Treatment of liver metastases from colorectal cancer with hepatic artery occlusion, intraportal 5-fluorouracil infusion, and oral allopurinol. A randomized clinical trial.

BACKGROUND: Regional therapy for colorectal liver metastases aimed at prolonging survival has not been tested fully in a randomized trial with untreated control subjects. This study explored the efficacy of temporary hepatic artery occlusion followed by intraportal infusion of 5-fluorouracil (5-FU) and oral allopurinol as biochemical modulators in prolonging the survival of patients with nonresectable liver metastases and no extrahepatic cancer. METHODS: Eighty-four patients were considered for randomization, of whom 24 were excluded at laparotomy because of extrahepatic cancer (n = 17) or resectable lesions (n = 5). In two patients, no cancer was identified in the liver. Thirty-two patients were allocated to receive treatment, and 28 were allocated to receive no regional or systemic treatment. Six patients were excluded after randomization because of major protocol violations. RESULTS: The median survival time for patients was 17 months (range, 0-66), and for control subjects, the median was 8 months (range, 0-31). Log rank analysis demonstrated a significant survival benefit for treatment versus no treatment (P = 0.0039). (In two patients, early death was due to toxicity from the wrong dose of 5-FU and the wrong route of administration, respectively; the mean and median survival were reduced by 1 month). CONCLUSION: This study identified a treatment modality that prolongs survival in patients with nonresectable liver metastases and no extrahepatic metastases from colorectal cancer, suggesting that control subjects receiving no therapy may not be necessary in future randomized trials.

Isolated hyperthermic liver perfusion with chemotherapy for liver malignancy.

In an open study of unresectable liver tumours, isolated regional perfusion with hyperthermia and cytotoxic drugs has been tested in 29 patients. Four patients had primary hepatocellular cancer, 10 patients had metastases from malignant melanoma, remaining from breast cancer, colorectal cancer, midgut carcinoids and miscellaneous primaries. At laparotomy the proper hepatic artery and portal vein were canulated and connected to a pump oxygenator. The inferior vena cava was canulated with a triple lumen catheter (Perfufix) allowing for porto-caval shunting, drainage of lower body and renal veins to the heart and separate drainage of liver veins to the pump oxygenator. Liver perfusion was performed with a mean flow of 900 ml per min. Melphalan and cis-platinum 0.5 mg/kg body-weight were added to the perfusate for 1 h after liver temperature reached 40 degrees C. Four patients died within 30 days of perfusion due to multiple organ failure. These patients had more than 50% of liver volume occupied by cancer. All surviving patients developed reversible hepato- and renal toxicity. Partial tumour regression was registered in 20% of the patients. Five patients have survived more than three years. Hyperthermic liver perfusion is feasible but in patients with massive liver tumour, there is a significant risk of developing multiple organ failure.

A survey on critical qualities and information sources on products purchased to the radiology department.

A survey on critical product qualities and sources of information on contrast media, CT and ultrasound machines, X-ray laboratories, angiography catheters and film was completed by 79% of the heads of radiology departments at Swedish hospitals. The respondents were asked to rank in order of preference as important information sources; own experience, opinions of colleagues, influence by sales representatives at the hospital or outside, fairs, congresses and scientific articles. The qualities of contrast media to rank were; low frequency of serious side-effects, low frequency of patient discomfort, easiness to handle, package size and price. For the other products technical performance, terms of delivery, terms of maintenance and price were ranked. Most important for contrast media was low frequency of serious side-effects and for the other products it was technical performance. The most important source of information regarding all products was the experience of the radiologist himself. In conclusion; high quality of the products and, safety and comfort of the patients are favoured over low price.

CT attenuation of normal liver parenchyma on delayed scanning with iohexol.

Twenty patients were examined with CT of the liver before, during, and 4 to 6 hours after i.v. administration of 60 g iodine (200 ml iohexol). The attenuation of normal liver parenchyma was measured. The mean attenuation of normal liver parenchyma on nonenhanced scanning was 62.6 HU and on delayed scanning 78.7 HU. It seems that iohexol is a suitable contrast medium for delayed scanning of the liver.

Combined angioplasty with the Kensey catheter and balloon angioplasty in occlusive arterial disease. A preliminary report.

The Kensey dynamic angioplasty catheter is an instrument for mechanical intravascular atherectomy using a rotating cam to recanalize occluded arteries. Twelve dynamic angioplasties were performed in 11 patients. The procedure was followed by an additional balloon dilatation in all cases. A technical success, i.e., a restored lumen, was recorded in 7 patients but only 4 had a functional improvement. No distal embolization or other serious complication occurred. This preliminary report shows that the therapeutic potential with this technique must be further investigated.

Demonstration of hepatic veins by computed tomography using axial and angulated scanning.

The main hepatic veins run obliquely into the inferior caval vein. They are often poorly demonstrated on conventional axial computed tomography (CT) performed with a vertical gantry. In order to determine whether CT with caudal tilting of the gantry could improve demonstration of the hepatic veins, 30 consecutive patients of whom 20 had focal lesions in the liver were examined with both a vertical and a 20 degree caudally tilted gantry. As a reference group, 10 patients were examined with a 20 degree cranially tilted gantry. In 14/30 (47%) of the non-enhanced examinations caudally angulated CT demonstrated the hepatic veins better than axial CT, while axial CT was the better technique in one patient. No additional tumors were detected with either technique, but the caudal angulation improved the anatomical location of tumors due to a better demonstration of their relation to hepatic veins. CT with cranial angulation did not in any patient improve the demonstration of veins when compared to axial CT. Angulated CT also included examination with contrast enhancement using bolus technique. In 20 out of 27 (74%) examinations with a caudally tilted gantry and contrast enhancement considered optimal for tumor detection, veins containing contrast medium were depicted for an anatomical description. Caudally angulated CT is a non-invasive technique which should be performed in patients in whom liver resection is considered.

Contrast enhancement of liver parenchyma and biliary tract related to liver function at delayed computed tomography.

Computed tomography (CT) of the liver was performed in 53 patients before, during and 4 to 6 hours after intravenous administration of approximately 60 g of iodine in metrizoate. At delayed CT, contrast medium was observed in the extrabiliary ducts in 20 patients (38%) and in the gallbladder in 28 (68%) of the 41 patients with no previous cholecystectomy. The increase in attenuation of liver parenchyma at delayed CT compared with the non-enhanced baseline CT ranged between 2 and 26 HU (mean 13.9). The material was divided into three groups with regard to liver function: normal, intermediate and pathologic. In the normal group contrast medium was observed in the gallbladder in 81 per cent and in the bile ducts in 57 per cent and the mean increase in attenuation of the liver parenchyma was 14.5 HU. In the pathologic group the same parameters were 40 per cent, 7 per cent and 10.6 HU, respectively. Contrast medium in the gallbladder and biliary ducts improved the information about anatomy. Pathology of the gallbladder and tumour growth along the hepatoduodenal ligament were better demonstrated. Delayed CT is a simple and non-invasive technique that may improve planning of liver surgery.

Comparison of non-enhanced, bolus enhanced, and delayed scanning techniques in computed tomography of hepatic tumours.

Non-enhanced, bolus contrast medium enhanced and 4 to 6 hours delayed computed tomography of the liver was performed in a prospective study of 53 patients. Forty patients had focal lesions, in 12 of these they were hypervascular. Contrast medium was administered as an initial bolus followed by a rapid injection of meglumine metrizoate (Isopaque Cerebral). The total iodine dose varied between 56 and 63 g, which gave an average increase in attenuation of 14 HU in normal parenchyma comparing delayed with non-enhanced scanning. Presence and extent of focal lesions were evaluated in a randomized and independent analysis by two radiologists. The percentage of examinations with correct tumour description was higher with bolus scanning (observer I 73%, observer II 75%) and delayed scanning (observer I 75%, observer II 78%) than with non-enhanced scanning (observers I and II 67%). An optimal bolus technique requires an exact timing of the contrast medium administration and scanning. Delayed scanning provides an excellent supplement when the bolus examination is suboptimal or shows equivocal findings.

Evaluation of intrahepatic tumour extent and prediction of resection size in liver tumours by computed tomography, ultrasonography and angiography.

Preoperative radiologic examinations were reviewed in 110 patients planned for liver resection. Forty-five patients had a CT examination within a month before the operation; 22 of these also had ultrasonography (US) and 38 had angiography. In a numeric analysis of lesions, true positive findings were observed at CT and US in 69 per cent and 61 per cent, respectively. Angiography, mainly performed to show the vascular anatomy and patency of the portal vein and not to optimize tumour detection, showed 55 per cent of the lesions. Attempts were made to predict resection size with CT by estimating intrahepatic tumour extent. CT showed correct tumour extent in 73 per cent but was inaccurate in 12 of 45 examinations. In 5 of these, tumour growth across the main and sagittal fissures was misinterpreted, with both under- and overestimations. Improvements of current imaging methods are needed to make the radiologic assessment prior to liver surgery more reliable.

Resectability of liver tumours evaluated by computed tomography.

In a retrospective study of CT examinations of liver tumours in 37 patients intra- and extrahepatic tumour growth was estimated in order to see if resectability could be predicted. The findings were compared with the evaluation at laparatomy. Four out of 15 tumours, resectable according to CT, turned out to be unresectable and 9 out of 37 CT examinations did not reveal the total extent of tumour growth. A more reliable preoperative radiologic assessment may be obtained by improvement of current CT techniques, by computed tomographic angiography, intraoperative ultrasound or MR imaging.