Martin Bodingbauer

Size of surgical margin does not influence recurrence rates after curative liver resection for colorectal cancer liver metastases.

The aim of this study was to examine the relationship between surgical margin status and site of recurrence after potentially curative liver resection for colorectal metastases using an ultrasonic dissection technique.

PHYSICAL PERFORMANCE AND HEALTH-RELATED QUALITY OF LIFE IN MEN ON A LIVER TRANSPLANTATION WAITING LIST

Twenty-six men on a liver transplant waiting list (12 had alcoholic cirrhosis, 8 suffered from posthepatitic cirrhosis, and 6 from cirrhosis of other etiologies) were eligible for this observation. Nineteen subjects underwent exercise testing to determine oxygen uptake at anaerobic threshold. In all patients dynamometry was performed to determine isokinetic muscle strength of knee extensor muscles, and handgrip. Quality of life was evaluated in all patients with the MOS SF-36 questionnaire. Child-Pugh A patients showed 54 +/- 8%, Child-Pugh B patients 36 +/- 2%, and Child-Pugh C patients 31 +/- 4% of VO2 max predicted at the anaerobic threshold (Kruskal-Wallis ANOVA, p < 0.05). Isokinetic muscle strength of the quadriceps femoris (left/right) was 149 +/- 20/134 +/- 14 Nm in Child-Pugh A, 108 +/- 16/114 +/- 19 Nm in Child-Pugh B, and 89 +/- 10/81 +/- 11 Nm in Child-Pugh C patients (Kruskal-Wallis ANOVA, p < 0.05). MOS-SF36 revealed a Child-Pugh class dependent reduced functional status (Kruskal-Wallis ANOVA, p < 0.05). No significant differences in target parameters were found when analysed according to the etiology of cirrhosis. Patients on the liver transplant waiting list do have a stage dependent reduction in physical health. These data are the basis for longitudinal studies measuring the effects of preoperative rehabilitation programs in these patients.

KiSS-1 overexpression as an independent prognostic marker in hepatocellular carcinoma: an immunohistochemical study

The KiSS-1 gene has been reported to play an important role as a metastasis suppressor gene in various human malignancies. However, there is little information about its possible role in hepatocellular carcinoma (HCC). In this study, we evaluated the prognostic significance of the expression of KiSS-1 and its receptor AXOR12 in 142 HCC tissue specimens by immunohistochemistry. By using a cutoff level of 50%, immunoreactivity of KiSS-1 and AXOR12 was found in 6 (4%) and 11 (8%) HCCs. The expression of KiSS-1 and AXOR12 in HCC correlated with each other (r = 0.42, p < 0.0001) and with the expression in corresponding, surrounding liver tissue (both r = 0.35, p < 0.0001). Positive AXOR12 immunoreactivity in HCC correlated with advanced pT-stage of tumors and low tumor grading (r = 0.18, p = 0.032; r = −0.18, p = 0.029). High KiSS-1 expression in HCC had a statistically significant influence on diminished disease-free and overall survival in uni- (p = 0.006 and p = 0.002) and multivariate analysis (r = 2.874, p = 0.027 and r = 2.913, p = 0.026). In this study, we report for the first time that elevated KiSS-1 expression level in HCC correlates with worsened clinical outcome, as an independent prognostic marker for the aggressiveness of HCC.

Prophylactic Bisphosphonate Treatment Prevents Bone Fractures After Liver Transplantation

A randomized controlled prospective open‐label single center trial was performed. At the time of transplantation patients were randomly assigned to one of two treatment arms: The study group of 47 patients received zoledronic acid (ZOL, 8 infusions at 4 mg during the first 12 months after LT), calcium (1000 mg/d) and vitamin D (800 IE/d). The control group consisted of 49 patients who received calcium and vitamin D at same doses (CON). The incidence of bone fractures or death was predefined as the primary endpoint. Secondary endpoints included bone mineral density (BMD), serum biochemical markers of bone metabolism, parameters of trabecular bone histomorphometry and mineralization density distribution (BMDD). Patients were followed up for 24 months. Analysis was performed on an intention‐to‐treat basis. The primary endpoint fracture or death was reached in 26% of patients in the ZOL group and 46% in the CON group (p = 0.047, log rank test). Densitometry results were different between the groups at the femoral neck at 6 months after LT (mean+/‐SD BMD ZOL: 0.80 ± 0.19 g/cm2 vs. CON: 0.73 ± 0.14 g/cm2, p = 0.036). Mixed linear models of biochemical bone markers showed less increase of osteocalcin in the ZOL group and histomorphometry and BMDD indicated a reduction in bone turnover. Prophylactic treatment with the bisphosphonate zoledronic acid reduces bone turnover and fractures after liver transplantation.

Osteopontin expression predicts overall survival after liver transplantation for hepatocellular carcinoma in patients beyond the Milan criteria

BACKGROUND & AIMS Microarray data showed that osteopontin overexpression predicts early HCC-recurrence after liver resection. Osteopontin (OPN) expression could serve as a predictor of HCC-recurrence after OLT. METHODS Osteopontin expression was investigated immunohistochemically in a unique population of 125 HCC-patients undergoing OLT between 1982 and 2002, including 81 patients (65%) outside the Milan criteria. Multivariate analysis of factors associated with median overall survival (OS) and time to recurrence (TTR) was performed. RESULTS Osteopontin was expressed in 40/125 (32%) of the HCCs. Overall survival post-OLT at 1, 2, 3, 5 years was 77%, 62%, 52%, and 43% (median survival 37 months). Overall survival was significantly longer without expression of OPN (p < 0.05; (median OS: 56 vs. 23 months). The same was true for median TTR (p = 0.008). Outside Milan criteria, patients without OPN-expression had better prognosis (median OS: 37.8 vs. 19.2 months, p = 0.003). Tumor recurrence in patients transplanted outside Milan criteria occurred in 43% (23 of 54) of patients without and 70% (19 of 27, p = 0.018) of patients with OPN-expression after a median TTR of 83.5 vs. 13.9 months. On multivariate analysis, vascular invasion and OPN-expression were independently associated with OS and TTR in HCC-patients after OLT. CONCLUSIONS Immunohistochemically detectable Osteopontin in HCC is an independent predictor of tumor recurrence and survival in patients beyond Milan criteria undergoing OLT.

Comparison between C0 and C2 monitoring in de novo renal transplant recipients: retrospective analysis of a single-center experience.

Background. Monitoring immunosuppression with cyclosporine microemulsion formulation (CsA-MEF) by using 2-hour CsA blood levels (C2) has been strongly recommended after kidney transplantation. The aim of our study was to evaluate the impact of C2 monitoring on the clinical outcome early after transplantation in a single-center setting. Methods. Nonsensitized, consecutive, de novo cadaveric kidney-transplant recipients were treated with CsA-MEF, mycophenolate mofetil, and steroids. Patients receiving transplants after January 2002 (n=89) were prospectively monitored by C2 levels (target: 1,500±200 ng/mL [fluorescence-polarization immunoassay]). They were retrospectively compared with the patients receiving transplants during 2001 (n=88) who had been monitored by C0 levels (target: 250±50 ng/mL). Results. In the intention-to-treat analysis, 40 (45.4%) patients in the C0 group and 25 (28.1%) patients in the C2 group received treatment for rejection (P=0.017). The incidence of histologically verified rejection of Banff grade I or higher was 20.45% in the C0 group and 13.48% in the C2 group (P=0.235). In the per-protocol analysis, incidence of treated rejection was 24.7%, and incidence of histologically verified rejection of Banff grade I or higher was 12.35% in the C2 group (P=0.004 and 0.160, respectively, vs. C0). Mean CsA-MEF doses were 1.7 to 2 times higher in the C2 group than in the C0 group throughout follow-up (P=0.019). In the C2 group, target C2 levels were achieved on average 4 days after transplantation, and there was no significant difference in C2 levels between patients who rejected and patients who did not reject. Conclusion. Kidney-transplant recipients monitored by C2 levels receive significantly higher doses of CsA-MEF and have a lower incidence of early acute allograft rejection than patients monitored by C0 levels. In C2 monitored patients, C2 levels are not predictive for the incidence of early allograft rejection.

The advantage of allocating kidneys from old cadaveric donors to old recipients: a single‐center experience

Abstract:  Background:  In January 1999 a new kidney allocation program was launched by the Eurotransplant Foundation, the ‘Eurotransplant Senior Program’ (ESP). Cadaveric donors above the age of 65 yr are allocated to kidney transplant recipients of the same age group.

Effect of intraportal infusion of tacrolimus on ischaemic reperfusion injury in orthotopic liver transplantation: a randomized controlled trial

The increased use of older and/or marginal donor organs in liver transplantation over the last decade calls for strategies to minimize ischaemic reperfusion (I/R) injury to prevent early graft failure. Tacrolimus, a very potent and effective calcineurin inhibitor, was selected because of its ability to ameliorate I/R injury. A randomized, blinded, controlled single‐centre trial of 26 liver transplant recipients was performed between February 2008 and December 2009. Donor organs were randomized to be perfused intraportally during liver transplantation with 1.5 l 5% albumin infusion containing either 20 ng/ml tacrolimus or placebo. The primary end point was liver function as assessed by aspartate transaminase (AST) or alanine transaminase (ALT) levels 6 days after transplantation. Treatment effectiveness was tested by transcriptome‐wide analysis of biopsies. There was no difference in the primary end point, i.e. AST (IU/l) and ALT (IU/l) at day 6 after transplantation between groups. Furthermore, choleastatic parameters as well as parameters of liver synthesis were not different between groups. However, tacrolimus treatment suppressed inflammation and immune response in the transplanted liver on a genome‐wide basis. Intrahepatic administration of tacrolimus did not result in a reduction of AST and ALT within the first week after transplantation. (ClinicalTrials.gov number: NCT00609388)

The effect of steroid pretreatment of deceased organ donors on liver allograft function: A blinded randomized placebo-controlled trial

Background & Aims Brain death-associated inflammatory response contributes to increased risk of impaired early liver allograft function, which might be counterbalanced by steroid pretreatment of the organ donor. The aim of this randomized controlled trial was to elucidate whether steroid pretreatment of liver donors improves early liver allograft function, prevents rejection and prolongs survival. Methods A placebo-controlled blinded randomized clinical trial was performed in three different centers in Austria and Hungary between 2006 and 2008. Ninety deceased organ donors received either 1000 mg of methylprednisolone or placebo 6 h before recovery of organs. The primary end point was the concentration slope of transaminases within the first week. The secondary end point included survival and biopsy-confirmed acute rejection (BCAR) within 3 years after transplantation. Results Of the 90 randomized donors, 83 recipients were eligible for study. The trajectories of ALT and AST were not different between treatments (p = 0.40 and p = 0.13, respectively). Eight subjects died in the steroid and 13 in the placebo group within 3 years after engraftment (RR = 0.63 95% CI [0.29, 1.36], p = 0.31). Eleven recipients experienced biopsy-confirmed rejection (BCAR) in the steroid and 11 in the placebo group (RR = 1.02 95% CI [0.50, 2.10], p = 1.00). No effect modification could be identified in the predefined strata of donor age, sex, cold ischemic time, and cause of donor death. Conclusions Steroid pretreatment of organ donors did not improve outcomes after liver transplantation.

Changes in liver surgery for colorectal cancer liver metastases under neoadjuvant treatment strategies

SummaryBACKGROUND: Liver resection remains the best treatment option for patients with colorectal cancer liver metastases. Major effort on the part of interdisciplinary groups has achieved an impressive gain of possible curative treatment possibilities. METHODS: Recent literature and personal data addressing modern liver surgery and chemotherapeutic treatment protocols are highlighted. RESULTS: Liver surgery has become safe due to technical improvement and the development of specialized centers. Treatment modalities for curative liver resection have expanded and realize better long-term results. Oncosurgical concepts have substantial impact on the prolongation of life expectancy of patients with metastatic colorectal cancer. CONCLUSION: Multimodal treatment strategies designed by different specialists in the management of advanced colorectal cancer have substantially increased the overall survival of these patients.ZusammenfassungGRUNDLAGEN: Die Leberresektion stellt die beste Therapieoption für Patienten mit kolorektalen Lebermetastasen dar. Durch intensive Zusammenarbeit von interdisziplinären Teams konnten die Möglichkeiten der potentiell kurativen Therapie deutlich erweitert werden. METHODIK: Es wird eine Übersicht über rezente Literatur und persönliche Daten, die sich mit moderner Leberchirurgie und neoadjuvanten chemotherapeutischen Protokollen beschäftigen, präsentiert. ERGEBNISSE: Die Leberchirurgie wurde sowohl durch technische Verbesserungen als auch durch die Zentralisierung der Anwendung zu einem sicheren Therapieverfahren. Die therapeutischen Möglichkeiten der kurativen Resektion konnten erweitert werden und mit ihnen die Langzeitprognose. Wesentlichen Beitrag zu dieser Lebensverlängerung stellen onkochirurgische Therapiekonzepte dar. SCHLUSSFOLGERUNGEN: Multimodale Therapiekonzepte, die von unterschiedlichsten Spezialisten in der Therapie des fortgeschrittenen kolorektalen Karzinoms erstellt wurden, haben zu einer beeindruckenden Verlängerung der Lebenserwartung dieser Patienten geführt.