Mycophenolate mofetil reduces calcineurin inhibitor-induced side effects after liver transplantation.
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Calcineurin↗
Biomedical subjects
T Steinmüller
Publications and source records attributed to T Steinmüller.
Mycophenolate mofetil for treatment of ongoing or chronic rejections after liver transplantation.
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Administration, Oral↗
Psychosocial stress of living donors after living donor liver transplantation.
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Adult↗
[Arterial port-catheter dislocation into the duodenum].
Arterial port-catheter dislocations into the duodenum are rare complications. We report on a 64-year-old male with sigmoid-resection for carcinoma, left hemihepatectomy and arterial port-catheter implantation into the common hepatic artery for liver metastases in both lobes and partial dislocation of the port system into the duodenum. Therefore, the port-catheter system had to be explanted after 8 cycles of cytostatic therapy and the duodenum had to be closed by a suture. Six months after surgery the patient felt well, a new singular metastasis in the right liver lobe could be treated successfully by laserinduced thermotherapy. At present the patient has no evidence for another metastasis.
Catheters, Indwelling↗
Combination prophylaxis with Hepatitis B immunoglobulin and lamivudine after liver transplantation minimizes HBV recurrence rates unless evolution of pretransplant lamivudine resistance.
BACKGROUND: Survival rates of hepatitis B patients after liver transplantation improved significantly by introduction of passive immunoprophylaxis. Due to viral escape mutations recurrence still occurs, but recently a combination prophylaxis with hepatitis B immunoglobuline plus lamivudine is evaluated in transplant centers in terms of a further reduction of recurrence rates. PATIENTS AND METHODS: Between 1996 and 2000 a postoperative combination prophylaxis with HBIg and lamivudine was initiated in 44 HBsAg positive liver transplant recipients. In total 14 patients were HBV-DNA negative and 30 were HBV-DNA positive at the time of evaluation. In 22 HBV-DNA positive patients a pre-operative lamivudine treatment (150 mg/die) was started. Five of them developed pre-transplant lamivudine resistance with high viral replication (mean HBV-DNA prior to transplantation 728 +/- 219 pg/ml). In all patients passive immunoprophylaxis was started in the anhepatic phase with application of 10.000 units hepatitis B immunoglobuline. It was continued after seroconversion to HBsAg negativity with an aimed titer of more than 100 U/l and only stopped in case of HBV recurrence. Lamivudine was also continued indefinitely after liver transplantation. RESULTS: Overall recurrence rate in the 44 patients, including retransplantations and patients with pretransplant lamivudine resistance, was 11.5 % under combination prophylaxis. Recurrence was seen only in one of 39 patients (2.6 %) without preoperative lamivudine resistance, in contrast 4 out of 5 patients (80 %) with pre-existing lamivudine resistance suffered from early hepatitis B recurrence. The single patient without preoperative lamivudine resistance, who developed recurrence was pre-transplant HBV-DNA negative without lamivudine treatment, but a postoperative seroconversion to negative HBsAg could not be achieved. The overall 3 year patient survival rate was 91 % in the study population. One patient, who was retransplanted with preoperative lamivudine resistance, died 4.5 months after retransplantation due to hepatitis B recurrence and sepsis, three other patients died for reasons not related to hepatitis B recurrence. Combination prophylaxis was well tolerated in all patients and no severe side effects were observed. CONCLUSION: Combination prophylaxis with hepatitis B immunoglobulin and lamivudine is safe and highly effective in prevention of HBV recurrence after liver transplantation, even in case of positive viral replication. In accordance with the results of other centers it should therefore be the standard regimen. However it fails in the majority of patients with preoperative evolution of YMDD mutations, in which the optimal management has to be determined yet. To minimize preoperative resistance formation universal preoperative antiviral treatment of HBV-DNA positive patients should be replaced by individualized indication for preoperative treatment.
Adult↗
[Orthotopic liver transplantation in case of TIPS stent dislocation].
Transjugular intrahepatic portosystemic shunts (TIPS) are indicated in patients with liver cirrhosis and portal hypertension for treatment of variceal bleeding or refractory ascites. Additionally implantation of stents may lead to stent dislocation or thrombosis in up to 20 % of cases. Detailed information about stent dislocation and its impact on subsequent orthotopic liver transplantation (OLT) is rare regarding the literature. We report on a patient suffering from ethyltoxic liver cirrhosis in which OLT was technically complicated by a thrombosed TIPS stent, dislocated in the portal vein. This stent was implanted prior to OLT due to refractory ascites and partial portal vein thrombosis. We conclude that TIPS stent insertion, especially in liver transplant candidates, should only be performed by radiologists in centers with expertise and experience.
Esophageal and Gastric Varices↗
Preoperative antiviral treatment and postoperative prophylaxis in HBV-DNA positive patients undergoing liver transplantation.
BACKGROUND: Despite passive immunoprophylaxis a significant number of patients, especially if hepatitis B virus (HBV) DNA is positive prior to transplantation, develop HBV recurrence. This number might be reduced by lowering viral replication pretransplant with antiviral agents and by postoperative combination of antiviral agents and passive immunoprophylaxis. PATIENTS AND METHODS: A total of 74 HBV-DNA positive patients who underwent liver transplantation between 9/88 and 4/00 were analyzed retrospectively. Before lamivudine or famciclovir were available, in total 40 patients did not receive any preoperative antiviral therapy. Since 11/93, 17 patients were treated with famciclovir 1500 mg daily, after 4/96 17 patients with lamivudine 150 mg daily prior liver transplantation. Posttransplant all patients received passive immunoprophylaxis aiming at a titer of more than 100 U/liter. In the 34 patients with preoperative antiviral therapy an additional prophylaxis with the respective antiviral agent was applied. RESULTS: Under preoperative famciclovir and lamivudine 30 and 71% of patients became HBV-DNA negative, respectively. Actuarial reinfection rate 2 years after liver transplantation was 48% without antiviral prophylaxis, which was not statistically different from 55% under perioperative famciclovir therapy. In contrast only 18% developed HBV recurrence under perioperative lamivudine treatment. During both antiviral regimens neither pre nor posttransplant severe side effects were observed. CONCLUSION: Perioperative application of famciclovir is not recommendable, whereas lamivudine seems to lower recurrence rates significantly. Whether the observed effect is due to pre- or postoperative application remains to be addressed in further studies. In addition the long-term course has to be awaited.
2-Aminopurine↗
Intraoperative measurement of intact parathyroid hormone in renal hyperparathyroidism by an inexpensive routine assay.
Although the kinetics of intraoperative intact parathyroid hormone (iPTH) are well characterised in primary hyperparathyroidism, no data are available for patients with renal hyperparathyroidism and renal insufficiency, partially because of the high costs of intraoperative quick iPTH measurement. Therefore we evaluated an inexpensive laboratory test with a duration of 18 min for intraoperative use and measured iPTH intraoperatively in 34 patients with renal hyperparathyroidism. Samples were taken before and 5 min and 15 min after parathyroid resection. Blood samples were put on ice immediately and sent to the hospital central laboratory via a pneumatic tube system. The first 76 probes were measured in parallel using three assays: the Nichols Quick PTH, the Roche Elecsys and the Biermann Immulite assay. The subsequent samples were only measured using the Elecsys assay. Determination of iPTH from 76 samples showed a correlation coefficient of 0.997 between the Immulite and Elecsys assay and a correlation coefficient of 0.987 for the Nichols Quick PTH and the Elecsys test. In renal hyperparathyroidism the mean iPTH was 26+/-2% of the starting value 5 min after subtotal parathyroidectomy and 18+/-2% after 15 min. Renal function influenced absolute iPTH values in patients with renal hyperparathyroidism but not relative changes. In patients with terminal renal insufficiency iPTH decreased from 615+/-57 pg/m before preparation to 109+/-13 pg/ml 15 min after subtotal resection. In contrast in patients after kidney transplantation iPTH decreased from a lower starting value of 341+/-94 pg/ml to 58+/-9 pg/ml after 15 min. The iPTH kinetics showed a biphasic clearance of iPTH with an initial dominant half-life of 3.2 min and a terminal half-life of 29.2 min. Half-life did not correlate with renal function. All operations were successful as indicated by an adequate drop in PTH (from 709+/-92 pg/ml preoperatively to 22+/-6 pg/ml at discharge) and calcium (from 2.57+/-0.04 mmol/l to 2.32+/-0.04 mmol/l). In conclusion, intraoperative measurement of iPTH is also reliable in patients with renal hyperparathyroidism. Elimination kinetics are similar to that in patients with primary disease. However, the half-life was not influenced by renal function. The availability of a quick, inexpensive, routine iPTH test might expand its use to renal hyperparathyroidism, specifically for surgical decisions in problem cases.
Female↗
Prospective randomized trial to assess the value of preemptive oral therapy for CMV infection following liver transplantation.
BACKGROUND: With the development of sensitive tests to detect cytomegalovirus (CMV) viremia, preemptive approaches become a reasonable alternative to general CMV prophylaxis. We performed a randomized trial comparing pp65-antigenemia guided preemptive therapy using oral ganciclovir with symptom-triggered intravenous ganciclovir treatment. METHODS: Eighty-eight of 372 liver transplant recipients developed antigenemia early after orthotopic liver transplantation. Twenty-eight symptomatic patients with antigenemia were excluded from randomization and treated with intravenous ganciclovir. Sixty pp65-antigen-positive asymptomatic patients were randomized to receive either oral ganciclovir 3x1 g/day for 14 days (group 1) or no preemptive treatment (group 2). Patients that developed CMV disease were treated with intravenous ganciclovir 2x5 mg/kg body weight for 14 days. The high-risk (Donor+/Recipient-) patients were equally distributed in the two study groups. RESULTS: Three of 30 (10%) patients on oral ganciclovir developed mild to moderate CMV disease compared with 6/30 (20%) patients in the control group. In the Donor+/Recipient- patients, the incidence of CMV disease was 1/6 and 3/7. All disease episodes resolved after intravenous treatment. The 1- and 3-year patient and organ survival was the same in the study groups and in the patients with or without CMV infection. No deaths related to CMV occurred. CONCLUSIONS: The positive predictive value of pp65-antigenemia for the development of CMV disease was very low, and, in 28/88 patients (32%), antigenemia did not precede symptoms. Therefore, pp65-antigenemia is of limited value in deciding on the timing and need for ganciclovir therapy after liver transplantation.
Administration, Oral↗
Liver transplantation for treatment of intrahepatic Osler's disease: first experiences.
BACKGROUND: Intrahepatic Osler's disease with multiple arteriovenous malformations and high intrahepatic shunting may lead to secondary pulmonary hypertension followed by right-heart stress and insufficiency. Until now, therapy with arterial embolization, banding, or ligation of the hepatic arteries is still limited and provides unsatisfactory long-term results. Liver transplantation offers another therapeutic option. METHODS: We report on four patients with intrahepatic involvement of Osler's disease who were liver transplanted between 1995 and 1999. All patients suffered from restricted liver function and right-heart insufficiency with multiple cardiac decompensations. One patient received one course of embolization, and another received six courses of embolization and then banding of the main hepatic artery before transplantation. In both patients, the clinical symptoms improved for only a few months. RESULTS: All patients had high degrees of intrahepatic arteriovenous shunting, and cardiac output measurements were between 8.0 to 13.3 L/min preoperatively. Preoperative mean pulmonary artery pressure was between 24 to 35 mmHg. After liver transplantation, cardiac output and right-heart diameter decreased or normalized and pulmonary pressure reached the normal range after 2 months. All patients received tacrolimus and steroids for primary immunosuppression. In one case, temporary hemodialysis was necessary for 2 weeks after transplantation, but renal function recovered completely. After follow-up time of 12 to 65 months, all patients had normal graft function and good cardiopulmonary condition. CONCLUSIONS: Indication for liver transplantation should be considered in patients with intrahepatic Osler's disease, high arteriovenous shunting with right-heart stress, and restricted liver function before irreversible fixed pulmonary hypertension leads to severe right-heart insufficiency or failure. Our therapeutic regimen of early liver transplantation in the case of intrahepatic Osler's disease in four patients has promising results.
Aged↗
[Surgical procedures and risk factors in therapy of benign multinodular goiter. A statistical comparison of the incidence of complications].
BACKGROUND: The best surgical approach for bilateral resections in the therapy of benign multinodular goiter is still controversial. METHODS: The purpose of this study was to compare different modes of resection concerning differences in complication rates and risk factors influencing the outcome. 2235 thyroid resections for multinodular goiter between 1985 and 1999 were analysed. RESULTS: When compared to bilateral subtotal resection (n = 327; 14.6%), those patients who received lobectomy and contralateral subtotal resection (n = 952; 42.6%) showed a statistically significant higher incidence of temporary hypocalcaemia (22.6% versus 15.9%) only. The "nerve at risk"-analysis demonstrated no significant difference of laryngeal nerve paralysis between the side of lobectomy and subtotal resection, respectively. In comparison to the entire patient population operations for recurrent goiters had an equal operative risk, whereas patients with goiter WHO III or an intrathoracic location had significant higher rates of temporary laryngeal nerve paralysis and hypocalcaemia. CONCLUSIONS: Lobectomy and contralateral subtotal resection offers numerous advantages concerning intraoperative variability and definitive resection of suspicious nodules. With an adequate standardized surgical technique and identification of the laryngeal nerve, the complication rate is comparable to bilateral subtotal resection.
Female↗
[Combined liver and kidney transplantation: indications and long-term follow-up].
INTRODUCTION: In patients suffering from chronic liver and kidney disease combined liver-kidney transplantation is the only therapeutic option. However, in these patients, it is mandatory to distinguish between chronic and acute renal failure prior to transplantation, because acute renal failure may recover after successful liver transplantation. In this study we investigated the indications and results of this combined procedure. PATIENTS AND METHODS: We report on 27 patients who underwent liver and kidney transplantation. The underlying diseases were viral hepatitis (n = 12), polycystic liver and kidney disease (n = 9), primary hyperoxaluria (n = 4), and cryptogenic cirrhosis (n = 2) with end-stage renal disease due to glomerulonephritis, diabetic nephropathy or renal failure caused by nephrotoxicity of immunosuppressive therapy after liver transplantation. Nine patients had lymphocytotoxic antibodies and 5/27 patients had a positive crossmatch pretransplant. RESULTS: One patient died due to bleeding complications, two patients lost the kidney graft due to initial non-function or technical problems. The incidence of acute and steroid-resistant rejections was 60% and 20% in patients with a positive cross-match compared to 32% and 14% in negative cross-match transplants. Only two patients experienced a rejection episode of the kidney (3.7%). No hyperacute rejection of the kidney graft occurred. Long-term patients and graft survival was not impaired in the presence of a positive cross-match. The 1- and 5-year survival rates of patients who underwent combined transplantation was 97% and 93% versus 91% and 83% in patients with liver transplantation alone. CONCLUSION: Combined liver-kidney transplantation is a safe treatment for endstage liver and kidney disease even in the face of a positive cross-match.
Adult↗
[Surgical therapy of liver hilus tumors].
Hilar resections and hemihepatectomies as surgical strategies for hilar cholangiocarcinoma achieve only limited rates of resectability and radicality. Principles of surgical oncology have to be applied in order to increase the numbers of patients undergoing resection as well as their long-term survival. Due to the anatomical architecture of the hepatic hilum and side-specific variations within the biliary tree, right trisectorectomy and principal portal vein resection have the potential to comply with basic rules of surgical oncology, i.e. wide tumor-free margins and a no-touch dissection technique. In our experience, 5-year survival after formally curative right trisectorectomy and portal vein resection is 65% in spite of advanced tumor stages. Resection of the entire biliary tract without dissection of the tumor is possible by combining total hepatectomy, partial pancreatoduodenectomy and liver transplantation. However, even this procedure does still not fully prevent tumor cell dissemination. So far, a putative alteration of tumor cell kinetics due to posttransplant immunosuppressive treatment results in an increased rate of implantation metastases.
Bile Duct Neoplasms↗
Simultaneous carotid artery reconstruction in patients undergoing other surgical interventions.
Abstract. We performed 343 vascular reconstructions of the supraaortal arteries from April 1996 to April 2000. Of these patients, 30 underwent combined vascular reconstructions - 22 combined extrathoracal and 8 combined transthoracal reconstructions. In 15 patients, carotid endarterectomy was combined with other cervical surgical interventions. In 10 patients, the vascular operation was combined with surgical interventions in other regions. No permanent complications were observed 8-52 months postoperatively, with the exception of one hemiparesis in the complex vascular operations. Consequently, we recommend the simultaneous surgical approach after careful individual assessment.
Adult↗
Liver transplantation for recurrent hepatocellular carcinoma in Europe.
BACKGROUND: Patient death after liver resection for hepatocellular carcinoma in cirrhosis is caused by tumor recurrence as well as by complications of cirrhosis. Liver transplantation represents the only simultaneous treatment of tumor and primary liver disease. Certain criteria regarding the number (up to three) and size (up to 5 cm) of tumor nodules have to be observed in order to ensure a low risk of extrahepatic spread or vascular infiltration. Liver transplantation, as treatment for recurrent hepatocellular carcinoma, has to observe the same rules. Only few patients have undergone liver transplantation for recurrent hepatocellular carcinoma in cirrhosis. The reason for this restraint is not fully evident. Poor survival rates after liver transplantation as therapy for advanced hepatocellular carcinoma in the 1980s and an increasing shortage of donor grafts are certainly two factors. METHODS: We report on two cases from our experience and review the European literature. RESULTS: Outcome in a few selected patients has been rather favorable, despite varying approaches. CONCLUSIONS: The only conclusion that can be drawn is that tumor control by liver transplantation is possible in individual patients suffering from recurrent hepatocellular carcinoma. Adult living donor liver transplantation is one way to overcome graft shortage. Other strategies, for example, salvage transplantation, are presented.
Carcinoma, Hepatocellular↗
Corticosteroid-free therapy after tacrolimus-based dual immunosuppression versus cyclosporine-based quadruple-induction therapy.
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Adrenal Cortex Hormones↗
Vascular invasion and histopathologic grading determine outcome after liver transplantation for hepatocellular carcinoma in cirrhosis.
Selection of patients suffering from hepatocellular carcinoma (HCC) in cirrhosis for liver transplantation follows limits of number and diameter of tumor nodules. It has not been investigated whether there is a correlation of these parameters with vascular invasion. From 1989 to 2000, 1,188 liver transplantations were performed in 1,087 patients, including 120 patients (11%) with an HCC in cirrhosis. Selection criteria were a maximal diameter of up to 5 cm if the tumor appeared to be uninodular or of up to 3 cm in the case of 2 or 3 nodules. The postoperative mortality rate was 1.7%. One-, 5-, and 10-year survival was 90%, 71%, and 60%, respectively. In 940 transplantation patients without an HCC, these rates were 93%, 87%, and 83% (P < .0001). Vascular invasion and histopathologic grading were identified as prognostic parameters by multivariate analysis. In a logistic regression analysis, histopathologic grading and maximal diameter showed a significant correlation with a vascular invasion. Analyzing tumors larger than 5 cm, i.e., tumors not fulfilling the selection criteria as a result of diagnostic inaccuracy or progression thereafter, the rates of vascular invasion were significantly (P < .01) lower in patients suffering from well-differentiated tumors (25%) when compared with moderately and poorly differentiated tumors (100%). Liver transplantation is a safe and effective long-term treatment for small HCC in cirrhosis. Tumor diameter and number of nodules in correlation with the histopathologic grading were predictive of a vascular invasion only in HCC larger than 5 cm.
Adult↗
Occurrence and clinical outcome of lamivudine-resistant hepatitis B infection after liver transplantation.
Lamivudine treatment of hepatitis B after orthotopic liver transplantation (OLT) is often accompanied by fast viral-resistance formation. Although no clinical data are available, in vitro data indicate that lamivudine-resistant reinfection has a mild course because of defective viral replication. Between 1996 and 1999, a total of 34 patients were treated with lamivudine because of hepatitis B recurrence after OLT. All patients developed reinfection despite long-term passive immunoprophylaxis with hepatitis B immunoglobulin, diagnosed by positive hepatitis B surface antigen and positive hepatitis B virus (HBV) DNA. Before treatment with lamivudine, 21 of these patients underwent a course of famciclovir and developed resistance. Monthly laboratory tests and sequential liver biopsies were performed during the follow-up period. Nineteen of 34 patients (56%) developed lamivudine resistance during the follow-up period of 12 to 49 months. One- and 3-year graft survival rates after the diagnosis of lamivudine resistance were 89% and 66%, respectively. In most cases, lamivudine resistance was associated with high viral replication (3,012 +/- 574 pg/mL 1 month after the diagnosis of lamivudine resistance); however, liver enzyme levels were only moderately elevated (alanine aminotransferase [ALT], 45 +/- 16 U/L). Only 3 patients (15%) showed a rapid increase in ALT level to more than 500 U/L within 3 months after resistance developed. All other patients had mildly elevated liver enzyme levels during the first 6 to 8 months after lamivudine resistance. In the later course, liver enzyme levels increased in most patients. Fourteen patients with elevated transaminase levels were switched to lamivudine plus interferon alfa (n = 8) or lamivudine plus famciclovir therapy (n = 6). This combination was successful in most cases, decreasing HBV DNA and liver enzyme levels. Four patients with lamivudine resistance died during follow-up, only 1 patient because of HBV reinfection. In addition, 2 patients underwent retransplantation because of hepatitis B cirrhosis of the first graft. Compared with historic courses of wild-type recurrence, lamivudine-resistant reinfection is characterized by a milder clinical course. Fulminant cases were not observed; however, in three cases, chronic liver failure developed. The combination of different antivirals diminished viral replication after lamivudine resistance. In the future, new antiviral agents, such as adefovir, might further expand therapeutic options.
Drug Resistance, Microbial↗