In situ splitting of deceased donor livers: an additional option for patients with hepatocellular carcinoma in cirrhosis.
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Biomedical subjects
Publications and source records attributed to Nils R Frühauf.
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The pig is a common large animal for experimental settings in many fields of surgery. In experimental surgery, there is a need for different narcotic procedures depending on the complexity of the surgical investigation. Narcotic procedures have to be safe, easy to handle, and should not influence the experimental results. We hereby present important aspects of handling and narcotic procedures for pigs. The aim of this publication is to supply an introduction for young surgical investigators who are planning or already have started investigations using pigs as an experimental animal. This publication is based on our institutional experience of narcotic and surgical procedures in more than 400 cases.
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HYPOTHESIS: Currently, standard planning for hepatic resection is based on the schematic description of the functional anatomy of the liver according to Couinaud, and on the evaluation of 2-dimensional computed tomographic imaging of the liver. Recent developments in image-based computer assistance allow patients' individual functional liver anatomy to be computed from mathematical analysis of standard multidetector computed tomographic scans. An intended resection can be performed virtually under realistic anatomic conditions, and the influence of different resection planes on blood supply and drainage within the remaining liver parenchyma can be calculated by a computer-assisted risk analysis. We evaluated the impact of computer-assisted risk analysis on operation planning for major hepatectomies, in particular on extent of resection or need for vascular reconstruction. DESIGN: Prospective cohort study. SETTING: Academic tertiary care referral center. PATIENTS: Twenty-five consecutive patients admitted to the hospital for major hepatectomy, of whom 4 had tumors deemed unresectable by both methods. INTERVENTIONS: Two-dimensional computed tomography was used to calculate the volume of the future liver remnant with the intended resection line manually determined, and then the volume of the future liver remnant was calculated again by computer-assisted risk analysis as the remaining liver volume not being devascularized but having both portal venous blood supply and hepatic venous drainage. MAIN OUTCOME MEASURES: The difference between the remaining functional liver volumes calculated by the 2 methods. RESULTS: The deviation between liver volumes determined by 2-dimensional computed tomography and by computer-assisted risk analysis was less than 20% in 14 of 21 patients, between 20% and 30% in 3, between 30% and 40% in 2, and 41% and 43% in 1 patient each. The most extensive deviations were found in extended left hepatectomy or when left hepatectomy was combined with additional wedge resection in the right lobe. In 7 cases, all with a deviation greater than 20%, the results of computer-assisted risk analysis led to a change of operation planning with regard to the extent of resection (n = 3) or the need for vascular reconstruction (n = 4), although in 1 of these cases resection was not performed because of peritoneal carcinomatosis. CONCLUSIONS: Image-based computer assistance allows for areas at risk for devascularization or venous congestion to be identified and precisely calculated before resection. In selected cases with small liver remnants, operation planning may be improved substantially by preoperative computer-assisted risk analysis.
The role of liver biopsy (LB) in donor selection for adult living donor liver transplantation remains controversial, since the procedure is associated with additional potential risks for the donor. From April 1998 to August 2004, 730 potential living donors for 337 adult recipients underwent our multistep evaluation program. In 144 candidates, LB was performed. LB was obtained in a percutaneous ultrasound-guided fashion by means of Menghini needle (32 cases) or Tru-cut needle (112 cases). The biopsy specimen was preserved in 5% formalin and processed with hematoxylin & eosin-stained sections. Thirty-one (21%) of 144 candidates who underwent an LB had a positive finding at histological examination that induced their exclusion from donation, of whom 21 had liver steatosis of varying kind and grade (10%-80%) and 10 had a nonsteatotic hepatopathy (non-A-D hepatitis in 6 cases, diffuse granulomatosis in 2, schistosomiasis in 1, fibrosis in 1). The only observed major complications related to LB were 2 intraparenchymal haematomas, both of which resolved spontaneously within a few months. In conclusion, based on these findings, we believe that preoperative LB in the donor selection for adult LDLT is necessary, once the initial donor screening and noninvasive evaluation is complete. Because other screening modalities can be unreliable, without preoperative LB a fraction of potential donors will be operated on inappropriately, risking both donor and recipient. The main objective of LB should be to ensure the donor's safety more than the preservation of the graft function.
OBJECTIVE: To evaluate the role of extended hepatectomy in locally advanced intrahepatic cholangiocarcinoma (ICC). SUMMARY BACKGROUND DATA: ICC is a rare tumor which has to be clearly distinguished from hepatocellular carcinoma and extrahepatic bile duct carcinoma. It is believed that long-term survival can only be achieved by surgical resection. METHODS: Between April 1998 and March 2003, 50 patients with locally advanced ICC (tumor involvement of more than 4 liver segments) underwent surgical exploration. Data were analyzed with regard to patients' characteristics, intraoperative details, pathologic findings, and outcome measured by tumor recurrence, treatment of recurrence, and survival. RESULTS: Resectability rate was 27 of 50 (54%). There were 19 extended right and 8 extended left hepatectomies. In addition, in 16 patients the following 29 procedures were performed: resection of hilar bifurcation (n = 12), partial resection of diaphragm (n = 6), partial resection of vena cava (n = 4), resection and reinsertion of left liver vein (n = 1), portal vein resection (n = 5), resection and reconstruction of right hepatic artery (n = 1). Complete tumor removal (R0-resection) was achieved in 16 patients. In 11 cases, there was microscopic tumor at the cutting margin (R1-resection). Following resection, the overall 1- and 3-year-survival rates were 69% and 55%. After R1-resection and explorative laparotomy, median survival was 5 and 7 months, respectively. Following R0-resection, the calculated median survival and 1- and 3-year-survival rates are 46 months, 94% and 82% (P = 0.0039; log-rank test). Tumor recurred in 6 of 16 patients, and so far 2 patients died of recurrence 28 and 46 months after operation. CONCLUSIONS: R0-resection can provide prolonged survival, even in patients with advanced ICC. In particular in solitary tumors without vascular invasion (UICC stage I, sixth classification) there is a major chance for long-term survival and cure. The poor results after R1-resection and the high operative morbidity do not justify palliative resections but underline the need for an improved preoperative assessment of resectability, as well as an aggressive intraoperative approach, to achieve complete tumor resection.
BACKGROUND: We report on our experiences with orthotopic liver transplantation (OLT) in HIV-infected patients. Between July 1998 and October 2001, five HIV-infected patients underwent OLT because of virus-induced liver cirrhosis. One patient suffered from hepatitis B virus (HBV)-, three patients from hepatitis C virus (HCV)- and one patient from HCV/HBV/HDV-related cirrhosis (HDV, hepatitis D virus). The mean duration of HIV infection was 15 years. Patients were prospectively followed up with a mean duration of 25.6 months. RESULTS: Three patients died 3, 10 and 31 months after OLT, respectively, due to graft failure. The causes of graft failure were: recurrent thrombosis of the hepatic artery, HCV-associated cholestatic hepatitis and chemotherapy-induced liver damage due to Hodgkin's disease, which was diagnosed 17 months after OLT, in addition to chronic HCV disease. The two survivors show a stable liver function and non-progredient HIV infection under antiretroviral therapy 61 and 23 months after OLT, respectively. CONCLUSIONS: A medium- or even long-term survival after OLT can be achieved in HIV-infected patients without progression of HIV disease under antiretroviral therapy. However, in our study three out of five patients died due to graft failure. Therefore, prognostic criteria have to be defined for the selection of HIV-infected patients, who may benefit from OLT.
BACKGROUND: Liver resection is the only potential cure for patients with colorectal liver metastasis. However, more than 30% of patients will develop tumour recurrence, probably caused by tumour cells disseminated before or during surgery. As prevention of cell dissemination is barely obtainable, alternative concepts have to be discussed. METHODS: The potential of leukocyte adhesion filters for the removal of cytokeratin positive cells (CK+) from blood was studied in 18 patients undergoing liver resection for colorectal liver metastasis. Blood sampling was done via a liver venous catheter during hepatic mobilisation. Filtration was done with an in-line WBF2 filter system. To define the relation between surgery and cell release we compared patients' pre-operative and intra-operative blood and bone marrow (BM) samples with their CK expression using immunochemical staining. RESULTS: CK+ cells were detected in BM samples of nine of 14 patients before surgery, indicating early dissemination. In ten of 18 patients CK+ cells were detected in blood samples during hepatic mobilisation; all ten patients underwent major liver surgery (R0 resection). In those patients recurrent disease was observed more often (P < or = 0.05). In 17 of 18 patients CK+ cells were not detectable after filtration procedure, which indicated cell adhesion to the filter medium. CONCLUSION: Liver resection due to metastasis leads to frequent intra-operative tumour cell shedding. As the detection of CK+ cells is correlated with disease recurrence, modification of surgical techniques to prevent cell dissemination, and additional therapeutic concepts such as advanced filtration technology, have to be discussed.
BACKGROUND: Bioartificial liver support systems providing a bridge to transplantation or even a definitive treatment of acute hepatic failure are a current focus of research. Different devices are used, although an impact on patient survival is doubtful for the time being. After developing a new flat membrane bioreactor, further preclinical studies have become necessary. Existing animal models of fulminant hepatic failure show common difficulties in defining a reproducible loss of functional liver tissue while considering systemic side effects. We now present a reproducible model with total hepatectomy in pigs, suitable to test the safety and efficacy of liver support systems. METHODS: Twelve pigs underwent total hepatectomy by using silicone tubes and a Y-adapter as vascular prosthesis; intracranial pressure was measured via a subdural probe. Anhepatic pigs were monitored under general anesthesia until death occurred. All were treated with a new flat membrane bioreactor (FMB) that contained porcine hepatocytes in 6 of the 12 cases. RESULTS: Our hepatectomy technique proved to be successful without requiring venovenous bypass circulation. Mean vascular clamping time was 9 minutes. The mean survival time was longer in animals treated with hepatocyte-equipped bioreactors than in untreated animals (24.8 +/- 4.3 vs 16.4 +/- 4.7 hours), which already showed increased intracranial pressure after 10 to 12 hours. Serum albumin levels indicated stable cell-specific functions of the FMB. CONCLUSIONS: The described technique of total hepatectomy is a well-reproducible animal model. The presented FMB maintained stable cell-specific functions and is a safe and efficient device.
Currently, orthotopic liver transplantation (LT) represents the treatment of choice for most end-stage liver diseases. Advances in surgical techniques and immunosuppressive therapy have markedly increased its success. However, the main obstacle in LT remains the lack of donor organs with a current mortality rate for patients on the waiting list of up to 20%. This chapter focuses on developments in SLT techniques and living-donor LT to alleviate this problem. SLT yields a net gain of organs, in that it uses one organ to save either an adult and a child, or two adults. The initially used technique of ex-situ splitting is being replaced progressively by the in-situ splitting technique, which yields better preserved grafts. The latest step has been the introduction of living-donor segmental LT. The systematic combination of both techniques may lead to a further reduction of mortality for patients on the waiting list for LT.
BACKGROUND: Based on the patient history of a 62-year-old man with a centrally located hepatocellular carcinoma we describe the potential influence of three-dimensional computed tomography (3D CT) on operation planning in extended left hepatectomy. METHOD AND RESULTS: By 3D reconstruction of the liver, not only variations of the intrahepatic vascular structure but also the number and extent of portal venous segments, as well as their relation to hepatic veins, can be visualized. Thus, areas at risk for either devascularization or venous congestion may be identified prior to liver resection. This is particularly important in extended hepatectomies with a small liver remnant, where already minor complications may have fatal consequences. CONCLUSION: In these resections, operation planning may be improved substantially by pre-operative 3D reconstruction.
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Neurotoxicity is a well-known side effect of tacrolimus-based immunosuppression after liver transplantation. Until now, only 31 cases of immunosuppression-associated leukoencephalopathy in liver transplant recipients reported in the literature are related to tacrolimus therapy. We report a patient who developed a posterior leukoencephalopathy syndrome, secondary to tacrolimus-based immunosuppression, after living donor liver transplantation. The special features of this case are the sudden and late onset of neurologic symptoms, a persistent comatose state, and increased signal intensity in follow-up MRI.
Ornipressin is a vasopressin analogue that can cause potent splanchnic vasoconstriction. It has been shown that, in combination with albumin infusion, ornipressin is able to reverse hepatorenal syndrome. However, its clinical use is limited by possible severe ischaemic complications. In our case, a 47-year-old man received a right hemihepatectomy for cholangiocellular carcinoma. On post-operative day three, he developed hepatorenal syndrome with ascites, peripheral oedema and oliguria (250-500 ml/day). Serum creatinine was increased to 3.5 mg/dl. The patient was treated with terlipressin, another vasopressin analogue with fewer side effects than ornipressin, (1 mg every 4 h intravenously) and hydroxyethyl starch (500 ml/day). Urine output increased to 3000 ml/day, serum creatinine decreased to normal range within 4 days and ascites and oedema disappeared. We hereby report the first case of successful treatment of hepatorenal syndrome with terlipressin and hydroxyethyl starch, which appears to be a safe and effective treatment.
There is a need for prolonged anesthesia procedures in experimental surgery. Animals in this study received fentanyl, Midazolam, and Propofol administered by continuous intravenous infusion for anesthesia along with controlled ventilation. Time of anesthesia was 413 +/- 95 min. Animals could be extubated 20 +/- 12 min after operation. Animals recovered completely from anesthesia by day 1 after surgery with almost normal physical activity. This study clearly shows that intravenous infusion anesthesia is safe and easy to handle in prolonged anesthesia for experimental surgery in swine. This anesthetic protocol can also be used for intraoperative transportation.
The two most promising surgical animal models of fulminant hepatic failure (FHF) for investigation of the safety and efficacy of new treatment modalities were analyzed in a porcine study. Animals underwent total hepatectomy or devascularization of hepatic artery and portal vein followed by portocaval (PC) shunting. Survival time, technical feasibility, safety, and reproducibility of the models were investigated. Devascularization seems to be most useful for studying the development and treatment of FHF caused by ischemia and its side effects. Total hepatectomy is superior for investigation of the anhepatic status and treatment of FHF by bioartifical liver support systems.
Epithelioid hemangioendothelioma of the liver is very uncommon and is quite difficult to distinguish from a cholangiocarcinoma or a metastatic liver disease by imaging diagnostics. However, the histological features are characteristic for this soft-tissue tumor. Although liver tumor is usually multifocal and a liver resection is not possible in most cases, we report a case of a multifocal epithelioid hemangioendothelioma of the liver that was completely resected. The tumor was associated with a solitary extrahepatic lesion, which was first discovered six months after the liver resection and which was also resected.
BACKGROUND/AIMS: Liver transplantation (LTx) is recognized as the treatment of choice for small hepatocellular carcinomas (HCC) in patients with end-stage liver failure. However, because of limited organ availability, not all those who qualify can benefit from full-size LTx. METHODOLOGY: Over a 28-month period, we transplanted 6 deceased donor split liver allografts in stable recipients with HCC and cirrhosis. RESULTS: There were 5 men and one woman with a median age of 60 years. Median waiting time to LTx was 82 days. Extended right split grafts (segments I, IV-VIII) were transplanted in 5 patients. One patient received a right split graft. In situ harvesting was performed in 4 instances and ex situ in the remaining 2. Median cold ischemia time was 10 hours. Primary non-function was not observed. Median intensive care unit stay was 4 days. There were neither vascular nor biliary complications. The postoperative course was uneventful in half of the patients. Two patients were re-operated because of an abscess caused by a liver necrosis in the marginal zone of segment IV. One patient died for reasons unrelated to liver function or to the surgical intervention. The remaining 5 patients are alive after a median follow-up of 20 months. CONCLUSIONS: Deceased donor split LTx constitutes an additional option for patients with HCC and cirrhosis. The potential risks of using "split livers" as well as the potential benefits of transplanting patients unlikely to survive the waiting list period must be evaluated on an individual basis.