Jan Stypułkowski

Relevance of Pre-Transplant α-fetoprotein Dynamics in Liver Transplantation for Hepatocellular Cancer.

BACKGROUND The magnitude of pre-transplant a-fetoprotein (AFP) changes has been advocated to be a superior predictor of hepatocellular cancer (HCC) recurrence following liver transplantation. The aim of this study was to compare AFP dynamics and last pre-transplant AFP as risk factors for post-transplant HCC recurrence. MATERIAL AND METHODS Data of 146 patients after liver transplantation for HCC were analyzed retrospectively. RESULTS While last pre-transplant AFP was a significant predictor of microvascular invasion (p=0.006) and poor tumor differentiation (p=0.020), AFP slope was associated only with microvascular invasion (p=0.029). Notably, last pre-transplant AFP (p<0.001), but not AFP slope (p=0.279), was an independent risk factor for recurrence. No significant effects of AFP slope were also found following division of patients into those with pre-transplant AFP <100 (p=0.260) and those with AFP >100 (p=0.178) ng/mL. Moreover, prediction of recurrence based on last pre-transplant AFP was superior (p=0.018) to those based on AFP slope. Recurrence-free survival at 5 years was superior in patients with pre-transplant AFP persistently at (97.3%) or dropping to <100 ng/mL (100.0%) as compared to patients with AFP rising to (75.0%) or persistently at >100 ng/mL (38.4%; p<0.001). CONCLUSIONS The risk of post-transplant HCC recurrence is dependent on the last pre-transplant AFP regardless of its previous dynamics.

Evolution Of The Results Of 1500 Liver Transplantations Performed In The Department Of General, Transplant And Liver Surgery Medical University Of Warsaw.

UNLABELLED Liver transplantation is a well-established treatment of patients with end-stage liver disease and selected liver tumors. Remarkable progress has been made over the last years concerning nearly all of its aspects. The aim of this study was to evaluate the evolution of long-term outcomes after liver transplantations performed in the Department of General, Transplant and Liver Surgery (Medical University of Warsaw). MATERIAL AND METHODS Data of 1500 liver transplantations performed between 1989 and 2014 were retrospectively analyzed. Transplantations were divided into 3 groups: group 1 including first 500 operations, group 2 including subsequent 500, and group 3 comprising the most recent 500. Five year overall and graft survival were set as outcome measures. RESULTS Increased number of transplantations performed at the site was associated with increased age of the recipients (p<0.001) and donors (p<0.001), increased rate of male recipients (p<0.001), and increased rate of piggyback operations (p<0.001), and decreased MELD (p<0.001), as well as decreased blood (p=0.006) and plasma (p<0.001) transfusions. Overall survival was 71.6% at 5 years in group 1, 74.5% at 5 years in group 2, and 85% at 2.9 years in group 3 (p=0.008). Improvement of overall survival was particularly observed for primary transplantations (p=0.004). Increased graft survival rates did not reach the level of significance (p=0.136). CONCLUSIONS Long-term outcomes after liver transplantations performed in the Department of General, Transplant and Liver Surgery are comparable to those achieved in the largest transplant centers worldwide and are continuously improving despite increasing recipient age and wider utilization of organs procured from older donors.

Limitations of predicting microvascular invasion in patients with hepatocellular cancer prior to liver transplantation

Microvascular invasion (MVI) is well known to negatively influence outcomes following surgical treatment of hepatocellular cancer (HCC) patients. The aim of this study was to evaluate the rationale for prediction of MVI before liver transplantation (LT). Data of 200 HCC patients after LT were subject to retrospective analysis. MVI was present in 57 patients (28.5%). Tumor number (p = 0.001) and size (p = 0.009), and alpha-fetoprotein (p = 0.049) were independent predictors of MVI used to create a prediction model, defined as: 0.293x(tumor number) + 0.283x(tumor size in cm) + 0.164xloge(alpha-fetoprotein in ng/ml) (c statistic  =  0.743). The established cut-off (≥2.24) was associated with sensitivity and specificity of 72%. MVI was not an independent risk factor for recurrence (p = 0.307), in contrast to tumor number (p = 0.047) and size (p < 0.001), alpha-fetoprotein (p < 0.001) and poor differentiation (p = 0.039). Recurrence-free survival at 5 years for patients without MVI was 85.9% as compared to 83.3% (p = 0.546) and 55.3% (p = 0.001) for patients with false negative and true positive prediction of MVI, respectively. The use of both morphological and biological tumor features enables effective pre-transplant prediction of high-risk MVI. Provided that these parameters are combined in selection of HCC patients for LT, pre-transplant identification of all patients with MVI does not appear necessary.

Liver Transplantation Outcomes in Recipients with High Model for End-Stage Liver Disease (MELD) Scores: The Relevance of MELD Scores

BACKGROUND The aim of this study was to assess risk factors for postoperative mortality after liver transplantation among patients with Model for End-Stage Liver Disease (MELD) scores ≥35, with special focus on the MELD scores. MATERIAL AND METHODS Data from 68 primary liver transplantations in patients with MELD scores ≥35 among 1376 liver transplantations performed in the Department of General, Transplant, and Liver Surgery (Medical University of Warsaw) between January 2002 and October 2014 were analyzed retrospectively. Postoperative (90-day) mortality was set as the primary outcome measure. RESULTS Postoperative mortality was 29.4% (20 of 68). The overall survival rates after 1, 5, and 10 years were 61.9%, 59.7%, and 59.7%, respectively. According to univariate analyses, MELD (p=0.014), conventional technique of liver transplantation (p=0.049), intraoperative fresh frozen plasma (p=0.040), and red blood cells (p=0.026) transfusions were risk factors for postoperative mortality. MELD score was the only independent risk factor for postoperative mortality (p=0.023) in multivariate analysis. According to receiver operating characteristics analysis, the optimal cut-off for MELD score in prediction of postoperative mortality was ≥43 (Area Under Curve=0.703, 95% Confidence Interval 0.575-0.831). Postoperative mortality was 21.4% and 42.3% among patients with MELD score <43 and ≥43, respectively (p=0.066). CONCLUSIONS MELD score is an important predictor of early mortality after liver transplantation, even among recipients with high MELD scores. In particular, patients with MELD score ≥43 should be considered as very high-risk candidates for liver transplantation.

Results of liver transplantation in patients with acute liver failure due to Amanita phalloides and paracetamol (acetaminophen) intoxication

Introduction Amanita phalloides and paracetamol intoxications are responsible for the majority of acute liver failures. Aim To assess survival outcomes and to analyse risk factors affecting survival in the studied group. Material and methods Of 1369 liver transplantations performed in the Department of General, Transplant, and Liver Surgery, Medical University of Warsaw before December 2013, 20 (1.46%) patients with Amanita phalloides (n = 13, 0.95%) and paracetamol (n = 7, 0.51%) intoxication were selected for this retrospective study. Overall and graft survival at 5 years were set as primary outcome measures. Results Five-year overall survival after liver transplantation in the studied group was 53.57% and 53.85% in patients with paracetamol and Amanita phalloides poisoning, respectively (p = 0.816). Five-year graft survival was 26.79% for patients with paracetamol and 38.46% with Amanita phalloides intoxication (p = 0.737). Risk factors affecting patient survival were: pre-transplant bilirubin concentration (p = 0.023) and higher number of red blood cells (p = 0.013) and fresh frozen plasma (p = 0.004) transfused intraoperatively. Likewise, higher number of red blood cells (p = 0.012) and fresh frozen plasma (p = 0.007) transfused were risk factors affecting 5-year graft survival. Surprisingly, donor and recipient blood type incompatibility was neither the risk factor for 5-year overall survival (p = 0.939) nor the risk factor for 5-year graft survival (p = 0.189). Conclusions In selected intoxicated patients urgent liver transplantation is the only successful modality of treatment. Risk factors affecting survival are in correspondence with the patients pre-transplant status (bilirubin level in serum) and intraoperative status (number of red blood cells and fresh frozen plasma transfused).

Ischemia-reperfusion injury and the risk of hepatocellular carcinoma recurrence after deceased donor liver transplantation

This study aimed to evaluate the effects of ischemia-reperfusion injury (IRI) on the risk of hepatocellular carcinoma (HCC) recurrence after liver transplantation. Data of 195 patients were retrospectively analysed. Post-reperfusion aspartate (AST), alanine transaminase, and lactate dehydrogenase (LDH) levels were the primary measures of IRI. Tumour recurrence was the primary endpoint. Post-reperfusion AST was a continuous risk factor for tumour recurrence in patients within Milan criteria (p = 0.035), with an optimal cut-off of 1896 U/L. Recurrence-free survival of patients within Milan criteria and post-reperfusion AST of <1896 and ≥1896 U/L was 96.6% and 71.9% at 5 and 3.7 years, respectively (p = 0.006). Additionally, post-reperfusion AST and LDH exceeding the upper quartile significantly increased the risk of HCC recurrence in patients within Milan criteria (p = 0.039, hazard ratio [HR] = 5.99 and p = 0.040, HR = 6.08, respectively) and to a lesser extent, in patients within Up-to-7 criteria (p = 0.028, HR = 3.58 and p = 0.039, HR = 3.33, respectively). No other significant IRI effects were found in patients beyond the Up-to-7 criteria and in analyses stratified for independent risk factors for recurrence: tumour number and differentiation, alpha-fetoprotein, and microvascular invasion. Thus, IRI exerts major negative effects on the risk of HCC recurrence after liver transplantation in patients within standard and extended criteria.

Reoperations for Intraabdominal Bleeding Following Deceased Donor Liver Transplantation.

UNLABELLED Intraabdominal hemorrhage remains one of the most frequent surgical complications after liver transplantation. The aim of the study was to evaluate risk factors for intraabdominal bleeding requiring reoperation and to assess the relevance of the reoperations with respect to short- and long-term outcomes following liver transplantation. MATERIAL AND METHODS Data of 603 liver transplantations performed in the Department of General, Transplant and Liver Surgery in the period between January 2011 and September 2014 were analyzed retrospectively. Study end-points comprised: reoperation due to bleeding and death during the first 90 postoperative days and between 90 postoperative day and third post-transplant year. RESULTS Reoperations for intraabdominal bleeding were performed after 45 out of 603 (7.5%) transplantations. Low pre-transplant hemoglobin was the only independent predictor of reoperation (p=0.002) with the cut-off of 11.3 g/dl. Postoperative 90-day mortality was significantly higher in patients undergoing reoperation as compared to the remaining patients (15.6% vs 5.6%, p=0.008). Post-transplant survival from 90 days to 3 years was non-significantly lower in patients after reoperation for bleeding (83.3%) as compared to the remaining patients (92.2%, p=0.096). Nevertheless, multivariable analyses did not reveal any significant negative impact of reoperations for bleeding on short-term mortality (p=0.589) and 3-year survival (p=0.079). CONCLUSIONS Surgical interventions due to postoperative intraabdominal hemorrhage do not appear to affect short- and long-term outcomes following liver transplantation. Preoperative hemoglobin concentration over 11.3 g/dl is associated with decreased risk of this complication, yet the clinical relevance of this phenomenon is doubtful.

Comparison of Total Tumor Volume, Size and Number of Colorectal Liver Metastases in Prediction of Survival in Patients after Liver Resection.

UNLABELLED Liver is the most common location of the colorectal cancer metastases occurrence. Liver resection is the only curative method of treatment. Unfortunately it is feasible only in 25% of patients with colorectal liver metastases, often because of the extensiveness of the disease. The aim of the study was to evaluate the predictive value of total tumor volume, size and number of colorectal liver metastases in patients treated with right hemihepatectomy. MATERIAL AND METHODS A retrospective analysis was performed in a group of 135 patients with colorectal liver metastases, who were treated with right hemihepatectomy. Total tumor volume was estimated based on the formula (4/3)πr³. Moreover, the study included an analysis of data on the number and size of tumors, radicality of the resection, time between primary tumor resection and liver resection, pre-operative blood serum concentration of carcinoembryonal antigen (CEA) and carcinoma antigen Ca 19-9. The predictive value of the factors was evaluated by applying a Cox proportional hazards model and the area under the ROC curve. RESULTS The univariate analysis has shown the predictive value of size of the largest tumor (p=0.033; HR=1.065 per each cm) on the overall survival, however no predictive value of number of tumors (p=0.997; HR=1.000) and total tumor volume (p=0.212; HR=1.002) was observed. The multivariate analysis did not confirm the predictive value of the size of the largest tumor (p=0.141; HR=1.056). In the analysis of ROC curves, AUROC for the total tumor volume, the size of the largest tumor and the number of tumors were 0.629, 0.608, 0.520, respectively. CONCLUSIONS Total tumor volume, size and number of liver metastases are not independent risk factors for the worse overall survival of patients with colorectal liver metastases treated with liver resection, therefore increased values of these factors should not be a contraindication for surgical treatment.