Our preclinical studies have shown that the widely used antiparasitic drug albendazole has potent antiproliferative activity against colorectal cancer (CRC) and hepatocellular carcinoma (HCC). This trial was designed to evaluate albendazole in a small number of patients (n = 7) with either HCC or CRC and hepatic metastases refractory to other forms of therapy. Albendazole was given at 10 mg/kg/day orally in two divided doses for a period of 28 days. To follow the effect of treatment, tumor markers, carcinoembryonic antigen (CEA) or α-feto protein (AFP), were measured routinely in these patients. A range of hematological and biochemical indices were also serially measured to monitor bone marrow, kidney or liver toxicity. Albendazole therapy resulted in a decrease in CEA in 2 patients. In the remaining 5 with measurable tumor markers, serum CEA or AFP was stabilized in 3 patients, while in the other 2, after an initial stabilization (5–10 days), the markers began to increase. In the 7 patients completing the trial, albendazole was well tolerated and there were no significant changes in any hematological, kidney or liver function tests, but 3 patients were withdrawn for severe neutropenia which was probably contributory to the death of 1 patient. These data support our previous experimental results demonstrating that albendazole has antitumor effects.

The usefulness of additional edge cryotherapy after liver resection for liver metastases from colorectal cancer to improve involved or inadequate (less than 1 cm) margins is uncertain. Design: Retrospective analysis of prospectively collected data. Setting: Department of surgery at a university hospital. Patients: Eighty-six consecutive patients with hepatic metastases from colorectal cancer in whom we applied additional edge cryotherapy to involved or inadequate margins. This group was compared with 134 patients who underwent resection without edge cryotherapy (control group) during the same period. Intervention: Potentially curative treatment was achieved by adding edge cryotherapy to insufficient resection sites in patients not eligible for further resection. Main Outcome Measures: Edge recurrence rate in the study group; validation of an additional treatment to improve curative resectability; and comparison of morbidity and local recurrence rates with the control group. Results: At a median follow-up of 39 months, 47 patients were alive and 39 had died. Local recurrence at the resection site was diagnosed in 9 patients (10%), of which 7 occurred in patients with involved margins and 2 in patients with resection margin less than 1 cm. Thirtysix patients (42%) experienced recurrence in the remnant liver. Extrahepatic recurrence occurred in 38 patients (44%), the lungs being the most common site (22 patients [26%]). Conclusions: Edge cryotherapy is a potent additional surgical treatment option in patients with liver metastases from colorectal cancer. The percentage of patients who can be treated for cure can be increased, especially if complex liver surgery is demanded.

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Hypothesis: Intraoperative echogenic appearance of liver metastases from colorectal cancer is a prognostic factor of outcome after curative treatment. Design: Retrospective analysis of prospectively collected data. Setting: Department of Surgery at a university hospital. Patients: One hundred forty-three consecutive patients with hepatic metastases from colorectal cancer who underwent liver resection with curative intent between 1992 and 1998. Intervention: Curative treatment was achieved by liver resection alone, liver resection plus edge cryotherapy, or liver resection plus cryotherapy to lesions not amenable to further resection. In patients with more than 2 lesions, a hepatic artery catheter was placed for regional chemotherapy. Main Outcome Measures: The echogenic appearance of the liver metastases was assessed by intraopera-tive ultrasound by a single person throughout the study using a 5-MHz ultrasound probe. The findings were prospectively entered into the database. Results: Fifty-four percent of patients had hyperechoic metastases. This group had significantly longer overall (log rank, PϽ.001) and recurrence-free survival (log rank, P=.004) compared with patients who had hypoechoic metastases (36%). A significantly higher percentage of mucinsecreting tumors were found in the hypoechoic patient group (2 , P =.001). Dukes stage of the primary tumor (P =.02), echogenicity of the liver secondaries (P=.04), and diameter of the largest resected metastasis (P=.01) were independent prognostic factors for recurrencefree survival in the Cox regression model. Conclusion: These results support the hypothesis that echogenicity of liver metastases from colorectal cancer is an independent prognostic factor of outcome after curative resection.