Wacław Hołówko

Incidence, pattern and clinical relevance of microbial contamination of preservation fluid in liver transplantation

BACKGROUND Transmission of pathogens via preservation fluid (PF) is a potential cause of infection among liver transplant recipients. Here, we evaluated the incidence and pattern of microbial contamination of PF and its impact on postoperative graft function after liver transplantation. MATERIAL/METHODS This longitudinal study included data from 41 primary liver transplantations and 5 re-transplantations performed between December 2010 and September 2011. Results of microbiological analyses of 92 PF samples collected before and after the back-table procedure were evaluated in order to establish the incidence and pattern of contamination. The impact of positive PF cultures on early graft function and rate of pathogen transmission was assessed. Post-transplant antibiotic protocol was based on piperacillin/tazobactam administration for a minimum of 10 days. RESULTS The incidence of contamination was 84.8% (39/46), both for samples collected before and after the back-table procedure. Gram-positive low-virulence organisms typical for superficial saprophytic flora, mainly coagulase-negative staphylococci, were predominant. There were no cases of pathogen transmission from PF to the recipient. Positive cultures of PF samples obtained after the back-table procedure were associated with significant elevation of aspartate (p=0.034) and alanine aminotransferase (p=0.048) on the first 5 postoperative days. No significant differences were found regarding serum bilirubin concentration (p=0.335) and international normalized ratio (p=0.137). CONCLUSIONS Despite high incidence of PF contamination, infections caused by pathogens isolated from PF were not observed. However, presence of pathogens in PF might lead to temporary impairment of graft function.

Early post-operative prediction of morbidity and mortality after a major liver resection for colorectal metastases

BACKGROUND An early prediction of poor outcomes is essential in the management of patients after a liver resection. The aim of this study was to evaluate the role of selected biochemical parameters on post-operative day 1 (POD 1) in the prediction of morbidity and mortality after a liver resection for colorectal metastases. METHOD This retrospective study was based on 236 major liver resections for colorectal metastases performed between 2006 and 2011. Results of biochemical tests of blood samples obtained on POD 1 were assessed as predictors of primary outcome measures (hepatic and overall morbidity, 90-day mortality) using multiple regression and receiver-operating characteristics (ROC). RESULTS Hepatic morbidity, overall morbidity and 90-day mortality rates were 18.6%, 28.0% and 4.7%, respectively. On the basis of multiple regression analysis and comparisons of the prediction models, serum bilirubin was selected for the prediction of hepatic (>2.05 mg/dl, sensitivity 69.2%, specificity 71.2%) and overall (>2.05 mg/dl, sensitivity 61.1% and specificity 71.2%) morbidity, and aspartate aminotransferase (AST) was selected for the prediction of 90-day mortality (>798 U/l, sensitivity 62.5% and specificity 90.4%). DISCUSSION Biochemical analyses of blood on POD1 enables stratification of patients into low- and high-risk groups for negative outcomes, with serum bilirubin associated with overall and hepatic morbidity and AST associated with mortality.

Evaluation of Total Tumor Volume and Pretransplantation α-Fetoprotein Level as Selection Criteria for Liver Transplantation in Patients With Hepatocellular Cancer

INTRODUCTION Appropriate selection of hepatocellular cancer (HCC) patients for liver transplantation is crucial to minimize the risk of recurrence and provide long-term outcomes comparable with those for other indications. Selection criteria based on total tumor volume (TTV) and α-fetoprotein (AFP) concentrations were proposed in a recent large study. The aim of this study was to evaluate the results of liver transplantation for HCC within and beyond these criteria. MATERIAL AND METHODS This retrospective study included 104 patients with HCC who underwent liver transplantation. Risk factors for overall survival and tumor recurrence were evaluated. Overall survival and cumulative tumor recurrence rate for patients with TTV <115 cm(3), AFP concentration <400 ng/mL, and no macrovascular invasion (76/104; 73.1%) were evaluated and compared with those for the remaining patients (28/104; 26.9%). RESULTS Pretransplantation AFP concentration >400 ng/mL (P = .016; hazard ratio [HR], 3.36; 95% confidence intervals [CI], 1.25-9.03) was the only risk factor for overall survival. TTV >115 cm(3) (P = .021; HR 4.29; 95% CI, 1.24-14.81) and AFP concentration >400 ng/mL (P = .002; HR 6.97; 95% CI, 2.02-24.03) were independent risk factors for recurrence. The estimated 3-year tumor recurrence rate was 4.2% for patients with TTV <115 cm(3), AFP concentration <400 ng/mL, and no macrovascular invasion compared with 57.2% for the remaining patients (P < .00001). The 3-year overall survival rate of patients within and beyond this criteria was 81.7% and 64.6%, respectively (P = .0628). CONCLUSIONS In contrast to other criteria, selection of HCC patients for liver transplantation on the basis of TTV and AFP concentration relates to both morphological features and tumor biology. Although fulfillment of these criteria was more than 1.5-fold higher than that of the Milan criteria, the rate of tumor recurrence was exceptionally low.

The relevance of intestinal dysbiosis in liver transplant candidates

The gut microbial ecosystem plays an important role in the pathogenesis of liver diseases. However, the association of microbial community structure with the severity of liver dysfunction is not completely understood.

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.

Initial prevalence of anal human papilloma virus infection in liver transplant recipients

Although liver transplant recipients are at increased risk of human papilloma virus (HPV)‐related anal cancer, limited data are available regarding the initial prevalence of anal HPV infection in this population. Anal swabs collected from 50 liver transplant recipients within the first three postoperative weeks were subjected to real‐time polymerase chain reaction for detection of the four HPV genotypes: 6, 11, 16, and 18. Predictors of any, low‐risk, and high‐risk anal HPV infection were evaluated. Overall, the prevalence of any anal HPV infection was 18.0%, with the corresponding rates for high‐ and low‐risk HPV genotypes being 8.0% and 10.0%, respectively. Infection with any type of anal HPV was higher in patients with hepatitis B virus (HBV) infection (P = 0.027), ≥3 sexual partners (P = 0.031), and alcoholic liver disease (P = 0.063). HBV infection was the only factor significantly associated with high‐risk HPV infection (P = 0.038). Male sex (P = 0.050), age ≥52 years (P = 0.016), ≥30 sexual partners (P = 0.003), age at first intercourse ≤18 years (P = 0.045), and time since first intercourse ≥38 years (P = 0.012) were identified as predictors of low‐risk HPV infection. These results indicate that HPV vaccination of liver transplant candidates and screening for anal HPV infection in high‐risk groups should be considered.

Long-term results of liver resection in the treatment of patients with hepatocellular carcinoma.

UNLABELLED The aim of the study was the analysis of the results of liver resection in the treatment of patients with hepatocellular carcinoma, taking into consideration the selected factors based on the departments material. MATERIAL AND METHODS Data of 122 patients subject to liver resection due to hepatocellular carcinoma at the Department of General, Transplantation and Liver Surgery, Medical University of Warsaw, were subject to retrospective analysis. The influence of selected factors on the long-term treatment results was determined, and the patient survival depending on the tumor stage as per the TNM scale was compared. The statistical significance threshold was set at p = 0.05. RESULTS 1- and 3-year overall survival and recurrence-free survival in the whole patient group was 82.1% and 56.3%, and 57.7% and 20.1%, respectively. The perioperative mortality rate was 1.6%. The neoplasm advancement exceeding the first stage on the TNM scale was associated with lower values of overall survival (p = 0.001, HR = 3.7) and recurrence-free survival (p = 0.00008, HR = 3.8). Elevation of AFP was the only independent prognostic factor for overall survival (p = 0.04, HR = 1.04 at alpha-fetoprotein levels > 1000 ng/ml), while the presence of neoplastic emboli in small blood vessels was an independent risk factor for HCC recurrence (p = 0.02, HR = 2.24). CONCLUSIONS The alpha-fetoprotein levels and presence in the histopathological examination of neoplastic emboli in small blood vessels are independent prognostic factors for outcome of patients operated for hepatocellular carcinoma. The diagnosis of neoplasm at stage 1 as per TNM significantly improves long-term results of resective treatment.

Transarterial Chemoembolization Prior to Liver Transplantation in Patients with Hepatocellular Carcinoma

BACKGROUND Transarterial chemoembolization (TACE) induces ischemic tumor necrosis, which is intensified by regional chemotherapy. By reducing the active tumor tissue, it can be assumed that patients on the waiting list for liver transplantation may benefit from this locoregional treatment. The aim of this study was to assess the relevance of TACE in hepatocellular carcinoma (HCC) patients before liver transplantation. MATERIAL AND METHODS A retrospective analysis was performed on data of 229 patients who were transplanted for HCC. A group of 75 patients were treated with TACE prior to liver transplantation. Tumor necrosis related to pretransplantation locoregional treatment was assessed in an explanted liver and classified into extensive (51-100%), moderate (26-50%) and limited (<25%) grades. Five-year recurrence-free survival was estimated using the Kaplan-Meier method and compared using the log-rank test. RESULTS In total, 143 HCC lesions were treated with TACE. Extensive necrosis was found in 63 (44.0%) tumors. Moderate and limited necrosis were observed in 42 (29.4%) and 38 (26.6%) tumors, respectively. In 36 (58.1%) explanted livers, every tumor was classified as extensively necrotic. The 5-year recurrence-free survival was estimated as 81.6% in the group not treated with TACE prior to liver transplantation (TACE-) and as 73.1% in the TACE+ group (p=0.169). Among patients not fulfilling the Milan criteria, 5-year recurrence-free survival was 63.1% in TACE- and 65.1% in TACE+ (p=0.656). CONCLUSIONS In conclusion, TACE prior to liver transplantation is effective in inducing tumor necrosis. However, evidence of benefits in long-term results after liver transplantation requires further confirmation.

Short and Long-Term Outcomes After Primary Liver Transplantation in Elderly Patients

UNLABELLED The number of elderly patients undergoing liver transplantation (LT) is increasing worldwide. The aim of the study was to evaluate the impact of recipient age exceeding 60 years on early and long-term outcomes after LT. MATERIAL AND METHODS This study comprised data of 786 patients after primary LT performed at a single center between January 2005 and October 2012. Patients over and under 60 years of age were compared with respect to baseline characteristics and outcomes: postoperative mortality (90-day) and 5-year patient (PS) and graft (GS) survival. Associations between recipient age exceeding 60 years and LT results were assessed in multiple Cox regression models. RESULTS Recipients older than 60 years (n=107; 13.6%) were characterized by more frequent hepatitis C virus infections (p<0.001), malignancies (p<0.001), and cardiovascular comorbidities (p<0.001); less frequent primary sclerosing cholangitis (p=0.002) and Roux-en-Y hepaticojejunostomy (p<0.001); lower Model for End-stage Liver Disease (MELD; p=0.043); and increased donor age (p=0.012). Fiveyear PS of older and younger recipients was 72.7% and 80.6% (p=0.538), while the corresponding rates of GS were 70.3% and 77.5% (p=0.548), respectively. Recipient age exceeding 60 years was not significantly associated with postoperative mortality (p=0.215), PS (p=0.525) and GS (p=0.572) in multivariate analyses. The list of independent predictors comprised MELD (p<0.001) for postoperative mortality; malignancies (p=0.003) and MELD (p<0.001) for PS; and malignancies (p=0.003), MELD (p<0.001) and donor age (p=0.017) for GS. CONCLUSIONS Despite major differences between elderly and young patients, chronological age exceeding 60 years alone should not be considered as a contraindication for LT.

Hepatic abscess: a rare complication after liver transplant.

This study was conducted to evaluate the predisposing factors, microbiology, treatment, and outcomes associated with hepatic abscess, a rare but serious complication which may accur after an orthotopic liver transplant (OLT).