or microwaves to expand the number of treatments performed with a curative intent. Nevertheless, several limitations have been documented when using these techniques (i.e., a traumatic puncture of the parenchyma, a limited size of lesions, and an inability to monitor the treatment in real-time).High-intensity focused ultrasound (HIFU) technology can achieve precise ablations of biological tissues without incisions or radiation. Current HIFU devices are based on an extracorporeal approach with limited access to the liver. We have developed a HIFU device designed for intraoperative use. The use of a toroidal transducer enables an ablation rate (10 cm3&#183;min-1) higher than any other treatment and is independent of perfusion.
The feasibility, safety, and accuracy of intraoperative HIFU ablation were evaluated during an ablate-and-resect prospective study. This clinical phase I and IIa study was performed in patients undergoing hepatectomy for liver metastases. The HIFU treatment was performed on healthy tissue scheduled for resection.Liver metastases measuring less than 20 mm will be targeted during phase IIb (currently ongoing). This set-up allows the real-time evaluation of HIFU ablation while protecting participating patients from any adverse effects related to this new technique.
Fifteen patients were included in phase I&#8211;IIa and 30 HIFU ablations were safely created within 40 s and with a precision of 1&#8211;2 mm. The average dimensions of the HIFU ablations were 27.5 x 21.0 mm2, corresponding to a volume of approximately 7.5 cm3. The aim of the ongoing phase IIb is to ablate metastases of less than 20 mm in diameter with a 5 mm margin.

Here, we present an ablate-and-resect prospective study to evaluate the feasibility, safety, and accuracy of intraoperative high-intensity focused ultrasound ablation in patients undergoing hepatectomy for liver metastases.

术中高强度聚焦超声装置治疗肝转移的可行性、安全性和准确性评价

Today, the only potentially curative option in patients with colorectal liver metastases is surgery. However, liver resection is feasible in less than 20% ...

Ultrasound-Guided Orthotopic Implantation of Murine Pancreatic Ductal Adenocarcinoma

The recent success of immune checkpoint blockade in melanoma and lung adenocarcinoma has galvanized the field of immuno-oncology as well as revealed the limitations of current treatments, as the majority of patients do not respond to immunotherapy. Development of accurate preclinical models to quickly identify novel and effective therapeutic combinations are critical to address this unmet clinical need. Pancreatic ductal adenocarcinoma (PDA) is a canonical example of an immune checkpoint blockade resistant tumor with only 2% of patients responding to immunotherapy. The genetically engineered KrasG12D+/-;Trp53R172H+/-;Pdx-1 Cre (KPC) mouse model of PDA recapitulates human disease and is a valuable tool for assessing therapies for immunotherapy resistant in the preclinical setting, but time to tumor onset is highly variable. Surgical orthotopic tumor implantation models of PDA maintain the immunobiological hallmarks of the KPC tissue-specific tumor microenvironment (TME) but require a time-intensive procedure and introduce aberrant inflammation. Here, we use an ultrasound-guided orthotopic tumor implantation model (UG-OTIM) to non-invasively inject KPC-derived PDA cell lines directly into the mouse pancreas. UG-OTIM tumors grow in the endogenous tissue site, faithfully recapitulate histological features of the PDA TME, and reach enrollment-sized tumors for preclinical studies by four weeks after injection with minimal seeding on the peritoneal wall. The UG-OTIM system described here is a rapid and reproducible tumor model that may allow for high throughput analysis of novel therapeutic combinations in the murine PDA TME.

We describe a protocol for the ultrasound guided implantation of murine-derived pancreatic ductal adenocarcinoma cell lines directly into the native tumor site. This approach resulted in pancreatic tumors detectable by ultrasound scanning within 2-4 weeks of injection, and significantly reduced the proportion tumor cell seeding on the peritoneal wall as compared to surgical orthotopic implantation.

毛尿胰腺腺腺腺癌超声引导正射植入

The recent success of immune checkpoint blockade in melanoma and lung adenocarcinoma has galvanized the field of immuno-oncology as well as revealed the ...

Detection of Lung Tumor Progression in Mice by Ultrasound Imaging

With ~1.6 million victims per year, lung cancer contributes tremendously to the worldwide burden of cancer. Lung cancer is partly driven by genetic alterations in oncogenes such as the KRAS oncogene, which constitutes ~25% of lung cancer cases. The difficulty in therapeutically targeting KRAS-driven lung cancer partly stems from having poor models that can mimic the progression of the disease in the lab. We describe a method that permits the relative quantification of primary KRAS lung tumors in a Cre-inducible LSL-KRAS G12D mouse model via ultrasound imaging. This method relies on brightness (B)-mode acquisition of the lung parenchyma. Tumors that are initially formed in this model are visualized as B-lines and can be quantified by counting the number of B-lines present in the acquired images. These would represent the relative tumor number formed on the surface of the mouse lung. As the formed tumors develop with time, they are perceived as deep clefts within the lung parenchyma. Since the circumference of the formed tumor is well-defined, calculating the relative tumor volume is achieved by measuring the length and width of the tumor and applying them in the formula used for tumor caliper measurements. Ultrasound imaging is a non-invasive, fast and user-friendly technique that is often used for tumor quantifications in mice. Although artifacts may appear when obtaining ultrasound images, it has been shown that this imaging technique is more advantageous for tumor quantifications in mice compared to other imaging techniques such as computed tomography (CT) imaging and bioluminescence imaging (BLI). Researchers can investigate novel therapeutic targets using this technique by comparing lung tumor initiation and progression between different groups of mice.

This protocol describes the steps taken to induce KRAS lung tumors in mice as well as the quantification of formed tumors by ultrasound imaging. Small tumors are visualized in early timepoints as B-lines. At later timepoints, relative tumor volume measurements are achieved by the measurement tool in the ultrasound software.

超声成像对小鼠肺肿瘤进展的检测

With ~1.6 million victims per year, lung cancer contributes tremendously to the worldwide burden of cancer. Lung cancer is partly driven by genetic ...

Analysis of Lymph Node Volume by Ultra-High-Frequency Ultrasound Imaging in the Braf/Pten Genetically Engineered Mouse Model of Melanoma

Tyr::CreER+,BrafCA/+,Ptenlox/lox&#160;genetically engineered mice (Braf/Pten mice) are widely used as an in vivo model of metastatic melanoma. Once a primary tumor has been induced by tamoxifen treatment, an increase in metastatic burden is observed within 4-6 weeks after induction. This paper shows how Ultra-High-Frequency UltraSound (UHFUS) imaging can be exploited to monitor the increase in metastatic involvement of the inguinal lymph nodes by measuring the increase in their volume.
The UHFUS system is used to scan anesthetized mice with a UHFUS linear probe (22-55 MHz, axial resolution 40 &#181;m). B-mode images from the inguinal lymph nodes (both left and right sides) are acquired in a short-axis view, positioning the animals in dorsal recumbency. Ultrasound records are acquired using a 44 &#181;m step size on a motorized mechanical arm. Afterward, two-dimensional (2D) B-mode acquisitions are imported into the software platform for ultrasound image post-processing, and inguinal lymph nodes are identified and segmented semi-automatically in the acquired cross-sectional 2D images. Finally, a total reconstruction of the three-dimensional (3D) volume is automatically obtained along with the rendering of the lymph node volume, which is also expressed as an absolute measurement.
This non-invasive in vivo technique is very well tolerated and allows the scheduling of multiple imaging sessions on the same experimental animal over 2 weeks. It is, therefore, ideal to assess the impact of pharmacological treatment on metastatic disease.

Melanoma is a very aggressive disease that quickly spreads to other organs. This protocol describes the application of ultra-high-frequency ultrasound imaging, coupled with 3D rendering, to monitor the volume of the inguinal lymph nodes in the Braf/Pten mouse model of metastatic melanoma.

超高频超声成像分析黑色素瘤Braf/Pten基因工程小鼠模型中的淋巴结体积

Tyr::CreER+,BrafCA/+,Ptenlox/lox&#160;genetically engineered mice (Braf/Pten mice) are widely used as an in vivo model of metastatic melanoma. Once a ...

适用于支气管镜新手的软式支气管镜检查

Systematic Bronchoscopy: the Four Landmarks Approach

Flexible bronchoscopy is a technically difficult procedure and has been identified as the most important procedure that should be integrated into a simulation-based training program for pulmonologists. However, more specific guidelines that govern bronchoscopy training are needed to meet this demand. To ensure patients a competent examination, we propose a systematic, stepwise approach, splitting the procedure into four &#34;landmarks&#34; to support novice endoscopists navigating the bronchial maze. The procedure can be evaluated based on three established outcome measures to ensure a thorough and effective inspection of the bronchial tree: diagnostic completeness, structured progress, and procedure time.
The stepwise approach relying on the four landmarks is used at all simulation centers in Denmark and is being implemented in the Netherlands. To provide instant feedback to novice bronchoscopists when training and to relieve time constraints from consultants, we suggest that future studies should implement artificial intelligence&#160;as a feedback and certification tool when training new bronchoscopists.

作者聚焦:在模拟基础环境中学习系统支气管镜检查 

Here, we present a protocol to navigate the bronchial maze in a structured manner, splitting the bronchoscopy into a stepwise approach-the four landmarks approach.

系统性支气管镜检查:四个标志方法

Flexible bronchoscopy is a technically difficult procedure and has been identified as the most important procedure that should be integrated into a ...

系统性支气管内超声 - 六个里程碑方法

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支气管内超声引导下顺铂瘤内注射对肺癌纵隔孤立复发的治疗

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系统性支气管镜检查:四个标志方法

系统性支气管镜检查:四个标志方法

系统性支气管镜检查:四个标志方法