Riccardo De Carlis

Current status and perspectives in split liver transplantation

Growing experience with the liver splitting technique and favorable results equivalent to those of whole liver transplant have led to wider application of split liver transplantation (SLT) for adult and pediatric recipients in the last decade. Conversely, SLT for two adult recipients remains a challenging surgical procedure and outcomes have yet to improve. Differences in organ shortages together with religious and ethical issues related to cadaveric organ donation have had an impact on the worldwide distribution of SLT. Despite technical refinements and a better understanding of the complex liver anatomy, SLT remains a technically and logistically demanding surgical procedure. This article reviews the surgical and clinical advances in this field of liver transplantation focusing on the role of SLT and the issues that may lead a further expansion of this complex surgical procedure.

Successful donation after cardiac death liver transplants with prolonged warm ischemia time using normothermic regional perfusion

The role of donation after cardiac death (DCD) in expanding the donor pool is mainly limited by the incidence of primary nonfunction (PNF) and ischemia‐related complications. Even greater concern exists toward uncontrolled DCD, which represents the largest potential pool of DCD donors. We recently started the first Italian series of DCD liver transplantation, using normothermic regional perfusion (NRP) in 6 uncontrolled donors and in 1 controlled case to deal with the legally required no‐touch period of 20 minutes. We examined our first 7 cases for the incidence of PNF, early graft dysfunction, and biliary complications. Acceptance of the graft was based on the trend of serum transaminase and lactate during NRP, the macroscopic appearance, and the liver biopsy. Hypothermic machine perfusion (HMP) was associated in selected cases to improve cold storage. Most notably, no cases of PNF were observed. Median posttransplant transaminase peak was 1014 IU/L (range, 393‐3268 IU/L). Patient and graft survival were both 100% after a mean follow‐up of 6.1 months (range, 3‐9 months). No cases of ischemic cholangiopathy occurred during the follow‐up. Only 1 anastomotic stricture completely resolved with endoscopic stenting. In conclusion, DCD liver transplantation is feasible in Italy despite the protracted no‐touch period. The use of NRP and HMP seems to earn good graft function and proves safe in these organs. Liver Transplantation 23 166–173 2017 AASLD

Sequential Use of Normothermic Regional Perfusion and Hypothermic Machine Perfusion in Donation After Cardiac Death Liver Transplantation With Extended Warm Ischemia Time.

The great potential of donation after cardiac death (DCD) in expanding the liver donor pool is limited by the inferior results due to the ischemic injury.1 Normothermic regional perfusion (NRP) and hypothermic machine perfusion (HMP) can improve the transplantation outcome.2,3 These technologies may

Pancreatico-duodenectomy and postoperative pancreatic fistula: risk factors and technical considerations in a specialized HPB center

Postoperative pancreatic fistula (POPF) is a common complication of pancreatic resection. Aim of this study is to identify variables related to the development of POPF, analyze their clinical significance and discuss our current approach to the pancreatico-jejunal anastomosis. A series of 129 patients undergoing pancreatico-duodenectomy (PD) have been analyzed. Patients were divided in two groups: group F, 26 patients who have developed POPF; group NF, 103 patients who have not developed POPF. Demographic, clinical and intraoperative data were compared. Seventy-six patients had an end-to-side (ES) pancreatico-jejuno anastomosis, 53 an end-to-end (EE) anastomosis. Fifteen patients developed grade A fistulas, seven grade B, and four grade C; two patients with grade C fistula died from septic shock. Preoperative bile duct lithiasis, diameter of the pancreatic duct and consistency of the pancreatic stump were significantly different between F and NF groups at multivariate analysis. POPF has been related to clinical and biological parameters: preoperative bile duct lithiasis and challenging pancreatico-jejunal anastomosis (with small pancreatic duct and friable pancreatic stump) are the most prominent according to our experience. As the incidence of POPF seems to be related to technically demanding surgery, we presently reserve the EE anastomosis to the cases in which a friable gland or a very small duct will make a direct anastomosis on the pancreatic duct unreliable. In case of grade C fistulas a total spleen-preserving pancreatectomy should be considered an adequate treatment to prevent the onset of a multi-organ failure or a septic shock if no other treatment seems suitable.

Donation After Cardiac Death Liver Transplantation After More Than 20 Minutes of Circulatory Arrest and Normothermic Regional Perfusion.

Donation after cardiac death (DCD) has resurged over the last decade as an additional source to overcome the organ shortage. The main limitation to widespread application of DCD livers is the fact that these organs inevitably sustain warm ischemia damage during circulatory arrest. In Italy, an even

The current role of laparoscopic resection for HCC: a systematic review of past ten years

The use of laparoscopic liver resection (LLR) has progressively spread in the last 10 years. Several studies have shown the superiority of LLR to open liver resection (OLR) in term of perioperative outcomes. With this review, we aim to systematically assess short-term and long-term major outcomes in patients who underwent LLR for hepatocellular carcinoma (HCC) in order to illustrate the advantages of minimally invasive liver surgery. Through an advanced PubMed research, we selected all retrospective, prospective, and comparative clinical trials reporting short-term and long-term outcomes of any series of patients with diagnosis of HCC who underwent laparoscopic or robotic resection. Reviews, meta-analyses, or case reports were excluded. None of the patients included in this review has received a previous locoregional treatment for the same tumor nor has undergone a laparoscopic-assisted procedure. We considered morbidity and mortality for evaluation of major short-term outcomes, and overall survival (OS) and disease-free survival (DFS) for evaluation of long-term outcomes. A total of 1,501 patients from 17 retrospective studies were included, 15 studies compare LLR with OLR. Propensity-score matching (PSM) analysis was used in 11 studies (975 patients). The majority of the studies included patients with good liver function and a single HCC. Cirrhosis at pathology ranged from 33% to 100%. Overall mortality and morbidity ranges were 0-2.4% and 4.9-44% respectively, with most of the complications being Clavien-Dindo grade I or II (range: 3.9-23.3% vs. 0-9.52% for Clavien I-II and ≥ III respectively). The median blood loss ranged from 150 to 389 mL; the range of the median duration of surgery was 134-343 minutes. The maximum rate of conversion was 18.2%. The median duration of hospitalization ranged from 4 to 13 days. The ranges of overall survival rates at 1-, 3- and 5-year were 72.8-100%, 60.7-93.5% and 38-89.7% respectively. The ranges of disease free survival rates at 1-, 3- and 5-year were 45.5-91.5%, 20-72.2% and 19-67.8% respectively. The benefits of LLR in term of complication rate, blood loss, and duration of hospital stay make this procedure an advantageous alternative to OLR, especially for cirrhotic patients in whom the use of LLR reduces the risk of post-hepatectomy liver failure. The limits of LLR can be overcome by robotic surgery, which could therefore be preferred. Further benefits of minimally invasive surgery derive from its ability to reduce the formation of adhesions in view of a salvage liver transplant. In conclusion, the results of this review seem to confirm the safety and feasibility of LLR for HCC as well as its superiority to OLR according to perioperative outcomes.

Minor laparoscopic liver resection for Hepatocellular Carcinoma is safer than minor open resection, especially for less compensated cirrhotic patients: Propensity score analysis

BACKGROUND Laparoscopic liver resection (LLR) has gained significant popularity over the last 10 years. First experiences of LLR compared to open liver resection (OLR) reported a similar survival and a better safety profile for LLR. MATERIALS AND METHODS This is a retrospective analysis of prospectively collected data of all consecutive patients treated by liver resection for HCC on liver cirrhosis between January 2005 and March 2017. The choice of procedure (LLR vs OLR) was generally based on tumor localization, history of previous upper abdominal surgery and patients preference. The type of resection and indication for surgery were unrelated to the adopted technique. Based on pre-operative variables and confirmed cirrhosis, a 1:1 propensity score matching (PSM) model was developed to compare outcomes of LLR and OLR in patients with HCC. Outcomes of interest included morbidity, mortality and long-term cure potential. RESULTS After-PSM, the LLR group demonstrated better perioperative results including: lower complication rate (50.7% in OLR vs 29.3% in LLR, p = 0.0035), significantly lower intra-operative blood loss (200 ml in OLR vs 150 ml in LLR, p = 0.007) and shorter hospital length of stay (median 9 days in OLR vs 7 days in LLR, p = 0.0018). Moreover there was no significant difference between the two groups in 3-year survival (76%, CI: 60%-86% in LLR vs 68%, CI: 55%-79% in OLR, p = 0.32) or recurrence-free survival rates (44%, CI: 28%-58%, vs 44%, CI: 31%-57%, p = 0.94). CONCLUSIONS Minor LLR appeared significantly safer compared to minor OLR for HCC. LLR was associated with fewer post-operative complication, lower operative blood loss and a shorter hospital stay along with similar survival and recurrence-free survival rates.

Liver grafts from donors after cardiac death on regional perfusion with extended warm ischemia compared with donors after brain death

Donation after circulatory death (DCD) in Italy constitutes a relatively unique population because of the requirement of a no‐touch period of 20 minutes. The first aim of this study was to compare liver transplantations from donors who were maintained on normothermic regional perfusion after circulatory death and suffered extended warm ischemia (DCD group, n = 20) with those from donors who were maintained on extracorporeal membrane oxygenation (ECMO) and succumbed to brain death (ECMO group, n = 17) and those from standard donors after brain death (donation after brain death [DBD] group, n = 52). Second, we conducted an explorative analysis on the DCD group to identify relationships between the donor characteristics and the transplant outcomes. The 1‐year patient survival for the DCD group (95%) was not significantly different from that of the ECMO group (87%; P = 0.47) or the DBD group (94%; P = 0.94). Graft survival was slightly inferior in the DCD group (85%) because of a high rate of primary nonfunction (10%) and retransplantation (15%) but was not significantly different from the ECMO group (87%; P = 0.76) or the DBD group (91%; P = 0.20). Although ischemic cholangiopathy was more frequent in the DCD group (10%), this issue did not adversely impact graft survival because none of the recipients underwent retransplantation due to biliary complications. Moreover, the DCD recipients were more likely to develop posttransplant renal dysfunction with the need for renal replacement therapy. Further analysis of the DCD group showed that warm ischemia >125 minutes and an Ishak fibrosis score of 1 at liver biopsy negatively impacted serum creatinine and alanine transaminase levels in the first posttransplant week, respectively. In conclusion, our findings encourage the use of liver grafts from DCD donors maintained by regional perfusion after proper selection.

HIV-positive to HIV-positive liver transplantation: To be continued

To the Editor: Although the recently reported outcomes of human immunodeficiency virus (HIV)-positive to HIV-positive liver transplantation (LT) performed in the UK and Switzerland are certainly promising, several challenges remain before this transplant option can be expanded. The main risks of this procedure include: HIV superinfection, transmission of drug resistance and/or donor-related infections, drug-related liver dysfunction, and an increased risk of rejection. For the first time in Italy, an HIV-positive man received successful LT for multifocal hepatocellular carcinoma (HCC) on a background of viral cirrhosis from an HIV-positive brain-dead donor in May 2017. The 50-year-old recipient with a 32-year history of infection secondary to injection drug use had refused to take antiretroviral therapy (ART) for almost 20 years of asymptomatic infection. After esophageal candidosis (CDC stage C3) in 2005, a regimen with efavirenz plus tenofovir/emtricitabine was started with clinical and immunological improvement. ART was switched in 2015 to rilpivirine and in July 2016 to dolutegravir, maintaining tenofovir/emtricitabine. Due to the long duration of infection and persistently undetectable HIV-RNA in the previous decade, HIV genotypic resistance testing did not show significant resistance to any drug class before LT. He was negative for HLAB⁄5701, while the virus strain was CCR5 tropic. Advanced liver disease was secondary to hepatitis B virus, hepatitis delta virus co-infection and previous hepatitis C virus infection. In 2016, five years after successful locoregional treatment of the HCC, two new untreatable nodules (within Milan criteria) were diagnosed and the patient was admitted to the waiting list for LT. The patient’s clinical history, and management of HIV infection over time are reported in the table with details of the other two HIV-to-HIV LT reported in the literature (see Table 1). The donor was a 52-year-old HIV-positive man who died from stroke. He was under his first ART regimen (abacavir/lamivudine and dolutegravir) with no history of treatment failure. At the time of organ donation his CD4 cell count was 501 cells/ mm (23%) and plasma HIV-RNA was detectable, with 198 copies/ml, probably resulting from ART suspension due to his severe clinical condition. HIV genotypic resistance test was available four days after liver procurement and no resistanceassociated mutations were reported for nucleosidic and nonnucleosidic reverse transcriptase inhibitors, protease inhibitors or integrase inhibitors. The graft rapidly recovered function after transplant, and no surgical or medical complication occurred. HIV-positive transplant recipients are known to have a higher rejection rate than negative subjects. The recipient received an immunosuppressive regimen associating basiliximab induction, low-dose steroids and tacrolimus. ART with the previous regimen of tenofovir/emtricitabine and dolutegravir was resumed on

Liver transplantation in the treatment of severe iatrogenic liver injuries

The place of liver transplantation in the treatment of severe iatrogenic liver injuries has not yet been widely discussed in the literature. Bile duct injuries during cholecystectomy represent the leading cause of liver transplantation in this setting, while other indications after abdominal surgery are less common. Urgent liver transplantation for the treatment of severe iatrogenic liver injury may-represent a surgical challenge requiring technically difficult and time consuming procedures. A debate is ongoing on the need for centralization of complex surgery in tertiary referral centers. The early referral of patients with severe iatrogenic liver injuries to a tertiary center with experienced hepato-pancreato-biliary and transplant surgery has emerged as the best treatment of care. Despite widespread interest in the use of liver transplantation as a treatment option for severe iatrogenic injuries, reported experiences indicate few liver transplants are performed. This review analyzes the literature on liver transplantation after hepatic injury and discusses our own experience along with surgical advances and future prospects in this uncommon transplant setting.