Fabio Melandro

Alpha-Fetoprotein and Novel Tumor Biomarkers as Predictors of Hepatocellular Carcinoma Recurrence after Surgery: A Brilliant Star Raises Again

Alpha-fetoprotein (AFP), des-γ-carboxy prothrombin (DCP), and lens culinaris agglutinin-reactive fraction of AFP (AFP-L3) have been developed with the intent to detect hepatocellular carcinoma (HCC) and for the surveillance of at-risk patients. However, at present, none of these tests can be recommended to survey cirrhotic patients at risk for HCC development because of their suboptimal ability for routine clinical practice in HCC diagnosis. Starting from these considerations, these markers have been therefore routinely and successfully used as predictors of survival and HCC recurrence in patients treated with curative intent. All these markers have been largely used as predictors in patients treated with hepatic resection or locoregional therapies, mainly in Eastern countries. In recent studies, AFP has been proposed as predictor of recurrence after liver transplantation and as selector of patients in the waiting list. Use of AFP modification during the waiting list for LT is still under investigation, potentially representing a very interesting tool for patient selection. The development of a new predictive model combining radiological and biological features based on biological markers is strongly required. New genetic markers are continuously discovered, but they are not already fully available in the clinical practice.

Cholangiocarcinoma: increasing burden of classifications.

Cholangiocarcinoma (CCA) is a very heterogeneous cancer from any point of view, including epidemiology, risk factors, morphology, pathology, molecular pathology, modalities of growth and clinical features. Given this heterogeneity, a uniform classification respecting the epidemiologic, pathologic and clinical needs is currently lacking. In this manuscript we discussed the different proposed classifications of CCA in relation with recent advances in pathophysiology and biology of this cancer.

From portal to splanchnic venous thrombosis: What surgeons should bear in mind

The present study aims to review the evolution of surgical management of portal (PVT) and splanchnic venous thrombosis (SVT) in the context of liver transplantation over the last 5 decades. PVT is more commonly managed by endovenous thrombectomy, while SVT requires more complex technical expedients. Several surgical techniques have been proposed, such as extensive eversion thrombectomy, anastomosis to collateral veins, reno-portal anastomosis, cavo-portal hemi-transposition, portal arterialization and combined liver-intestinal transplantation. In order to achieve satisfactory outcomes, careful planning of the surgical strategy is mandatory. The excellent results that are obtained nowadays confirm that, even extended, splanchnic thrombosis is no longer an absolute contraindication for liver transplantation. Patients with advanced portal thrombosis may preferentially be referred to specialized centres, in which complex vascular approaches and even multivisceral transplantation are performed.

Laparoscopy in Liver Transplantation: The Future Has Arrived

In the last two decades, laparoscopy has revolutionized the field of surgery. Many procedures previously performed with an open access are now routinely carried out with the laparoscopic approach. Several advantages are associated with laparoscopic surgery compared to open procedures: reduced pain due to smaller incisions and hemorrhaging, shorter hospital length of stay, and a lower incidence of wound infections. Liver transplantation (LT) brought a radical change in life expectancy of patients with hepatic end-stage disease. Today, LT represents the standard of care for more than fifty hepatic pathologies, with excellent results in terms of survival. Surely, with laparoscopy and LT being one of the most continuously evolving challenges in medicine, their recent combination has represented an astonishing scientific progress. The intent of the present paper is to underline the current role of diagnostic and therapeutic laparoscopy in patients waiting for LT, in the living donor LT and in LT recipients.

Early Urine Output Predicts Graft Survival After Kidney Transplantation

BACKGROUND In kidney transplantations, the identification of early postoperative parameters with high predictive power for the development of late allograft dysfunction has important implications for clinical practice. This study sought to determine these parameters in a single-center cohort. METHODS We studied 82 deceased donor renal transplantation. We assessed the following measures: dialysis-dependent delayed graft function (ddDGF), extended DGF, serum creatinine level at day 7, creatinine reduction ratio at day 7, urine output at day 1 and at day 7 posttransplantation (UO7). RESULTS Only UO7 showed a significant result upon multivariate analysis (P < .0001). It was less influenced by dialysis with respect to measures based upon serum creatinine. By Receiver Operating characteristic (ROC) analysis, it showed an elevated area under the curve (0.811), with a cut-off value of 500 mL/24 h, showing high sensitivity (98.5%). CONCLUSIONS UO7 may be of clinical utility to assess the risk for subsequent renal dysfunction.

Does Caval Reconstruction Technique Affect Early Graft Function after Liver Transplantation? A Preliminary Analysis

BACKGROUND In the past decades, the inferior vena cava (IVC) reconstruction technique has undergone several evolutions, such as biopump, piggyback technique (PB), and laterolateral approach (LLPB). Several advantages are reported comparing the PB technique to biopump use. However, comparison between PB and LLPB has not been as well investigated. The aim of this study was to compare the results in terms of immediate graft function and intermediate graft survival among 3 subgroups characterized by distinct caval reconstruction techniques. METHODS We retrospectively analyzed a cohort of 200 consecutive adult patients who underwent liver transplantation from January 2001 to December 2009. The patients were stratified according to 3 caval reconstructive techniques: biopump (n=135), PB (n=32) and LLPB (n=33). RESULTS The LLPB group showed the shortest cold and warm ischemia times and the best immediate postoperative graft function. Survival analysis revealed LLPB patients to present the best 1-year graft survival rates: namely, 90.9% versus 75.0% and 74.1% among the PB and biopump groups, respectively (log-rank tests: LLPB vs biopump: P=.03; LLPB vs PB: P=.05). In our experience, LLPB showed the best graft survivals with an evident reduction in both cold and warm ischemia times. However, it is hard to obtain an irrefutable conclusion owing to the retrospective nature of this study, the small sample, and the different periods in which the groups were transplanted. CONCLUSIONS LLPB technique was a safe procedure that minimized the sequelal of ischemia-reperfusion damage. This technique yielded results superior to venovenous bypass. No definitive conclusions can to be obtained in this study comparing classic PB or LLPB.

Delayed Graft Function Decreases Early and Intermediate Graft Outcomes After Expanded Criteria Donor Kidney Transplants

Use of expanded criteria donors (ECD) has increased worldwide in previous years because of the donor scarcity. However, ECD are related to a greater risk of complications and shorter graft longevity. Delayed graft function (DGF) which impacts renal graft survival, represents one of the most common complications posttransplantation. The purpose of this study was to analyse DGF incidence among ECD kidneys and its role on early and intermediate recipient and graft survivals. We prospectively analyzed 46 ECD cases divided as group A (absence of DGF; n = 23) and B (DGF; n = 23). Group B was composed of older donors (P = .033) with longer cold ischemia times (P = .017), and greater incidences of acute rejection episodes (ARE) (P < .0001). Comparing group A with group B, we observed 1-year and 3-year overall recipient survivals to be 95.7% and 95.7% versus 91.3% and 91.3%, respectively (P = not significant). Censored 1-year and 3-year overall graft survivals were 100% and 92.9% versus 85.6% and 79.9%, respectively (P = .026). Analyzing the patients with DGF without (n = 9) versus with concomitant ARE (n = 14), no differences were noted in recipient and graft survivals. The incidence of DGF was strictly related to increased donor age, greater cold ischemia time, and presence of an ARE while DGF did not have a role in recipient survival, it reduced, graft survival. Concomitant ARE was not related to an impaired graft function.

Hyaluronan coating improves liver engraftment of transplanted human biliary tree stem/progenitor cells

BackgroundCell therapy of liver diseases with human biliary tree stem cells (hBTSCs) is biased by low engraftment efficiency. Coating the hBTSCs with hyaluronans (HAs), the primary constituents of all stem cell niches, could facilitate cell survival, proliferation, and, specifically, liver engraftment given that HAs are cleared selectively by the liver.MethodsWe developed a fast and easy method to coat hBTSCs with HA and assessed the effects of HA-coating on cell properties in vitro and in vivo.ResultsThe HA coating markedly improved the viability, colony formation, and population doubling of hBTSCs in primary cultures, and resulted in a higher expression of integrins that mediate cell attachment to matrix components. When HA-coated hBTSCs were transplanted via the spleen into the liver of immunocompromised mice, the engraftment efficiency increased to 11% with respect to 3% of uncoated cells. Notably, HA-coated hBTSC transplantation in mice resulted in a 10-fold increase of human albumin gene expression in the liver and in a 2-fold increase of human albumin serum levels with respect to uncoated cells. Studies in distant organs showed minimal ectopic cell distribution without differences between HA-coated and uncoated hBTSCs and, specifically, cell seeding in the kidney was excluded.ConclusionsA ready and economical procedure of HA cell coating greatly enhanced the liver engraftment of transplanted hBTSCs and improved their differentiation toward mature hepatocytes. HA coating could improve outcomes of stem cell therapies of liver diseases and could be immediately translated into the clinic given that GMP-grade HAs are already available for clinical use.

Adult Wilms tumor: Case report.

Wilms tumor (WT) occurs infrequently in adults. Even rarer is adult WT with extension by direct intravascular spread into the right side of the heart. The present report describes a WT with intracaval and intracardiac extension in a 38-year-young man. In addition, thrombus extension above the infrahepatic IVC represents a major technical topic for surgeons because of the possible occurrence of uncontrollable hemorrhages and tumor fragmentation. We report the results of a surgical approach to caval thrombosis including the isolation of the IVC from the liver as routinely performed during liver harvesting. The morphologic and immune-histochemical findings confirmed the diagnosis.

Graft macrosteatosis and time of T-tube removal as risk factors for biliary strictures after liver transplantation.

Biliary strictures (BS) remain a significant problem following liver transplantation (LT), representing an important cause of morbidity. The purpose of this follow‐up study was to evaluate the incidence and risk factors associated with BS after LT. From 2001 to 2009, 244 consecutive patients underwent LT at our center. Multiple donor and recipient variables were collected for each patient. Exclusion criteria were hepaticojejunostomy, living‐donor LT, and follow‐up less than three months. We reviewed 177 patients, all of whom underwent an end‐to‐end choledochocholedochostomy and T‐tube placement. BS occurred in 23% of patients. Multivariate analysis revealed that graft macrovesicular steatosis >25% (p = 0.05, OR 3.38) and time of T‐tube removal less than six months (p = 0.02, OR 2.53) were independent risk factors for BS. Biliary strictures did not affect patient and graft survival. Donor macrovesicular steatosis represents a risk factor for BS, contributing to liver damage through a reduction in hepatic blood flow. Time of T‐tube removal seems to play a role in the development of BS, although it is unclear whether it represents the cause or the consequence of the development of BS.