肿瘤外科新热点：可使肿瘤发光的荧光剂

马里兰州国家海港——美国和荷兰研究者在美国肿瘤外科学会(SSO)年度癌症研讨会上报告称，眼见为实，尤其是在术中提高肿瘤的可视性，将有助于改善肿瘤完全切除的机会。应用近红外(NIR)荧光成像和便携式摄像机，可减少外科医生在手术过程中对手术边缘或淋巴结的主观判断。

宾州大学外科学系的Sunil Singhal博士报告称，在早期人体试验中，小型便携式红外摄像机已成功用于肺鳞癌和腺癌切除术中识别染料浸染的肿瘤(包括非临近的恶性肿瘤)。目前仍有40%的肿瘤患者的肿瘤不能完全切除，其中约1/4的患者肿瘤小于2 cm。

为提高切除几率，Singhal博士及其同事考察了能够安全到达肿瘤部位并使之在近红外光谱下产生荧光的光学对照剂。在临床前动物研究中，他们发现吲哚菁绿(ICG)在毒性、光稳定性、药动学以及费用方面具有综合优势。该染料目前用于视网膜血管造影术，其荧光发射特点有助于观察者区分荧光染料与血管或组织。

他们还开发了一款名为FloCam的术中设备，由光源和NIR摄像机部分组成，术中可将NIR影像传送至计算机显示器。

在动物实验中，该系统可发现肉眼或X线微断层摄像术不能识别的残留肿瘤。病理检查发现，该染料能够非常精确界定肿瘤边缘与正常周围组织，尤其是对具有新生血管特征的肿瘤。

在针对38例患者的早期人体试验中，该系统在术中可有效识别36例患者的肿瘤部位，仅1例黑色素瘤和1例肉瘤患者未能识别。

典型病例包括1例64岁不吸烟男性患者，因咳嗽就诊，发现右肺上叶有1枚2.5 cm肿瘤。纵隔影像学和病理学检查显示为非恶性肿瘤，但术中染料显示右肺下叶存在此前未检测到的肿瘤热点。

另1例1A期肿瘤患者，荧光成像系统检出非常小的肿瘤，接受化疗后1年仍然存活。但若未检出该肿瘤， 1年后将会因肿瘤转移而再次住院，甚至死亡。

混合示踪剂

在另一项研究中，荷兰癌症研究所的Oscar R. Brouwer博士及其同事应用一种新的混合型放射性示踪剂改善术中对前哨淋巴结的识别和切除效果。该示踪剂是由ICG与锝-99混合而成的纳米胶体悬浮液。

在全部96例头颈部、躯干或四肢恶性黑色素瘤患者中，该混合示踪剂均有助于术前SPECT/CT和术中放射性和荧光指导下的前哨淋巴结活检。

研究者指出，该混合示踪剂特别适用于颈部前哨淋巴结和不能蓄积专利蓝的前哨淋巴结的识别。

Singhal博士的研究得到SSO和宾州大学资助，Brouwer博士的研究由荷兰癌症研究所资助，研究者均报告无利益冲突。

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By: NEIL OSTERWEIL, Oncology Practice

NATIONAL HARBOR, MD – Seeing is believing, especially when enhanced visualization of tumors during surgery helps improve chances for complete resection, investigators said at the annual Society of Surgical Oncology Cancer Symposium.

With near-infrared (NIR) fluorescence imaging and a portable camera that can be used in an operating room, surgeons can eliminate some of the guesswork involved in identifying involved surgical margins or lymph nodes, researchers from the U.S. and the Netherlands reported in oral and poster sessions.

In early human trials, a small, portable infrared camera has been successful at identifying dye-impregnated tumors – including noncontiguous pockets of malignancy – during surgery to resect squamous cell carcinomas and adenocarcinomas of the lung, reported Dr. Sunil Singhal, of the department of surgery at the University of Pennsylvania, Philadelphia.

"Even in this day and age, surgeons leave behind disease in 40% of the cases, and in about a quarter of those cases the tumor was within two centimeters of where the surgeon was working," Dr. Singhal said.

To improve the odds, he and his colleagues have been investigating optical contrast agents that can be delivered safely to tumors and cause them to fluoresce under light in the near-infrared portion of the spectrum. In preclinical studies with dogs, they found that indocyanine green had the right combination of toxicity, photostability, pharmacokinetics, and cost. The dye, currently used in retinal angiography, has an emission profile that makes it easy for observers to discriminate between the fluorescing dye and blood or tissues, Dr. Singhal said.

They also developed an intraoperative device, dubbed the "FloCam," which consists of a light source and near-infrared (NIR) camera that sits above the patient and sends images to a computer monitor showing the operation in NIR.

In animal studies, the system found evidence of residual disease that was not visible to the naked eye or on x-ray microtomography. On pathologic examination, they saw that the dye was "remarkably precise in delineating margins from normal surrounding tissues," particularly in tumors with neovascular features.

Dr. Singhal said that the imaging technique has been effective at identifying tumor sites during surgery in 36 of 38 patients in early human trials, failing only for 1 patient with melanoma, and for 1 with a sarcoma.

One patient was a 64-year-old nonsmoking man who presented with a cough and was found to have a 2.5 cm right upper lobe lung tumor. Evaluation of the mediastinum with imaging and pathology samples was negative for malignancy, but during surgery, the dye highlighted previously undetected tumor hotspots in the right lower lobe.

"This is another patient who would have gone home [with a diagnosis of] stage 1A. I would have walked down to the recovery room, say ‘I cured you,’ and he would come back 1 year later with metastatic disease and die. This patient, who had minimal disease when we discovered it, got chemotherapy and is still alive at the 1-year mark," Dr. Singhal said.

Green hybrid

In a separate study, investigators in the Netherlands reported on improved intraoperative sentinel node identification and harvesting using a novel hybrid radiopharmaceutical tracer combining indocyanine green with technetium-99m in a nanocolloid suspension.

They found that in 96 patients with malignant melanomas of the head and neck, trunk, or extremities, the hybrid tracer, facilitated both preoperative SPECT/CT imaging and intraoperative radio- and fluorescence-guide sentinel node biopsy in all patients.

"The hybrid tracer was found to be particularly useful for the detection of sentinel nodes in the neck, and for sentinel nodes that failed to accumulate patent blue dye," wrote Dr. Oscar R. Brouwer from the division of nuclear medicine at the Netherlands Cancer Institute in Amsterdam, and colleagues in a scientific poster.

Dr. Singhal’s studies were supported by the Society of Surgical Oncology and the University of Pennsylvania. He reported having no financial disclosures. Dr. Brouwer’s study was supported by the Netherlands Cancer Institute. He reported having no financial disclosures.