Shum Cheuk Fan, Bahler Clinton D, Low Philip S, Ratliff Timothy L, Kheyfets Steven V, Natarajan Jay P, Sandusky George E, Sundaram Chandru P
Department of Urology, Indiana University School of Medicine , Indianapolis, Indiana.
Department of Chemistry, Institute for Drug Discovery, Purdue University , West Lafayette, Indiana.
J Endourol Case Rep. 2016 Nov 1;2(1):189-197. doi: 10.1089/cren.2016.0104. eCollection 2016.
Partial nephrectomy is now the preferred surgical option for small renal tumors because it allows nephron preservation without compromising oncologic clearance. Its outcomes depend on the surgeon's ability to continuously identify the edges of the tumor during resection, thus leaving an adequate margin around the tumor without excessive removal of normal parenchyma, as well as keeping a short ischemic time. Folate receptors are highly abundant in the normal kidney, and there is a difference in folate receptor expression between malignant and normal renal tissues. Thus, the use of fluorescent agents that target folate receptors should result in differential fluorescence between the tumor and surrounding parenchyma during partial nephrectomy, which, in turn, helps tumor demarcation for identification and resection. A phase 2 study on the novel use of OTL38 in robot-assisted laparoscopic partial nephrectomy is currently in progress in our institution. The outcomes of the first three cases have shown the possible advantages of OTL38 in intraoperative tumor identification before resection and recognition of residual disease in the surrounding parenchyma after resection. The tumors typically appeared dark while the surrounding parenchyma showed brighter fluorescence. Immediately after tumor resection, the margins of all the specimens appeared to have a uniformly bright fluorescence, suggestive of an intact margin of normal renal parenchyma along the plane of excision. The pattern of intraoperative fluorescence correlates well with immunohistochemistry. No OTL38-related adverse effects have been seen among these three patients. We present the outcomes of these three cases, illustrated with intraoperative and immunohistochemistry images.
部分肾切除术目前是小肾肿瘤的首选手术方式，因为它能够保留肾单位，同时不影响肿瘤切除的彻底性。其手术效果取决于外科医生在切除过程中持续识别肿瘤边缘的能力，从而在肿瘤周围留出足够的切缘，避免过度切除正常肾实质，同时保持较短的缺血时间。叶酸受体在正常肾脏中高度丰富，恶性和正常肾组织之间叶酸受体表达存在差异。因此，使用靶向叶酸受体的荧光剂应能在部分肾切除术中使肿瘤与周围实质产生不同的荧光，进而有助于肿瘤边界的识别与切除。我们机构目前正在进行一项关于OTL38在机器人辅助腹腔镜部分肾切除术中新用途的2期研究。前三例病例的结果显示了OTL38在术前术中肿瘤识别以及术后识别周围实质残留疾病方面可能具有的优势。肿瘤通常呈现深色，而周围实质显示出较亮的荧光。肿瘤切除后立即观察，所有标本的切缘似乎都有均匀明亮的荧光，提示沿切除平面的正常肾实质切缘完整。术中荧光模式与免疫组织化学结果相关性良好。这三名患者均未出现与OTL38相关的不良反应。我们展示这三例病例的结果，并配有术中及免疫组织化学图像。
