Management of primary and renal hyperparathyroidism: guidelines from the German Association of Endocrine Surgeons (CAEK).

BACKGROUND AND AIMS: The purpose of this review is to provide updated recommendations for the surgical management of primary (pHPT) and renal (rHPT) hyperparathyroidism, formulating a new guideline of the German Association of Endocrine Surgeons (CAEK). METHODS: Evidence-based recommendations for the diagnosis and therapy of pHPT and rHPT were assessed by a multidisciplinary panel using PubMed for a comprehensive literature search together with a structured consensus dialogue (S2k guideline of the Association of the German Scientific Medical Societies, AWMF). RESULTS: During the last 20 years, a variety of new preoperative localization procedures, such as sestamibi-SPECT, 4D-CT, and various PET/CT procedures, were established for pHPT. High-resolution imaging, together with intraoperative parathyroid hormone (IOPTH) measurement, enabled focused or minimally invasive surgery to become the most favored surgical technique. Patients with pHPT and nonlocalizing imaging have a higher risk of multiglandular disease. Surgical therapy provides very high cure rates, with a clear relation to the surgeon's experience in parathyroid procedures. Reoperative parathyroidectomy, children with pHPT or familial forms, and parathyroid carcinoma are addressed and require special surgical expertise. A multidisciplinary team of experienced nephrologists, transplant, and endocrine surgeons should assess the diagnosis and treatment of renal HPT. CONCLUSION: Surgery is the only curative treatment for pHPT and should be considered for all patients with pHPT. For rHPT, a more selective approach is required, and parathyroidectomy is indicated only when conservative treatment options fail. In parathyroid carcinoma, the adequacy of local resection influences local disease control.

[Case volume and complications after thyroid gland surgery in Germany: an analysis of routine data from 48,387 AOK patients]. / Fallvolumen und Komplikationen nach Schilddrüsenoperationen in Deutschland: eine Routinedatenanalyse von 48.387 AOK-Patienten.

BACKGROUND: Many studies showed that hospital and surgeon volume have a significant influence on the complication rates of thyroid surgery. The present study investigates whether this relationship applies in subtotal as well as total lobe resections. Furthermore, it is still unclear which threshold for the hospital-related case volume can be determined, above which the risk of complications lies below the current national average. MATERIAL AND METHODS: The study was based on nationwide routine data for persons insured with the Local General Sickness Fund (AOK) who had undergone thyroid surgery in 2014-2016. Permanent vocal cord palsy, bleeding and wound infection needing revision were recorded using indicators. The effect of the case volume on the indicators and the case number threshold was determined using logistic regression. RESULTS: Permanent vocal cord palsy was observed in 1.3% and bleeding or wound infections needing revision in 1.6% and 0.3% of the cases. Compared to hospitals with >450 surgeries per year, the risk of permanent vocal cord palsy in hospitals with fewer than 201, 101 and 51 surgeries was significantly increased (OR [95% CI]: 1.5 [1.1-2.1]; 1.5 [1.1-2.1]; 1.8 [1.3-2.5]). The threshold needed to achieve a risk for permanent vocal cord palsy below the national average (1.3%) was 265 thyroid surgeries per year (95% CI: 110-420). For bleeding or wound infection in need of revision, no association between volume and outcome was found. CONCLUSION: The present study showed that the risk of postoperative permanent vocal cord palsy decreased with increasing case volume. The broad confidence interval of the threshold makes clear case volume recommendation difficult. In order that the risk for a postoperative permanent vocal cord palsy is not likely above the national average, the annual case volume should reach 110 thyroid interventions.

[Speech therapy after thyroid gland operations in Germany: analysis of routine data from 50,676 AOK patients]. / Logopädie nach Schilddrüsenoperationen in Deutschland: eine Routinedatenanalyse von 50.676 AOK-Patienten.

BACKGROUND: This study investigated the frequency of postoperative speech therapy in the context of vocal cord palsy after thyroid surgery based on nationwide routine data. Additionally, volume-outcome relationships were examined. MATERIAL AND METHODS: Nationwide routine data from insured patients of the Local Health Insurance Fund (AOK) who underwent thyroid surgery for a benign thyroid disease between 2013 and 2015 were analyzed. Postoperative speech therapy was determined based on prescription data. Transient and permanent vocal cord palsy were determined using indicators. The effect of hospital volumes (volume quintiles) on prescription of postoperative speech therapy was determined by multivariate logistic regression. RESULTS: A total of 50,676 thyroid gland operations were identified. The overall frequency of postoperative speech therapy prescription was 6.5%. In AOK patients with transient or permanent vocal cord palsy, the frequencies of postoperative speech therapy prescription were 56.1% and 75.2%, respectively. The prescription volume of the normal case (≥21 units of speech therapy) was exceeded in 0.7% of the AOK patients. In the two lowest case volume categories the risk of postoperative speech therapy exceeding the prescription volume of the normal case was significantly higher compared to the highest case volume hospitals (odds ratios: 1.2 and 1.8, respectively). CONCLUSION: This study presents the reality of healthcare with respect to the frequency of speech therapy prescription after thyroid gland surgery in Germany. In addition, it was determined that the risk of postoperative speech therapy prescription exceeding the volume of the normal case after thyroid gland operations decreases with increasing case volumes of hospitals.

[Complications after thyroid gland operations in Germany : A routine data analysis of 66,902 AOK patients]. / Komplikationen nach Schilddrüsenoperationen in Deutschland : Eine Routinedatenanalyse von 66.902 AOK-Patienten.

BACKGROUND: Routine data from hospitals in the public healthcare system allow the analysis of large patient datasets without generating additional documentation efforts for hospitals. This study reports the frequencies of postoperative complications after thyroid surgery based on routine nationwide data. Moreover, volume-outcome relationships were investigated. MATERIAL AND METHODS: Nationwide routine data from insured patients of the Local Health Insurance Fund (AOK) who underwent thyroid surgery between 2008 and 2010 were analyzed. Complications were determined based on indicators for permanent vocal cord palsy, re-bleeding with re-operations and wound infections with specific treatment. The effect of hospital volumes (volume quintiles) on the indicators was determined by multivariate logistic regression. RESULTS: A total of 66,902 thyroid gland operations were identified. The overall frequency of permanent vocal cord palsy was 1.5 %, re-bleeding 1.8 % and wound infections 0.4 %. In the four lowest case volume categories the risk of permanent vocal cord palsy was significantly higher compared to the highest case volume hospitals (odds ratio 1.5, 1.7, 1.7 and 2.2, respectively). CONCLUSION: This study represents the reality of healthcare for thyroid surgery in Germany. Additionally, it was determined that the risk for permanent vocal cord palsy after thyroid gland operations decreased with increasing case volumes of hospitals.

No influence of immunosuppression on insulin sensitivity and beta-cell function in living donor liver transplantation.

In liver transplantation alterations of glucose metabolism are common but not well understood. Influence of immunosuppression is widely presumed but has not proven until now. Using a frequently sampled intravenous glucose tolerance test with a minimal modeling technique of glucose disappearance we analyzed insulin sensitivity (SI) and beta-cell function (first and second phase of pancreatic beta-cell secretion, Phi 1 and Phi 2) in living donor liver transplantation of the right lobe. Initial immunosuppression in recipients was done with tacrolimus, prednisolone, and basiliximab induction. Donors and recipients were investigated before and 10 days, 6 months, and 1 year after operation. Normal SI of controls (donors before operation) decreased markedly 10 days after right lobectomy to SI 2.22 +/- 0.35 x 10(-4) min(-1) x microU/mL (P < .001); Phi 2 was compensatory increased. All parameters normalized within 1 year. Recipients were insulin-resistant with hyperinsulinemia before transplantation. After transplantation no parameter was significantly different from donors; all normalized equally to donors over 1-year follow-up. Thus, immunosuppression in recipients has no influence on glucose metabolism because liver function itself seems to play a more pronounced role than known until now.

Chronically rejected rat kidney allografts induce donor-specific tolerance.

Previous studies on pathophysiological mechanisms of chronic graft rejection demonstrated the impact of both alloresponsiveness and nonspecific immunological events on the process. To study the role of alloantigen-specific factors further, we hypothesized an acceleration of chronic graft rejection after presensitization. Chronically rejected renal allografts in the established Fischer 344 --> Lewis rat model were replaced sequentially by native allografts of donor origin. Grafting of second allografts was performed 2, 4, 8, and 12 weeks after the original transplantation and followed long term. Second allografts demonstrated significantly ameliorated functional and structural alterations with few cellular infiltrates. These changes were independent from the time interval between first and second engraftment (2-12 weeks); immunosuppressive treatment after the second engraftment was not influential. The nonresponsiveness was not restricted to the second kidney allografts, as heart allografts of donor origin in these recipients also functioned indefinitely, whereas third-party grafts (Lewis x Brown Norway F1) and Fischer 344 heart grafts in untreated Lewis control rats were acutely rejected. Thus, donor-specific and tissue-nonspecific graft acceptance is achieved by second engraftment of donor-specific allografts in a model of chronic graft rejection. Those observations demonstrate the synergistic effects of alloresponsiveness and of the injured graft itself for the development of chronic graft failure.

The effect of FK506 versus cyclosporine on glucose and lipid metabolism--a randomized trial.

In order to evaluate the effect of cyclosporine (CsA) versus FK506 on glucose and lipid metabolism, an oral glucose tolerance test (OGTT) was performed in 101 patients after orthotopic liver transplantation (OLT) (mean interval after OLT: 511 days). The liver graft recipients had been randomized prospectively to two groups prior to OLT to receive either immunosuppression with CsA, azathioprine, and corticosteroids (CsA group) or FK506 and corticosteroids (FK group). Along with the OGTT, serum insulin, insulin C-peptide and glucagon as well as serum lipids were monitored. There was no statistically significant difference in the occurrence of impaired glucose tolerance (IGT) or manifest diabetes mellitus disease between the two groups. In fact, not a single patient developed new-onset diabetes in any group. In male and female patients, serum levels of cholesterol and triglycerides increased significantly under FK506 and CsA treatment after OLT. Cholesterol was significantly higher in the CsA group in men, in women this was marked, but not significant. While triglycerides were significantly higher in women on CsA treatment, there was no such difference in men. In conclusion, both CsA and FK506 proved to have similar effects on glucose metabolism, while there was a different spectrum of serum lipid alterations.

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.

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.

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.

Cytokine pattern during rejection and infection after liver transplantation--improvements in postoperative monitoring?

Despite improvements in immunosuppression, rejection occurs in 50% of liver transplant patients and may cause significant morbidity. The most frequent cause of death after liver transplantation is severe infection. Determination of the cytokine network may lead to earlier detection of patients at risk for severe rejection and infection. For this purpose, 81 patients with 85 liver transplants were monitored for cytokines and neopterin on a daily basis. During the first postoperative month, 28 patients (34.6%) developed acute rejection; 14 patients were successfully treated with methylprednisolone (steroid-sensitive rejection), while 14 patients required additional treatment with FK506 and OKT3 (steroid-resistant rejection). Ten patients developed severe infections, and 11 patients experienced asymptomatic cholangitis. Patients with an uneventful postoperative course (n=37) were the control group. One-year patient survival was 88.9%: 1 patient died because of chronic rejection and Pseudomonas urosepsis; a further 4 patients died of aspergillus pneumonia and bacterial sepsis. Soluble TNF-RII, sIL-2R-, and IL-10 levels were significantly elevated 3 days prior to or at the onset of acute steroid-resistant rejection (P < or = 0.01 versus steroid-sensitive rejection and on uneventful postoperative course). An increase in IL-8, neopterin, and sTNF-RII was indicative of severe infection 3 days prior to onset of infection. In this group of patients, a simultaneous increase in IL-10 indicated a lethal outcome of severe infection. During the second week of acute steroid-resistant rejection and lethal infection, a significant rise in IL-1beta, IFN-gamma, and IL-6 was observed (P < or = 0.01 versus control groups). The different patterns in neopterin- and cytokine-increase could differentiate between severe rejection and severe infection. Furthermore, the increase in these parameters indicated severe rejection--i.e., steroid resistance at the onset of acute rejection--which could prompt us to initiate rescue therapy immediately. The ability to detect patients at risk for severe or lethal infection may result in intensified infectious screening and more aggressive antiinfectious treatment. Therefore, routine monitoring of these parameters may lead to changes in therapeutic management of severe acute rejection and infection after liver transplantation.

Regulation of glucose tolerance in patients after liver transplantation: impact of cyclosporin versus tacrolimus therapy.

BACKGROUND: We investigated the factors regulating glucose homeostasis in 10 healthy (control) subjects, as well as in stable, long-term, liver-grafted patients receiving monotherapy in the form of either cyclosporin A (n=10) or tacrolimus (n=10). METHODS: We measured insulin sensitivity, first- and second-phase insulin secretion, with a minimal modeling technique based on the analysis of glucose, insulin, and C-peptide profiles during frequently sampled intravenous glucose tolerance tests (FSIGTT). Proinsulin levels, as a marker of beta-cell dysfunction, were measured in the fasting state and during FSIGTT. RESULTS: Glucose and insulin concentrations before and after glucose loading did not differ in liver transplant patients and in control subjects. Fasting C-peptide levels in both liver-grafted groups were higher than in healthy subjects and remained elevated during FSIGTT (P<0.05). Intravenous glucose tolerance [(K(G)), i.e. the slope of the regression of logarithm of the blood glucose concentrations vs. time], insulin sensitivity, and first-phase insulin secretion did not differ in liver-grafted groups and healthy subjects. Second-phase insulin secretion was about 56% higher in liver-grafted patients than in controls (P<0.05). Body mass index was the overall determinant of insulin sensitivity in all groups. CONCLUSIONS: Long-term monotherapy with cyclosporin A or tacrolimus has no deleterious effects on insulin sensitivity, first-phase insulin secretion, and insulin synthesis in liver transplant patients. Normal insulin sensitivity (posthepatic insulin effect) and enhanced second-phase insulin secretion (prehepatic insulin) point to an accelerated hepatic insulin clearance rate in liver transplant patients. Increased hepatic insulin clearance is compensated by enhanced insulin secretion, indicating that insulin clearance is the major determinant of pancreatic function in liver-grafted patients.

A prospective randomized trial comparing interleukin-2 receptor antibody versus antithymocyte globulin as part of a quadruple immunosuppressive induction therapy following orthotopic liver transplantation.

BACKGROUND: Quadruple immunosuppressive induction therapy has been shown to markedly reduce the incidence of acute rejection episodes without increasing the incidence of infectious complications after liver transplantation. However, the use of polyclonal antibody preparations (e.g. antithymocyte globulin [ATG]) is associated with side effects such as fever and tachycardia. To evaluate the efficacy and the safety of a monoclonal antibody directed against the interleukin-2 receptor (BT563) in comparison with ATG as part of a quadruple induction regimen, a prospective, randomized study was conducted. METHODS: Eighty consecutive adult recipients of primary orthotopic liver transplants were randomized to receive either BT563 (10 mg/day; days 0-12; n=39) or ATG (5 mg/kg/day; days 0-6; n=41) in addition to the standard immunosuppressive protocol consisting of cyclosporine, and prednisolone, and azathioprine. RESULTS: Patients treated with BT563 had a significantly lower incidence of steroid-sensitive rejection episodes (3 vs. 11; P<0.025) and also significantly fewer drug-related side effects (4 vs. 18, P<0.038) when compared with patients treated with ATG. The incidence of infectious complications was not different between the two groups. Patient survival did not differ significantly between the two groups (84.6% at 1, 2, and 3 years in the BT563 group and 90.2% at 1 year and 87.8% at 2 and 3 years for the ATG group). Analysis of graft function showed an advantage for the BT563 group in terms of postoperative bilirubin levels. However, no differences were observed in long-term follow-up between the two groups. CONCLUSIONS: Our results indicate that treatment with anti-interleukin-2 receptor antibody as part of quadruple induction therapy after orthotopic liver transplantation is safe and effective and shows fewer steroid-sensitive rejection episodes as well as fewer side effects when compared with quadruple induction therapy including ATG.

Review article: liver transplantation for hepatocellular carcinoma.

Despite recent advances in techniques of in situ tumour ablation, surgical therapy remains at present the mainstay treatment for primary hepatic malignancies. After an initial endeavour in the establishment of liver transplantation as a treatment option, in particular for unresectable liver tumours, only a few indications, for example early hepatocellular carcinoma in cirrhosis, are currently agreed upon. Other indications, such as peripheral cholangiocarcinoma and hepatocellular carcinoma in noncirrhotics have largely been abandoned or are still under debate, as is the case with fibrolamellar carcinoma. The selection of patients suffering from hepatocellular carcinoma in cirrhosis for liver transplantation is still based on tumour size and node number, because the current state of diagnostic imaging fails to reliably predict the most important prognostic parameter: vascular infiltration. Other selection criteria are under investigation. Studies on multimodal therapy are also underway but have not yet demonstrated a clear benefit.

Preoperative contrast-enhanced MRI of the parathyroid glands in hyperparathyroidism.

RATIONALE AND OBJECTIVES: To evaluate the sensitivity of contrast-enhanced MRI in the preoperative detection of abnormal parathyroid glands in patients with clinical evidence of hyperparathyroidism. METHODS: Twenty-eight patients with biochemical evidence of hyperparathyroidism underwent contrast-enhanced preoperative MRI of the parathyroid glands. Two blinded readers assessed the MR images by consensus, and MR results were subsequently correlated with those from surgery (location, diameter, weight) and histopathology. RESULTS: MRI depicted 32 of 39 surgically proved abnormal parathyroid glands (sensitivity 82%; 95% confidence interval, 66%-92%), and 1 of 114 (0.9%) was incorrectly considered abnormal. All ectopic glands were correctly identified (2 mediastinal, 1 submandibular). Sensitivity was superior for adenomas but less for hyperplasia (adenomas 87%; 95% confidence interval, 67%-97%; hyperplasia 75%; 95% confidence interval, 47%-92%). Among all lesions, atypical signal characteristics on MRI were observed in 34% of lesions (9% hyperintense signals on T2- and T1-weighted images; 25% isointense signals on T2- and T1-weighted images), with improved lesion detection after contrast administration in 17% of lesions. CONCLUSIONS: MRI of the parathyroid glands presented a sensitive imaging modality, thus demonstrating its high potential to preoperatively detect abnormal glands. Moreover, in a minor proportion of patients with atypical parathyroid lesion characteristics, contrast administration may increase lesion detectability.

Evidence for impaired glucose effectiveness in cirrhotic patients after liver transplantation.

To evaluate the impact of acute and chronic liver disease and single immunosuppression (cyclosporine A [CSA] or FK506) on insulin sensitivity and glucose effectiveness in liver-grafted patients, we performed a frequently sampled intravenous glucose tolerance test (FSIGTT) in nondiabetic patients after orthotopic liver transplantation (OLT) with acute liver failure ([ALF] group, n = 9, with CSA therapy), in patients after OLT with chronic liver disease (CSA group, n = 8; FK506 group, n = 8), and in 9 healthy control subjects. Insulin sensitivity and glucose effectiveness were determined by analyzing glucose and insulin data from the FSIGTT with Bergman's minimal model technique for glucose. The intravenous glucose tolerance index ([KG] ie, the slope of the regression of the logarithm of blood glucose concentration) was not different between the ALF group (2.17 +/- 0.16 min(-1)) and controls (2.29 +/- 0.13 min(-1)), but was lower (P < .05) in both groups with chronic liver disease (CSA group, 1.46 +/- 0.1; FK506 group, 1.61 +/- 0.11 min(-1)) compared with the ALF group (P < .05). A positive relation for the KG and glucose effectiveness was found in all liver-grafted patients and controls. Insulin sensitivity was not different between all liver-grafted patients and controls. The body mass index (BMI) was the overall determinant of insulin sensitivity in all groups. Single immunosuppressive therapy does not impair insulin sensitivity in liver-grafted patients. The lower glucose effectiveness in liver-grafted patients with chronic liver disease but not in patients after ALF points to a defect in the regulation of glucose-mediated glucose uptake in peripheral tissue.

Liver transplantation and diabetes mellitus.

Post-transplant diabetes mellitus (PTDM) is a common complication after orthotopic liver transplantation (oLT). In our study, we investigated the prevalence and risk factors one year after transplantation in 618 patients who underwent oLT between 1990 and 1996 in a single center. The influence of steroid medication and hepatitis B or C (HBV/HCV) was also studied. Before oLT 66 of the 618 patients were diabetic. After transplantation 37 of these 66 (56%) patients showed no further signs of DM. Of the 552 patients without DM before transplantation 39 (7.2%) developed new onset PTDM. There was no influence of steroid medication on the presence of PTDM (steroids 10.4% PTDM, no steroids 12.5% PTDM). In addition we found no influence of HBV or HCV-infection on PTDM development. Analysis for risk factors showed no significant influence of the diagnosis leading to oLT, of FK506 or Cyclosorin A medication, age, gender or Child-Pugh class. Five year patient survival was not influenced by the presence of PTDM, especially patients with a preexisting DM showed no reduced survival. However, a subgroup of patients with new onset insulin-requiring PTDM showed significantly reduced 5 year survival (p<0.05). In conclusion we found new onset PTDM in 7.2% of patients undergoing oLT one year after the operation. On the other hand in more than 50% of patients with preexisting DM, the disease was no longer present post-transplant. This could be an indication that DM is dependent on liver function in these patients. Patients with preexisting DM should not be excluded from transplantation if indicated. Development of new onset insulin-requiring PTDM could be an important prognostic factor for patient survival after oLT. Further investigations are necessary to evaluate the prognostic meaning of PTDM and the pathophysiologic mechanisms.

[Accuracy of the CT-estimated weight of the right hepatic lobe prior to living related liver donation (LRLD) for predicting the intraoperatively measured weight of the graft]. / Voraussagegenauigkeit der präoperativen CT-gestützten Gewichtsbestimmung des rechten Leberlappens bezüglich des intraoperativen Transplantatgewichts bei Leberlappen-Lebendspendern.

PURPOSE: Due to the shortage of cadaver donors, living related liver donation (LRLD) has emerged as an alternative to cadaver donation. The expected graft weight is one of the main determinants for donor selection. This study investigates the accuracy of preoperatively performed CT-volumetry to predict the actual weight of the right liver lobe graft. MATERIALS AND METHODS: In a prospective study the weight of the right hepatic lobe was calculated by volumetric analysis based on CT in 33 patients (21 females, 12 males, mean age 42.1 years, median age 41 years) prior to living related liver donation. Graft weight was calculated as the product of CT-based graft volume and 1.00 g/ml (the approximated density of healthy liver parenchyma). The calculated weight was compared with the intraoperatively measured weight of the harvested right hepatic lobe. The difference was used to determine a correction factor for estimating the actual graft weight. RESULTS: Based on the assumption of a parenchymal density of 1.00 g/ml, the preoperatively estimated graft weight (mean 980 g +/- 168 g) deviated +33 % from the intraoperatively measured right hepatic lobe weight (mean 749 g +/- 170 g). By reducing the preoperatively predicted weight of the right hepatic lobe with a correction factor of 0.75, the actual graft weight can be calculated. CONCLUSION: Preoperative estimation of the weight of the right hepatic lobe based on CT of living related liver donors predicts the weight of the right lobe graft with sufficient accuracy by applying a single correction factor. Intraoperative fluid loss (i.e., blood, bile) from the harvested liver as well as variations in parenchymal density may contribute to the observed preoperative overestimation of the actual graft volume by CT-based volumetry.

[Characterization of hepatic tumors with contrast-enhanced ultrasound and digital grey-scale analysis]. / Charakterisierung von Lebertumoren durch kontrastverstärkte Sonographie und digitale Graustufenbestimmung.

PURPOSE: The characterization of different liver tumors is of therapeutic and prognostic relevance and has been the purpose of several studies. Although ultrasound offers the opportunity to detect hepatic tumors without ionizing radiation, its previous techniques did not lead toward a definitive differentiation of different tumor entities. The purpose of this study was the clinical evaluation of contrast enhanced ultrasound followed by quantitative digital analysis in patients with focal hepatic tumors. MATERIALS AND METHODS: In a prospective study, 50 patients (18 females, 32 males, age 28 to 83 years, mean age 59.4 years) with liver tumors previously detected by CT (n = 47) or MRI (n = 3) were examined by ultrasound of the upper abdomen using conventional technique and phase inversion technique after intravenous application of sulfur-based contrast enhancer SonoVue. At scheduled intervals after application of the contrast enhancer, a digital image was stored and the characteristic signal course of each lesion determined semiquantitatively. The gold standard was either resection (n = 17), percutaneous needle biopsy (n = 19) or the clinical course (n = 14). RESULTS: While the percentage of tumors correctly characterized by CT/MRI amounted to 78 %, the percentage increased from 60 % using conventional ultrasound to 86 % using contrast enhanced ultrasound including grey-scale analysis. Typical graphs were achieved for different tumor entities on digital grey-scale analysis. The optimal intervals for the differentiation of particular entities were 20 and 100 seconds after injection. CONCLUSION: Quantification of contrast enhanced ultrasound is an addition to the previous diagnostic procedure in hepatic tumors. It offers the possibility of an investigator-independent characterization of lesions and should be evaluated in further studies.

Preemptive therapy in CMV-antigen positive patients after liver transplantation--a prospective trial.

OBJECTIVE: Preemptive therapy with intravenous ganciclovir and CMV-hyperimmunoglobulin in asymptomatic CMV pp65-antigen positive patients was compared with treatment of only symptomatic CMV-disease after liver transplantation in an open prospective study. PATIENTS AND METHODS: 48 out of 200 liver transplant recipients became positive during six weeks follow-up after transplantation. 17 out of these 48 patients who were already symptomatic at the time of positive antigen testing were successfully treated with ganciclovir and CMV-hyperimmunoglobulin. 31 asymptomatic antigen-positive patients were randomised to receive preemptive therapy or to receive therapy only at onset of clinical symptoms. RESULTS: Only two out of 15 patients in this latter group without preemptive therapy developed CMV-syndrome and were successfully treated with intravenous ganciclovir. 13 patients did not experience any clinical symptoms or disease and were therefore spared unneccessary toxicity and costs. The overall incidence of CMV-infection and -disease in the whole study population of 200 liver transplant recipients was 25% and 10%. As expected, CMV-negative patients who received an organ from a seropositive donor were at a higher risk of CMV-infection and -disease, but did not show more severe infections clinically. Patients with IL-2 receptor antibody induction therapy seemed to have a higher risk for CMV-infection and -disease.