Łukasz Masior

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).

Surgical treatment of gall-bladder cancer.

Despite the aggressive nature and poor prognosis of gall-bladder cancer there is a group of patients who can achieve significant benefits from a radical surgical treatment. The possibility of obtaining long-term survival, even in case of patients with locally advanced cancer and metastases to regional lymph nodes, prompts to verify nihilistic approach to the treatment of this disease. Obviously such therapy can and should be performed only in centers specializing in hepatobiliary surgery. Due to the high recurrence rate, most of which are systemic, the hope of improving treatment outcomes should be sought in the use of combination therapy, based on a new chemotherapy and chemoradiotherapy regimens with the addition of targeted therapy. Unfortunately, the current application of these methods did not bring the expected benefits.

Surgical treatment of hepatic Echinococcus granulosus

Introduction Infections caused by metacestode stage of the Echinococcus granulosus in humans result in disease named cystic echinococcosis. Aim To present the outcomes of patients treated surgically for cystic echinococcosis of the liver. Material and methods One hundred and nineteen patients treated in the period between 1989 and 2014 due to E. granulosus infection in the Department of General, Transplant, and Liver Surgery, Medical University of Warsaw were selected for this retrospective study. Diagnostic protocol included imaging examinations, i.e. ultrasonography and computed tomography of the abdomen. Blood samples where used to proceed sequential enzyme-linked immunosorbent assay (ELISA) using Em2plus antigen as well as polymerase chain reaction (PCR) to detect E. granulosus. Results Surgery was the choice for treatment for almost all of the patients (98.3%). In 40 (34.2%) patients right hemihepatectomy, in 19 (16.2%) patients left hemihepatectomy, and in 21 (17.9%) patients bisegementectomy were performed. Postoperative complications occurred in 4 (3.4%) patients. In 3 patients biliary fistula requiring endoscopic treatment was observed, and 1 patient had subdiaphragmatic abscess successfully treated with drainage under ultrasound guidance. None of the patients died in the postoperative period, and the 1-, 5-, and 10-year survival rates were 100.0%, 90.9%, and 87.9%, respectively. Conclusions Surgical treatment of the symptomatic cystic echinococcosis is the modality of choice for E. granulosus infection of the liver. Despite substantial development of diagnostic methods and new management opportunities, echinococcal infection still presents a challenge for epidemiologists, pharmacologists, and clinicists.

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.

Pushing the age limit and reducing the number of contraindications of liver resections in cancer-bearing patients — a case report

Liver resections are performed in increasing numbers due to oncological indications. Thus, the indications for surgical treatment of liver tumors are constantly expanding. Advanced age and other comorbidities often exclude this group of patients from treatment by liver resection. Patient C.S. (80 y.a., height 166 cm, weight 97 kg, ASA = 4) with risk factors was admitted for resection of metastatic lesions (adenocarcinoma) of the cecum to the liver. The patient was diagnosed with hypertension, atherosclerosis, stable coronary heart disease, type 2 diabetes, chronic renal failure (eGFR = 37), obesity, degenerative spinal lesions, sigmoid colon diverticulitis, dystonic tremor of the head. Previously operated upon and had amputation of the uterus with appendages (2005), cholecystectomy, right hemicolectomy (2012) complicated by respiratory failure with the need for ventilation seven days post-surgery. Prior to surgery, the patient had imaging tests such as ultrasound, CT and MRI scans of the abdomen, which confirmed a 55mm metastatic tumor in the seventh segment of the liver. The results were analyzed during a radiological and surgical consultation in order to prepare the safest available surgical access and the scope of the planned resection. A cardiac echocardiography was performed and the patient had a cardio-, neuro- and anesthetic consultation. The patient was fully informed about the high risk of complications and possible operational failure. During surgery a right hemihepatectomy was performed. The resected lobe weighed 712 g. Blood loss was < 500 ml, 2 units RBC and 2 units FFP were transfused. The surgery and the postoperative period proceeded without serious complications. The only problem was a short-lived biliary fistula, which healed spontaneously. Age and comorbid conditions are often a contraindication for surgery, but with proper medical support, the opportunity to interact with other professionals and thorough preparation of the patient and the team of surgeons, the risk of failure can be significantly minimized. A modern, personalized, multidisciplinary approach towards each patient can expand indications and reduce contraindications for hepatic resection.

Liver Transplantation in Patients with Cryptogenic Cirrhosis Provides Excellent Long-Term Outcome

BACKGROUND Cryptogenic cirrhosis (CC) is an indication for liver transplantation in 5-9% of recipients. Diagnosis is made when other diagnostic possibilities have been ruled out. The aim of this study was to present long-term outcomes of liver transplantation for CC. MATERIAL AND METHODS There have been 1367 liver transplantations performed during the years 1994-2013 in the Department of General, Transplant and Liver Surgery at the Medical University of Warsaw. This retrospective study comprised 55 patients after liver transplantation for CC (4.0%). Perioperative mortality (30 days) and patient and graft 1-, 5-, and 10-year survival rates were set as outcome measures. RESULTS Peri-operative mortality reached 10.9% (6 of 55). The 1-, 5- and 10-year patient and graft survival rates were 85.2%, 78.8%, and 73.9%, respectively, and 83.3%, 74.5%, and 74.5%, respectively. In univariate analyses, the following parameters significantly influenced patient survival: pre-operative aspartate (AST; p=0.013) and alanine (ALT; p=0.043) aminotransferases activity, INR (p=0.040), bilirubin concentration (p=0.045), and donor age (p=0.033). Similarly, graft survival was significantly associated with AST (p=0.013), ALT (p=0.043), bilirubin concentration (p=0.044), INR (p=0.038), and recipient sex (p=0.049). In multivariable analyses, a tendency towards worse patient and graft survival was observed in patients with higher pre-operative AST (p=0.078 for patient survival and p=0.063 for graft survival). Analyses of the pathological reports indicated that underlying immunological processes were the most probable cause of liver damage in 16 of 51 patients (31.4%). CONCLUSIONS Long-term outcomes of liver transplantation in patients with cryptogenic liver cirrhosis are encouraging. Analysis of the clinical course, biochemical parameters, and factors influencing outcomes suggest an underlying autoimmunological etiology of cirrhosis in this population of patients.