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Biomedical subjects

N R Frühauf

Publications and source records attributed to N R Frühauf.

At least 19 recordsLinked to original sources

[Surgical therapy of intrahepatic cholangiocellular carcinoma].

BACKGROUND: Intrahepatic cholangiocarcinoma (ICC) is the second most common primary hepatic malignancy. Tumor resection is the treatment of choice, but so far the value of hepatic resection has not been well defined. We report results with an aggressive surgical approach for the treatment of this tumor entity. PATIENTS AND METHODS: Between April 1998 and June 2004, 54 liver resections were performed in 120 patients with ICC. In 24 patients, 39 additional procedures were performed: resection of hilar bifurcation (n=18), partial resection of diaphragm (n=6), vascular resection and reconstruction (n=15). RESULTS: There were 30 R0, 21 R1, and three R2 resections. After R1/R2 resection and explorative laparotomy, the median survival times are 9 months and 6 months, respectively. Following R0 resection, the calculated median survival is 46 months, and the 1-, 3-, and 5-year survival rates are 83%, 58%, and 48%, respectively. CONCLUSION: The presented data show that R0 resection leads to a significant prolongation of survival in patients with ICC. In contrast, incomplete tumor removal does not provide a survival benefit. These results justify an aggressive surgical approach to achieve a R0 resection. The low resectability rate of less than 50% underlines the need for improved preoperative staging.

Bile Duct Neoplasms↗

Biotransformation of cyclosporin in primary rat, porcine and human liver cell co-cultures.

The purpose of this study was to investigate the species-specific cyclosporin biotransformation in primary rat, human, and porcine liver cell cultures, and to investigate the suitability of a modified sandwich culture technique with non-purified liver cell co-cultures for drug metabolism studies. A sandwich culture was found to enhance hepatocellular metabolic activity and improve cellular morphology and ultrastructure. The cyclosporin metabolites AM9 and AM1 were formed in porcine and human liver cell sandwich co-cultures at levels corresponding to the respective in vivo situations. In contrast, metabolite profiles in rat hepatocytes were at variance with the in vivo situation. However, for all cell types, the overall metabolic activity was positively influenced by sandwich co-culture. The initial levels of albumin synthesis were higher in sandwich cultures than in those without matrix overlay. It is hypothesized that the sandwich culture system provides an improved microenvironment and is, therefore, an advantageous tool for in vitro studies of drug metabolism.

Animals↗

Liver resection for hepatocellular carcinoma in non-cirrhotic liver without underlying viral hepatitis.

BACKGROUND: Hepatocellular carcinoma (HCC) arising in normal liver parenchyma is rare and the outcome after hepatectomy is not well documented. METHODS: Between June 1998 and September 2003, 33 patients without viral hepatitis underwent resection for HCC in a non-cirrhotic, non-fibrotic liver. Data were analysed with regard to operative details, pathological findings including completeness of resection, and outcome as measured by tumour recurrence and survival. RESULTS: Twenty-three major hepatectomies and ten segmentectomies or bisegmentectomies were performed. After potentially curative resection, 19 of 29 patients were alive at a median follow-up of 25 months, with calculated 1- and 3-year survival rates of 87 and 50 per cent respectively. Survival was significantly better after resection of tumours without vascular invasion (3-year survival rate 89 versus 18 per cent; P = 0.024). Disseminated recurrence developed in nine of 29 patients, leading to death within 28 months of operation in all but one of the nine. CONCLUSION: These data justify hepatic resection for HCC arising in non-cirrhotic, non-fibrotic liver without underlying viral hepatitis. Liver transplantation is rarely indicated because the outcome is good after resection of tumours without vascular infiltration, whereas vascular invasion is invariably associated with diffuse extrahepatic recurrence.

Adult↗

[Mesohepatectomy-an alternative to extended hepatectomy in the treatment of central liver tumors].

Mesohepatectomy was performed in seven patients with a primary or secondary central liver tumor. We describe the surgical procedure for mesohepatectomy (removal of segments IVa/IVb/V/VIII +/- I) in the treatment of central hepatic tumors. This technically demanding but safe approach requires careful vascular dissection to maintain blood supply and venous drainage of the two remaining liver parts. Mesohepatectomy results in one or two large resection planes bearing a considerable risk of parenchymal necrosis or biliary leakage. Its major advantage over extended hepatectomy is the preservation of functioning liver tissue. Thus, the risk of postoperative liver failure is reduced and, in case of intrahepatic recurrence, the chance for repeat hepatectomy improved. Mesohepatectomy should be considered in selected cases of central liver tumors in which extended resection would be associated with a high risk of liver insufficiency.

Adenoma, Liver Cell↗

Terlipressin and gelafundin: safe therapy of hepatorenal syndrome.

BACKGROUND AND AIM: Hepatorenal syndrome (HRS) occurs in about 20 % of patients with liver cirrhosis and ascites and is characterized by intensive renal vasoconstriction, low glomerular filtration rate but preserved tubular function and normal renal histology. The potential of terlipressin and albumin to reverse HRS after a time period of 14 days has already been shown. However, intravenous albumin is expensive (approximately 25 per 50 ml 20% albumin in Germany) and has limited availability in some settings. Therefore we used an artificial plasma substitute, Gelatinepolysuccinat, which is less expensive (approximately 12 per 500 ml). The aim of our present study was to examine the effects of terlipressin and Gelatinepolysuccinat on renal function and hemodynamics in a time period of six days. METHODS AND PATIENTS: Seven consecutive patients with cirrhosis and hepatorenal syndrome were included in a pilot study of terlipressin (6 mg /24 h iv) therapy associated with i.v. Gelatinepolysuccinat (Gelafundin 4% Infusionslösung, Company Braun, Mw: 30 000 D). RESULTS: In five of the seven patients treatment was associated with a marked reduction of serum creatinine after six days (3.85 +/- 0.44 mg/dl vs.1.9 +/- 0.32 mg/dl; p< 0.018). Creatinine clearance improved (20 +/- 8.8 ml/min vs. 43 +/- 11.7 ml/min; p<0.12). There was a remarkable improvement in circulatory function in all patients, with an increase in mean arterial pressure (58+/-4.4 mmHg vs. 75 +/- 4.5 mmHg, p< 0.001). No patient developed signs of intestinal, myocardial or distal ischemia. CONCLUSIONS: Terlipressin and Gelatinepolysuccinat appear to be a safe and effective treatment of hepatorenal syndrome.

Antihypertensive Agents↗

[Organ transplantation in human immunodeficiency virus-infected patients. Results of a survey in German transplantation centres].

BACKGROUND: Despite considerable advances following the introduction of highly active antiretroviral therapy, organ transplantation is usually denied categorically for human immunodeficiency virus (HIV) patients, and it is presented in German transplantation law as a contraindication. Today, this should be questioned critically. METHOD: A survey at all 87 German transplant centres was done concerning (1) how many HIV-positive patients were transplanted before and after February 2000, (2) willingness of the centres to transplant HIV-infected patients in the future, and (3) course of transplanted HIV patients so far. RESULTS: With a response rate of 78%, 39% of the questioned centres were accepting HIV patients in the future for transplantation, and 39% rejected this. Twenty percent voted for individual case decision. Three centres had practiced liver transplantation in 11 patients. CONCLUSION: The decision to transplant HIV-positive patients in Germany is mostly based on individual cases and not refused in general. However, prospective studies on this issue are justified and needed.

Acquired Immunodeficiency Syndrome↗

[Liver transplantation in elderly patients].

Since the first liver transplantation (OLT) was performed by Starzl in 1963, this has become the standard therapy for end stage chronic liver disease and acute hepatic failure. It is also the therapy of choice in selected cases of hepatic malignancy. Due to the optimization of intra- and perioperative management, new immunosuppressant drugs and improved organ procurement, the clinical outcome in patient and graft survival has increased continuously. The shortage of donor organs has led to the development of new surgical techniques such as split- and living related transplantation. OLT should also be offered to elderly patients. Careful evaluation and patient selection results in good patient and graft survival after transplantation, which is comparable to that in with younger recipients.

Age Distribution↗

Postoperative ICU management in liver transplant patients.

The unique pathophysiology of end-stage liver disease (ESLD) has important implications on critical care treatment after liver transplantation. To determine hemodynamic parameters and responses, each patient must be carefully evaluated for the individual clinical appearance of cirrhosis and portal hypertension. Although data are limited, recent progress in the treatment of ESLD and its complications, such as hepatorenal syndrome (HRS), portopulmonary hypertension (PPH), and hepatopulmonary syndrome (HPS) is evident. The improved understanding of the pathophysiology of ESLD has resulted in novel treatments and approaches to the problems that emerge as patients get critically ill or undergo orthotopic liver transplantation (OLT). These issues become much more relevant with increased adult-to-adult living donor liver transplantation, where the scheduled operation allows a precise preoperative management in an Intensive Care Unit (ICU).

Critical Care↗

[Intraoperative radiotherapy in Germany].

BACKGROUND: Intraoperative radiotherapy (IORT) represents an attractive method for local tumour control after surgical resection. IORT was introduced into multimodal treatment protocols in the 1980s. Aim of this study was to analyse the actual clinical and scientific activity of IORT in Germany. METHODS: Questionnaires were sent to 102 centres in Germany. The analysis was focussed on indications in general surgery including bone tumours to evaluate the activity of IORT. The literature was analysed by a medline search for the years 1975 to 2001. RESULTS: Questionnaires were answered by 92% of the centres. 24 departments are working with IORT in Germany (16 of them are university hospitals). Main Indications for IORT treatment are rectum carcinoma and soft tissue sarcoma. Furthermore, IORT is used in patients suffering from gastric, pancreatic and bile duct malignancies. Some IORT programs are also targeting on patients with head and neck malignancies and brain tumours. German institutions published within the last 5 years about 14% of all " Medline"-listed publications concerning IORT. CONCLUSION: There is an profound activity of IORT in Germany, which is concentrated on a few centres. A need for better national and international cooperation of centres performing IORT for clinical trials and to collect significant numbers of patients seems to be evident.

Bile Duct Neoplasms↗

Filtration of malignant cells: tumour cell depletion in an ex vivo model using a leukocyte adhesion filter.

The clinical use of leukocyte adhesion filters is based on differentiated depletion of blood cells, although most of the mechanisms of filtration are still unclear. There is also evidence that leukocyte adhesion filters can remove disseminated tumour cells from patients' blood. The following proves this observation and consists of three parts: in the first part we analysed the depletion capacity of the LeucotrapWB filter medium (Pall) in an employed small-scale model for the cell line HT29 (colorectal origin) in phosphate-buffered saline (PBS) solution. A depletion rate of more than 99.6% for HT29 cells was seen. In the second part of the study, samples of whole blood were spiked with HT29 cells in a similar setting, showing comparable results. In the last part, defined cell suspensions of various human primary tumours were admixed to whole blood samples and afterwards filtrated in a scale-up model. Again, a nearly complete tumour cell reduction was seen after filtration. Results show a significant tumour cell reduction and, for most cases, a complete depletion of tumour cells independently from quality and origin of the tumour tissue. These experiments and further investigation are supposed to help to reduce the risk of dissemination of tumour cells in patients undergoing oncological surgery.

Cell Adhesion↗

Management of iatrogenic lesions of the biliary tract.

A wide spectrum of iatrogenic biliary complications is encountered. Most are the results of preventable trauma or technical mishaps during cholecystectomy. There is no doubt that the incidence of iatrogenic lesions of the bile tract increased since the introduction of laparoscopic cholecystectomy. These include bile leakage, biliary tree obstruction, postsurgical strictures and various types of biliary fistulas. The purpose of this article is to review the clinical features of these iatrogenic lesions with emphasis of their interventional and surgical management.

Biliary Tract↗

Rescue hepatectomy for initial graft non-function after liver transplantation.

BACKGROUND: Early retransplantation is the therapy of choice in patients with initial graft nonfunction (INF). In rare cases the patients' conditions deteriorate dramatically with severe cardiovascular and/or pulmonary insufficiency while on the waiting list for retransplantation. In this life-threatening situation removal of the graft and temporary portocaval shunt before allocation of a new liver proved to be effective. Our experience with this two-stage hepatectomy and subsequent liver transplantation in patients with complicated INF is reported. METHODS: Hepatectomy was performed in 20 patients with INF associated with severe cardiovascular and pulmonary insufficiency while on the waiting list for emergency liver retransplantation. The mean age was 41.75+/-16.64 years. The time period between primary transplantation and hepatectomy was 2.80+/-2.84 days with a range from 1 to 9 days. RESULTS: Hepatectomy reduced the need for vasopressive agents and improved pulmonary function in the majority of patients. Four patients died before a liver was available due to brain death in one patient and multiorgan failure in three patients. In the remaining 16 patients liver transplantation could be performed after 19.82+/-15.34 hr (range 6.58 to 72.50 hr). Two of the 16 transplanted patients died on the first postoperative day due to multiorgan failure and pneumonia. The remaining 14 of 16 patients survived retransplantation, but 7 died between days 13 and 105 mostly due to sepsis. Seven patients were discharged from the hospital in good condition and show long-term survival. CONCLUSION: Hepatectomy was able to stabilize the cardiovascular and pulmonary function. This study confirms the beneficial effects of hepatectomy and subsequent liver transplantation as a life-saving procedure in patients with INF complicated by cardiovascular and/or pulmonary instability.

Adolescent↗

Arterial chemoembolization before liver transplantation in patients with hepatocellular carcinoma: marked tumor necrosis, but no survival benefit?

BACKGROUND/AIMS: Hepatic artery chemoembolization was introduced in the treatment of patients with unresectable hepatocellular carcinoma waiting for liver transplantation. The rationale for this preoperative treatment was to control tumor growth during the waiting period and to improve long-term survival. This study aimed to investigate whether preoperative chemoembolization not only induces marked tumor necrosis but also has a survival benefit. METHODS: In this study 21 patients with hepatocellular carcinoma who underwent pretransplant chemoembolization (group I) were compared with 21 historical control patients (group II) without preoperative chemoembolization in a case-control study. The number of pretransplant chemoembolizations in each patient in group I varied between 1 and 5 with a mean of 2.44+/-1.15. In addition, six patients of this group received preoperative systemic chemotherapy. RESULTS: Overall, there were no differences in survival between the groups with and without pretransplant chemoembolization at 1 year (60.8% vs 61.5%) and at 3 years (48.4% vs 53.9%). In group I, three patients developed unexplained severe pneumonia, leading to death very early after liver transplantation. Marked tumor necrosis (>50%) was found in 14 cases in group I. In 6 out of these 14 patients, total tumor necrosis was observed. CONCLUSION: Although preoperative chemoembolization or chemotherapy induced marked tumor necrosis, these patients showed no benefit in survival compared to historical controls, and appeared to be at higher risk of developing immediate postoperative infective complications.

Carcinoma, Hepatocellular↗

Biliodigestive anastomosis after intraoperative irradiation in swine.

A large animal model was established to investigate the feasibility and suitable dosage of intraoperative radiation therapy (IORT) to the hepatic hilum before biliary-enteric anastomosis is performed. Twenty-two Pietrain Hampshire pigs underwent gallbladder and proximal bile duct resection followed by IORT using 20-40 Gy and performing biliary-enteric anastomosis. In the follow-up period of 56 days, pigs developed dose-dependent complications like stenosis of the biliary-enteric anastomosis. Results demonstrate that IORT of the liver hilum up to 20 Gy is safe with acceptable early complications in the presented animal model. The porcine biliary-enteric anastomosis can tolerate intraoperative irradiation up to a dosage of 40 Gy without disruption.

Anastomosis, Roux-en-Y↗