[68 Ga]Ga-Prostate-Specific Membrane Antigen PET/CT: a novel method for imaging patients with hepatocellular carcinoma.

PURPOSE: Prostate-specific membrane antigen (PSMA) is not only highly expressed on the surface prostate cancer cells but is also elevated during angiogenesis in other cancer cell types, including hepatocellular carcinoma (HCC). This study aimed to evaluate the feasibility of using PET/CT imaging with [68Ga]Ga-PSMA-11 in HCC and its impact on patient management. METHODS: Fifteen patients (13 men and two women; aged 55.6 ± 18.2 years) with HCC were enrolled in this prospective, single-institution study. All patients underwent contrast-enhanced MRI/CT, [68Ga]Ga-PSMA-11 PET/CT, and histopathological verification of lesions. RESULTS: No radiopharmaceutical-related adverse events were noted. Visual interpretation showed increased accumulation of [68Ga]Ga-PSMA-11 in all HCC patients. The tumor-to-liver ratio (TLR) was 3.6 ± 2.1, and the maximal standardized uptake value (SUVmax) was 13.5 ± 7.1. There were no significant differences in the SUVs or TLR between newly diagnosed and recurrent patients. No statistically significant relationship was found between serum concentration of tumor markers (i.e., AFP, CA 19-9, CEA) and PET parameters. Results of the [68Ga]Ga-PSMA-11 PET/CT changed the treatment strategy in five (33%) patients. PSMA staining showed visible heterogeneity in terms of intensity and distribution: the reaction was weak and only observed in a few vessels in pseudoglandular patterns of HCC, while it was homogeneously strong, with some hot spots, in trabecular patterns of HCC. CONCLUSION: [68Ga]Ga-PSMA-11 PET/CT can detect PSMA expression in vivo in patients with HCC and is useful for guiding treatment strategies. Further investigation of the clinical utility of this method in HCC is warranted.

Results of liver transplantation in the Department of General, Transplant and Liver Surgery at the Medical University of Warsaw in patients with chronic hepatitis B and C viruses infection.

INTRODUCTION: Cirrhosis related to hepatitis C virus (HCV) and hepatitis B virus (HBV) infection is the most frequent indication for liver transplantation worldwide. Progress in prophylaxis of posttransplant HBV recurrence has led to major improvements in long-term outcomes of patients after liver transplantation. Conversely, impaired posttransplant survival of patients with HCV infection was reported in several studies, mainly due to recurrence of viral infection. The purpose of this study was to compare long-term results of liver transplantation between patients with HBV monoinfection, HCV monoinfection and HBV/HCV coinfection. MATERIAL AND METHODS: A total of 1090 liver transplantations were performed in the Department of General, Transplant and Liver Surgery in cooperation with the Department of Immunology, Internal Medicine, and Transplantology at the Transplantation Institute Medical University of Warsaw between December 1994 and May 2012. After exclusion of patients with cirrhosis of non-viral etiology, patients with malignant tumors, and patients with acute liver failure, the final study cohort comprised 209 patients with HBV (HBV+/HCV- subgroup; n = 56) or HCV (HBV-/HCV+ subgroup; n = 119) monoinfection or HBV/HCV coinfection (HBV+/HCV+; n = 34). These subgroups of patients were compared in terms of long-term results of transplantations, defined by 5-year patient and 5-year graft survival estimates. RESULTS: Overall and graft survival rates after 5-years for the whole study cohort were 74.5% and 72.6%, respectively. Five-year overall survival was 70.4% for patients within the HBV+/HCV- subgroup, 77.8% for patients within the HBV-/HCV+ subgroup, and 68.5% for patients within the HBV+/HCV+ subgroup. The corresponding rates of graft survival were 67.0%, 76.3%, and 68.5% for patients within the HBV+/HCV-, HBV-/ HCV+, and HBV+/HCV+ subgroups, respectively. Observed differences were non-significant, both in terms of overall (p = 0.472) and graft (p = 0.461) survival rates. CONCLUSIONS: Both overall and graft survival rates after liver transplantations performed in the Department of General, Transplant and Liver Surgery in cooperation with the Department of Immunology, Internal Medicine, and Transplantology at the Transplantation Institute Medical University of Warsaw in patients with HBV and HCV infection are comparable to those reported by other European and American centers. In contrast to other studies, obtained results do not confirm the negative impact of HCV infection on long-term outcomes of patients.

Liver volume: a point of no return in liver transplantation?

INTRODUCTION: In patients with cirrhosis, only a 75% liver volume (LV) is expected compared with age­matched healthy individuals. Changes in LV might be an indicator of therapeutic effectiveness or disease progression. OBJECTIVES: To establish whether LV is a prognostic factor in chronic liver disease irrespective of etiology and LV impacts the outcomes of liver transplant (LT). PATIENTS AND METHODS: In total, 135 consecutive LT recipients were prospectively included in this study: 38 women and 97 men. The median (minimum-maximum) age was 51 (21-70) years; body mass index (BMI), 27.3 (17.3-39.2) kg/m2; Child-Pugh class (CPC), C; Model of End­Stage Liver Disease (MELD), 16 (7-47) points; and the third lumbar vertebra skeletal muscle index (L3SMI), 47.7 (19.7-73.4) cm2/m2. Liver volume and L3SMI were calculated based on computed tomography scans at listing for LT. The receiver operating characteristic (ROC) curve was analyzed to determine the accuracy of LV in mortality prediction after LT. RESULTS: Liver volume differed significantly among patients in terms of chronic liver disease etiology, with the lowest values noted in those with hepatitis C virus infection. Liver volume was neither a prognostic factor of disease progression and need for LT with respect to the CPC and MELD scores nor correlated with BMI and L3SMI (P >0.05). The area under the ROC curve of LV in mortality prediction was 0.573 (95% CI, 0.403-0.743). Liver volume smaller than the median tended to be positively associated with the risk of prolonged intensive care unit stay and death (P = 0.057 and P = 0.058, respectively). CONCLUSIONS: Low liver volume did not seem be a point of no return in LT candidates.

Small bowel transplantation--harvesting technique and graft preparation in pigs.

BACKGROUND: In more and more frequently occurring short bowel syndrome, requiring total parenteral nutrition therapy, the complications of the latter not seldom prevent its use. The idea of treating these patients with small bowel transplantation pushed the authors to start the program aiming at development of small bowel harvesting, preservation and transplantation technique in experimental settings. Additionally, an attempt to find which, if any, and to what extent, histological changes of the preserved bowel may be of prognostic value for the early transplant failure. MATERIAL/METHODS: The experiment was carried out on 20 pigs. Two distinct techniques, corresponding to two clinical circumstances in humans, were tested. In the first group of animals, the small bowel was harvested during a model of multivisceral operation, corresponding to the organ harvesting from a brain-dead donor. In the remaining pigs, an isolated segment of the small bowel was explanted, constituting a model of a living related donor surgery. All small bowels were preserved in hypothermia, in Celsior preserving solution for a different, predefined period. During 16 procedures, the harvested small bowel segment was replanted in the same donor, using different vascular anastomotic techniques. RESULTS: Vascular thrombosis was significantly more frequent in grafts anastomosed by end-to-side technique, as well as in more proximal bowel segments, regardless the anastomotic technique. Following two hours of reimplantation, excised bowel segments did not demonstrate significant differences on histological examination, as compared to the hypothermia-preserved segments (from the same donor) of the same age from primary excision. In most cases, the increase of mucosal damage with preservation time was observed, although statistical significance was reached only for the presence of erosions and necrotic lesions. CONCLUSIONS: On the basis of this experiment one may state, that an ileal graft, assuring the long vascular pedicle (derived from ileocolic vessels) and vascular end-to-end anastomoses are at lesser risk of early vascular thrombosis. While applying the presented technique of purging the graft and its preservation, the act of transplantation itself practically does not influence the histological structure of the bowel, thus is not related to the early graft failure which seems to depend, to the greatest extent, upon the technical aspects of the procedure.

Results of liver transplantation for hepatocellular cancer.

BACKGROUND: Liver transplantation (LTx) for hepatocellular carcinoma (HCC) in cirrhotic liver is nowadays generally accepted treatment modality. AIM OF STUDY: Overview of the indications and results of the LTx in the patients with HCC, the first one performed in 2001. MATERIAL/METHODS: Among 357 adult liver transplant recipients in the period 1994-04.2005, in 26 (7%) the indication was HCC (16 men: 10 women, age 20-65, mean 46.5 years). HCC developed in cirrhotic liver in 25 pts. 12 (48%) were Child C, 10 (30%)--Child B and 3 (12%)--Child A patients. As underlying disease in 2 patients (8%) was alcoholic cirrhosis, in 7 (28%)--HBV cirrhosis, in 12 (48%)--HCV cirrhosis and in 4 (16%)--HBV/HCV cirrhosis. Milano criteria were met in 20 patients (77%). The mean waiting list time was 2.9 months (range 1-6 months). Seven patients underwent liver resection and 1 transarterial chemoembolization prior to LTx. 11 patients (42%) were operated on with use of veno-venous bypass, in 15 patients (58%) the piggy back technique was applied. Rapamycine based immunosuppression was preferred in post-LTx treatment. RESULTS: Operative mortality was 0.4 patients required relaparotomy for intraperitoneal bleeding. 21 patients (81%) are alive in good general condition, 19--free of the disease. 5 patients died 7-28 months after LTx (mean 16.7). The mean survival time is 20 months (range 1-38). CONCLUSIONS: Liver transplantation is safe and effective method of treatment of the selected patients with HCC in cirrhotic liver. Further investigations concerning the precise indications, timing of the transplantation and adjuvant treatment are necessary.

Effectiveness of Fractionated Plasma Separation and Absorption as a Treatment for Amanita Phalloides Poisoning.

BACKGROUND Fractionated plasma separation and absorption (FPSA) is an extracorporeal liver support method that detoxifies accumulated toxins. There are limited data of its use in the treatment of Amanita phalloides intoxication. The objective of this study was to investigate whether FPSA before liver transplantation improves patients' short-term post liver transplantation survival in Amanita phalloides poisoning. MATERIAL AND METHODS The study population consisted of ten patients who had liver transplantation (LT) due to acute liver failure (ALF) caused by Amanita phalloides poisoning. Six patients were treated with FPSA before liver transplantation. All the patients who were started on FPSA were also placed on the liver transplantation list according to emergent liver transplantation criteria. RESULTS Patients treated with FPSA were in a more severe clinical condition presenting in higher mean MELD, total bilirubin, INR and ammonia along with more frequent hypoglycemia and hepatic encephalopathy grade 3/4. FPSA group had longer mean waiting time on the recipient list (3.5 vs. 1.25 days) but inferior thirty-day survival rate (16.5% vs. 100%). CONCLUSIONS When conservative medical modalities are ineffective, the only treatment for Amanita phalloides poisoning is a liver transplant. Although FPSA treated patients had inferior post-LT survival, FPSA was found to prolong the pre surgical waiting time for critically ill patients, consequently giving a chance of life-saving procedure.

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.

Epithelioid hemangioendothelioma of the liver as a rare indication for liver transplantation.

AIM: To investigate the indications and outcomes of liver transplantation for hepatic epithelioid hemangioendothelioma (HEHE). METHODS: Between 1989 and August 2013, in the Department of General, Transplant, and Liver Surgery, Medical University of Warsaw, 1306 orthotopic liver transplantations (OLTx) were performed, including 72 retransplantations. Unresectable HEHE was an indication for OLTx in 10 patients (0.8% of primary OLTx), the mean age of the patients was 40.5 ± 13.3 years (range 23-65 years), and the male-to-female ratio was 2:8. Kaplan-Meier survival analysis in HEHE, hepatocellular carcinoma (HCC), and other OLTx recipients groups was performed. The differences in mortality were compared using the χ(2) test. A P-value < 0.05 indicated statistical significance. RESULTS: No concomitant liver disease was found in any patient. There was no neoadjuvant chemotherapy or radiotherapy. Liver function test results were normal in most of the patients. The levels of alpha-fetoprotein, carcinoembryonic antigen, and carbohydrate antigen 19-9 were normal. In immunohistochemical staining, the neoplastic cells were positive for factor VIII-related antigen, CD31, and CD34, which are endothelial cell markers, and negative for cytokeratin 19, cytokeratin 7, and HepPar-1. Nine patients were alive without tumor recurrence. One patient died 2 mo after OLTx due to septic complications. No morbidity was observed. Maximum follow-up was 11.4 years, with a minimum of 1 mo. The cumulative survival rate at the end of follow-up in HEHE patients was 87.5% compared with 54.3% in the HCC group and 76.3% in the other OLTx recipients group (χ(2) test = 1.784, df = 2, P = 0.409). CONCLUSION: Unresectable HEHE, without extrahepatic metastases is an excellent indication for liver transplantation. Long-term survival is very good and much better than in HCC patients and the entire group of OLTx patients.

Results of liver transplantation in the treatment of Budd-Chiari syndrome.

BACKGROUND: Budd-Chiari syndrome (BCS) is a rare disorder which can lead to liver failure. It arises from an occlusion of small vessels and/or thrombosis of the major hepatic veins. Polycythemia vera is believed to be one of the most common factors causing BCS. In cases not responding to other measures, liver transplantation may be a successful method of radical treatment. The purpose of this study was to assess the value and results of liver transplantation in the treatment of Budd-Chiari syndrome. MATERIAL/METHODS: This retrospective study included all the cases of LTx (liver transplantation) performed because of BCS in the Department of General, Transplant and Liver Surgery, Medical University of Warsaw and it covered the period from 2000 to 2009. Twenty-four patients (8 men, 16 women) with the average age of 33 ± 11 presented with BCS, 6 patients (25%) underwent previous surgical therapy, 2 patients were treated by mesocaval "H" anastomosis (portosystemic shunts) and 4 patients received TIPSS (transjugular intrahepatic portosystemic shunt) prior to LTx. Polycythemia vera was an underlying risk factor in 11 cases. Two patients needed early retransplantation (re-LTx). In immunosuppressive therapy, schema with glucocorticosteroids and FK-506 predominated. RESULTS: Four cases of bleeding to peritoneal cavity requiring surgical intervention were observed; 3 patients died in the early post-transplant period due to multiorgan failure and 1 late death occurred because of internal causes. Actual survival rate was 83% at 5 years. CONCLUSIONS: In the late stage, Budd-Chiari syndrome should be considered as an indication for liver transplantation, especially when other measures such as porto-systemic shunts are scarce and ineffective.

1000 liver transplantations at the Department of General, Transplant and Liver Surgery, Medical University of Warsaw--analysis of indications and results.

THE AIM OF THE STUDY: was to analyze indications and results of the first one thousand liver transplantations at Chair and Clinic of General, Transplantation and Liver Surgery, Medical University of Warsaw. MATERIAL AND METHODS: Data from 1000 transplantations (944 patients) performed at Chair and Clinic of General, Transplantation and Liver Surgery between 1994 and 2011 were analyzed retrospectively. These included 943 first transplantations and 55 retransplantations and 2 re-retransplantations. Frequency of particular indications for first transplantation and retransplantations was established. Perioperative mortality was defined as death within 30 days after the transplantation. Kaplan-Meier survival analysis was used to estimate 5-year patient and graft survival. RESULTS: The most common indications for first transplantation included: liver failure caused by hepatitis C infection (27.8%) and hepatitis B infection (18%) and alcoholic liver disease (17.7%). Early (< 6 months) and late (> 6 months) retransplantations were dominated by hepatic artery thrombosis (54.3%) and recurrence of the underlying disease (45%). Perioperative mortality rate was 8.9% for first transplantations and 34.5% for retransplantations. Five-year patient and graft survival rate was 74.3% and 71%, respectively, after first transplantations and 54.7% and 52.9%, respectively, after retransplantations. CONCLUSIONS: Development of liver transplantation program provided more than 1000 transplantations and excellent long-term results. Liver failure caused by hepatitis C and B infections remains the most common cause of liver transplantation and structure of other indications is consistent with European data.