Renal Function in De Novo Liver Transplant Recipients Receiving Different Prolonged-Release Tacrolimus Regimens-The DIAMOND Study.

UNLABELLED: DIAMOND: multicenter, 24-week, randomized trial investigating the effect of different once-daily, prolonged-release tacrolimus dosing regimens on renal function after de novo liver transplantation. Arm 1: prolonged-release tacrolimus (initial dose 0.2mg/kg/day); Arm 2: prolonged-release tacrolimus (0.15-0.175mg/kg/day) plus basiliximab; Arm 3: prolonged-release tacrolimus (0.2mg/kg/day delayed until Day 5) plus basiliximab. All patients received MMF plus a bolus of corticosteroid (no maintenance steroids). PRIMARY ENDPOINT: eGFR (MDRD4) at Week 24. Secondary endpoints: composite efficacy failure, BCAR and AEs. Baseline characteristics were comparable. Tacrolimus trough levels were readily achieved posttransplant; initially lower in Arm 2 versus 1 with delayed initiation in Arm 3. eGFR (MDRD4) was higher in Arms 2 and 3 versus 1 (p = 0.001, p = 0.047). Kaplan-Meier estimates of composite efficacy failure-free survival were 72.0%, 77.6%, 73.9% in Arms 1-3. BCAR incidence was significantly lower in Arm 2 versus 1 and 3 (p = 0.016, p = 0.039). AEs were comparable. Prolonged-release tacrolimus (0.15-0.175mg/kg/day) immediately posttransplant plus basiliximab and MMF (without maintenance corticosteroids) was associated with lower tacrolimus exposure, and significantly reduced renal function impairment and BCAR incidence versus prolonged-release tacrolimus (0.2mg/kg/day) administered immediately posttransplant. Delayed higher-dose prolonged-release tacrolimus initiation significantly reduced renal function impairment compared with immediate posttransplant administration, but BCAR incidence was comparable.

[Diagnosis of and therapy for hepatocellular carcinoma]. / Diagnostik und Therapie des hepatozellulären Karzinoms.

The interdisciplinary guidelines at the S3 level on the diagnosis of and therapy for hepatocellular carcinoma (HCC) constitute an evidence- and consensus-based instrument that is aimed at improving the diagnosis of and therapy for HCC since these are very challenging tasks. The purpose of the guidelines is to offer the patient (with suspected or confirmed HCC) adequate, scientifically based and up-to-date procedures in diagnosis, therapy and rehabilitation. This holds not only for locally limited or focally advanced disease but also for the existence of recurrences or distant metastases. Besides making a contribution to an appropriate health-care service, the guidelines should also provide the foundation for an individually adapted, high-quality therapy. The explanatory background texts should also enable non-specialist but responsible colleagues to give sound advice to their patients concerning specialist procedures, side effects and results. In the medium and long-term this should reduce the morbidity and mortality of patients with HCC and improve their quality of life.

[Incidence of posthepatectomy liver failure and biliary leakage : A cohort study]. / Inzidenz von Leberversagen und Galleleckagen nach Leberteilresektion : Eine Kohortenstudie.

BACKGROUND: The International Study Group of Liver Surgery (ISGLS) defined posthepatectomy liver failure as pathological values for the international normalized ratio (INR) and bilirubin 5 days after liver resection. The occurrence of biliary leakage was defined as a drainage bilirubin to serum bilirubin ratio > 3 at day 3 or later after resection or interventional surgical revision due to biliary peritonitis. A confirmatory explorative analysis was carried out. PATIENTS AND METHODS: The study involved an evaluation of primary liver resection from the years 2009 and 2010. Primary endpoints were the incidence of posthepatectomy liver failure and biliary leakage in accordance with the ISGLS definition. Secondary endpoints were complications and 90-day mortality. Results are displayed as median values (minimum and maximum). RESULTS: A total of 214 liver resections were included from the years 2009 and 2010. Patients were an average of 61.5 years old (min. 18, max. 83 years). The incidence of liver failure was 7.4 % (16 out of 214) and fatal in 7 patients. In 31 % (65 out of 214) a biliary leakage occurred, 14 (23 %) patients developed a type B, 1 patient(5 %) a type C leakage and 50 leakages were clinically inapparent. The incidence of clinically relevant biliary leakages was 7 % (15 out of 214). The sensitivity of the definition was 100 % and the specificity 75 %. The incidence of Dindo-Calvien complications > 3b was 10.2 %, of sepsis 5.6 % and the 90-day mortality was 6.5 %. Multivariate analysis did not reveal independent predictive factors for biliary leakage or liver failure. CONCLUSION: The definition for posthepatectomy liver failure was found to be valid in this cohort. The incidence of postoperative biliary leakage is over-estimated with the current definition and delivers a large number of false positive results without clinical relevance.

[Percutaneous radiofrequency ablation of liver tumors using the LeVeen 4 cm array probe]. / Radiofrequenzablation von Lebertumoren mittels 4 cm Schirmelektrode.

BACKGROUND: The purpose of this study was to evaluate safety and efficacy of a radiofrequency ablation system in clinical practice. METHODS: In 35 patients (age 63,9 +/- 12,6 years, range 22 - 83) a total of 65 liver tumors were percutaneously treated using a 200 watt radiofrequency generator and a LeVeen 4 cm array probe (RF3000, Boston Scientific). The interventions were performed under CT guidance in local anaesthesia and sedation. Adapted to the tumor size, the LeVeen Probe was repositioned during the procedure with an additional safety margin of 1 cm. Primary tumors were colorectal in 22, and mamma tumors (n = 4), zystic pancreas tumors (n = 2), gastric cancer (n = 1), zystadenocarcinoma of the liver (n = 1), lung cancer (n = 1), gastrointestinal stroma tumor (n = 1), duodenal carcinoma (n = 1), cholangiocellular carcinoma (n = 1) and hepatocellular carcinoma (n = 1). Post interventional control and follow-up was performed with multislice-CT (collimation 2.5 mm, unenhanced and contrast enhanced, arterial and portal filling) at 4 weeks, and every three months. RESULTS: One to 4 metastases were treated per patient during one or up to 4 procedure sessions. Mean lesion size was 2,3 +/- 1,2 cm (range 0,2 to 7,0). The corresponding size of the necrosis achieved was 4,6 +/- 1,4 cm (range 2,0 - 8,2). Primary technical success with complete tumor ablation was reached in 60 of 65 lesions. In 4 cases two treatment sessions were necessary in order to achieve the intended results. In one case the procedure was aborted because of a close relationship between lesion and right colon. 63 tumors were treated in sedation and local anesthesia. General anesthesia was necessary in two cases, in one who refused intervention in sedation, and in another case with insufficient analgetic effect. Morbidity was 9.2 %: Bleeding complications (n = 3, one arterial bleeding from the ablation tract, two intrahepatic bleedings with extrahepatic hematoma) were confirmed by selective angiography of the hepatic artery and were treated with coil embolisation of the respective segmental arteries. One case with subcapsular tumor ablation suffered from a large subcapsular hematoma requiring a blood transfusion. In one case with a subphrenic location of the metastasis, the needle electrode had passed the costophrenic recessus and resulted in an hematothorax. This patient was treated by pleural drainage for two days. One patient suffered from fever up to 39 degrees C and inflammation of the biliary tract and received a cholecystectomy 22 days post interventionally. There was no peri interventional mortality. Mean follow-up is 5,6 +/- 3,3 months (range 0 to 13). 21 of 35 patients showed no evidence of tumor recurrence. One case is scheduled for a second treatment session for complete tumor ablation. 13 of 35 patients suffered from tumor recurrence, either local recurrences and/or new metastases. At the sites of prior RF-ablation 9 local recurrences were detected in 7 patients, two cases with isolated local recurrences and 5 cases with local recurrences and new metastases. 6 Patients showed no evidence for local recurrences but new metastases. In these 11 cases a total of 37 metastases were found at new locations. In three patients tumor recurrence was treated by means of a second RF-ablation. The remaining 10 patients received chemotherapy. CONCLUSION: RF-ablation can be performed in local anaesthesia and sedation with low peri interventional morbidity and mortality. Using the LeVeen probe and a 200 watt generator, appropriate necroses can be achieved. CT follow-up is required every three months because of the tumor recurrence rate and reinterventions may be required.

[Surgery and interventional techniques in biliary tract diseases. Combined procedure or concurrent procedure?]. / Chirurgie und interventionelle Techniken bei Gallenwegserkrankungen. Kombiniertes Vorgehen oder konkurrierende Verfahren?

Bile duct stones, benign lesions of the bile duct, and malignant stenoses are principal entities requiring an interdisciplinary approach to diagnosis and treatment. There are unequivocal indications for surgical and interventional approaches. In many situations sparse data do not allow for clear-cut recommendations, which leads to a competition of surgical and interventional modes of treatment. In cholecystocholedocholithiasis, therapeutic splitting--endoscopic stone extraction and laparoscopic cholecystectomy--is at present the preferred strategy. The laparoscopic approach, including common bile duct exploration, may prove advantageous in the future. Emergency situations caused by choledocholithiasis--purulent cholangitis and biliary pancreatitis--require interventional treatment. For bile duct injuries with biliary leakage and treatment of short strictures, transpapillary or transhepatic prostheses may be adequate. In extended strictures or bile duct defects, surgical repair is required. In malignant stenoses, surgical treatment provides the longest survival. If operability is excluded, an interventional approach offers substantial palliation. The results of the different forms of stents and prostheses are comparable.

[Budd-Chiari syndrome--a rare manifestation of hereditary thrombophilia]. / Budd-Chiari Syndrom--eine seltene Manifestation der hereditären Thrombophilie.

Budd-Chiari syndrome is a rare manifestation of hereditary or acquired thrombophilia. We saw a case of Budd-Chiari syndrome in a 30-year-old woman leading to initial diagnostic difficulties. She underwent surgical side-to-side shunt and 9 weeks later an almost normal liver could be demonstrated on computerized tomography. Budd-Chiari syndrome should be considered if the Chiari triad with abdominal pain, hepatomegaly and ascites occurs in a patient. If necessary, invasive diagnostic procedures (e.g. angiography) must be performed. Therapeutic options are anticoagulative therapy and porto-systemic shunt, either as a TIPS or a surgical shunt. If severe liver failure occurs or liver cirrhosis is present, orthotopic liver transplantation is an additional option which also cures hereditary thrombophilia.

[Transarterial chemoembolization (TACE) of the hepatocellular carcinoma (HCC) in patients with portal vein thrombosis--experiences]. / Transarterielle Chemoembolisation (TACE) des Hepatozellulären Karzinoms (HCC) bei Patienten mit Pfortaderthrombose--Erfahrungen.

PURPOSE: Comparative analysis of the course of disease in patients with initial diagnosis of portal vein thrombosis in HCC treated with sequential TACE. Evaluation of the efficacy and safety of the method in a selected patient cohort. PATIENTS AND METHODS: The study included 22 patients with HCC that were palliatively treated at least 3 times with TACE. All patients presented a portal vein thrombosis in the initial CT investigation. The TACE-procedure was carried out in regular intervals using a suspension consisting of a fixed dosage of Mitomycin C (10 mg) and 10-20 ml Lipiodol. Follow-up investigations were carried out with contrast enhanced Multislice-CT before and after TACE and control of the laboratory panel (i. e. blood count, liver enzymes and coagulation). RESULTS: Mean survival was 15.7 months (95%-CI 11.6-19.8) with a mean follow-up after last TACE of 6.1 +/- 4.8 months. The mean number of TACE procedures was 5.5 +/- 2.7. During the investigation period 17 / 22 (77.3%) patients died. In 23.5% retrospective analysis revealed a liver decompensation as the cause of death and in 58.8% patients died from the tumor disease. The cumulative 1-, 2- and 3-year survival was 55.0, 21.0 and 0%. The mean tumor size was 7.2 +/- 3.4 cm. Unifocal tumors were found in 18.2% of the cases whereas multifocal tumors were found in 81.8%. In 59.1% of the patients tumor extended to both liver lobes. In case of tumor infiltration of the portal vein survival was significantly worse compared to patients with no evidence of a tumor thrombosis (p = 0.01; cumulative 1- and 2-year survival 46% and 8% vs. 77% and 46%). CONCLUSION: The palliative treatment of the HCC with TACE shows an improvement of survival. There was no increase of death due to liver decompensation in our cohort. Patients with a tumor infiltration of the portal vein showed a significantly worsened survival. The presence of a portal vein thrombosis at the initial diagnosis of the HCC is not an absolute contraindication for TACE treatment but patients have to be elected carefully with critical regard to their liver function.

Effect of pentosan polysulphate in minipigs with experimental pulmonary emboli.

As a result of treatment with pentosan polysulphate in minipigs with experimental pulmonary emboli a decrease in mean pulmonary arterial pressure, an increase in blood flow of pulmonary artery and an increase in plasminogen activator was seen, compared with control animals who received saline infusion only.

Experimental pulmonary embolism with electrically activated autologous blood.

Pulmonary thromboembolism is one of the most frequent causes of death in our days. Notwithstanding the great efforts made in clinical and experimental medicine there has been no success as yet in filling the existing gaps in the understanding of pathophysiology of this disease. The blood electrically activated in vitro by direct current reacts like an endogenic thrombogenic substance. On the condition that such a substance is injected into the inferior vena cava, the clot is introduced into the pulmonary circulation and gives rise to pulmonary thromboembolism of a varying degree, each depending on the electrically activated blood injected. In the animal experiment it has thus become feasible, under standardized and reproducible conditions, to produce severe thromboembolism or chronic microembolism with subsequent hypertrophy of the right ventricle. The object of this contribution is a demonstration of a new, easy, and effective method for the induction of pulmonary embolism, which can be treated by thrombolysis.

Preoperative imaging of hilar cholangiocarcinoma: surgical evaluation of standard practises.

UNLABELLED: It was the goal of this study to compare the results of the preoperative diagnostic workup (ERC, MRC, and PTC) with the tumor extent of the surgical specimen in patients with hilar cholangiocarcinoma (hilCC). PATIENTS AND METHODS: Between 9/97 and 12/2002 82 patients with hilCC were treated at our institution. In 59 patients tumor resection was feasible. Preoperative ERC, MRC and PTC - blinded for the idendity of the patients - were analysed retrospectively and compared with the surgical specimen. RESULTS: PTC resulted in significantly superior visualization of the bile ducts including the hilar lesion compared to ERC and MRC (p < 0.01). ERC, MRC and PTC were correct in predicting tumor extent in 29, 36 and 53 % of cases, respectively. The extent of the tumor was overestimated in 42 % (ERC), 41 % (MRC) and 31 % (PTC). Underestimation or wrong assessment or no decision at all occurred in 31, 23 and 16 %, respectively. In 20 patients results of all three diagnostic methods were available allowing a statistical comparison regarding the resection to be performed: PTC was superior to ERC (McNemar test:p < 0.01), but not to MRC. In the patients with overestimated tumor extent both the rate of curative resections and survival were similar to the other resected patients. DISCUSSION: In contrast to most reports in the literature, ERC and MRC were found to be of limited reliability regarding the assessment of tumor extent. PTC proved to be the most reliable approach. Overestimation of the tumor extent, which may lead to exclude the patient from potentially curative surgery, was the most common mistake in each diagnostic modality.