Transarterial chemoembolization of liver metastases in patients with uveal melanoma.

Metastases from uveal melanoma are often confined to the liver. Palliative hepatic chemoembolization has been considered to be a reasonable treatment approach. We enrolled 14 patients with hepatic metastases from uveal melanoma into a pilot trial of transarterial chemoembolization (TACE). All patients received additional systemic immuno-chemotherapy or best supportive care. In 31 procedures 100mg/m(2) of cisplatine was continuously infused by means of a power injector preceding embolization by manual injection of polyvinyl alcohol particles. In three procedures cisplatine was replaced by 200mg/m(2) carboplatine because of increased serum creatinine levels. Tumor response was evaluated using RECIST criteria. Fourteen patients received 34 TACE's (mean: 2.4 treatments). Eight patients (57%) achieved partial response (PR), four patients (29%) had stable disease and two patients (14%) tumor progression. Median time to progression was 8.5 months (5-35 months). Median survival after first TACE was 14.5 months in responders compared to 10 months in non-responders (p=0.18, not significant) and 11.5 months (3-69 months) in all patients. In seven patients with metastases occupying less than 25% of liver volume median survival was 17 months compared to 11 months in seven patients with tumor involvement of more than 25% (p=0.02) with partial response rate of 86% and 29%, respectively. TACE of liver metastases from uveal melanoma is well tolerated and may prolong survival in patients with limited tumor extension.

[C-arm CT for chemo-embolization of liver tumors]. / C-Arm-CT bei der Chemoembolisation von Lebertumoren.

Local efficacy of transarterial chemo-embolization (TACE) is enhanced if selective treatment is performed. Selectivity of TACE mainly depends on vascular anatomy but also on the identification and catheterization of tumor feeding arteries. Correlation of vascular territories and target tumor volume in angiographic projection images is more difficult if tumors are not hypervascularized and contrast of liver parenchyma is inhomogeneous.C-arm CT offers the option of selective perfusion imaging via tumor-feeding arteries. This allows the comparison of perfusion images and baseline cross-sectional imaging to evaluate if tumors are covered completely by local treatment and to change the catheter position if necessary. Furthermore the uptake of embolization material, such as lipiodol can be checked by C-arm CT.In a prospective study of 75 TACE of liver tumors and liver metastases we evaluated the appropriateness of 85 catheter positions ready for delivery by perfusion C-arm CT and compared the diagnostic confidence of angiography and perfusion C-arm CT in terms of judgment of correct catheter position for the planned treatment. Diagnostic confidence was improved by perfusion C-arm CT in 55% of cases and in 11 cases (13%) catheter positions were inappropriate and had to be corrected. The reasons for catheter repositioning were incomplete coverage of the target tumor by perfusion volume (mismatch) in 6 cases, inappropriate perfusion of adjacent liver parenchyma in 2 cases and non-selective tumor perfusion via collateral arteries in 3 cases. C-arm CT allowed sufficient visualization of uptake of lipiodol in all cases evaluated.The diagnostic benefit of C-arm CT increases if tumors are treated more selectively, are not strongly hypervascular, are located centrally and if the enhancement of liver parenchyma is inhomogeneous. C-arm CT causes additional working time and contrast load, which is relatively low compared to angiography. Radiation exposure of 151 microGy per C-arm series necessitates careful and therapy-oriented assessment of indications.

[Chemoembolization of hepatocellular carcinomas: which factors determine therapeutic response and survival?]. / Chemoembolisation des hepatozellulären Karzinoms: Welche Faktoren bestimmen Therapieansprechen und Uberleben?

PURPOSE: To determine independent prognostic factors influencing the survival of patients with hepatocellular carcinoma (HCC) treated with transcatheter arterial chemoembolization (TACE). MATERIALS AND METHODS: Ninety-one patients with unresectable HCC were treated with 269 repetitive TACE. The dosages of epirubicin (40-60 mg) and ethiodized oil (8-20 ml) were adjusted to tumor size and liver function. The impact of tumor size, macroscopic tumor type, tumor location, portal vein infiltration, capsular infiltration, tumor vascularization, uptake of ethiodized oil within the tumors, Child-Pugh-Class and Okuda-Stage on patient survival were evaluated by means of univariate and multivariate regression analysis. RESULTS: The following independent prognostic factors were found: tumor type (nodular vs. infiltrating, p = 0 008), tumor size (p = 0.01), Child-Pugh-Class (A vs. B; p = 0.02) and grade of tumor vascularization (p = 0.04). In 57 patients with HCC of the nodular type, the median survival time was significant longer than in 32 patients with HCC of the infiltrating type (17.0 months vs. 7.9 months; p < 0.003; 2 tumors could not be classified). The 1-, 2- and 3-year-survival rates were significantly higher in 57 patients with Okuda-Stage I disease, compared to 34 patients with Okuda-Stage II and III disease (73%, 31% and 8% vs. 23%, 6% and 4% p < 0.0001). CONCLUSIONS: Tumor type, tumor size and grade of liver cirrhosis have an independent impact on prognosis of patients with HCC treated by TACE. An appropriate selection of patients is necessary to improve patients survival.

Prospective investigation of autonomic cardiac neuropathy in diabetes mellitus.

Forty-five patients with clinically manifest diabetes mellitus were investigated (25 male, 20 female, 48 +/- 10 yrs, 14 diabetes type 1, 31 type 2). Duration of manifestation was 12.2 +/- 9.7 yrs.Vibration thresholds and thermal thresholds were assessed. Respiratory sinus arrhythmia (RSA) was measured during deep respiration at 6/min. The QTc-interval was assessed according to Bazett's formula. MIBG-SPECT was carried out in all 45 cases. Patients with abnormal MIBI perfusion scintigraphy had previously been excluded from the study. RSA was abnormal in 12/45 patients. The MIBG-SPECT was abnormal in 28/45 cases with dorso-septal lack of activity. No difference was seen between type 1 and 2 diabetics with regard to either vibration and thermal thresholds or RSA and MIBG-SPECT. Abnormal MIBG-SPECT was correlated with vibration threshold and abnormal heart RSA tests but not with abnormality in QTc. The mean QTc-interval was 419 +/- 24 ms (QTc normal in 36, abnormal > or = 440ms in 9). It was longer in female than in male patients. There exists no significant correlation of QTc-interval results with either heart rate variability or MIBG-SPECT. The QTc-interval is not a sensitive parameter of autonomic cardiac denervation.

[MRI-guided percutaneous radiofrequency ablation of hepatic neoplasms--first technical and clinical experiences]. / MRT-gestützte perkutane Radiofrequenzablation hepatischer Neoplasien--Erste technische und klinische Erfahrungen.

PURPOSE: To evaluate the safety and efficacy of MR-guided radiofrequency ablation (RFA) of hepatic neoplasms. MATERIAL AND METHODS: 16 hepatic neoplasms (1.3-3.0 cm in diameter) in 11 patients were treated by 22 percutaneous RFA sessions during a prospective study. 16 G, MR-compatible cooled-tip electrodes with active lengths of 2 cm and 3 cm, respectively, were placed under MR-guidance in an open 0.2 Tesla MR system (Magnetom Open, Siemens, Erlangen) using fast T1-weighted sequences. Pretreatment studies, evaluation of tumor necrosis (one week after last RFA), and further follow-up studies every 3 months were performed using 1.5 Tesla MR systems. RESULTS: The mean procedure time was 2.8 (1.5-3.3) h. Complications related to percutaneous treatment were not encountered. 14 of 16 neoplasms (87%) showed no CM enhancement during MRI after the last RFA and were judged to be completely necrotic. In 11 tumors one treatment session was necessary, in 4 tumors two and in one tumor three. Follow-up studies revealed persistent complete necrosis in 13 of 14 (93%) tumors during a period of 3-18 (median: 11.8) months. In 5 patients new intrahepatic tumors developed that were not suitable for further RFA treatment because of their number, size and location. CONCLUSION: MR-guided RFA using single cooled tip electrodes is safe and technically effective for treatment of hepatic neoplasms up to 3 cm in size, however further improvements are necessary.

Growth characteristics and imaging properties of the morris hepatoma 3924A in ACI rats: a suitable model for transarterial chemoembolization.

PURPOSE: For experimental studies investigating modalities and efficacy of transarterial chemoembolization (TACE) in hepatocellular carcinoma (HCC) an animal model resembling the human situation as closely as possible would be appropriate. Specifically, reproducible tumor growth characteristics with the capability for appropriate in vivo imaging to monitor treatment efficacy are required. METHODS: Morris hepatoma 3924A was implanted into the liver of 30 ACI rats. Tumor growth was followed by angiography (n = 10), ultrasound (US, n = 30), native computed tomography (CT, n = 16), and native magnetic resonance imaging (MRI, n = 30) between day 8 and day 36 after implantation. The radiological morphological characteristics were compared with the macroscopic and microscopic histological findings of the explanted tumors. RESULTS: In all 30 animals a solitary liver tumor was found and macroscopically no signs of metastases, ascites, or peritoneal tumor were visible. On histopathological examination tumor sizes ranged between 27 +/- 3 mm(3) (day 8) and 3468 +/- 79 mm(3) (day 36). The first signs of tumor necrosis occurred at day 16. US allowed tumor visualization from day 8, MRI from day 8, angiography from day 10, and CT from day 14. CONCLUSIONS: The tumor model has the potential to be used for the visualization of tumor growth by MRI and US. The potential for monitoring therapeutic effects of TACE needs to be investigated.

[Animal experiment studies on the effectiveness of permanent occlusion of the hepatic artery in transarterial chemoembolization]. / Tierexperimentelle Untersuchungen zur Effektivität der permanenten Okklusion der Arteria hepatica bei der Transarteriellen Chemoembolisation.

PURPOSE: To evaluate the effect of permanent occlusion of the hepatic artery on the efficacy of transarterial chemoembolization (TACE) in an animal model. MATERIAL AND METHODS: 12 days after inoculation of the Morris hepatoma 3924 A in 15 male ACI rats, TACE with Mitomycin C (0.25 mg/kgBW) + Lipiodol (0.2 ml/kgBW) without (n = 5) and with permanent occlusion of the hepatic artery (n = 5) was performed. Control group consisted of 5 rats. Tumor volume was determined by MRI (1.0 T, T1 [TR/TE, 400/14 ms]) before and 12 days after therapy. RESULTS: Compared to the control group, TACE without and with permanent occlusion of the hepatic artery showed a significant reduced tumor growth after 12 days (p = 0.017 and p = 0.005). However, permanent occlusion did not improve the retarding effect on tumor growth (p = 0.9). CONCLUSION: The effectiveness of TACE in an animal model using a cytostatic-/lipiodol-emulsion is not improved by permanent occlusion of the hepatic artery.

[Benign bile duct stenoses. Treatment with flexible metal wire stent or silicone prostheses (Yamakava) in nonresectable stenoses or high surgical risk cases]. / Benigne Gallenwegstenosen. Behandlung mit flexiblen Metallgitterstents oder Silikonprothesen (Yamakava) bei nichtresezierbaren Stenosen oder hohem Operationsrisiko.

INTRODUCTION: High benign biliary stenoses, which can occur as a complication of disease or surgery, may be difficult to correct by open surgery and may also carry a high risk. An alternative to surgery is the percutaneous implantation of a flexible metallic stent or silicon prosthesis at the affected site. METHODS: Twelve patients with benign biliary stenoses have been operated on in our department since March 1992, and the therapeutic success was reviewed in this study. RESULTS: Six received a Palmaz stent and six a silicon prosthesis, with a follow-up after completion of treatment of more than 7 years and more than 3 years, respectively. Fifty percent of the patients with a stent experienced no problems and 66% of the stents remained patent (including one requiring operative intervention to restore patency). No further surgery was necessary in any of the patients with a silicon prosthesis. CONCLUSION: When the advantages and disadvantages of the various procedures are considered, long-term splinting with a wide-lumened silicon prosthesis (Yamakava) appears to be a promising alternative to surgery for the treatment of benign biliary stenosis.

[Percutaneous radiofrequency ablation of hepatic neoplasms using a "cluster" electrode--first clinical results]. / Perkutane Radiofrequenzablation hepatischer Neoplasien unter Verwendung von "Cluster"-Ablationssonden--Erste klinische Erfahrungen.

PURPOSE: To evaluate feasibility, safety and efficacy of percutaneous radiofrequency ablation (RFA) of hepatic neoplasms using a clustered electrode. MATERIAL AND METHODS: Percutaneous, CT-guided RFA using a clustered electrode was performed in 12 patients with a total of 15 hepatic neoplasms (2.0-6.0 cm in diameter). RESULTS: A total of 17 percutaneous RFA was performed. The mean total procedure time was 2.0 h (1.5-2.5 h). Placement of the clustered electrode within the neoplasms using a inter- or subcostal approach under local anesthesia was possible in all cases. Complications related to percutaneous treatment and technical problems were not encountered. Diameter of the ablated areas ranged between 3.0-7.0 cm. Technical success was observed in 13 of 15 neoplasms (86.6%). During a mean follow-up of 7.25 months (range 3-12 months) 8 of 12 neoplasms showed a complete necrosis. CONCLUSION: Percutaneous RFA using a clustered electrode is a feasible, safe and effective procedure for the treatment of hepatic neoplasms up to 6 cm in size.

[Yamakawa prosthesis with prolonged placement as a therapy concept exemplified by benign biliary stricture]. / Yamakawa-Prothese mit prolongierter Verweildauer als Therapiekonzept am Beispiel einer benignen biliären Striktur.

AIM: As an alternative method to the operative revision of benign bile duct strictures, we report the use of a large-bore bile duct prosthesis (Yamakawa prosthesis) in one patient. METHODS: Bilateral percutaneous transhepatic implantation of Yamakawa prostheses (14 F right side, 12 F left side) was performed without adjunctive balloon dilatation. The prostheses were exchanged every 8 weeks under continuous antibiotic treatment and were finally removed after 8 months. RESULTS: Control cholangiography showed a normal intrahepatic biliary system on the right side and a 50% stenosis at the orifice of the left hepatic duct. Follow-up over 18 months showed no signs of recurrent disease. CONCLUSIONS: In comparison to balloon dilatation and implantation of metallic stents, prolonged bilateral splinting with large-bore Yamakawa prostheses seems to be an alternative for the treatment of benign bile duct strictures.

[Transjugular intrahepatic portosystemic shunt in children. Initial clinical experiences and literature review]. / Der transjuguläre intrahepatische portosystemische Shunt bei Kindern. Erste klinische Erfahrungen und Literaturübersicht.

PURPOSE: To present special methodical and clinical findings of transjugular intrahepatic portosystemic shunts (TIPSS) in children and to discuss potential indications. PATIENTS AND METHODS: Between 1993 and 1996, 6 children aged 2-13 years were treated by TIPSS-insertion. In four cases, the underlying disease was extrahepatic biliary atresia (EHBA) and in two cases liver fibrosis secondary to treatment of neoplasms during early childhood. Indications for TIPSS insertion were variceal bleeding resistant to other treatment modalities in three patients, hypersplenism in one patient and both bleeding and hypersplenism in two. Portal vein punctures were performed using 16-gauge needles, because 19-gauge fine-needles showed insufficient stiffness. The mean follow-up was 24.5 months. RESULTS: Shunt insertion succeeded in all children with a mean procedure time of 5.2 hours. Periportal fibrosis associated with EHBA, atypical course of hepatic veins and small diameters and distances of vessels were conditions making the procedure difficult. Bleeding ceased in all patients, peripheral platelet counts rose by a mean value of 58%. Procedure-related complications were minor extrahepatic bleeding in one child and temporary haemolysis in another child. Restenosis resulted in three patients and were treated successfully by means of transjugular interventions. 5 children remain free of symptoms to this day, one child underwent successful orthotopic liver transplantation 8 months after TIPSS. CONCLUSIONS: TIPSS insertion is technically more difficult in children and has to consider child growth and possible subsequent liver transplantation. Potential indications are recurrent variceal bleeding, also of intestinal origin, resistant to standard treatment and clinically significant hypersplenism.

[Intra-arterial calcium stimulation for preoperative localization of insuloma]. / Intraarterieller Kalzium-Stimulationstest zur präoperativen Lokalisationsdiagnostik des Insulinoms.

PURPOSE: Objective is to evaluate the efficacy of the intraarterial calcium test in the preoperative localisation of insulinomas. MATERIAL AND METHOD: To stimulate the pathological release of insulin, calcium gluconate (0.015 meq Ca++/kg) was selectively injected into the arteries supplying the pancreas. Prior to calcium injection and 30, 60, 90 and 120 seconds later, 5 ml samples of blood were obtained from the right or from both right and left hepatic veins. Insulin levels were then determined by mean of immunoassays. A twofold increase in insulin level in the venous sample after 30 or 60 seconds localised the insulinoma to the region of the pancreas supplied by the selectively injected artery. Results of the calcium test were prospectively analysed in 6 patients and compared with operative findings. RESULTS: All 6 patients had a surgically proved solitary and benign insulinoma. Calcium stimulation with venous sampling provided true-positive localisation of insulinomas in all patients without suspicion of liver metastasis. All 6 patients currently have normal insulin levels after a mean period of 16 months (range 4-24 months) with no evidence of hypoglycaemia on fasting. CONCLUSION: Intraarterial stimulation with calcium and hepatic vein samplings for insulin gradients is a very sensitive minimally invasive functional method and may replace transhepatic portal venous samplings for the preoperative detection of insulinomas.

Insulinoma and islet cell hyperplasia: value of the calcium intraarterial stimulation test when findings of other preoperative studies are negative.

PURPOSE: To evaluate the efficacy of the intraarterial calcium test in localizing sources of hyperinsulinism that remain undetectable at preoperative morphologic studies. MATERIALS AND METHODS: Twenty-four patients with clinically proved endogenous hyperinsulinism due to tumorous insulin production were prospectively enrolled. They underwent ultrasound (US), computed tomography, magnetic resonance imaging, endoscopic US, abdominal arteriography, and a calcium test, in which insulin concentrations were measured in hepatic venous blood after selective intraarterial calcium stimulation. The results of the calcium test in seven patients (five women, two men; age range, 30-66 years; mean age, 47 years) with negative findings of morphologic studies are described. RESULTS: Six solitary insulinomas (mean diameter, 0.73 cm) and one nodular hyperplasia were diagnosed after surgery. In all seven cases, calcium test findings allowed accurate localization of the pathologic source of insulin secretion. In three of these seven cases, results of arterial calcium stimulation with hepatic venous sampling (ASVS) affected intraoperative management. An increase in insulin concentration after stimulation in the hepatic artery was not observed, making hepatic metastases unlikely. CONCLUSION: ASVS, which is procedurally simpler than transhepatic pancreatic venous sampling, is effective for localizing sources of hyperinsulinism not detected with preoperative morphologic studies.