Department of Neurosurgery, Johns Hopkins University School of Medicine.
Department of Neurosurgery, University of Maryland School of Medicine; Marlene and Stewart Greenebaum Comprehensive Cancer Center, University of Maryland School of Medicine.
J Vis Exp. 2022 May 9(183). doi: 10.3791/64048.
The present protocol describes a standardized paradigm for rodent brain tumor resection and tissue preservation. In clinical practice, maximal tumor resection is the standard-of-care treatment for most brain tumors. However, most currently available preclinical brain tumor models either do not include resection, or utilize surgical resection models that are time-consuming and lead to significant postoperative morbidity, mortality, or experimental variability. In addition, performing resection in rodents can be daunting for several reasons, including a lack of clinically comparable surgical tools or protocols and the absence of an established platform for standardized tissue collection. This protocol highlights the use of a multi-functional, non-ablative resection device and an integrated tissue preservation system adapted from the clinical version of the device. The device applied in the present study combines tunable suction and a cylindrical blade at the aperture to precisely probe, cut, and suction tissue. The minimally invasive resection device performs its functions via the same burr hole used for the initial tumor implantation. This approach minimizes alterations to regional anatomy during biopsy or resection surgeries and reduces the risk of significant blood loss. These factors significantly reduced the operative time (<2 min/animal), improved postoperative animal survival, lower variability in experimental groups, and result in high viability of resected tissues and cells for future analyses. This process is facilitated by a blade speed of ~1,400 cycles/min, which allows the harvesting of tissues into a sterile closed system that can be filled with a physiologic solution of choice. Given the emerging importance of studying and accurately modeling the impact of surgery, preservation and rigorous comparative analysis of regionalized tumor resection specimens, and intra-cavity-delivered therapeutics, this unique protocol will expand opportunities to explore unanswered questions about perioperative management and therapeutic discovery for brain tumor patients.
本方案描述了一种标准化的啮齿动物脑肿瘤切除和组织保存范例。在临床实践中,最大限度地切除肿瘤是大多数脑肿瘤的标准治疗方法。然而,目前大多数可用的临床前脑肿瘤模型要么不包括切除,要么使用耗时且导致术后发病率、死亡率或实验变异性高的手术切除模型。此外,由于缺乏临床可比的手术工具或方案,以及缺乏标准化组织收集的既定平台,在啮齿动物中进行切除可能令人生畏。本方案强调使用多功能、非消融性切除装置和从该装置的临床版本改编的集成组织保存系统。本研究中使用的装置结合了可调吸力和孔径处的圆柱形刀片,以精确探测、切割和抽吸组织。微创切除装置通过用于初始肿瘤植入的相同骨孔完成其功能。这种方法最大限度地减少了活检或切除手术中对区域解剖结构的改变,并降低了大量失血的风险。这些因素显著缩短了手术时间(<2 分钟/只动物),提高了术后动物存活率,降低了实验组之间的变异性,并使切除组织和细胞具有高活力,可用于未来的分析。通过约 1400 次/分钟的刀片速度,这一过程得到了促进,允许将组织收获到一个无菌的封闭系统中,该系统可以充满所需的生理溶液。鉴于研究和准确模拟手术影响、保存和严格的区域性肿瘤切除标本的比较分析以及腔内递药的重要性日益增加,这种独特的方案将为探索脑肿瘤患者围手术期管理和治疗发现的未解决问题提供更多机会。