First experience and technical aspects of isolated liver perfusion for extensive liver metastasis.

BACKGROUND: New drugs and modalities for locoregional tumor treatment in recent years may offer new potential for isolated liver perfusion in patients with nonresectable liver tumors. The purpose of this study was to prove the feasibility of arterial isolated liver perfusion and to assess the tolerance of perfusion with high-dose tumor necrosis factor (TNF). METHODS: Twelve patients with extensive liver metastases previously treated unsuccessfully with systemic chemotherapy underwent isolated hyperthermic liver perfusion using a heart-lung machine. High doses of mitomycin were administered in the first six and a combination of TNF and melphalan in the last six patients. RESULTS: No operative death occurred and no direct postoperative liver failure was observed in any patient. In cases of variations of the arterial hepatic blood supply, the perfusion was done through the splenic artery or an angiography catheter. Histologic analysis of tumor biopsy specimens obtained on the first postoperative day revealed major tumor necrosis in 8 of 12 patients. CONCLUSIONS: Isolated arterial perfusion of the liver is a complex surgical procedure that is feasible in patients with anatomic variations of the hepatic artery. The remarkable histologic response to perfusion in several pretreated patients, especially after application of high-dose TNF and melphalan, suggests that this modality is very effective in tumor killing.

High-dose mitomycin C in isolated hyperthermic liver perfusion for unresectable liver metastases.

In order to reduce systemic side effects and increase intrahepatic mitomycin C (MMC) concentrations, isolated hyperthermic liver perfusion (IHLP) has been performed using MMC. This article describes the pharmacokinetics of MMC in IHLP and presents our clinical experience with its use in six patients suffering from unresectable liver metastases. Primary tumors consisted of colorectal carcinomas in three cases, breast cancer in two, and a choroidal melanoma in one. Dosages of MMC varied between 0.5 and 1.0 mg MMC/kg body weight. MMC was added as a bolus directly into the extracorporeal circuit. Intrahepatic temperature was elevated to 40.0-41.0 degrees C by hyperthermic perfusion. MMC concentrations were measured in peripheral blood (preperfusion, then at 5, 30, and 55 min during perfusion, and finally at 5 and 60 min and 6 and 24 h after perfusion) and in recirculating perfusate (5, 30, and 55 min). While markedly elevated MMC concentrations (maximum 6290 ng/mL) were found in the liver perfusate, systemic concentrations remained low (maximum 45 ng/mL), indicating no considerable leakage. MMC concentrations in the perfusate constantly decreased during perfusion. After rinsing with 1500 mL saline, a mean concentration of 52.5+/-33 ng MMC/mL was measured in the washout from 5 patients. In 1 patient with a colorectal carcinoma, MMC concentrations in the perfusion medium were 10-fold and in the plasma 2-fold higher than in the other patients. This high MMC concentration caused severe intrahepatic vascular damage and finally led to the patient's death. In conclusion, IHLP and intrahepatic perfusion with MMC resulted in a high response of hepatic tumors. Systemic exposure of MMC can be reduced effectively by isolated perfusion. However, hepatic toxicity of MMC must be considered.

[Intraoperative (hyperthermic) intraperitoneal chemotherapy--considerations and aspects of safe intra- and postoperative treatment with cytostatic drugs]. / Intraoperative (hypertherme) intraperitoneale Chemotherapie-Uberlegungen und Aspekte zum sicheren intra- und postoperativen Umgang mit Zytostatika.

The application of open intraoperative intraperitoneal chemotherapy following cytoreductive surgery for the treatment of pseudomyxoma peritonei or peritoneal carcinomatosis requires safety precautions for the medical and non-medical personnel. In agreement with already existing rules, precautions were established which result in an optimum of safety. These concern the preparation of the cytostatic drugs, the application in the operating room as well as personal precautions intra- and postoperatively. After the establishment of theses recommendations, 22 patients were treated with open intraperitoneal chemotherapy in 1.5 years without any severe accidents. Therefore, a safe intraoperative use of cytotoxic drugs is possible. At the moment, the indication for such an approach may be given in peritoneal carcinomatosis from appendix, colon or ovarian cancer. In the future, an adjuvant application in other gastrointestinal malignancies (e.g. T3/T4 gastric carcinoma) may be considered.

[A new port catheter system of aluminum oxide ceramics]. / Ein neues Portkathetersystem aus Aluminiumoxidkeramik.

Implantable port catheter systems are becoming increasingly important, as they often permit out-patient treatment for many indications that would otherwise require hospitalization. Moreover, they also increase the safety/reliability of infusion therapy in critical inpatients. For a variety of reasons, the materials used so far, i.e. steel, titanium and various plastics have not been completely satisfactory. The main disadvantage of metallic systems is the formation of artefacts in tomographic images, while the shortcomings of plastics are mechanical, e.g. chip formation and early membrane failure. Against this background, a port catheter system made of alumina ceramic, which is largely free of the disadvantages of the other materials, was developed. The expected advantages in terms of complication rate and radiological artefacts, were fully confirmed by the evaluation of 160 monitored patients.

[Chemoembolization of hepatocellular carcinoma--computed tomographic follow-up observation]. / Chemoembolisation hepatozellulärer Karzinome--computertomographische Verlaufsbeobachtung.

The prognosis of unresectable hepatocellular carcinomas is bad. Untreated, survival is 1.6 to 2.5 months. Systemic chemotherapy has little effect and is associated with marked side effects. Tumour cells are supplied almost exclusively by the hepatic artery, whereas normal liver tissue is supplied by the hepatic artery and portal vein. Consequently, interruption of arterial blood flow results in damage to the carcinoma without affecting the rest of the liver. Lipiodol is an oily contrast medium which is taken up selectively by the tumour and can be demonstrated in tumour, in the interstitium and in blood vessels. We used lipiodol emulsified with cisplatin and epirubicin successfully in 22 patients with inoperable liver cell carcinomas. The treatment was well tolerated, apart from some nausea and mild upper abdominal discomfort. Survival time from first diagnosis and the first embolisation was ten months longer than expected survival or that following systemic chemotherapy.

[Chemoembolization of hepatocellular carcinoma with lipiodol, epirubicin and cisplatin]. / Chemoembolisation hepatozellulärer Karzinome mit Lipiodol, Epirubicin und Cisplatin.

The therapeutic effect of combined chemoembolization with lipiodol, epirubicin and cisplatin in 22 patients with nonresectable tumours, predominantly in livers with cirrhotic transformation, was analysed. Lipiodol was demonstrated in tumour tissue on average three months, maximally six months, after injection. Repeat embolization was done, if possible, after storage had subsided. There were only minor side effects. Quality of life suffered only from the, though delayed, continuing cancer growth. Survival rate was 73% after six months, 54% after one year.