Local recurrence of colorectal cancer after 'curative' surgery is a major clinical problem. Typically, 50-70 per cent of patients presenting to a surgical clinic will undergo apparently curative surgery for disease and of these about 10-25 per cent will develop local recurrence, in either the tumour bed or bowel wall. The wide differences in local recurrence rate both between and within institutions is probably caused by variation in surgical technique. The main causes of local recurrence are inadequate excision of the primary tumour or the draining lymph nodes, and intraoperative tumour cell implantation. The most significant single factor prognostic of local recurrence is Dukes' tumour stage. Other important factors include tumour grade and fixity, level of the tumour in the rectum, blood and lymphatic vessel invasion, inadvertent perforation of the tumour during resection, and the surgeon's experience. The prognosis of patients with local recurrence is poor. Prevention of recurrence by adequate surgery and adjuvant therapy as well as its early detection offer the best prospect of improving results.

Local recurrence of colorectal cancer: The problem, mechanisms, management and adjuvant therapy

The incidence of colorectal cancer in the United States is increasing. Because more than half of patients with colorectal cancer have liver metastases develop, the number of patients with hepatic metastases also is increasing. Unfortunately, metastatic disease will be limited to the liver in perhaps 25% of these patients and confined to only one lobe of the liver 25% of this subgroup. Consequently, solitary or unilobar colorectal metastases are found in as few as 5% of patients with colorectal cancer. The median survival of patients with unresected hepatic metastases is approximately 10.6 months. Patients with solitary lesions or small tumor burdens may attain a median survival of 16-20 months, but 5-year survivors are extremely rare. In contrast, rates of 5-year survival average approximately 36% after resections of solitary hepatic lesions and may approach the same level in selected patients with multiple lesions. Factors that appear to adversely effect survival include detection of metastatic disease because of signs or symptoms of disease, an elevated carcinoembryonic antigen (CEA) level, elevated liver function tests, poorly differentiated primary lesions, lymph node-positive primary lesions, extrahepatic sites of metastases, more than four hepatic lesions, bilobar disease, a satellite pattern of metastases in the liver, positive margins of the liver resection, positive extrahepatic lymph nodes, and more than 10 units of blood transfusion during the perioperative period. Operative mortality for liver resections should remain approximately 4%, and major morbidity should be in the range of 20-30%. Modalities other than surgical resection have not improved survival in patients with colorectal hepatic metastases. Thus, when feasible, patients with metastatic colorectal cancer limited to one lobe of the liver should undergo hepatic resection. Unfortunately, only approximately 5% of patients with colorectal cancer fall into this category, so resection of hepatic metastases can improve overall survival of patients with colorectal cancer by only 1-2%.

Surgical treatment of liver metastases in patients with colorectal cancer

The surgical management of locally recurrent rectal cancer may involve major procedures and is not for the faint-hearted. Nevertheless, such treatment is preferable to chemotherapy and radiotherapy; the latter will fail over a period of months during which the patient is likely to experience intractable pain. Radical surgery offers good palliation and a better quality of life. Survival is prolonged by such operations which may be curative in up to one-third of patients. Nevertheless, surgeons must be realistic in their assessment of and discussions with patients.

Surgical management of locally recurrent rectal cancer

PURPOSEA phase I/II study was designed to determine the maximum-tolerated dose (MTD) of iodine 125-labeled monoclonal antibody A33 (125I-mAb A33), its limiting organ toxicity, and the uptake and retention of radioactivity in tumor lesions.PATIENTS AND METHODSPatients (N = 21) with advanced chemotherapy-resistant colon cancer who had not received prior radiotherapy were treated with a single 125I-mAb A33 dose. 125I doses were escalated from 50 to 350 mCi/m2 in 50-mCi/m2 increments. Radioimmunoscintigrams were performed for up to 6 weeks after 125I-mAb A33 administration.RESULTSAll 20 patients with radiologic evidence of disease showed localization of 125I to sites of disease. Twelve of 14 patients, who underwent imaging studies 4 to 6 weeks after antibody administration, had sufficient isotope retention in tumor lesions to make external imaging possible. No major toxicity was observed, except in one patient with prior exposure to mitomycin who developed transient grade 3 thrombocytopenia. Although the isot...

Phase I/II study of iodine 125-labeled monoclonal antibody A33 in patients with advanced colon cancer.

The concept of radioguided surgery, which was first developed some 60 years ago, involves the use of a radiation detection probe system for the intraoperative detection of radionuclides. The use of gamma detection probe technology in radioguided surgery has tremendously expanded and has evolved into what is now considered an established discipline within the practice of surgery, revolutionizing the surgical management of many malignancies, including breast cancer, melanoma, and colorectal cancer, as well as the surgical management of parathyroid disease. The impact of radioguided surgery on the surgical management of cancer patients includes providing vital and real-time information to the surgeon regarding the location and extent of disease, as well as regarding the assessment of surgical resection margins. Additionally, it has allowed the surgeon to minimize the surgical invasiveness of many diagnostic and therapeutic procedures, while still maintaining maximum benefit to the cancer patient. In the current review, we have attempted to comprehensively evaluate the history, technical aspects, and clinical applications of radioguided surgery using gamma detection probe technology.

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A comprehensive overview of radioguided surgery using gamma detection probe technology

• Preliminary data using B72.3 murine monoclonal antibody labeled with iodine 125 suggested that both clinically apparent as well as occult sites of colorectal cancer could be identified intraoperatively using a hand-held gamma detecting probe. We report the preliminary data of a multicenter trial of this approach in patients with primary or recurrent colorectal cancer. One hundred four patients with primary, suspected, or known recurrent colorectal cancer received an intravenous infusion of 1 mg of B72.3 monoclonal antibody radiolabeled with 7.4×10 Bq of iodine 125. Twenty-six patients with primary colorectal cancer and 72 patients with recurrent colorectal cancer were examined. Using the gamma detecting probe, 78% of the patients had localization of the antibody in their tumor; this included 75% of primary tumor sites and 63% of all recurrent tumor sites; 9.2% of all tumor sites identified represented occult sites detected only with the gamma detecting probe. The overall sensitivity was 77% and a predictive value of a positive detection was 78%. A total of 30 occult sites in 26 patients were identified. In patients with recurrent cancer, the antibody study provided unique data that precluded resection in 10 patients, and in another eight patients it extended the potentially curative procedure. ( Arch Surg . 1991;126:349-352)

Ian Lavery

Papers

Radioimmunoguided surgery using iodine 125 b72.3 in patients with colorectal cancer