Davide Ghinolfi

Risk analysis of ischemic‐type biliary lesions after liver transplant using octogenarian donors

The use of octogenarian donors to increase the donor pool in liver transplantation (LT) is controversial because advanced donor age is associated with a higher risk of ischemic‐type biliary lesions (ITBL). The aim of this study was to investigate retrospectively the role of a number of different pre‐LT risk factors for ITBL in a selected population of recipients of octogenarian donor grafts. Between January 2003 and December 2013, 123 patients underwent transplantation at our institution with deceased donor grafts from donors of age ≥80 years. Patients were divided into 2 groups based on the presence of ITBL in the posttransplant course. Exclusion criteria were retransplantations, presence of vascular complications, and no availability of procurement liver biopsy. A total of 88 primary LTs were included, 73 (83.0%) with no posttransplant ITBLs and 15 (17.0%) with ITBLs. The median follow‐up after LT was 2.1 years (range, 0.7‐5.4 years). At multivariate analysis, donor hemodynamic instability (hazard ratio [HR], 7.6; P = 0.005), donor diabetes mellitus (HR, 9.5; P = 0.009), and donor age–Model for End‐Stage Liver Disease (HR, 1.0; P = 0.04) were risk factors for ITBL. Transplantation of liver grafts from donors of age ≥80 years is associated with a higher risk for ITBL. However, favorable results can be achieved with accurate donor selection. Donor hemodynamic instability, a donor history of diabetes mellitus, and allocation to higher Model for End‐Stage Liver Disease score recipient all increase the risk of ITBL and are associated with worse graft survival when octogenarian donors are used. Liver Transplantation 22 588‐598 2016 AASLD.

Outcome of laparoscopic splenectomy for malignant hematologic diseases

Aim The role of laparoscopic splenectomy in the treatment of hematological diseases is still controversial. The aim of this study was to assess whether the benign or malignant nature of hematological diseases may influence the outcome of laparoscopic splenectomy. Patients and methods Between August 1997 and March 2002, 63 unselected patients with hematologic diseases underwent a laparoscopic splenectomy. Patients were divided into two groups according to the benign (Group A, 38 patients) or malignant (Group B, 25 patients) nature of the hematological diseases. Results Patients in group B were significantly (a) older, (b) had larger spleens that more frequently needed accessory incisions for specimen retrieval, (c) had greater transfusion requirements, and (d) were fed later than patients in group A. There were no statistically significant differences among the two groups in terms of (a) body-mass index, (b) operative time, (c) conversion rate, (d) blood loss, (e) pain medication requirements, and (f) hospital stay. Two postoperative deaths occurred among patients in group B, but none of them was related to surgery. Conclusions The results of the study showed that: a) the nature of the disease does not influence the outcome of laparoscopic splenectomy, b) the size of the spleen might increase the risk of conversion, but it is no longer a contraindication to laparoscopic splenectomy, and c) laparoscopic splenectomy can be effectively performed in the treatment of malignant hematologic diseases.

Use of Elderly Donors in Liver Transplantation: A Paired-match Analysis at a Single Center.

Objective: To evaluate the use of elderly donors in liver transplantation (LT) and identify risk factors associated with a worse outcome. Summary Background Data: Use of livers from very old donors could expand the donor pool but is not universally implemented. Methods: This is a retrospective, single-center medical record review. From January 2001 to December 2014, 1354 LTs were performed. After exclusion of donors <18 years, ABO-incompatible LT, re-LT and UNOS 1 status patients, LT recipients were stratified into 2 groups based on donor age: 18–69 (n=692) vs. ≥70 years (n=515) then matched using a propensity score approach. Two groups were finally matched (young group = 448 cases; old group = 515 cases). Results: The median (interquartile range [IQR]) follow-up was 5.0 (2.0–8.4) years. Comparing the 2 identified groups, no differences were observed regarding early retransplants (1.8 vs. 2.9; P = 0.3), HCV-related death (7.6 vs. 8.7%; P = 0.6), vascular (5.8 vs. 5.0%; P = 0.7), and biliary complications (16.5 vs. 18.6%; P = 0.4). On multivariate analysis, independent risk factors for graft loss were: HCV-positive recipient (HR = 2.1; 95% CI = 1.6–2.7; P < 0.001), donor age (HR = 1.0; 95% CI = 1.0–1.0; P < 0.001), cold ischemia time (HR = 1.0; 95% CI = 1.0–1.0; P = 0.042), and donor history of diabetes mellitus (HR = 1.48; 95% CI = 1.03–2.13; P = 0.036). Conclusions: Use of elderly donors is not associated per se with an increased risk of vascular and biliary complications. In the presence of cold ischemia time and diabetes mellitus, appropriate donor-to-recipient matching is warranted.

Strategies to optimize the use of marginal donors in liver transplantation

Liver transplantation is the treatment of choice for end stage liver disease, but availability of liver grafts is still the main limitation to its wider use. Extended criteria donors (ECD) are considered not ideal for several reasons but their use has dramatically grown in the last decades in order to augment the donor liver pool. Due to improvement in surgical and medical strategies, results using grafts from these donors have become acceptable in terms of survival and complications; nevertheless a big debate still exists regarding their selection, discharge criteria and allocation policies. Many studies analyzed the use of these grafts from many points of view producing different or contradictory results so that accepted guidelines do not exist and the use of these grafts is still related to non-standardized policies changing from center to center. The aim of this review is to analyze every step of the donation-transplantation process emphasizing all those strategies, both clinical and experimental, that can optimize results using ECD.

Impact of pretransplant dialysis on early graft function in pediatric kidney recipients.

Delayed graft function (DGF) is a frequent complication of kidney transplantation (KT) that may affect both short‐ and long‐term graft outcome. It has been reported that pretransplantation peritoneal dialysis was correlated with a better recovery of graft function than hemodialysis in adult kidney recipients. However, the effect of pretransplantation dialysis mode (PDM) seemed to be unclear on the early outcome of KT in pediatric recipients. In this study, the potential impact of PDM on early graft function was evaluated in 174 pediatric patients who underwent KT by using cadaveric donors. The primary outcome parameter was the time to reach a serum creatinine (SCr) level 50% of the pretransplantation value [T1/2(SCr)], while DGF was defined as a T1/2(SCr) >3 days after KT (n = 40). By stratifying kidney recipients for normal function graft or DGF, this latter group showed a significantly higher body weight (BW) on the day of KT (P = 0.014), body surface area (BSA) (P = 0.005), warm ischemia time (WIT) (P = 0.022), early SCr on the day 1 after KT (P < 0.001), and T1/2(SCr) (P < 0.001), whereas lower urine volume (UV) collected in the first 24 h after KT (P < 0.001) and fluid load (P < 0.001) occurred. Univariate exponential correlation that was carried out between T1/2(SCr) and all the other variables had shown a better value than the linear correlation for BW (R2 = 0.28 vs. R2 = 0.04), BSA (R2 = 0.29 vs. R2 = 0.03), and SCr (R2 = 0.51 vs. R2 = 0.28). In a multivariate regression analysis performed by entering T1/2(SCr) as dependent variable and following a forward stepwise method, cold ischemia time (CIT) (P = 0.027) but not PDM (P = 0.195) reached significance. In a Cox regression analysis carried out with T1/2(SCr) as dependent variable, neither CIT nor PDM gained significance. This study suggests that PDM does not affect early graft function in pediatric kidney recipients.

Beyond the Limit: Approaching Systematic Use of Nonagenarian Donors in Liver Transplantation.

AST, alanine aminotransferases; ALT, alanine aminotransferases; bil., bilirubin; BMI, body mass index; CIT, cold ischemia time; CVA, cerebrovascular accident; ETOH, ethanolic; HA, hepatic artery; HCV, hepatitis C virus; HBP, high blood pressure; ICU, intensive care unit; MELD, model for end-stage liver disease; POD, postoperative day. Use of livers from very old donors is a way to expand the donor pool, but this practice is not universally implemented due to concerns about the risk of primary nonfunction (PNF), delayed graft function (DGF), and worse long-term graft survival. Recently, our experience with use of octogenarian deceased liver donors was reported and showed favorable overall long-term results when proper donor evaluation and donor-to-recipientmatching are assured. Beyond some anecdotal case reports, wider use of nonagenarian donors is still scarce. During the last 18 months, four nonagenarian donors were reported to our Unit for evaluation for liver transplantation (LT). Donors were evaluated as per our institutional flow chart, as reported elsewhere. One donor graft was discarded and three were procured and transplanted. Graft biopsy was obtained on surgeon evaluation at time of procurement, livers retrieved with dual portal and arterial perfusion, and transplantations performed with cava replacement and simultaneous arterial and portal reperfusion. The clinical characteristics of donors and recipients are summarized in Table 1 along with their clinical outcome. All recipients were discharged from hospital in good clinical conditions. Trans T-tube cholangiography 3 months after LT showed no bile duct abnormalities and no vascular or biliary complications occurred at a mean follow-up of 11 months. One patient experienced Pseudomonas aeruginosa wound infection treated with antibiotics and vacuum-assisted closure therapy. The patient transplanted for hepatitis C virus (HCV)-related cirrhosis underwent a preLT course of sofosbuvir and ribavirin for 36 weeks, was HCV-RNA negative at the time of transplantation, and remained negative at 12 weeks.

Everolimus-based immunosuppression in a case of ABO-incompatible liver transplantation with calcineurin inhibitor-related posterior occipital syndrome.

Dear Sirs, Owing to its high immunological risk, ABO-incompatible liver transplantation (LT) is usually performed with triple or quadruple calcineurin inhibitor (CNI)-based immunosuppression and association with nondrug immunological treatment modalities, such as plasmapheresis or splenectomy [1,2]. The use of preoperative rituximab has been recently reported in small series of living-related liver transplants too [3]. However, management of CNI-related complications may be challenging for the transplant physician due to the increased risk of graft rejection in case of CNI minimization or withdrawal. We report here an

Octogenarian donors in liver transplantation grant an equivalent perioperative course to ideal young donors

BACKGROUND Use of grafts from very old donors for liver transplantation is controversial. AIM To compare the perioperative course of patients receiving liver grafts from young ideal vs octogenarian donors. METHODS Analysis of the perioperative course of patients receiving liver grafts from young, ideal (18-39 years) vs octogenarian (≥80years) deceased donors between 2001 and 2014. RESULTS 346 patients were studied: 179 (51.7%) received grafts aged 18-39 years whereas 167 (48.3%) received a graft from a donor aged ≥80years. Intra-operative cardiovascular (p=0.2), coagulopathy (p=0.5) and respiratory (p=1.0) complications and incidence of reperfusion syndrome (p=0.3) were similar. Patients receiving a young graft required more fresh frozen plasma units (p≤0.03) but did not differ for the need of packed red cells (p=0.2) and platelet (p=0.3) transfusions. Median ICU stay was identical (p=0.4). Patients receiving octogenarian vs young grafts did not differ in terms of death or re-transplant (p=1.0) during the ICU stay. Similar cardiovascular, respiratory, renal, infectious and neurological postoperative complication rates were observed in the two groups. CONCLUSIONS Octogenarian donors in liver transplantation grant an equivalent perioperative course to ideal young donors.

Recurrence of hepatocellular carcinoma after direct acting antiviral treatment for hepatitis C virus infection: Literature review and risk analysis

Although studies suggest decreased incident hepatocellular carcinoma (HCC) after treatment with direct-acting antivirals (DAAs) for hepatitis C virus (HCV) infection, data are conflicting regarding risk and aggressiveness of recurrence in patients who have a history of treated HCC. This review analyses data available in literature in order to elucidate the impact of DAAs on the risk of HCC recurrence after successful treatment of the tumor. Overall 24 papers were identified. The available data cannot be considered definitive, but the initial alarmist data indicating an increased risk of recurrence have not been confirmed by most subsequent studies. The suggested aggressive pattern (rapid growth and vascular invasion) of tumor recurrence after DAAs still remains to be confirmed. Several limitations of the available studies were highlighted, and should drive future researches. The time-to-recurrence should be computed since the last HCC treatment and results stratified for cirrhosis and sustained viral response. Any comparison with historical series is of limited interest because of a number of biases affecting these studies and differences between enrolled patients. Prospective intention-to-treat analyses will be probably the best contribution to drive clinical practice, provided that a randomized trial can be difficult to design.

A simple new technique to prevent bleeding in transplant nephrectomy

Abstract  Renal transplantectomy is still a frequent procedure for a transplant surgeon. Nevertheless, it is constantly marred by complications, first of all bleeding. In fact, the local circumstances after the operation and the general health state of the uremic patients lead to a high incidence of this complication. To avoid this, we adopt a particular technique for renal extracapsular transplantectomy, performing three running sutures between the two faces of the renal capsule. This prevents the formation of the hematoma which is the basis of the continuous bleeding and following infection. We collected a series of nine patients who underwent transplantectomy in which we used this technique. No complications were noted.