Impact of Future Remnant Liver Volume on Post-Hepatectomy Regeneration in Non-Cirrhotic Livers

Objective: The purpose of the study is to detect if some parameters can be considered as predictors of liver regeneration in two different patient populations composed of in living donors for adult to adult living donor liver transplant and patients with hepatic malignancies within a single institution.Summary Background Data: Preoperative multi-detector computed tomography volumetry is an essential tool to assess the volume of the remnant liver. Methods: a retrospective analysis from an ongoing clinical study on 100 liver resections, between 2004 and 2010. 70 patients were right lobe living donors for liver transplantation and 30 patients were resected for treatment of tumors. Pre-surgical factors such as age, weight, height, body mass index (BMI), original liver volume, future remnant liver volume (FRLV), spleen volume, liver function tests, creatinine, platelet count, steatosis, portal vein embolization (PVE) and number of resected segments were analyzed to evidence potential markers for liver regeneration. Results: Follow-up period did not influence the amount of liver regenerated: the linear regression evidenced that there is no correlation between percentage of liver regeneration and time of follow-up (p=0.88). The pre-surgical variables that resulted markers of liver regeneration include higher preoperative values of BMI (p=0.01), bilirubin(p=0.04), glucose (p=0.05) and GGT (p=0.014); the most important association was revealed regarding the lower FRLV (pConclusions: Liver regeneration follows similar pathway in living donor and in patients resected for cancer. Small FRLV tends to regenerate more and faster, confirming that a larger resections may lead to a greater promotion of liver regeneration in patients with optimal conditions in terms of body habitus, preoperative liver function tests and glucose level

The role of basiliximab in the evolving renal transplantation immunosuppression protocol

Basiliximab is a chimeric mouse-human monoclonal antibody directed against the alpha chain of the interleukin-2 (IL-2) receptor on activated T lymphocytes. It was shown in phase III trials to reduce the number and severity of acute rejection episodes in the first year following renal transplantation in adults and children, with a reasonable cost-benefit ratio. The drug does not increase the incidence of opportunistic infections or malignancies above baseline in patients treated with conventional calcineurin inhibitor-based immunosuppression. In the field of renal transplantation, basiliximab does not increase kidney or patient survival, despite the reduction in the number of rejection episodes. Basiliximab may reduce the incidence of delayed graft function. In comparison with lymphocyte-depleting antibodies basiliximab appears to have equal efficacy in standard immunological risk patients. Recently, IL-2 receptor monoclonal antibodies have been used with the objective of reducing or eliminating the more toxic elements of the standard immunosuppression protocol. Several trials have incorporated basiliximab in protocols designed to avoid or withdraw rapidly corticosteroids, as well as protocols which substitute target-of-rapamycin (TOR) inhibitors for calcineurin inhibitors

Single Balloon Enteroscopy for Endoscopic Retrograde Cholangiography in a Patient with Hepaticojejunostomy after Liver Transplant

We report a case of a post-transplant patient with hepaticojejunostomy in whom we used a single balloon enteroscopy to access the biliary tree. This procedure seems to be safe and feasible for approaching the biliary anastomosis by means of the overtube and fixation of the small bowel by the balloon

The addition of simvastatin administration to cold storage solution of explanted whole liver grafts for facing ischemia/reperfusion injury in an area with a low rate of deceased donation: a monocentric randomized controlled double-blinded phase 2 study.

BACKGROUND: Liver transplantation is the best treatment for end-stage liver disease. The interruption of the blood supply to the donor liver during cold storage damages the liver, affecting how well the liver will function after transplant. The drug Simvastatin may help to protect donor livers against this damage and improve outcomes for transplant recipients. The aim of this study is to evaluate the benefits of treating the donor liver with Simvastatin compared with the standard transplant procedure. PATIENT AND METHODS: We propose a prospective, double-blinded, randomized phase 2 study of 2 parallel groups of eligible adult patients. We will compare 3-month, 6-month, and 12-month graft survival after LT, in order to identify a significant relation between the two homogenous groups of LT patients. The two groups only differ by the Simvastatin or placebo administration regimen while following the same procedure, with identical surgical instruments, and medical and nursing skilled staff. To reach these goals, we determined that we needed to recruit 106 patients. This sample size achieves 90% power to detect a difference of 14.6% between the two groups survival using a one-sided binomial test. DISCUSSION: This trial is designed to confirm the effectiveness of Simvastatin to protect healthy and steatotic livers undergoing cold storage and warm reperfusion before transplantation and to evaluate if the addition of Simvastatin translates into improved graft outcomes. TRIAL REGISTRATION: ISRCTN27083228

Case report: Trans-papillary free stenting of the cystic duct and of the common bile duct in a double biliary ducts anastomoses of a right lobe living donor transplantation

Background: One of the major issues related to the living donor liver transplantation recipient outcome is still the high rate of biliary complication, especially when multiple biliary ducts are present and multiple anastomoses have to be performed. Case presentation and conclusion: We report a case of adult-to-adult right lobe living donor liver transplantation performed for a recipient afected by alcohol-related cirrhosis with MELD score of 17. End-stage liver disease was complicated by refractory ascites, portal hypertension, small esophageal varices and portal gastropathy, hypersplenism, and abundant right pleural efusion. Here in the attached video we described the adult-to-adult LDLT procedures, where a right lobe with two biliary ducts draining respectively the right anterior and the right posterior segments has been transplanted. LDLT required a biliary reconstruction using the native cystic and common bile ducts stented trans-papillary with two 5- French 6 cm long soft silastic catheter. None major complications were detected during post-operative clinical courses. Actually, the donor and the recipient are alive and well. The technique we describe in the video, allow to keep the biliary anastomoses protected and patent without having the risk of creating cholestasis and the need of invasive additional procedure. No living donor right lobe transplantation should be refused because of the presence of multiple biliary ducts

How important is the role of iterative liver direct surgery in patients with hepatocellular carcinoma for a transplant center located in an area with a low rate of deceased donation?

IntroductionHepatocellular carcinoma (HCC) accounts for nearly 90% of primary liver cancers, with estimates of over 1 million people affected by 2025. We aimed to explore the impacting role of an iterative surgical treatment approach in a cohort of HCC patients within the Milan criteria, associated with clinical risk factors for tumor recurrence (RHCC) after liver transplant (LT) and loco-regional therapies (LRT), as well as liver resection (LR) and/or microwave thermal ablation (MWTA).MethodsWe retrospectively analyzed our experience performed during an 8-year period between January 2013 and December 2021 in patients treated for HCC, focusing on describing the impact on preoperative end-stage liver disease severity, oncologic staging, tumor characteristics, and surgical treatments. The Cox model was used to evaluate variables that could predict relapse risks. Relapse risk curves were calculated according to the Kaplan–Meier method, and the log-rank test was used to compare them.ResultsThere were 557 HCC patients treated with a first-line approach of LR and/or LRTs (n = 335) or LT (n = 222). The median age at initial transplantation was 59 versus 68 for those whose first surgical approach was LR and/or LRT. In univariate analysis with the Cox model, nodule size was the single predictor of recurrence of HCC in the posttreatment setting (HR: 1.61, 95% CI: 1.05–2.47, p = 0.030). For the LRT group, we have enlightened the following clinical characteristics as significantly associated with RHCC: hepatitis B virus infection (which has a protective role with HR: 0.34, 95% CI: 0.13–0.94, p = 0.038), number of HCC nodules (HR: 1.54, 95% CI: 1.22–1.94, p < 0.001), size of the largest nodule (HR: 1.06, 95% CI: 1.01–1.12, p = 0.023), serum bilirubin (HR: 1.57, 95% CI: 1.03–2.40, p = 0.038), and international normalized ratio (HR: 16.40, 95% CI: 2.30–118.0, p = 0.006). Among the overall 111 patients with RHCC in the LRT group, 33 were iteratively treated with further curative treatment (12 were treated with LR, two with MWTA, three with a combined LR-MWTA treatment, and 16 underwent LT). Only one of 18 recurrent patients previously treated with LT underwent LR. For these RHCC patients, multivariable analysis showed the protective roles of LT for primary RHCC after IDLS (HR: 0.06, 95% CI: 0.01–0.36, p = 0.002), of the time relapsed between the first and second IDLS treatments (HR: 0.97, 95% CI: 0.94–0.99, p = 0.044), and the impact of previous minimally invasive treatment (HR: 0.28, 95% CI: 0.08–1.00, p = 0.051).ConclusionThe coexistence of RHCC with underlying cirrhosis increases the complexity of assessing the net health benefit of ILDS before LT. Minimally invasive surgical therapies and time to HCC relapse should be considered an outcome in randomized clinical trials because they have a relevant impact on tumor-free survival

Clinical and Molecular-Based Approach in the Evaluation of Hepatocellular Carcinoma Recurrence after Radical Liver Resection

Background: Hepatic resection remains the treatment of choice for patients with early-stage HCC with preserved liver function. Unfortunately, however, the majority of patients develop tumor recurrence. While several clinical factors were found to be associated with tumor recurrence, HCC pathogenesis is a complex process of accumulation of somatic genomic alterations, which leads to a huge molecular heterogeneity that has not been completely understood. The aim of this study is to complement potentially predictive clinical and pathological factors with next-generation sequencing genomic profiling and loss of heterozygosity analysis. Methods: 124 HCC patients, who underwent a primary hepatic resection from January 2016 to December 2019, were recruited for this study. Next-generation sequencing (NGS) analysis and allelic imbalance assessment in a case-control subgroup analysis were performed. A time-to-recurrence analysis was performed as well by means of Kaplan-Meier estimators. Results: Cumulative number of HCC recurrences were 26 (21%) and 32 (26%), respectively, one and two years after surgery. Kaplan-Meier estimates for the probability of recurrence amounted to 37% (95% C.I.: 24-47) and to 51% (95% C.I.: 35-62), after one and two years, respectively. Multivariable analysis identified as independent predictors of HCC recurrence: hepatitis C virus (HCV) infection (HR: 1.96, 95%C.I.: 0.91-4.24, p = 0.085), serum bilirubin levels (HR: 5.32, 95%C.I.: 2.07-13.69, p = 0.001), number of nodules (HR: 1.63, 95%C.I.: 1.12-2.38, p = 0.011) and size of the larger nodule (HR: 1.11, 95%C.I.: 1.03-1.18, p = 0.004). Time-to-recurrence analysis showed that loss of heterozygosity in the PTEN loci (involved in the PI3K/AKT/mTOR signaling pathway) was significantly associated with a lower risk of HCC recurrence (HR: 0.35, 95%C.I.: 0.13-0.93, p = 0.036). Conclusions: multiple alterations of cancer genes are associated with HCC progression. In particular, the evidence of a specific AI mutation presented in 20 patients seemed to have a protective effect on the risk of HCC recurrence

Imaging of hepatocellular carcinoma recurrence after liver transplantation

Liver transplantation (LT) provides the highest survival benefit to patients with unresectable hepatocellular carcinoma (HCC). The Milan criteria have been developed for the selection of LT candidates with the goal of improving survival and maintaining an acceptable risk of HCC recurrence. Despite this, recurrence of HCC after LT occurs in up to 20% of cases and represents a major concern due to the poor prognosis of these patients. Furthermore, several extended criteria for the selection of LT candidates have been proposed to account for the growing demand for organs and the resultant increase in the risk of HCC recurrence. Radiologists should be aware that HCC can recur after LT with multiple organ involvement. Knowledge of the location and radiologic appearance of recurrent HCC is necessary to ensure the choice of the most appropriate therapy. This paper aims to comprehensively summarize the spectrum of HCC recurrence after LT and to examine and discuss the imaging features of these lesions. CRITICAL RELEVANCE STATEMENT: This paper aims to share a review of imaging findings of HCC recurrence after LT and to make radiologists familiar with the spectrum of this disease

Liver Transplantation for Unresectable Intrahepatic Cholangiocarcinoma: The Role of Sequencing Genetic Profiling

: Intrahepatic cholangiocarcinoma (iCCA) is a rare and aggressive primary liver tumor, characterized by a range of different clinical manifestations and by increasing incidence and mortality rates even after curative treatment with radical resection. In recent years, growing attention has been devoted to this disease and some evidence supports liver transplantation (LT) as an appropriate treatment for intrahepatic cholangiocarcinoma; evolving work has also provided a framework for better understanding the genetic basis of this cancer. The aim of this study was to provide a clinical description of our series of patients complemented with Next-Generation Sequencing genomic profiling. From 1999 to 2021, 12 patients who underwent LT with either iCCA or a combined hepatocellular and cholangiocellular carcinoma (HCC-iCCA) were included in this study. Mutations were observed in gene activating signaling pathways known to be involved with iCCA tumorigenesis (KRAS/MAPK, P53, PI3K-Akt/mTOR, cAMP, WNT, epigenetic regulation and chromatin remodeling). Among several others, a strong association was observed between the Notch pathway and tumor size (point-biserial rhopb = 0.93). Our results are suggestive of the benefit potentially derived from molecular analysis to improve our diagnostic capabilities and to devise new treatment protocols, and eventually ameliorate long-term survival of patients affected by iCCA or HCC-iCCA

How important is the role of iterative liver direct surgery in patients with hepatocellular carcinoma for a transplant center located in an area with a low rate of deceased donation?

Introduction: Hepatocellular carcinoma (HCC) accounts for nearly 90% of primary liver cancers, with estimates of over 1 million people affected by 2025. We aimed to explore the impacting role of an iterative surgical treatment approach in a cohort of HCC patients within the Milan criteria, associated with clinical risk factors for tumor recurrence (RHCC) after liver transplant (LT) and loco-regional therapies (LRT), as well as liver resection (LR) and/or microwave thermal ablation (MWTA). Methods: We retrospectively analyzed our experience performed during an 8-year period between January 2013 and December 2021 in patients treated for HCC, focusing on describing the impact on preoperative end-stage liver disease severity, oncologic staging, tumor characteristics, and surgical treatments. The Cox model was used to evaluate variables that could predict relapse risks. Relapse risk curves were calculated according to the Kaplan-Meier method, and the log-rank test was used to compare them. Results: There were 557 HCC patients treated with a first-line approach of LR and/or LRTs (n = 335) or LT (n = 222). The median age at initial transplantation was 59 versus 68 for those whose first surgical approach was LR and/or LRT. In univariate analysis with the Cox model, nodule size was the single predictor of recurrence of HCC in the posttreatment setting (HR: 1.61, 95% CI: 1.05-2.47, p = 0.030). For the LRT group, we have enlightened the following clinical characteristics as significantly associated with RHCC: hepatitis B virus infection (which has a protective role with HR: 0.34, 95% CI: 0.13-0.94, p = 0.038), number of HCC nodules (HR: 1.54, 95% CI: 1.22-1.94, p < 0.001), size of the largest nodule (HR: 1.06, 95% CI: 1.01-1.12, p = 0.023), serum bilirubin (HR: 1.57, 95% CI: 1.03-2.40, p = 0.038), and international normalized ratio (HR: 16.40, 95% CI: 2.30-118.0, p = 0.006). Among the overall 111 patients with RHCC in the LRT group, 33 were iteratively treated with further curative treatment (12 were treated with LR, two with MWTA, three with a combined LR-MWTA treatment, and 16 underwent LT). Only one of 18 recurrent patients previously treated with LT underwent LR. For these RHCC patients, multivariable analysis showed the protective roles of LT for primary RHCC after IDLS (HR: 0.06, 95% CI: 0.01-0.36, p = 0.002), of the time relapsed between the first and second IDLS treatments (HR: 0.97, 95% CI: 0.94-0.99, p = 0.044), and the impact of previous minimally invasive treatment (HR: 0.28, 95% CI: 0.08-1.00, p = 0.051). Conclusion: The coexistence of RHCC with underlying cirrhosis increases the complexity of assessing the net health benefit of ILDS before LT. Minimally invasive surgical therapies and time to HCC relapse should be considered an outcome in randomized clinical trials because they have a relevant impact on tumor-free survival