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We report a case of a patient with locally advanced bile duct carcinoma treated with 4500 cGy external beam radiotherapy, followed 3 weeks later by intracatheter 915 MHz microwave hyperthermia and radiotherapy delivered through a biliary U-tube placed at the time of surgery. Heating was to 43-45 degrees C for 1 hour followed immediately by intracatheter Iridium-192 seeds to deliver 5000 cGy over a 72 hour period. Prior to treatment, a thermal dosimetry study in phanton was conducted, using the same type of U-tube catheter tubing as in the patient. Orthogonal X rays of the patient's porta hepatis region were used to reconstruct the catheter geometry in the phantom. Proper insertion depth was determined thermographically to obtain maximum heating at the center of the tumor. The maximum SAR was 8.8 watts per kilogram per watt input. During the treatment, the average power applied was 30 W. Six months after therapy, the patient is asymptomatic. Although alkaline phosphatase, SGOT and SGPT have remained elevated, bilirubin has returned to normal and computerized tomographic scans and cholangiograms remain stable. A duodenal ulcer developed after therapy and is healing well with conservative medical management. This case demonstrates that hyperthermia applied through biliary drainage catheters is technically feasible and clinically tolerated. We believe the use of intracatheter hyperthermia in conjunction with external and/or intracatheter radiotherapy in selected patients with unresectable bile duct carcinomas warrants further study.

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Patients with primary and/or metastatic colorectal cancer who had been scheduled for operative intervention were injected intravenously with 200 micrograms of a high-affinity anti-carcinoembryonic antigen (CEA) monoclonal antibody labeled with 2 mCi of 111-indium (Indacea). Patients were imaged by gamma camera at 24 and 48 hours. Primary tumors were identified in 3/10 cases and were not visualized in 3/10 cases. Four scans were considered equivocal. Hepatic metastases were identified as image defects in 5/13 cases and were not visualized in 8/13 cases. All tumors contained CEA by immunoperoxidase staining. In all cases, the primary tumor uptake (5.44 +/- 1.07% ID/kg) was much higher than the uptake of the adjacent fat (0.18 +/- 0.04% ID/kg). There was a direct correlation between tumor CEA content, tumor radioactivity, and the imaging of primary tumor by Indacea. High liver uptake (30.3 +/- 3.0% ID/kg), seen when scanning all patients, was the main limitation of imaging and led to photopenic visualization of hepatic metastases. These results suggest that selection of patients with colorectal carcinoma on the basis of tumor CEA content will lead to improved rates of tumor imaging by Indacea in post-surgical scanning.

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Patients with primary, recurrent, or metastatic colorectal adenocarcinoma were given injections of 200 micrograms of anticarcinoembryonic antigen (CEA) monoclonal antibody labeled with 2 mCi of 111In (Indacea). Patients were imaged at 24 and 48 h. Celiotomy was performed on 40 patients between 3 and 17 days post-Indacea injection. Of 16 primary tumors, 11 (69%) were imaged. Of six extrahepatic recurrences, none was imaged. Intrahepatic metastases were visualized as negative images in 10 of 24 (42%) patients. On the basis of the activity in tissue expressed as a percentage of the total radioactive dose per kg injected into the patient (% ID/kg), extrahepatic tumors that were imaged using Indacea had a significant uptake of radiolabel in the tumor [5.99 +/- 0.91% ID/kg (SE)] and in the associated normal mesenteric lymph nodes (12.0 +/- 2.4% ID/kg). The CEA content of these tumors was high (13.3 +/- 4.7 micrograms/g), and, histologically, the CEA was located primarily apically or intraluminally. Intrahepatic tumor imaging correlated only with tumor size. The greatest Indacea uptake was seen in normal liver (22.1 +/- 3.2% ID/kg). Low Indacea uptake was seen in fat (0.21 +/- 0.05% ID/kg) and bowel wall (1.11 +/- 0.17% ID/kg). In conclusion, Indacea imaging of colorectal carcinoma is specific for high concentrations of accessible CEA in CEA-bearing tumors or in lymph nodes draining these tumors. The successful clinical use of monoclonal antibodies for tumor imaging and therapy will require careful selection of patients for a number of antigen-related parameters including antigen content and distribution in tumors. This information will only come from careful correlation between image results and tissue analysis. High uptake by normal liver tissue is the major unresolved problem with labeled antibody imaging.

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This study was undertaken to determine the effect of tumor size and tumor carcinoembryonic antigen (CEA) content on the uptake of indium 111 (111In)-labeled anti-CEA monoclonal antibody in nude mice bearing xenografts. The tumor cell lines were WiDr, SW403, and LS174T, human colon cancer derivatives. The murine breast carcinoma cell line EMT-6 was used as a control. Tumor CEA levels (ng/g of tumor +/- standard error of the mean [SEM], measured by enzyme immunoassay (EIA) were: EMT-6, 0; WiDr, 105 +/- 5.7; LS174T, 2052 +/- 198; SW403, 17,575 +/- 1,785. The 111In-labeled monoclonal antibody was injected intravenously into mice bearing a single tumor. At 48 hours postinjection, scintiscan was performed, and the mice were killed so that biodistribution studies could be performed. The uptake of the monoclonal antibody was expressed as percent injected counts per minute per gram of tissue +/- SEM. The non-CEA-producing tumor, EMT-6, showed the lowest tumor uptake (1.4 +/- 0.3). WiDr, an intermediate CEA-producing tumor, showed some tumor uptake (16.4 +/- 1.5). The high CEA-producing tumors, SW403 and LS174T, had high tumor uptake (29.5 +/- 5.0 and 51.1 +/- 6.1, respectively). Biodistribution and scintiscan quality were closely related. Although LS174T had the best tumor uptake, SW403 had the highest CEA tumor content, indicating tumor CEA content cannot entirely predict scintiscan and biodistribution results. Tumor-to-blood (T/B), tumor-to-liver (T/L), and liver-to-blood (L/B) ratios were calculated for each animal and compared with tumor size. It was found that T/L had a negative correlation with tumor size (r = -0.72) and L/B had a positive correlation with tumor size (r = 0.94). These ratios may be useful clinically to follow response to therapy.

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Tumor imaging and biodistribution of an indium-labeled monoclonal antibody (MAB) to carcinoembryonic antigen (CEA) [anti-CEA MAB-diethylenetriaminepentaacetic acid (DTPA)-111In] have been investigated using LS174T human colon cancer xenografts in nude mice. Antibody specificity, dose, and specific activity were examined with respect to tumor uptake and quality of scintiscans at different times following injection. The CEA-bearing LS174T tumors were imaged specifically with anti-CEA MAB-DTPA-111In. Using 62.5 ng of indium-labeled MAB (50 microCi/micrograms) the ratio of activity in tissue expressed as a percentage of the total radioactive dose injected into the animal per gram tissue for tumor:blood increased from 0.66 +/- 0.02 (SE) at 1 h to 14.8 +/- 1.1 at 72 h. Scintiscan quality improved with the rise in tumor:blood ratio until 48 h. At longer intervals insufficient counts remained for imaging. The tumor:blood ratio and the scintiscan quality were not improved by increasing the MAB dose to 625 or 6250 ng but good images were obtained at longer times postinjection. By decreasing the 111In from 50 to 10 microCi/micrograms of MAB, the unbound 111In was decreased from 7 microCi/micrograms (14%) to 0.2 microCi/micrograms (2%). Even with the lower specific activity (9.8 microCi/micrograms) of the 10-microCi/micrograms preparation, scintiscan quality at the 62.5-ng dose was maintained. This anti-CEA MAB-DTPA-111In preparation was stable, retained immunological activity, did not require column chromatography to remove unbound 111In, was specific for a CEA-bearing tumor, and was effective for tumor imaging over a wide range of antibody doses (3 to 300 micrograms MAB/kg body weight). This anti-CEA MAB-DTPA-111In preparation is feasible and practical for imaging CEA-bearing tumors in humans.

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Incidental cholelithiasis was encountered at the time of celiotomy in 56 patients. Thirty-three of the patients underwent concomitant cholecystectomy. The overall morbidity and mortality were 27 and 3 percent, respectively, but only one complication (3 percent) was clearly related to the cholecystectomy. Cholecystectomy was not performed in 23 patients. Within 6 months of primary celiotomy, acute cholecystitis developed in 11 patients, 3 had attacks of biliary colic, and 2 became jaundiced. Fifteen patients (65 percent) underwent cholecystectomy and 6 of the 15 (40 percent) required common bile duct exploration. Concomitant cholecystectomy adds minimal morbidity to the operation and should be performed unless specific contraindications exist. Left untreated, cholelithiasis becomes symptomatic and leads to subsequent operation in most patients, which may require a more extensive procedure producing greater morbidity.

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