Using a weaning immunosuppression protocol in liver transplantation recipients with hepatocellular carcinoma: A compromise between the risk of recurrence and the risk of rejection?

Hepatocellular carcinoma (HCC) recurrence rate after liver transplantation (LT) is still up to 1520%, despite a careful selection of candidates and optimization of the management within the waiting list. To reduce tumour recurrence, the currently adopted post-transplant strategies are based on the administration of a tailored immunosuppression (IS) regimen. Drug-induced depression of the immune system is essential in preventing graft rejection, however has a well-established association with oncogenesis. The immune system has a key role as a defending mechanism against cancer development, preventing vascular invasion and metastasis. Thus, IS drugs represent one of few modifiable non-oncological risk factors for tumour recurrence. In HCC recipients, a tailored IS therapy, with the aim to minimize drugs' doses, is essential to gain the optimal balance between the risk of rejection and the risk of tumour recurrence. So far, a complete withdrawal of IS drugs after LT is reported to be safely achievable in 25% of patients (defined as "operational tolerant"), without the risk of patient and graft loss. The recent identification of non-invasive "bio-markers of tolerance", which permit to identify patients who could successfully withdraw IS therapies, opens new perspectives in the management of HCC after LT. IS withdrawal could potentially reduce the risk of tumour recurrence, which represents the major drawback in HCC recipients. Herein, we review the current literature on IS weaning in patients who underwent LT for HCC as primary indication and we report the largest experiences on IS withdrawal in HCC recipients

Liver transplantation in a patient with complete portal vein thrombosis, is there a surgical way out? A case report

Introduction: Due to the complexity of the surgical procedure portal vein thrombosis (PVT) has long been considered an absolute contraindication to liver transplantation (LT). The presence of a large splenorenal shunt (SRS) could make portal anastomosis a valid option.Presentation of case: We report the case of a 37-year-old female patient with Grade III PVT and a large SRS, who underwent orthotopic LT. Liver was implanted using a 1992-Belghiti piggyback technique and portal anastomosis was performed using the large spleno-renal shunt. We observed good graft reperfusion and postoperative Doppler ultrasound showed normal portal vein flow. She was discharged on postoperative day 7, with an excellent graft function. At six months follow-up, patient is alive with normal hepatic vascularization.Discussion: Due to paucity of reports, there is currently no consensus on the indication to LT and/or surgical technique. In the present case, once the transplant benefit was evaluated, the Grade III PVT was not considered a contraindication to LT.Conclusion: The presence of a Grade III PVT associated with a large SRS should not be considered a contraindication for LT, and the use of the shunt vein should be considered a feasible option to perform portal anastomosis. (C) 2016 The Author(s). Published by Elsevier Ltd on behalf of IJS Publishing Group Ltd

How do synchronous lung metastases influence the surgical management of children with hepatoblastoma? An update and systematic review of the literature

Approximately 20% of children with hepatoblastoma (HB) have metastatic disease at diagnosis, most frequently in the lungs. In children with HB, lung metastatic disease is associated with poorer prognosis. Its treatment has been approached with a variety of methods that integrate chemotherapy and surgical resection. The timing and feasibility of complete extirpation of lung metastases, by chemotherapy and/or metastasectomy, is crucial for the surgical treatment of the primary liver tumor, which can vary from major hepatic resections to liver transplantation (LT). In children with unresectable HB, which can be surgically treated only by LT, the persistence of unresectable metastases after neoadjuvant chemotherapy excludes the possibility of recurring to LT with consequent negative impact on patients' outcomes. Due to limited evidence and experience, there is no consensus amongst oncologists and surgeons across institutions regarding the surgical treatment for HB with synchronous metastatic lung disease. This narrative review aimed to update the current management of pulmonary metastasis in children with HB and to define its role in the decision-making strategy for the surgical approach to primary liver tumours

Vascular anomalies of the celiac trunk and implications in treatment of HCC with TACE. Description of a case and review of the literature

Knowledge of the vascular anatomy of the upper abdomen is important in the daily practice of surgeons specialized in the hepatobiliary and pancreatic area, and for general surgeons and radiologists, mainly those involved in interventional radiology. Since anatomical variants of the celiac axis and hepatic arteries are common, an accurate description of vascularization is required before procedures to avoid iatrogenic vascular changes. We reported a case of a young male patient with HBV related cirrhosis, who came to our institution for the treatment of 2 HCC nodules. The preprocedural contrast-enhanced CT examination showed combined variations of celiac trunk, hepatic arteries, gastroduodenal artery, and right inferior phrenic artery. The careful pre- and intraprocedural evaluation of vascularization allowed us to perform transarterial chemoembolization of the 2 nodules without complications. The incidence and developmental and clinical significance of this variation is discussed with a detailed review of the literature. Knowledge of such a case has important clinical significance in abdominal operations or invasive arterial procedures

Intention-to-treat survival benefit of liver transplantation in patients with hepatocellular cancer

The debate about the best approach to select patients with hepatocellular cancer (HCC) waiting for liver transplantation (LT) is still ongoing. This study aims to identify the best variables allowing to discriminate "high-" and "low-benefit" patients. To do so, the innovative concept of intention-to-treat (ITT) survival benefit of LT has been created. Data of 2103 adult HCC patients consecutively enlisted during the period 1987-2015 were analyzed. Three rigorous statistical steps were used in order to create the ITT survival benefit of LT: the development of an ITT LT and a non-LT survival model, and the individual prediction of the ITT survival benefit of LT defined as the difference between the median ITT survival with (based on the first model) and without LT (based on the second model) calculated for each enrolled patient. Four variables (MELD, alpha-fetoprotein, Milan-Criteria status and radiological response) displayed a high effect in terms of delta-benefit. According to these risk factors, four benefit groups were identified. Patients with three-four factors ("no-benefit group", n=405/2103; 19·2%) had no benefit of LT compared to alternative treatments. Inversely, patients without any risk factor ("large-benefit group", n=108; 5·1%) yielded the highest benefit from LT reaching 60 months. CONCLUSION: The here presented innovative ITT transplant survival benefit allows to better select HCC patients waiting for LT. The obtained stratification may lead to an improved and more equal way for organ allocation. Patients with no benefit should be de-listed, whilst patients with large benefit ratio should be prioritized for LT. This article is protected by copyright. All rights reserved

Calcineurin-Inhibitor Minimization in Liver Transplant Patients with Calcineurin-Inhibitor-Related Renal Dysfunction: A Meta-Analysis

BACKGROUND: Introduction of calcineurin-inhibitor (CNI) has made transplantation a miracle in the past century. However, the side effects of long-term use of CNI turn out to be one of the major challenges in the current century. Among these, renal dysfunction attracts more and more attention. Herein, we undertook a meta-analysis to evaluate the efficacy and safety of calcineurin-inhibitor (CNI) minimization protocols in liver transplant recipients with CNI-related renal dysfunction. METHODS: We included randomized trials with no year and language restriction. All data were analyzed using random effect model by Review Manager 5.0. The primary endpoints were glomerular filtration rate (GFR), serum creatinine level (sCr) and creatinine clearance rate (CrCl), and the secondary endpoints were acute rejection episodes, incidence of infection and patient survival at the end of follow-up. RESULTS: GFR was significantly improved in CNI minimization group than in routine CNI regimen group (Z = 5.45, P<0.00001; I(2) = 0%). Likely, sCr level was significantly lower in the CNI minimization group (Z = 2.84, P = 0.005; I(2) = 39%). However, CrCl was not significantly higher in the CNI minimization group (Z = 1.59, P = 0.11; I(2) = 0%). Both acute rejection episodes and patient survival were comparable between two groups (rejection: Z = 0.01, P = 0.99; I(2) = 0%; survival: Z = 0.28, P = 0.78; I(2) = 0%, respectively). However, current CNI minimization protocols may be related to a higher incidence of infections (Z = 3.06, P = 0.002; I(2) = 0%). CONCLUSION: CNI minimization can preserve or even improve renal function in liver transplant patients with renal impairment, while sharing similar short term acute rejection rate and patient survival with routine CNI regimen

Relationship between GH/IGF-1 Axis, graft recovery, and early survival in patients undergoing liver transplantation

High levels of IGF-1 have been reported in patients with initial poor function of the graft after liver transplantation (LT). Correlation with other clinical variables or early survival has not been extensively investigated