Die Milan Kriterien sind zu unflexibel und schließen zu viele Patienten mit biologisch günstigem HCC von der Lebertransplantation (LTX) aus. Neben Tumorgröße bestimmen vor allem biologische Aggressivität und Inflammation die Prognose. Das Ziel dieser Studie war es den prognostischen Einfluss von präoperativen serologischen Faktoren der Tumorinvasivität (AFP) und pro-inflammatorischen Reaktion (C-reaktives Protein; CRP) auf das Outcome nach LTX zu evaluieren.

Background: The Milan criteria (MC) are too restrictive in selecting suitable liver transplant (LT) patients with hepatocellular carcinoma (HCC). Apart from alpha-fetoprotein (AFP), parameters of inflammation are discussed to improve the selection process. The aim of this retrospective study was to analyze the prognostic impact of combining AFP and C-reactive protein (CRP) in LT for HCC. Patients and methods: 119 patients following LT for HCC were analyzed. Tumors were classified as Milan In or Milan Out. The impact of clinical, serological and histopathological features on posttransplant outcome was analyzed by uni- and multivariate analysis. Results: Only AFP >100ng/ml (Odds ratio [OR] = 13.31), CRP >0.8mg/dl (OR = 13.97) and microvascular invasion (MVI; OR = 15.77) were identified as independent predictors of HCC relapse. Posttransplant HCC recurrence rates were 2.3%, 14% and 84% in patients with low (AFP ≤100 ng/ml + CRP ≤0.8 mg/dl), intermediate (AFP >100 ng/ml or CRP >0.8 mg/dl) and high (AFP >100 ng/ml + CRP >0.8 mg/dl) serological tumor viability (STV). In the Milan Out cohort, the actuarial 5-year recurrence-free survival rates were 91.7% in low and 83.6% in intermediate STV (log rank = 0.496), and thus not different from Milan In patients (88.4%; 82.5%). In contrast, it was 0% in high STV beyond MC patients. High STV was identified as the most powerful clinical predictor of MVI (OR = 7.5; p = 0.002). Conclusion: STV based on standard variables AFP and CRP may indicate futile LT and, thereby, safely increase the number of eligible transplant candidates.

Durch die Up-to-seven (UTS) Kriterien (Summe aus Anzahl und max. Tumorgröße ≤7 in Summe) erweitert sich der Pool an geeigneten Lebertransplantationskandidaten mit einem Hepatozellulären Karzinom (HCC). Allerdings beruhen diese auf pathologischen und nicht auf klinischen Tumorvariablen sowie auf das Fehlen von mikrovaskulärer Tumorinvasion (MVI). 18F-FDG PET ist ein hocheffektives diagnostisches Tool um Tumore mit MVI zu identifizieren. Das Ziel dieser Studie war es die UTS Kriterien basierend auf präoperativem Tumorstaging kombiniert mit 18F-FDG PET zu validieren.

Aims: Surgical trauma by ischemia reperfusion (I/R) injury is discussed to promote risk of hepatocellular carcinoma (HCC) recurrence following liver transplantation (LT). Treatment with prostaglandin E1 was shown to attenuate I/R damage in liver transplant patients. The aim of this retrospective study was to assess the impact of treatment with the stable PGE1-analog alprostadil (Minprog®, Pfizer Pharma) on risk of HCC recurrence after LT. Methods: A total of 106 liver transplant patients with HCC were included in this study. Fifty-nine of them underwent early post-LT treatment with PGE1, while 47 patients did not. The impact of treatment with alprostadil along with other relevant clinical and histopathologic parameters on overall and recurrence-free survival was assessed by uni- and multivariate analysis. Subgroup analysis was performed according to Milan staging. Results: Twenty-five patients were suffering from HCC recurrence (23.6%). Tumor recurrence rate was significantly higher in the non-PGE1-group (36.2%) as compared to the PGE1-subpopulation (13.6%; P=0.006). In multivariate analysis, only absence of vascular invasion (HR 32.5), well/moderate tumor differentiation (HR 3.2) and AFP level ≤400 IU/ml (HR 4.1) were identified as independent predictors of recurrence-free outcome (P<0.05), while PGE1-tretment did not reach statistical significance (HR 2.6). In contrast, PGE1-treatment (HR 5.1) along with tumor grading (HR 6.1) was assessed as variable with independent prognostic impact in patients with HCC beyond the Milan criteria (P=0.005). In the subset of Milan Out recipients, 3- and 5-year recurrence-free survival rates were 84% and 78% following alprostadil therapy, but only 31.3% and 25% without PGE1-treatment, respectively (P<0.001). Conclusions: This is the first study to demonstrate a beneficial impact of PGE1 treatment in liver transplant patients with HCC, possibly related to attenuation of I/R injury. Particularly patients with advanced HCC (exceeding Milan criteria) may, thereby, achieve excellent outcome.

Hintergrund: Es wird vermutet, dass die perioperative Gabe von Erythrozytenkonzentraten (EK) negative immunsuppressive und immunmodulatorische Effekte hat. Das Ziel dieser Studie war es, den Einfluss des Transfusionsbedarfs auf das Risiko für ein Tumorrezidiv nach Lebertransplantation (LTX) wegen eines hepatozellulären Karzinoms (HCC) zu analysieren.

BACKGROUND:Surgical stress by hepatic ischaemia-reperfusion (I/R) is supposed to promote intra- and extrahepatic tumour recurrence. Treatment with prostaglandin E1 (PGE1) has been shown to attenuate hepatic I/R injury in liver transplant patients, but the potential anti-cancer effects have not been analysed.AIM:To evaluate the impact of PGE1 therapy on risk of hepatocellular carcinoma (HCC) recurrence in liver transplant patients.METHODS:A retrospective review of 106 liver transplant patients with HCC was conducted. Fifty-nine patients underwent early post-liver transplantation (LT) treatment with the stable PGE1 analogue alprostadil. Administration of alprostadil was correlated with outcome in uni- and multivariate analysis. Subgroup analysis focused on patients with HCC beyond the Milan criteria (Milan Out) on radiographic imaging.RESULTS:Three- and 5-year recurrence-free survival rates were 87.9% and 85.7% in the PGE1-group, but only 65.3% and 63.1% in the non-PGE1-population (P = 0.003). Multivariate Cox regression analysis identified absence of PGE1-treatment (HR = 11.42), along with presence of poor tumour grading (HR = 2.69) and microvascular tumour invasion (HR = 35.8) to be independently associated with early (within 12 months) HCC recurrence. In Milan Out-patients, only therapy with PGE1 (HR = 5.09) and well/moderate tumour differentiation (HR = 6.51) were independent promoters of recurrence-free survival.CONCLUSIONS:Treating hepatic ischaemia-reperfusion injury with alprostadil reduces the risk of early HCC recurrence following LT. In particular patients with HCC exceeding the Milan criteria seem to benefit from PGE1-treatment. The molecular mechanisms of the anti-tumour effects need to be further assessed.

Ischämie-Reperfusion (I/R) setzt pro-inflammatorische Mediatoren frei, welche die intra- und extraheaptische Tumorentwicklung unterstützen. C-reaktives Protein (CRP) ist ein etablierter Marker für Inflammation und „chirurgischen Stress“. Das Ziel dieser Studie war es, den prognostischen Stellenwert des früh nach Lebertransplantation (LTX) exprimierten CRP-Spiegels auf das Überleben bei Patienten mit einem hepatozellulären Karzinom (HCC) zu analysieren.

AIM:The aim of this trial was to evaluate the impact of conversion from a calcineurin-inhibitor (CNI)-based immunosuppressive regimen to mycophenolate mofetil (MMF) and reduced-dose CNI on long-term renal function and survival in a series of 63 liver transplant patients with CNI-induced renal dysfunction.METHODS:CNI dosage was significantly tapered after introduction of 2,000 mg MMF per day. Renal function was assessed by determination of serum creatinine levels and calculated creatinine clearance (CCl). The impact of relevant clinical parameters on renal function and survival post-conversion was analyzed by univariate and multivariate analysis.RESULTS:At 60 months post-conversion, mean creatinine level had significantly declined from 197.2±58.3 μmol/l at baseline to 160.0±76.5 μmol/l, and mean CCl has significantly increased from 38.4±13.4 ml/min at baseline to 47.9±21.1 ml/min (p<0.001), respectively. Forty-six patients (73.1%) demonstrated sustained renal response to modified immunosuppression. Full-dose MMF medication (p=0.006) and the early conversion (p=0.02) were identified as independent predictors of persistent renal function improvement. Sustained renal response to MMF plus reduced-dose CNI was identified as the most relevant independent promoter of long-term survival (hazard ratio 6.9). Five-year survival rate post-conversion was 93.9% in renal responders and 64.3% in renal non-responders (log rank<0.001).CONCLUSIONS:Sustained renal response to MMF and CNI dose reduction promotes long-term survival in liver transplant patients with CNI-induced renal dysfunction.

Transplant InternationalVolume 23, Issue s2 p. 3-23 Free Access Presentation Abstracts First published: 06 September 2010 https://doi.org/10.1111/j.1432-2277.2010.01152.xAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat Volume23, Issues2Special Issue: Abstracts of the 19th Annual Congress of the German Transplantation Society, Hamburg, Germany, 7-9 October 2010October 2010Pages 3-23 RelatedInformation

The aim of this retrospective trial was to analyze the value of preoperative (18)F-fluoro-deoxyglucose positron emission tomography ((18)F-FDG PET) to predict parameters of tumor aggressiveness among liver transplant (OLT) patients with hepatocellular carcinoma (HCC). Fifty-five patients with HCC underwent (18)F-FDG-PET during evaluation for OLT. Nineteen patients demonstrated increased (18)F-FDG uptake on PET pre-OLT (PET(+)), and 36 patients revealed negative PET findings (PET(-)). PET(+) patients showed a relative risk of 9.5 and 6.4 for poor differentiation and for microvascular invasion (MVI) in the HCC at explant pathology, respectively. Of the 10 patients (18.2%) who developed HCC recurrences, 9 (90%) revealed increased (18)F-FDG uptake pre-OLT; only 1 (10%) showed a PET(-) status (P < .001). Apart from poor tumor differentiation, PET(+) status was identified as an independent predictor of tumor recurrence post-OLT (odds ratio, 23.9). Our study demonstrated that (18)F-FDG uptake on PET is a reliable preoperative predictor of tumor recurrence after OLT in patients with HCC, triggered by its high association with poor tumor differentiation and MVI.