Reconstruction of bile duct using the side-to-side anastomosis in 389 orthotopic liver transplantations.
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Adolescent↗
Biomedical subjects
G Blumhardt
Publications and source records attributed to G Blumhardt.
Rejection episodes after liver transplantation during primary immunosuppression with FK506 or a cyclosporine-based regimen: a controlled, prospective, randomized trial.
As part of a European multicenter study to investigate the potency of FK506 in primary immunosuppression after liver transplantation, this comparison with our conventional cyclosporine-based quadruple regimen was carried out as a controlled, prospective, randomized trial. The 121 patients entering the study were randomly assigned to receive immunosuppressive regimens consisting either of FK506 and prednisolone (FK/n = 61) or of cyclosporine, prednisolone, azathioprine, and a 7-day course of rabbit antithymocyte globulin (CsA/n = 60). Rejection was suspected in the case of scant production of light bile or biochemical graft dysfunction, without evidence of vascular, biliary, or infectious complications. A liver biopsy for confirmation of the diagnosis was obtained each time. Initial therapy entailed a 3-d course of high-dose methyl-prednisolone. Steroid resistant rejections were treated with OKT3 monoclonal antibody or, in the group of primary CsA administration, conversion to FK506 as another treatment option. One-year patient (FK: 90.2%; CsA: 96.7%) and graft survival (FK: 88.5%; CsA: 91.7%) did not differ significantly. Overall, 41 patients (33.9%) experienced 50 acute, cellular rejection episodes (RE) [FK: 25 RE in 21 patients (34.4%); CsA: 25 RE in 20 patients (33.3%)]. The histological grading ranged from mild (FK: 14/25; CsA: 8/25) to moderate (FK: 9/25; CsA: 16/25) and severe (FK: 2/25; CsA: 1/25): not significantly different between the two groups. In the CsA-based group, three additional rejection episodes were classified as early chronic (n = 1) and chronic rejection (n = 2).(ABSTRACT TRUNCATED AT 250 WORDS)
Adolescent↗
Long-term follow-up of hepatitis B virus-infected recipients after orthotopic liver transplantation.
The outcome after OLT was studied in 53 patients with chronic hepatitis B virus (HBV)* infection, 15 of whom had, in addition, evidence of hepatitis delta virus (HDV) superinfection. Nine of 53 patients received short-term immunoprophylaxis with anti-hepatitis B surface (HBs) hyperimmunoglobulin up to 1 week after OLT and 44 of 53 patients received long-term unlimited immunoprophylaxis. Eight of 9 (89%) patients with short-term immunoprophylaxis showed reactivation of replication with HBV DNA in serum > 10 pg/ml independently of the preoperative HBV DNA level and HBsAg reappeared in all cases. Four (44%) patients in this group lost their graft because of fulminant hepatitis or cirrhosis and required retransplantation, and 2 patients (22%) died after reinfection in the second graft. Nineteen of 44 (43%) patients with long-term immunoprophylaxis developed HBV values > 10 pg/ml after transplant and 12 of 44 (27%) became HBsAg+ again. Most of them had quantifiable HBV DNA levels before OLT. Retransplantation was required in 5 of 44 (11%) patients and 4 of them died after HBV recurrence. The frequency of HBV reactivation and the development of viral hepatitis after OLT were associated with the preoperative presence of HBV, as determined by the molecular hybridization assay. With nested polymerase chain reaction, all 53 patients were HBV-DNA+ in the serum before and after OLT. with just one exception, none of the patients with HDV superinfection died, in spite of increased HDV replication after OLT. The data indicate that long-term immunoprophylaxis with anti-HBs hyperimmunoglobulin after OLT improves the prognosis in HBV-infected patients. The preoperative detection of HBV DNA in serum by molecular hybridization assay is correlated with graft infection and represents a prognostic parameter. The presence of HDV may have a protective effect after OLT.
Adult↗
Neurotoxicity after orthotopic liver transplantation. A comparison between cyclosporine and FK506.
Neurotoxicity represents a serious complication following orthotopic liver transplantation. Neurotoxicity may be evoked by various perioperative factors or develop due to drug-specific toxicity of immunosuppression. We evaluated the incidence of neurotoxicity in 121 patients, 61 randomly assigned to FK506 and 60 to CsA-based immunosuppression. The incidence of moderate or severe neurotoxicity was markedly higher in patients treated with FK506 in the early postoperative period (21.3% vs. 11.7% in patients receiving CsA), after retransplantation (100% vs. 0% in patients receiving CsA), and late (8 of 10 patients; P < or = 0.05 vs. CsA). Furthermore late neurotoxicity was highly associated with severe infections and MOFS, which had a lethal outcome in more than 50% of the patients. Patients who subsequently died developed neurologic symptoms in 67% of the cases. These patients also experienced moderate or severe neurotoxicity significantly more often in the early postoperative period compared with patients with a successful outcome (50% vs. 17.3%; P < or = 0.01). However, various blood and serum parameters, including ALT, bilirubin, urea, creatinine and glucose, when analyzed alone or in multivariate fashion, also correlated significantly with the incidence and severity of early postoperative neurotoxicity, indicating that neurotoxicity following LTX may be caused by various factors and is not exclusively a drug-specific side effect of immunosuppression.
Adolescent↗
Nephrotoxicity following orthotopic liver transplantation. A comparison between cyclosporine and FK506.
Nephrotoxicity represents a serious side effect of immunosuppression following liver transplantation. In order to compare the nephrotoxic action of CsA and FK506 in a clinical setting, we evaluated the incidence of early and late nephrotoxicity in 121 patients, 60 of whom were randomly assigned to CsA- and 61 to FK506-based immunosuppression. Early postoperative renal insufficiency (between PODs 0 and 30; SCr 1.5-3 mg/dl) was observed to a similar extent in patients treated with CsA (38.3%) and FK506 (42.6%). Early postoperative acute renal failure (ARF) (SCr > 3 mg/dl) was observed in 18.0% of patients in the FK506 treatment group and 18.3% of patients receiving CsA therapy. Approximately half the patients with ARF required hemodialysis (CsA: 11.7%; and FK506: 8.2%). All patients with early postoperative ARF requiring hemodialysis survived for more than one year. New onset of late ARF (between PODs 30 and 365) was observed in 6.6% of patients receiving FK506 therapy and in 1.7% in the CsA treatment group as a result of severe infection with multiple organ failure syndrome (MOFS). There was 100% mortality in patients with late ARF requiring hemodialysis. Etiology and prognosis of early and late ARF seem to be completely different. Early ARF was associated with severe coagulopathy and a rise in bilirubin and free hemoglobin, and was accompanied by impaired liver function. Mean onset of hemodialysis in CsA-treated patients was POD 1 and in FK506-treated patients POD 6, which disclosed a different time course of drug-specific nephrotoxicity of CsA and FK506 in early ARF. In contrast, late ARF occurred in both treatment groups only as a part of the MOFS in association with severe infections, an observation consistent with the assumption of overimmunosuppression rather than a primary nephrotoxic effect. Late renal insufficiency appeared in 23.3% of CsA- and in 29.4% of FK506-treated patients, and represented a slowly progressing form of drug-specific nephrotoxicity of CsA and FK506. These preliminary results demonstrate a similar outcome in terms of both early and late nephrotoxicity, but longer follow-up will delineate the overall efficacy and toxicity in humans.
Acute Kidney Injury↗
Extended bile duct resection--a new oncological approach to the treatment of central bile duct carcinomas? Description of method and early results.
Since the results of surgical resection and transplantation in the treatment of central bile duct carcinomas have been poor and neither radiotherapy nor chemotherapy has shown promising results, a new attempt to achieve curative resection has been made to combine liver transplantation with the Kausch-Whipple operation. With this operation the complete biliary system can be resected without touching the region of the hepatoduodenal ligament. Our intention is to avoid tumor cell spread by this "no-touch technique." Tumor cell spread is very likely to occur with the commonly used technique of close dissection near the centrally located carcinoma. In the seven patients operated on so far, we observed that the combination of total hepatectomy, partial duodenopancreatectomy and liver transplantation can be performed with fewer postoperative problems than "cluster transplantation" and probably has the same oncological benefit in terms of more radical resections at least for central biliary carcinomas. Theoretically, the radicalness of the resection should be greater than with liver transplantation or bile duct resection alone. Whether this concept helps to achieve better results in surgical treatment of early Klatskin tumors can only be evaluated after a longer follow-up. So far, six of seven patients have survived the operation without great problems and have been discharged from the hospital. The quality of life after this procedure seems to be better than with total pancreatic resection or even with replacement of the pancreas.
Adult↗
Donor criteria in hepatic transplantation.
The early outcome of 201 liver grafts transplanted consecutively between September 1988 and November 1991 was investigated retrospectively. Donors were categorized according to their hospitalization periods in an intensive care unit (ICU) prior to harvesting, their causes of death, and the variables generally believed to be critical in liver donation, such as arterial hypotension (n = 69; 34.3%), cardiopulmonary resuscitation (n = 20; 9.9%), elevated serum-aminotransferases (s-AT) (n = 11; 5.5%), or an age over 50 years (n = 16; 8.0%). Ninety-one donors (45.3%) spent less than 24 h in an ICU; 29 donors (14.4%) and 14 donors (7.0%) had hospitalization periods generally considered critical of 4-6 days and more than 6 days, respectively. The most common causes of death were subarachnoidal bleeding (n = 70; 34.8%), isolated head injuries (n = 68; 33.8%), and polytraumata (n = 33; 16.4%). The postischemic hepatocellular damage was evaluated comparing peak post-transplant s-AT, which did not differ significantly between groups; nor did donor and recipient ages or cold ischemia times. Fourteen grafts (7.0%) showed a reversible preservation injury presenting with post-transplant s-AT elevated above 2000 IU/l. Five cases (2.5%) of a primary non-functioning graft (PNF) underwent early retransplantation successfully. Serum-aminotransferases (AST: 4944 +/- 2280 IU/l; ATL: 3186 +/- 1918 IU/l) were significantly (P < 0.01) elevated as compared to primary functioning grafts (AST: 699 +/- 935 IU/l; ALT: 620 +/- 701 IU/l). The donor structure of both groups reflected the distribution of variables in the entire collective. No significant overrepresentations were observed.(ABSTRACT TRUNCATED AT 250 WORDS)
Adolescent↗
Bacterial and fungal colonization and infections using oral selective bowel decontamination in orthotopic liver transplantations.
Bacterial and fungal infections are a major cause of morbidity and mortality after orthotopic liver transplantation. In the immunocompromised host, infections are thought to arise from the gut, which is almost always colonized with potential pathogens. Using oral selective bowel decontamination (SBD), potential pathogens can be eradicated from the gut and infections prevented. In this catamnestic study we have reviewed gastrointestinal colonization, bacterial and fungal infections, and bacterial resistance to standard antibiotics in our first 206 liver transplant patients while under SBD. With few exceptions, gram-negatives were eradicated from the gastrointestinal tract and secondary colonization was inhibited. In spite of unsatisfactory elimination of Candida, probably because nystatin doses were too low, Candida infections were rare (n = 4) and none was fatal. One and two-year survival rates were 93% and 92%, respectively. The bacterial and fungal infection rate was 27.8% with an infection-related mortality of 1.95%. Infections with aerobic gram-positive bacteria prevailed and only 11 gram-negative and 11 fungal infections occurred; among the latter, Aspergillus and Mucor were the most serious and responsible for three of the six deaths in this series. With regard to the development of resistance, we found an increasing number of enterococci and coagulase-negative staphylococci resistant to ciprofloxacin and imipenem, respectively, but unlikely as a consequence of SBD.
Administration, Oral↗
Technique and results of biliary reconstruction using side-to-side choledochocholedochostomy in 300 orthotopic liver transplants.
OBJECTIVE: The authors evaluated the complication rate and outcome of side-to-side common bile duct anastomosis after human orthotopic liver transplantation. SUMMARY BACKGROUND DATA: Early and late biliary tract complications after orthotopic liver transplantation remain a serious problem, leading to increased morbidity and mortality. Commonly performed techniques are the end-to-end choledochocholedochostomy and the choledochojejunostomy. Both techniques are known to coincide with a high incidence of leakage and stenosis of the bile duct anastomosis. The side-to-side bile duct anastomosis has been shown experimentally to be superior to the end-to-end anastomosis. The authors present the results of 316 human liver transplants, in which a side-to-side choledochocholedochostomy was performed. METHODS: Biliary tract complications of 370 transplants in 340 patients were evaluated. Three hundred patients received primary liver transplants with side-to-side anastomosis of donor and recipient common bile duct. Thirty-two patients with biliary tract pathology received a bilioenteric anastomosis, and in eight patients, side-to-side anastomosis was not performed for various reasons. Clinical and laboratory investigations were carried out at prospectively fixed time points. X-ray cholangiography was performed routinely in all patients on postoperative days (PODs) 5 and 42. In patients with suspected papillary stenosis, endoscopic retrograde cholangioscopy and papillotomy were performed. RESULTS: One biliary leakage (0.3%) was observed within the early postoperative period (PODs 0 through 30) after liver transplantation. No stenosis of the common bile duct anastomosis was observed during this time. Late biliary stenosis occurred in two patients (0.6%). T tube-related complications were observed in 4 of 300 primary transplants (1.3%). Complications unrelated to the surgical technique, including papillary stenosis (5.7%) and ischemic-type biliary lesion (3.0%), which must be considered more serious in nature than complications of the anastomosis or T tube-related complications, were observed. Papillary stenosis led to frequent endoscopic interventions and retransplantations in 1.3%. CONCLUSIONS: Side-to-side common bile duct anastomosis represents a safe technique of bile duct reconstruction and leads to a low technical complication rate after human orthotopic liver transplantation. Ischemic-type biliary lesion evoked by preservation injury, arterial ischemia, cholestasis, and cholangitis may represent a new entity of biliary complication, which markedly increases the morbidity after human liver transplantation. Therefore, this complication should be the subject of further research.
Adolescent↗
Nephrotoxicity after orthotopic liver transplantation in cyclosporin A and FK 506-treated patients.
Nephrotoxicity represents a serious side-effect of immunosuppression following orthotopic liver transplantation. In order to preserve the therapeutic potential of cyclosporin (CsA) and FK 506 in human liver transplantation and to differentiate the nephrotoxic action of either drug in a clinical setting, we evaluated the incidence of early and late nephrotoxicity in 121 patients, 60 randomly assigned to CsA- and 61 to FK 506-based immunosuppression. Early postoperative renal insufficiency (between POD0 and 30; SCr 1.5-3 mg/dl) was observed to a similar extent in patients treated with CsA (36.7%) and FK 506 (42.6%). Early postoperative acute renal failure (ARF; SCr > 3 mg/dl) occurred in 18.3%, regardless of the immunosuppressive management. Approximately 50% of patients with ARF required hemodialysis (CsA: 11.7%; and FK 506: 8.3%). Mean onset of hemodialysis in CsA-treated patients was POD1 and in FK 506-treated patients, POD6, which demonstrated a different time course of drug-specific nephrotoxicity of CsA and FK 506 in early ARF. All patients with early postoperative ARF requiring hemodialysis survived more than 1 year (100% survival). New onset of late ARF (between POD30 and 365), however, occurred in 6.5% under FK 506 and in 1.7% under CsA immunosuppression due to severe infections with the multiple organ failure syndrome. This observation was consistent with the assumption of over-immunosuppression rather than a primary nephrotoxic effect. Mortality of patients with late ARF requiring hemodialysis was 100%. Late renal insufficiency appeared in 23.3% of CsA- and in 29.4% of FK 506-treated patients, and represented a slowly progressing form of drug-specific nephrotoxicity. These preliminary results demonstrated a similar outcome in terms of early and late nephrotoxicity, but longer follow-up will delineate its overall efficacy and toxicity in humans.
Creatinine↗
The correlation of serum hyaluronan of liver donors with posttransplant liver function.
Primary organ non-function occurs in 2-17% of patients after liver transplantation (LTX). Liver function tests focus on hepatocytes, underestimating the importance of non-parenchymal cells such as endothelium. Liver endothelium metabolises hyaluronan (HA). The function of endothelium can be estimated by measuring the concentration of HA in serum. We evaluated two organ donor groups, the first with HA levels below 200 microg/l and the second with HA levels above 200 microg/l. Both groups degraded more than 60% of HA during the first 6 h after reperfusion. Determination of hyaluronic acid in patients after LTX gives valuable information about the functional state of liver endothelium. It does not necessarily parallel the release of transaminases. In this study, there was no correlation between the levels of HA in the donor and posttransplant liver function. High HA in organ donors are most likely a consequence of different degrees of trauma and a higher release of HA into the circulation rather than impaired endothelial function.
Adult↗
Results of liver transplantation in acute liver failure caused by viral hepatitis.
Fulminant liver failure due to acute viral hepatitis is the most common emergency indication for liver transplantation. The postoperative course is highly correlated with the type and duration of infection. The complication rate is lowest in fulminant hepatitis B patients and highest in subacute hepatitis C/NANB patients.
Bilirubin↗
Selection of small hepatocellular carcinoma improves long-term results of hepatic transplantation for malignancy.
Liver transplantation for advanced hepatocellular carcinoma is often followed by early tumour recurrence and death. At the beginning of the liver transplantation programme at Berlin Virchow we decided to offer liver transplantation only to patients with solitary tumours not exceeding a maximum diameter of 5 cm or to patients with two or three tumour nodes with a maximum diameter of 4 cm. From September 1988 to October 1993 435 liver transplants were performed in 403 patients. Of these, 32 patients (8%) had a histologically confirmed hepatocellular carcinoma (29 males, 3 females, median age 56 years). The overall actuarial survival according to Kaplan-Meier for the whole series of 32 patients with hepatocellular carcinoma was 82%, 78%, and 78% at 1, 2 and 3 years, respectively. Tumour size alone did not seem to be a relevant factor when comparing patients with tumours up to or larger than 3 cm in diameter. Patients with solitary tumours had a better prognosis than patients with multiple tumours. The largest difference was found between patients with stage I-III (UICC) tumours and those with stage IVA tumours: 1-, 2- and 3-year survival rates were 89% throughout in the former group, while the corresponding figures for patients with stage IVA tumours were 63%, 47% and 47%. Efforts should be made to identify stage IVA tumours preoperatively in order to use the precious resource of scarce donor livers in an optimal way.
Actuarial Analysis↗
Does concommitant splenectomy raise the mortality of liver transplant recipients?
Within a 17-month period, 130 orthotopic liver transplantations were performed in our hospital. Nine of these were retransplantations and were not included in our analysis. In the remaining 121 patients, splenectomy was performed in 34 patients, either synchronously with the transplant procedure (27 patients) or in the postoperative period (7 patients). Indications for splenectomy were lienalis-steal syndrome in 15 patients and hypersplenism in 15 cases. The number of rejection episodes was fairly equal in both groups (splenectomized vs. non-splenectomized, 61.7% vs. 63.9%, respectively). There was a marked difference in the frequency of infectious episodes (61.7% vs. 25.3%) that resulted in a decreased survival rate (77.5% vs. 95.4%) for splenectomized patients. Therefore, we recommend splenectomy only for very selected patients and investigate the banding of the splenic artery as an alternative.
Female↗
Severe neurotoxicity after liver transplantation: association between FK 506 therapy and hepatitis C virus disease.
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Brain↗
Causes of death following liver transplantation in FK 506- and cyclosporine-treated patients.
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Acute Kidney Injury↗
Outcome following orthotopic liver transplantation in HBsAg-positive patients using short- or long-term immunoprophylaxis.
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Antibodies, Monoclonal↗
Increased rejection after liver transplantation in FK 506-treated patients is associated with viral hepatitis C disease.
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Cyclosporine↗