Fabio Ferla

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

Split-Liver Full-Left Full-Right: Proposal for an Operative Protocol

INTRODUCTION Worldwide, organ shortage is a major limiting factor to transplantations. One possible way to face graft scarcity is splitting full livers into hemilivers; this procedure would allow transplantation in 2 adult recipients with the use of a single organ from a deceased donor. OBJECTIVE The goal of this study was to describe an adult-to-adult split liver operative protocol and share it between centers interested in exploring this procedure. MATERIALS AND METHODS A literature review was first conducted to elaborate on the present protocol; second, selection criteria for suitable deceased donors were identified. The technical aspects of performing the procurement were also analyzed; finally, the recipient selection criteria and the transplantation criteria were determined. RESULTS The donor characteristics should be consistent with the following: age≤55 years; weight≥70 kg; body mass index<28 kg/m2; intensive care unit stay<7 days; sodium level<160 mEq/L if the intensive care unit stay is >2 days; maximum transaminase value 3 times normal; hemodynamic stability; negative for hepatitis B surface antigen, hepatitis C virus, and human immunodeficiency virus; macrosteatosis<20%; macroscopic adequacy; and absence of anatomic anomalies requiring complex reconstruction. The procurement hospital should provide the preoperative computed tomography scan, liver dissector, and the intraoperative ultrasound. Indication for in situ or ex situ splitting depends on the hepatic vein outflow anatomy. Graft-to-recipient weight ratio should be ≥1%, and the graft-to-recipient spleen size ratio should be ≥0.6. United Network for Organ Sharing status 1 and 2A recipients are excluded, as are patients with transjugular intrahepatic portosystemic shunts. Hemiliver transplants are performed as in living-donor liver transplantation, and portal hyperflow is corrected by splenic artery ligation, splenectomy, and portal infusion of vasoactive drugs. CONCLUSIONS The present protocol was proposed to test the validity of the full-left full-right split liver procedure. A retrospective analysis found that 130 transplantations were suitable for this procedure according to the present protocol in the period January 1, 2008, through December 31, 2011 (65 donors). We believe that these numbers could be greatly increased once this procedure is proven feasible and safe within the proposed criteria.

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.

LESS technique for liver resection: the progress of the mini-invasive approach: A single-centre experience

Abstract Introduction: During the last years, the safety and efficacy of the laparoscopic approach for liver masses located in the left lobe have been demonstrated, encouraging the mini-invasive approach and, in more recent times, the LESS technique (Laparo Endoscopic Single Site), in an attempt to reduce the biological invasiveness related to surgical trauma. Material and methods: From January 2009 to December 2010, 39 patients underwent laparoscopic liver resection at our institution. In 14 of these, the LESS technique was used. The aim of our study is to evaluate the short-term outcome of this group of patients. Results: We recorded the following results: Mean operative time of 187 min (range 145–420 min), mean intraoperative blood loss of 214 ml (range 50–700 ml), postoperative morbidity rate of 21.4%, one postoperative death (related to acute heart failure related to severe aortic valve stenosis). Excluding this patient from the statistical analysis, the morbidity rate was 14.3%. The median hospital stay was five days. Discussion: The LESS technique for liver resections is safe and effective in selected patients and in centres with high expertise in laparoscopic liver surgery.

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.

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.