A multimodality localization technique for radio-guided surgery

Background Intraoperative localization of image or endoscopy-detected lesions occasionally pose surgical challenges due to the small lesion size and/or difficult anatomic exposure. Identification of such lesions can be facilitated using a hand-held gamma probe with utilization of Tc-99m macroaggregate albumen (MAA) localization technique. The radiopharmaceutical injection can be performed using ultrasound (US) or endoscopy guidance. Case presentations The clinical use of the Tc-99m MAA protocol gamma probe-guided surgery was discussed in three representative cases. Surgical indication was diagnostic exploration in two patients with suspicious lymphadenopathy, and determination of extent of surgical resection in a patient with polyposis. Lesion localization with 100 microcurie (3.7 MBq) Tc-99m MAA prior to surgical exploration resulted in definitive localization of lesions intraoperatively. Conclusion The use Tc-99m MAA deposition technique at the site of surgical target is a highly efficient radio-guided surgery technique with definitive impact on the success of surgical exploration in selected indications.


Background
The role of gamma probes in surgical oncology practice has been well established [1][2][3][4][5][6][7][8][9]. Surgical performance with intraoperative gamma probe detection is critically dependent on target to surrounding background ratio (TBR). This ratio, for localization techniques that involve systemic administration of radiopharmaceuticals, is a function of radiopharmaceutical uptake and clearance kinetics. Probe's ability to discern the target signal also is a major technical factor in the clinical success. A minimum TBR of 1.5:1 is needed in the operative field for the operating surgeon to be comfortable that the differences between the target tissue and normal adjacent tissue are real [10]. Obtaining a satisfactory TBR is always a significant technical challenge with localization techniques using systemic administration of radiopharmaceuticals. Administration of a locally-entrapped radiopharmaceutical in or around the target tissue results in an ideal TBR. clinical decision was made for an excision biopsy. The node was injected with Tc-99m macroaggregate albumen (MAA) and lymphazurin blue 2 h prior to the planned operation. At surgery, the hot-spot was readily identified. Probe localization was distinctly focal over a level-I node, which was accessed with minimal dissection. Blue dye facilitated surgical exposure and dissection. Surgical pathology revealed chronic inflammatory changes ( Figure  1).

Case 2
A 65 year-old woman with history of colorectal cancer (CRC) and non-Hodgkin's lymphoma of the scalp, presented with mediastinal and retroclavicular lymphadenopathy. CRC was diagnosed 2 years ago, and was treated with R-colon resection. Scalp lymphoma was diagnosed 6 months ago, when the patient presented with a 15 cm scalp lesion. Staging work-up at that time revealed positive FDG uptake in the scalp lesion (SUV:18), multiple mediastinal and R-retroclavicular lymph node (SUV:3.2), and a 12 cm liver lesion (SUV: 8.5). Biopsy of the liver lesion was consistent with the colon primary. Nodal findings were concluded to indicate a stage III lymphoma, and a sequential intensity-modulated radiation therapy (IMRT) and chemotherapy using CHOP regimen was administered. There was a complete clinical and FDG-PET/CT response in the scalp lesion. Post-treatment FDG-PET/CT showed persistence of mediastinal and R-retroclavicular nodal uptake. The R-retroclavicular node was injected with Tc-99m MAA and lymphazurin blue 2 h prior to the planned operation. At surgery, the hot-spot was readily identified. Probe localization was distinctly focal over an internal jugular-innominate vein confluence lymph node. The target was accessed through an incision made over the hot-spot. The line-of-sight provided a safe surgical dissection. The blue dye facilitated surgical exposure and dissection. Surgical pathology revealed a chronic granulomatous disease. The patient was restaged to have a stage I scalp lymphoma, and remained in complete remission following treatment. Stage IV CRC was also concluded to be a liver-only disease, which allowed her to be considered for liver-directed therapy ( Figure 2).

Case 3
A 69 year-old man presented with anemia, subsequent colonoscopy revealed a right colon cancer and multiple polyps throughout the colon. Severe dysplastic changes were noted in a sessile polyp in the transverse colon and in a pedunculated polyp in the sigmoid colon of villous type. The descending colon polyp was completely excised colonoscopically and the site was submucosally injected with Tc-99m MAA and lymphazurin blue 18 h prior to a planned operation. At surgery, the ascending colon lesion was readily identified. None of the polyps were palpable. A slight, relatively diffuse discoloration of submucosal blue dye was noted at the site of injection. Probe localization was distinctly focal. A total abdominal colectomy was performed with 2-cm margins distal to the focal Tc-99m a) Right axillary lymphadenopathy demonstrated on mammogram MAA signal. Surgical pathology confirmed complete resection with free margins (Figure 3).

Gamma probe-guided surgery protocol
The patients receive an injection of 0.1 mCi (0.037 MBq) (in 0.1 ml solution) Tc-99m MAA the morning of planned surgery. Lymph node injections are given most conveniently under US. For colon polyp localization, the injec-tion using the same activity and volume is given endoscopically. Surgical exploration is scheduled within 6 hours post injection of the radiopharmaceutical. The injected activity might be doubled if surgery is planned 6-12 hours after the injection (Table 1)

Conclusion
Major applications of the technique include localization of lymph nodes and colonic polyps. The technique may also be used in localization of non-palpable breast lesions as an adjunct to needle/wire localization techniques.

Competing interests
The author(s) declare that they have no competing interests.
A and B) Sigmoid colon polyp and endoscopic injection of the base Figure 3 A and B) Sigmoid colon polyp and endoscopic injection of the base. C) Intaoperative gamma probe localization of Tc-99m MAA injection site. D and E) Distribution of multiple polyps in the resected specimen.