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Background: The liver is the site of distant failure in > 33% of patients with colorectal adenocarcinoma. Liver resection is the only potentially curative option in these patients. Patients with incompletely resected liver lesions (due to the proximity to critical vascular structures) are at high risk of dying of progressive disease in the liver. This pilot study was performed to determine whether the intraoperative implantation of iodine-125 (I-125) seeds could reduce the recurrence and improve the survival of patients with incompletely resected liver metastases., Methods: Fifty-six patients with unresectable or residual disease after surgical resection of liver metastases from colorectal carcinoma underwent permanent implantation with I-125 seeds to deliver 160 gray to the periphery of the target volume., Results: The 1-, 3-, and 5-year actuarial control rates of liver disease were 41%, 23%, and 23%, respectively. The 5-year actuarial control of liver disease was better for patients with a solitary metastasis (39%) than for those with multiple metastases (9%) (P = 0.04). The 1-, 3-, and 5-year actuarial overall survival rates were 71%, 25%, and 8%, respectively (median, 20 months; 95% confidence interval, 17-23). The radiation-related complications were minimal., Conclusions: I-125 liver brachytherapy is feasible with minimal radiation-related morbidity. Good prognostic factors for long term liver control and survival are the presence of a solitary metastasis, postresection minimal residual disease requiring smaller volume implants, and no prior liver resections. Future prospective trials should be directed toward this patient population, which has the highest probability of obtaining improved results from the local dose escalation provided by brachytherapy. Adjuvant regional chemotherapy clearly is needed due to the high rate of liver recurrence and ultimate death from liver failure observed in spite of liver resection and brachytherapy.

Recurrence of colorectal carcinomas occurs in about 50% of the cases with localized neoplasia. It is understood that the tumor recurrence is due to residual micrometastases not found during surgery or extraregional (peripheral blood or bone marrow). We developed a procedure to detect non-visible, abdominal metastases using a radiolabeled anti-tumor cell antibody injected before the operation (radioimmunoguided surgery RIGS). However, even with the best technique, it is not possible to remove all micrometastasis if a hematogenic dissemination happens. Based on the knowledge of disturbing humoral immune reaction is mounted against shed tumor associated antigens (TAA), we developed a new method to reduce and correct the B cell response and B cell recruitment due to chronic TAA immun complex presentation on follicular dendritic cells (immune corrective surgery, ICS). This method is based on a selective lymphadenectomy. The target lymph nodes were those loaded with TAA-immune complex. The detection method used was the injection of radiolabeled antibody able to recognize the immune complex. From 20 patients (stage I, II and III) treated with ICS, 17 survived more than 5 years 'showing a statistically significant increase of survival compared to patients treated with standard procedures. In conclusion, these data show that surgery of colorectal cancer should be selectively extended to specific anatomical regions in order to remove hidden micrometastases, and more importantly, correct postoperative immune processes that could suppress the T cell response against residual tumor cells.

Since 1986, 191 patients with recurrent colorectal cancer have undergone surgical exploration 2 to 43 days after injection of 1.0 to 0.25 mg of monoclonal antibody (MAb) (B72.3 or 17-1A) radiolabeled with 5.0 to 1.0 mCi of 125I. The intraoperative use of a hand-held gamma detector (Neoprobe 1000) demonstrated that MAb identified tumor in 73% of cases. Clearer intraoperative definition of tumor margins and identification of occult tumor assisted the surgeon in the resection of liver metastases as well as nodal and pelvic disease. Unsuspected nodal disease was identified. The external use of the Neoprobe to scan the sacral region and intrarectal and intravaginal use led to the avoidance of operative procedures by defining inoperable disease. In approximately 25% of cases, the surgical procedure was modified based on Neoprobe findings. RIGS system provides a method of immediate intraoperative staging which may prevent additional recurrences, lead to earlier institution of adjuvant therapy, and result in improved survival.

During the past 14 years, eight patients have undergone two or more major hepatic procedures in an attempt to control metastatic colon cancer confined to the liver. A total of 19 operations was performed. In all cases, a rising level of carcinoembryonic antigen was the main indicator for surgical intervention. There were no operative deaths. Major complications occurred in 15 per cent. Following the first hepatic intervention, two patients remain alive and free of disease at 43 and 47 months (56 and 100 months since diagnosis), respectively. In the six patients who have died, survival from the first hepatic intervention ranged from 17 to 38 months (median 27 months). Age, sex, location of primary, size of primary, interval from primary operation to second operation, and site of hepatic metastasis did not influence survival. In carefully selected patients with metastatic colon carcinoma confined to the liver, encouraging results can be obtained by performing multiple surgical procedures.

From January 1986 to December 1987, 32 patients with recurrent colorectal cancer had second-look radioimmunoguided surgery (RIGS system). All patients had pathologic confirmation of recurrence. The RIGS system identified 81% of recurrences, and in six patients recurrent tumor was identified only by RIGS. All patients had physical examination, carcinoembryonic antigen (CEA) assay, and computerized tomography of the abdomen and pelvis. Detection of recurrence was based on symptoms in six, elevated CEA value in 25, and physical examination in one. The CEA was elevated preoperatively in 30 patients; two false-negative results occurred in symptomatic patients who had pelvic recurrence. The median CEA value in those with liver recurrence was 30 ng/ml (range 5.2 to 298) and for pelvic recurrence 13 ng/ml (range 1.9 to 31) (P less than .05). The overall sensitivity of CT was 41% (abdomen other than liver 37%, liver 56%, and pelvis 22%). The combination of elevated CEA, symptoms, and physical findings identified 100% of recurrences. We conclude that a rising CEA remains the most accurate indicator of recurrence. CT should not be done routinely to detect recurrent colorectal cancer unless CEA is elevated or the patient is symptomatic. In our study the intraoperative use of the RIGS system aided the surgeon in identifying occult tumors.