الفهرس 
AnatomyOnly 14 pages are availabe for public view
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Abstract
The primary goal of the oncological surgeon in the operative treatment of solid tumours is to perform a complete resection, usually at a microscopic level, this ability is enhanced by a technique known as the ”Radioimmunoguided Surgery” (RIGS).
The evolution of the RIGS system is based on the radioimmunodetection, which was first by external imaging immunoscintigraphy, then intraoperative detection radioimmunoguided surgery.
The radioimmunodetection exploits the expression of tumour associated antigens (TAM) found on the surface of human adenocarcinomas, which are targeted by radiolabeled monoclonal antibodies.
Colorectal cancer is the most frequently studied tumour by the Radioimmunodetection (RAID) because a number of antigens and monoclonal antibodies associated with the tumour are available.
The concept of radioimmunodetection was first explored by Pressman, using radiolabeled polyclonal antibodies and demonstrated antibody targeting of tumours in animals.
Carcinoembryonic antigen was first described in 1965 as a tumour associated antigen and as a target for radiolabeled antibodies.
Antibodies used in humans were first polyclonal, and produced imaging with inconstant sensitivities varying from 84% to 40%.
With the advent of the Monoclonal antibody imaging in 1979, tumour detection by radiolabeled monoclonal antibody and external imaging was reported in animal models and in humans.
The original planar imaging technique was substituted by the single photon emission CT (SPECT) which improved imaging sensitivity to 90%, but with more false-positive results.
Immunoscintigraphy has shown superiority over CT in detecting pelvic and intraabdominal recurrences, 100 versus 43% and in detecting metastases in normal sized lymph nodes, however, CT has been superior in detecting liver metastases, 84% versus 43%.
Surgically speaking, the immunoscintigraphy could not provide information about the depth of the tumour in the intestinal wall. Also it was rarely able to detect tumour deposits less than 2 cm in diameter.
The original concept of the RIGS was first developed and tested in animal models using human colorectal adenocarcinoma xenografts and the I-131-labeled anti-CEA monoclonal antibody. The radioactivity was detected by intraoperative. In patients, localization in gross tumour was found in 67%.
In 1986, Tumour associated glycoproteins were discovered (TAG-72), which were found to be expressed in 94% of primary adenocarcinoma colon.
Original laboratory investigations using anti-TAG-72 murine monoclonal antibody B 72.3 against human xenografts in mice resulted in improved localization. In patients, localization was 83% in primary and 77% in recurrent colorectal cancer. Recently, a second-generation anti-TAG-72 MoAb CC 49 has been developed and shown an 8-fold affinity to TAG than the B 72.3. The localization was 86% in primary and 97% in recurrent cases, thus exceeding the results with B 72.3. RIGS could then localize lesions smaller than 1 cm., while estimating tumour depth of penetration to assess resectability.
The RIGS showed superiority over the historic histologic techniques. About 40-77% of RIGS-positive histologically negative lymph nodes were found to contain micrometastases by using the anticytokeratin antibody staining (a very expensive and sophisticated method). Schneebaum also found that patients who developed recurrences in the periportal lymph node regions were previously localized by RIGS but were negative by either frozen section or hematoxylin and eosin staining. This suggested that RIGS- localized micrometastases may progress to histologically positive lesions by time.
The RIGS provided immediate intraoperative staging information in 80-88% of patients, causing changes in therapeutic plans in 25-50%. Also this provided better selection of patients that would benefit from major resection, as the 5-year survival rate of the RIGS-resectable patients was 60% compared to 0% in the RIGS-unresectable. RIGS also helped select patients with isolated liver or organ metastasis, who would benefit from extensive surgery, which has significant morbidity and mortality. RIGS detected metastases in the gastrohepatic area in 50% of patients with isolated hepatic metastasis, and those were alive 2-5 years after hepatic resection with removal of involved gastrohepatic area. This suggested the inclusion of the gastrohepatic area as a part of liver resection in patients with isolated liver metastasis. Also RIGS allowed resection of involved scarred tissues not detected by other methods. RIGS also allowed immunological analysis of host response to microscopic tumour by localizing lymph nodes containing metastases or tumour antigens.
RIGS is still limited in use, due to inefficiency of available targeting monoclonal antibodies (70-80% tumour binding versus a desired 100%) and the inability of detect central small intrahpeatic lesions, so that intraoperative ultrasound probe must be used in conjunction.