Protein kinase C inhibitor sotrastaurin in de novo liver transplant recipients: a randomized phase II trial.

Efficacy and safety of protein kinase C inhibitor sotrastaurin (STN) with tacrolimus (TAC) was assessed in a 24-month, multicenter, phase II study in de novo liver transplant recipients. A total of 204 patients were randomized (1:1:1:1) to STN 200 mg b.i.d. + standard-exposure TAC (n = 50) or reduced-exposure TAC (n = 52), STN 300 mg b.i.d. + reduced-exposure TAC (n = 50), or mycophenolate mofetil (MMF) 1 g b.i.d. + standard-exposure TAC (control, n = 52); all with steroids. Owing to premature study termination, treatment comparisons were only conducted for Month 6. At Month 6, composite efficacy failure rates (treated biopsy-proven acute rejection episodes of Banff grade ≥1, graft loss, or death) were 25.0%, 16.5%, 20.9% and 15.9% for STN 200 mg + standard TAC, STN 200 mg + reduced TAC, STN 300 mg + reduced TAC and control groups, respectively. Median estimated glomerular filtration rates were 84.0, 83.3, 81.1 and 75.3 mL/min/1.73 m(2), respectively. Gastrointestinal events (constipation, diarrhea, and nausea), infection, and tachycardia were more frequent in STN groups. More patients in STN groups experienced serious adverse events compared with the control group (62.3-70.8% vs. 51.9%). STN-based regimens were associated with a higher efficacy failure rate and higher incidence of adverse events with no significant difference in renal function between the groups.

Sotrastaurin in calcineurin inhibitor-free regimen using everolimus in de novo kidney transplant recipients.

Sotrastaurin, a novel selective protein-kinase-C inhibitor, inhibits early T cell activation via a calcineurin-independent pathway. Efficacy and safety of sotrastaurin in a calcineurin inhibitor-free regimen were evaluated in this two-stage Phase II study of de novo kidney transplant recipients. Stage 1 randomized 131 patients (2:1) to sotrastaurin 300 mg or cyclosporine A (CsA). Stage 2 randomized 180 patients (1:1:1) to sotrastaurin 300 or 200 mg or CsA. All patients received basiliximab, everolimus (EVR) and prednisone. Primary endpoint was composite efficacy failure rate of treated biopsy-proven acute rejection, graft loss, death or lost to follow-up. Main safety assessment was estimated glomerular filtration rate (eGFR) by MDRD-4 at Month 12. Composite efficacy failure rates at 12 months were higher in sotrastaurin arms (Stage 1: 16.5% and 10.9% for sotrastaurin 300 mg and CsA; Stage 2: 27.2%, 34.5% and 19.4% for sotrastaurin 200 mg, 300 mg and CsA). eGFR was significantly better in sotrastaurin groups versus CsA at most time points, except at 12 months. Gastrointestinal and cardiac adverse events were more frequent with sotrastaurin. Higher treatment discontinuation, deaths and graft losses occurred with sotrastaurin 300 mg. Sotrastaurin combined with EVR showed higher efficacy failure rates and some improvement in renal allograft function compared to a CsA-based therapy.

Efficacy of sotrastaurin plus tacrolimus after de novo kidney transplantation: randomized, phase II trial results.

Sotrastaurin, a novel immunosuppressant, blocks early T cell activation through protein kinase C inhibition. Efficacy and safety of sotrastaurin with tacrolimus were assessed in a dose-ranging non-inferiority study in renal transplant recipients. A total of 298 patients were randomized 1:1:1:1 to receive sotrastaurin 100 (n = 77; discontinued in December 2011) or 200 mg (n = 73) b.i.d. plus standard tacrolimus (sTAC; 5-12 ng/mL), sotrastaurin 300 mg (n = 75) b.i.d. plus reduced tacrolimus (rTAC; 2-5 ng/mL) or enteric-coated mycophenolic acid (MPA) plus sTAC (n = 73); all patients received basiliximab and corticosteroids. Composite efficacy failure (treated biopsy-proven acute rejection ≥ grade IA, graft loss, death or loss to follow up) rates at Month 12 were 18.8%, 12.4%, 10.9% and 14.0% for the sotrastaurin 100, 200 and 300 mg, and MPA groups, respectively. The median estimated glomerular filtration rates were 55.7, 53.3, 64.9 and 59.2 mL/min, respectively. Mean heart rates were faster with higher sotrastaurin doses and discontinuations due to adverse events and gastrointestinal adverse events were more common. Fewer patients in the sotrastaurin groups experienced leukopenia than in the MPA group (1.3-5.5% vs. 16.5%). Sotrastaurin 200 and 300 mg had comparable efficacy to MPA in prevention of rejection with no significant difference in renal function between the groups.

Diabetes mellitus is no independent risk factor for perioperative mortality following hepatic resection.

For patients with concomitant diabetes mellitus an increased perioperative mortality and morbidity in hepatic resections has repeatedly been described. Other studies, however, demonstrated equal outcome data in diabetic and non-diabetic patients. As patient populations were selected for underlying disease, conflicting results may reflect patient selection criteria rather than impact of diabetes mellitus on outcome measures. Therefore, a multivariate analysis in a largely unselected patient population has been performed to determine the independent prognostic value of diabetes mellitus in liver surgery. From a prospective database 633 adult patients undergoing hepatic resection without preceding major abdominal surgery or chemotherapy have been identified. Besides diabetes mellitus, demographic data, variables expressing the functional reserve of the liver, and parameters of surgical technique were analyzed for their impact on mortality and morbidity. 75 patients were diabetic (11.8 %) and 96 hepatic resections (15.2 %) were performed in cirrhotic patients. In the univariate analysis, concomitant diabetes was associated with an increased mortality compared to all non-diabetic patients (10.7 % vs. 5.3 %, p = 0.047). Diabetic patients, however, were also significantly older and presented a higher prevalence of liver cirrhosis. Multivariate modeling finally identified only age, albumin, cirrhosis, extent of surgery, and era of surgery as independent variables with an impact on perioperative mortality. Overall, complications were detected in diabetic and non-diabetic patients with a comparable frequency (44 % vs. 36 %, p = 0.179). Also, the length of in-hospital stay did not significantly differ between both groups (18.5 +/- 1.7 vs. 17.7 +/- 1.0 days, p = 0.119). Rates of postoperative renal impairment, prolonged ascites or pneumonia, however, were higher in diabetics than in other patients. Following established cardiopulmonary and surgical selection criteria, diabetes mellitus is not an independent risk-factor for perioperative mortality in hepatic resections. Although the overall postoperative morbidity was not different in diabetic and non-diabetic patients, a specific pattern of complications has been identified, mandating particular attention in the postoperative course of diabetic patients.

Anti-TNF-alpha therapy for acute rejection in intestinal transplantation.

INTRODUCTION: We present our experience with infliximab rescue therapy for steroid- and OKT3-resistant rejection after intestinal transplantation (ITx). METHODS: Twelve ITx and one multivisceral transplant recipients were immunosuppressed with tacrolimus, rapamycin, daclizumab, steroids (n = 10) or tacrolimus, campath, and steroids (n = 3). RESULTS: In two patients, severe acute rejection did not resolve despite steroid bolus therapy plus 5 to 10 days of OKT3 treatment. Signs of moderate rejection persisted in the distal portions of the grafts. Treatment with infliximab, a chimeric anti-TNF-alpha antibody (four infusions of 3 mg/kg body weight), induced a complete remission of histological and clinical signs of rejection. Two further patients with steroid-resistant rejection received two courses of infliximab (3 mg/kg body weight) as antirejection therapy. All rejection episodes resolved completely. CONCLUSIONS: Infliximab effectively treats steroid and OKT3 resistant acute rejection episodes of intestinal transplantations.

Primary immunosuppression with tacrolimus after liver transplantation: 12-years follow-up.

The early safety and efficacy of tacrolimus after liver transplantation has been shown in two multicenter trials. Herein, we report our single-center long-term follow-up of a randomized controlled trial. As part of a European multicenter trial, 121 patients entered the study at our institution and were randomly assigned to receive either tacrolimus and steroids (n=61) or a quadruple protocol (n=60) using ciclosporin A, steroids, azathioprine, and antithymocyte globulin (ATG). Twelve-year figures of patient survival were 74% in the tacrolimus group and 66% in the cyclosporine-based group. Graft survival after 12 years was 69% in the tacrolimus group compared to 56% in the cyclosporin-based group (not significant, p=0.15). The total rate of graft loss and retransplantation decreased significantly in the tacrolimus arm (p<0.05). De novo malignancies increased significantly in the ciclosporin-based group and dominated as single cause of death beyond 5 years posttransplant. The use of tacrolimus after liver transplantation resulted in a decreased rate of graft loss over the long-term. An increased number of de novo malignancies in the ciclosporin-based group may be attributable to the use of ATG as induction therapy.

[Consensus-recommendations for sirolimus in liver transplantation]. / Konsensusempfehlung zum Einsatz von Sirolimus in der Lebertransplantation.

Sirolimus is an m-TOR inhibitor without renal side effects and potentially protects against the development of malignancy. Due to a higher incidence of complications in two trials and an official warning in the drug information, the use of Sirolimus in liver transplantation is limited. The participants of this consensus meeting had to analyse and evaluate the literature with respect to the potential role of Sirolimus in liver transplantation. This consensus statement follows the scheme normally employed for the presentation of guidelines including the grading of evidence (1a-5) and the extent of recommendation (A-C). Moreover, the consensus included the experience of the authors with respect to the handling of Sirolimus after liver transplantation.

CMV, EBV, HHV6, and HHV7 infections after intestinal transplantation without specific antiviral prophylaxis.

PURPOSE: To analyze the incidence and relevance of viral infections after intestinal transplantation (ITx) without specific antiviral prophylaxis. METHODS: Eleven patients (median age 34 years; range 26 to 58 years) who underwent ITx received no CMV/EBV prophylaxis but rather preemptive treatment. Viral monitoring for CMV or EBV polymerase chain reactions (PCR) in peripheral blood and graft biopsies, for HHV6-, and HHV7-PCR; for adeno-/rotavirus antigen and serology was performed based on clinical indications. RESULTS: Median time under risk was 19 months (range 2 to 39). CMV: The donor (D)-to-recipient (R) status prior to ITx was: D+/R+ (4); D+/R- (3); D-/R- (2); D-/R+ (2). Eight patients showed no positive CMV-PCR. Three episodes of tissue invasive CMV disease occurred in two patients. There were two asymptomatic CMV infections but no episodes of CMV disease. None of the R(-) recipients developed CMV infection or enteritis irrespective of the donor status. EBV: Four patients experienced six episodes of transient significant EBV-viremia. Two patients developed EBV enteritis concurrently with CMV enteritis during acute rejection. There were no PTLD. CMV and EBV enteritis only occurred during or immediately after steroid and OKT3 therapy. None of the patients developed significant HHV6 and HHV7 infection or viremia. There was one episode of adeno- and rotavirus enteritis. CONCLUSIONS: Despite witholding specific antiviral prophylaxis against CMV and EBV, we observed no such infections in 60% to 80% of patients. Donor-recipient matching regarding CMV was not predictive for the occurrence of CMV-related complications. HHV6 and HHV7 have not contributed to posttransplant morbidity.

A dermoid cyst in the greater omentum as a rare epigastric tumor.

A 36-year-old female presented with unspecific epigastric discomfort, without weight loss, night sweat or fever. Ultrasound and computed tomography showed a solid tumor with a diameter of 9 cm in the left upper abdomen, without any connection to the stomach, the pancreas or spleen. Laparoscopy showed a connection to parts of the greater omentum. Two days after laparoscopic resection the patient was discharged from hospital. Histology revealed the rare diagnosis of a dermoid cyst. A possible malignant degeneration of the tumor has to be considered, and therefore the tumor should be resected. Since the operation the patient is asymptomatic and without tumor recurrence.

Right hepatic lobectomy for recurrent cholangitis after combined bile duct and right hepatic artery injury during laparoscopic cholecystectomy: a report of two cases.

BACKGROUND: Bile duct injuries in combination with major vascular injuries may cause serious morbidity and may even require liver resection in some cases. We present two case studies of patients requiring right hepatic lobectomy after bile duct and right hepatic artery injury during laparoscopic cholecystectomy. PATIENTS: Two patients sustained combined major bile duct and hepatic artery injury during laparoscopic cholecystectomy. Surgical management consisted of immediate hepaticojejunostomy with reconstruction of the artery in one patient and hepaticojejunostomy alone in the other patient. In both cases the initial postoperative course was uncomplicated. RESULTS: After 4 and 6 months both patients suffered recurrent cholangitis due to anastomotic stricture. Both developed secondary biliary cirrhosis and required right hepatic lobectomy with left hepaticojejunostomy. The patients remain well 31 months and 4.5 years after surgery. CONCLUSIONS: The outcome of bile duct reconstruction may be worse in the presence of combined biliary and vascular injuries than in patients with an intact blood supply of the bile ducts. We recommend arterial reconstruction when possible in early recognized injuries to prevent late strictures. Short-term follow-up is most important for early recognition of postoperative strictures and to avoid further complications such as secondary biliary cirrhosis.

Coadministration of either cyclosporine or steroids with humanized monoclonal antibodies against CD80 and CD86 successfully prolong allograft survival after life supporting renal transplantation in cynomolgus monkeys.

BACKGROUND: Recent studies have shown some efficacy using monotherapy with monoclonal antibodies (mAb) against CD80 and CD86 receptors after life-supporting renal transplantation in non-human primates. Our study was designed to evaluate the efficacy of combinations of the same mAbs with either microemulsion cyclosporine (CsA) or steroids. METHODS: Unilateral renal transplantation was performed in 16 blood group-matched and MLR-mismatched cynomolgus monkeys that were assigned to four different treatment groups. All monkeys in groups I, II, and IV were treated with the combination of a CD80 (h1F1) and CD86 (h3D1) mAb given at 20 mg/kg each preoperatively, then 5 mg/kg at weekly intervals starting postoperative (po) day 0 until poday 56 (9 doses). In group I the animals (n=4) were treated with mAbs only. In group II (n=4) mAbs were combined with a CsA regimen adjusted daily to maintain target 24 hr trough levels of 150-300 ng/ml CsA for poday 0 to poday 56. In group III (n=4) the animals received CsA monotherapy according to the same regimen as group II. In group IV methylprednisone was administered at 2 mg/kg IV on poday 0-2, then at 0.5 mg/kg/day prednisone per gavage that was and tapered to 0.2 mg/kg/day on which they were maintained until poday 56. All animals were off all immunosuppressive treatment after poday 56 and were then followed until poday 119. RESULTS: The mean survival of groups I-IV was 74 (range 9-119 days), 113 (96-119 days), 39 (22-71 days), and 79 days (6 to 119), respectively. All animals in group I showed clinical evidence of acute severe rejection (fever, creatinine increase, anuria) within the first week posttransplant, including those that retained renal function until poday 119. Only one animal in group II had a moderate clinical rejection during the treatment period and three of four animals survived the intended follow-up period. All animals in group III had multiple biopsy proven or severe clinical rejection episodes within the first 21 days and only one animal survived beyond poday 40. Moderate or severe acute rejection was diagnosed in three of four animals of group IV within the first 28 days post transplant and only one animal survived until poday 119. CONCLUSION: Our data show that combining a calcineurin inhibitor or prednisone with mAbs designed to block costimulatory signals does not antagonize the immunosuppressive efficacy of these mAbs. In addition, combining CsA with mAbs directed against the CD80 and CD86 receptors significantly prolongs graft survival when compared to CsA monotherapy. Therefore clinical trials of humanized mAbs to CD80 and CD86 used in combination with conventional immunosuppression can be considered.

Comparison of the effects of tacrolimus and cyclosporine on the pharmacokinetics of mycophenolic acid.

Mycophenolate mofetil (MMF) is almost completely absorbed from the gut and is rapidly de-esterified into its active drug, mycophenolic acid (MPA). The main metabolite is glucuronidated MPA (MPAG), which is excreted into bile and undergoes enterohepatic recirculation. Studies in healthy volunteers treated with cholestyramine show that interruption of the enterohepatic recirculation decreases MPA exposure by approximately 40%. Published data show a difference in mycophenolic acid plasma concentrations between kidney transplant recipients treated with MMF plus cyclosporine (CsA) and those treated with MMF plus tacrolimus (TRL). However, the interpretation of these data is complicated by interpatient differences in variables that may influence MMF pharmacokinetics (e.g., underlying disease, co-medication, and time since transplantation). To understand the influence of TRL and CsA on MMF pharmacokinetics (PK) more completely, the authors eliminated confounding variables in clinical studies by performing drug interaction studies in inbred rats. To achieve a steady state, 3 groups of Lewis rats (n = 8 per group) were treated once daily with oral CsA (8 mg/kg), TRL (4 mg/kg), or placebo on days 0-6 before all rats began once-daily oral treatment with MMF (20 mg/kg) on day 7. Combined treatment with either MMF + CsA, MMF + TRL, or MMF + placebo was continued for 1 week (days 8-14). Thereafter, CsA and TRL treatments were stopped but MMF treatment was continued on days 14-21. Blood was sampled during the 24 hours subsequent to dosing on day 7 (after the first MMF dose), on day 14 (after multiple MMF doses) and on day 21 (after CsA/TRL washout). Rats in the MMF + TRL group and in the MMF + placebo group showed a second peak in the MPA-PK profiles consistent with enterohepatic recirculation of MPA. The MPA-PK profiles for the MMF + CsA-treated animals did not show a second MPA peak. On Day 14, the mean plasma MPA-AUC(0-24 hours) for the CsA-treated animals was significantly less than MPA exposures for rats in the MMF + TRL- and the MMF + placebo-treated groups. Furthermore, in contrast to results from other investigators, co-administration of CsA and MMF significantly increased MPAG-AUC(0-24 hours). Serum creatinines did not differ among rats in the three groups. CsA but not TRL decreased MPA plasma levels and increased MPAG-AUC(0-24 hours). These data suggest that CsA inhibits MPAG excretion into bile and offer an explanation for the well-known increased MPA exposure in organ transplant patients caused by conversion from CsA- to TRL-based immunosuppression.

Quadruple tacrolimus-based induction therapy including azathioprine and ALG does not significantly improve outcome after liver transplantation when compared with standard induction with tacrolimus and steroids: results of a prospective, randomized trial.

BACKGROUND: Tacrolimus in combination with prednisolone has been proven to be a safe and effective immunosuppressive induction therapy in solid organ transplantation. However, it remains unclear whether a tacrolimus-based quadruple induction regimen with azathioprine and an antilymphocytic preparation could further improve the results after orthotopic liver transplantation. Therefore, we designed a prospective, randomized study to compare the immunosuppressive efficacy of dual (tacrolimus and prednisolone) and quadruple (tacrolimus, azathioprine, ALG Merieux and prednisolone) induction after liver transplantation. METHODS: After randomization, 120 consecutive patients of primary liver transplants were divided into the dual group (n=59) and the quadruple group (n=61) and followed for a minimum of 3 years. RESULTS: Patient survival at 3 years was 88.2% in the dual versus 94.9% in the quadruple group. Overall 25 patients in each group (41 and 42%, respectively) developed acute rejection. There was no difference in the number and severity of rejections. In each group only four patients required OKT3-therapy, however, although three of four patients in the quadruple group responded to OKT3 and cleared rejection, none of the four patients in the dual group were treated successfully with OKT3 (P<0.02). Rejection in these patients resolved only after additional treatment with mycophenolate mofetil. Adverse events and infections were equally distributed in both groups. Asymptomatic Cytomegalovirus infections were more common in the quadruple group (P<0.02). As of today, only one patient developed posttransplant lymphoproliferative disease (dual group). CONCLUSIONS: The data from our single-center study indicate that both tacrolimus-based dual and quadruple immunosuppressive induction regimens yield similar safety and effectiveness after liver transplantation.

Prognostic factors in patients with differentiated thyroid carcinoma.

OBJECTIVE: To study the prognostic factors in patients with differentiated thyroid carcinoma. DESIGN: Retrospective analysis. SETTING: University hospital, Germany. PATIENTS: 139 consecutive patients who underwent surgery for follicular (n = 42) and papillary thyroid carcinoma (n = 97). MAIN OUTCOME MEASURES: Survival rate, type of operation (systematic lymphadenectomy or no lymphadenectomy). RESULTS: Median observation time was 72 months (range 1-203). The 5 and 10 year survival rates in patients with papillary carcinoma were 92% and 89% respectively, and in those with follicular carcinoma 88% and 80%, respectively. Prognostic factors for papillary carcinoma were distant metastases, age, and extrathyroidal growth, and for follicular carcinoma they were distant metastases, extrathyroidal extension, and multifocal growth. The Union International contre le Cancer and European Organisation for Research and Treatment of Cancer scores and the age, grade, extent and size score were all highly significant. The extent of lymphadenectomy, primary or secondary thyroidectomy, and partial or total thyroidectomy did not influence survival. CONCLUSION: Staging and score systems may be helpful in calculating prognosis in differentiated thyroid carcinoma, but the benefit of systematic lymphadenectomy remains controversial.

Complications associated with different surgical approaches to differentiated thyroid carcinoma.

INTRODUCTION: With the good prognosis associated with differentiated carcinoma, the morbidity and mortality of different surgical approaches are of crucial importance. METHODS: At the Department of Surgery (Virchow Klinikum Berlin), 139 patients who underwent surgery for differentiated thyroid carcinoma between 1979 and 1994 were reviewed, focussing on postoperative complications. In 113 and 18 patients, respectively, primary and completion thyroidectomy was performed. In five patients, less than total thyroidectomy and in three patients only palliative surgery was carried out. We performed thyroidectomy without systematic lymphadenectomy (LAD) in 70 patients (51.1%). In 15 patients (10.8%), lymphadenectomy of the lateral compartment and, in 53 patients (38.1%), central LAD was performed. LAD did not significantly influence survival time in either follicular (n = 42) or papillary carcinoma (n = 97). RESULTS: No patient died because of postoperative complications. Permanent laryngeal nerve palsy occurred in no patients after thyroidectomy without LAD, in one patient after central LAD (1.9%) and in one patient after lateral LAD (6.7%). Transient laryngeal nerve palsy was seen in ten patients [six (8.6%) after thyroidectomy only, two (3.7%) after central LAD and two (13.3%) after lateral LAD] (P = 0.19). Hypocalcemia was distributed equally within the LAD groups: total transient hypocalcemia could be recorded in 54 patients (38.8%), but permanent hypocalcemia occurred only in one patient (0.7%). Postoperative recovery was delayed in patients when a more radical approach was used (P = 0.03). CONCLUSION: The magnitude of the benefit of LAD in therapy for differentiated thyroid carcinoma is still controversial. This more radical approach is not necessarily accompanied, however, by higher morbidity and mortality.

A randomized, placebo-controlled trial with anti-interleukin-2 receptor antibody for immunosuppressive induction therapy after liver transplantation.

The introduction of quadruple induction therapy after liver transplantation with the murine anti-interleukin-2 receptor (IL-2R) antibody (BT563) has decreased the incidence of serious side effects, such as tachycardia, hypertension, rash, fever and nausea since it does not lyse its target cell. To investigate the immunosuppressive efficacy of BT563, a placebo-controlled trial was performed and BT563 was added to the standard triple induction after liver transplantation. Forty consecutive recipients of primary orthotopic liver transplants (OLT) (median age 47 yr [range 18-65]) were randomized. All patients received triple immunosuppression with cyclosporine A (CyA), prednisolone (PRED) and azathioprine (AZA). In addition, 19 patients received BT563 (Biotest, Dreieich, Germany) at a dose of 10 mg/d from day 0 until day 12. The remaining 21 patients received a placebo infusion at the same days after transplantation. Minimal follow-up for all patients was 3 yr. Patient survival at 3 yr was 74% in the BT563 group and 90% in placebo group. Similar results were observed for graft survival. Two acute rejection episodes were detected in the BT563 group and 9 acute rejections (5 steroid-resistant) were observed in the placebo group (p < 0.034). The incidences of sepsis, pneumonia, cholangitis, urinary tract infections as well as cytomegalo-virus (CMV) infections were similar in both groups. Side effects of the BT563 therapy and/or post-transplant lymphoproliferative disease (PTLD) were not detected. Quadruple induction therapy with BT563 significantly reduces the incidence of rejection episodes after liver transplantation, while infectious complications and/or PTLD is not increased. Therefore, the anti-IL2 receptor antibody BT563 constitutes a safe and efficient addition to the immunosuppressive induction regimen following OLT.

[Orthotopic liver transplantation in therapy of advanced polycystic liver disease]. / Orthotope Lebertransplantation zur Therapie der fortgeschrittenen polycystischen Lebererkrankung.

Polycystic liver disease (PLD) is an autosomal-dominant hereditary disease which usually presents together with polycystic kidney degeneration (ADPKD). The renal problems determine the course of this disease. Due to the development of dialysis an increasing number of patients present with symptoms from their liver cysts: These range from compression caused by hepatomegaly, which can severely limit the quality of life, to chronic liver failure. Ten patients with advanced symptoms of PLD underwent orthotopic liver transplantation, five of them with combined renal transplantation. Postoperative complications occurred in three patients. One patient died postoperatively from multiorgan failure after experiencing coagulopathy of unknown origin. After follow-up of 6-60 months, all patients had better quality of life after transplantation. There was a complete relief of symptoms; liver or renal failure did not occur. Liver transplantation should be considered in patients with highly symptomatic PLD. In the case of severe hepatomegaly or liver and renal failure the combined liver and renal transplantation are able to cure the PLD and ADPKD without rising the disadvantage of immunosuppression incurred with single organ transplantation.

[Effect of lymph node dissection on prognosis of colon carcinoma]. / Einfluss der Lymphknotendissektion auf die Prognose des Kolonkarzinoms.

Surgical treatment is essential for the prognosis of colon carcinoma. The extension of the lymph node excision depends on several factors, as operative technique and quality of the histopathological examination. In a retrospective analysis of 278 patients who had undergone curative primary resection for colon carcinoma the influence of lymph node excision on the prognosis has been proved. In the period of the analysis (between 1985 and 1993) the mean number of dissected lymph nodes could be increased. This had a strong influence on the prognosis. Whereas in early tumor stages and in patients with an extended lymph node metastasis no correlation between the quantity of lymph node excision and the prognosis could be found, patients with an extended local tumor growth without lymph node metastasis (pT3/4 pN0; p < 0.03) and patients with local lymph node metastasis (pN1; p < 0.0001) gained from the radical lymphadenectomy.