Renal Vessel Extension With Cryopreserved Vascular Grafts: Overcoming Surgical Pitfalls in Living Donor Kidney Transplant.

In LDKT, right kidneys and kidneys with anomalous vascularization are often deferred because of concerns on complications and vascular reconstructions. To date, only few reports have examined renal vessel extension with cryopreserved vascular grafts in LDKT. The aim of this study is to investigate the effect of renal vessel extension on short-term outcomes and ischemia times in LDKT. From 2012 to 2020, recipients of LDKT with renal vessels extension were compared with standard LDKT recipients. Subset analysis of rights grafts and grafts with anomalous vascularization, with or without renal vessel extension, was performed. Recipients of LDKT with (n = 54) and without (n = 91) vascular extension experienced similar hospital stays, surgical complications and DGF rates. For grafts with multiple vessels, renal vessel extension granted a faster implantation time (44±5 vs. 72±14 min), which resulted comparable to that of standard anatomy grafts. Right kidney grafts with vascular extension had a faster implantation time compared to right kidney grafts without vascular lengthening (43±5 vs. 58±9 min), and a comparable implantation time to left kidney grafts. Renal vessel extension with cryopreserved vascular grafts allows faster implantation time in right kidney grafts or grafts with anomalous vascularization, maintaining similar surgical and functional outcomes.

Hypothermic oxygenated perfusion in extended criteria donor liver transplantation-A randomized clinical trial.

Hypothermic Oxygenated Perfusion (HOPE) of the liver can reduce the incidence of early allograft dysfunction (EAD) and failure in extended criteria donors (ECD) grafts, although data from prospective studies are very limited. In this monocentric, open-label study, from December 2018 to January 2021, 110 patients undergoing transplantation of an ECD liver graft were randomized to receive a liver after HOPE or after static cold storage (SCS) alone. The primary endpoint was the incidence of EAD. The secondary endpoints included graft and patient survival, the EASE risk score, and the rate of graft or other graft-related complications. Patients in the HOPE group had a significantly lower rate of EAD (13% vs. 35%, p = .007) and were more frequently allocated to the intermediate or higher risk group according to the EASE score (2% vs. 11%, p = .05). The survival analysis confirmed that patients in the HOPE group were associated with higher graft survival one year after LT (p = .03, log-rank test). In addition, patients in the SCS group had a higher re-admission and overall complication rate at six months, in particular cardio-vascular adverse events (p = .04 and p = .03, respectively). HOPE of ECD grafts compared to the traditional SCS preservation method is associated with lower dysfunction rates and better graft survival.

Heterotopic segmental liver transplantation on splenic vessels after splenectomy with delayed native hepatectomy after graft regeneration: A new technique to enhance liver transplantation.

We describe a patient with liver metastases from colorectal cancer treated with chemotherapy and hepatic resection, who developed unresectable multifocal liver recurrence and who received liver transplantation using a novel planned technique: heterotopic transplantation of segment 2-3 in the splenic fossa with splenectomy and delayed hepatectomy after regeneration of the transplanted graft. We transplanted a segmental liver graft after in-situ splitting without any impact on the waiting list, as it was previously rejected for pediatric and adult transplantation. The volume of the graft was insufficient to provide liver function to the recipient, so we performed this novel operation. The graft was anastomosed to the splenic vessels after splenectomy, and the native liver portal flow was modulated to enhance graft regeneration, leaving the native recipient liver intact. The volume of the graft doubled during the next 2 weeks and the native liver was removed. After 8 months, the patient lives with a functioning liver in the splenic fossa and without abdominal tumor recurrence. This is the first case reported of a segmental graft transplanted replacing the spleen and modulating the portal flow to favor graft growth, with delayed native hepatectomy.

Preliminary experience of sequential use of normothermic and hypothermic oxygenated perfusion for donation after circulatory death kidney with warm ischemia time over the conventional criteria - a retrospective and observational study.

Donation after circulatory death (DCD) is a potential source of reducing organ demand. In Italy, DCD requires a 20-min no-touch period that prolongs warm ischemia and increases delayed graft function (DGF) risk and graft loss. We report here our preliminary experience of sequential use of normothermic regional perfusion (NRP), as standard procedure, and hypothermic oxygenated perfusion (HOPE), as an experimental technique of organ preservation, in 10 kidney transplants (KT) from five DCD Maastricht III with extensive functional warm ischemia time (fWIT) up to 325 min. During NRP, renal function tests were evaluated to accept organs which were retrieved according to standard fashion with biopsy. While waiting for pathology and cross-match results, organs were preserved with HOPE through pressure- and temperature-controlled arterial pulsatile flow. All grafts with Karpinski score ≤4 were used for conventional single KT with mean cold ischemia time of 584 ± 167 min and mean fWIT of 151 ± 132 min. At the end of HOPE, lactate levels increased significantly in all cases with DGF (P = 0.0095), which were 3/10 (30%). No primary nonfunctions were recorded, and all patients had sCr < 1.5 mg/dl at 6-month post-KT. NRP and HOPE for DCD may overcome fWIT limits safely, and lactate during HOPE predicts DGF.

Combined liver-dual kidney transplant: Role in expanded donors.

Kidney injury is a common clinical feature among liver transplantation (LT) candidates that heavily affects prognosis and complicates the surgical decision-making process. Up to 20% of patients undergoing LT demonstrate some degree of renal impairment, and 2% will benefit from a combined liver-kidney transplantation (LKT). We present a case-control study of all patients who underwent LKT and combined liver-dual kidney transplantation (LDKT) from November 2013 to March 2016. For the selection of LDKT candidates, a histological-based algorithm was applied: when evaluating extended criteria donors (ECDs), with any Remuzzi score between 4 and 7, we would consider performing a LDKT instead of a simple LKT. Study groups were similar for recipient variables. In the LDKT group, donor age, donor risk index, and donor body mass index were found to be significantly higher. Biopsies obtained from all pairs of kidney grafts in the LDKT group demonstrated the following Remuzzi scores: 4+4, 4+4, 7+1, 4+5. Despite longer operative times for the LDKT procedure, no differences were observed regarding the main investigated outcome parameters. Overall survival was 100% (LDKT) and 91% (LKT, P > 0.99). This is a preliminary experience which might indicate that LDKT is a safe, feasible, and resource-effective technique. The evaluation of a larger cohort, as well as the experience from other centers, would be needed to clearly identify its role in the ECD era. Liver Transplantation 23:28-34 2017 AASLD.

Plasma citrulline after small bowel transplantation: effect of time from transplantation, acute cellular rejection, and renal failure.

BACKGROUND: Plasma citrulline concentration (CIT) depends on its synthesis by enterocytes and its catabolism by renal tubules. To evaluate CIT applicability as a marker of acute cellular rejection (ACR) after intestinal transplantation (ITx), CIT was investigated according to time from ITx, episodes of ACR, and creatinine clearance (CrCl). METHODS: Twenty-four adult ITx recipients were prospectively studied. The results were compared with those of 19 healthy controls (HCs) and of 29 patients with chronic renal failure (CRF). RESULTS: In ITx recipients, CIT was lower than in HCs during the first two postoperative weeks; it then progressively increased and reached the range observed in HCs, approximately between the 31st and the 45th postoperative day. A positive association with postoperative days (R = 0.63; p < 0.0001) and a negative association with CrCl (R = -0.57; p < 0.0001) were observed. CIT was higher in patients with CRF than in HCs (p < 0.0001). CIT sensitivity and specificity in detecting ACR after the 45th postoperative day were 38% and 83%, using CIT threshold observed in HCs, and 69% and 77%, respectively, using CIT threshold adjusted for CRF degree. CONCLUSIONS: Adjusting CIT threshold for CRF degree almost doubled the sensitivity of CIT as a non-invasive marker of ACR in ITx recipients.

Combined heart-liver transplantation: a single-center experience.

Combined orthotopic heart and liver transplantation (CHLT) is a lifesaving procedure for patients with end-stage heart-liver disease. We reviewed the long-term outcome of patients who have undergone CHLT at the University of Bologna, Italy. Fifteen patients with heart and liver failure were placed on the transplant list between November 1999 and March 2012. The pretransplant cardiac diagnoses were familial amyloidosis in 14 patients and chronic heart failure due to chemotherapy with liver failure due to chronic hepatitis in one patient. CHLT was performed as a single combined procedure in 14 hemodynamically stable patients; there was no peri-operative mortality. The survival rates for the CHLT recipients were 93%, 93%, and 82% at 1 month and 1 and 5 years, respectively. Freedom from graft rejection was 100%, 90%, and 36% at 1, 5, and 10 years, respectively, for the heart graft and 100%, 91%, and 86% for the liver graft. The livers of eight recipients were transplanted as a "domino" with mean overall 1-year survival of 93%. Simultaneous heart and liver transplantation is feasible and was achieved in this extremely sick cohort of patients. By adopting the domino technique, we were able to enlarge the donor cohort and include high-risk patients.

Technical aspects of intestinal transplantation.

PURPOSE OF REVIEW: Intestinal transplantation includes an heterogeneous group of procedures in which different compositions of organs are transplanted. The current classification includes four groups according to the inclusion of the liver and/or the stomach in the graft: isolated intestinal transplantation, liver-intestinal transplantation, multivisceral transplantation, and modified multivisceral transplantation. Variants exist, the technical evolution having been slow, yet constant over years. RECENT FINDINGS: The most relevant early technical improvements were aimed at achieving better feasibility and safety of the most difficult aspects of the different procedures, such as removal of the recipient's diseased organs, performing of vascular reconstructions and prevention of complications as with retention of the donor's duodenum and pancreas in liver-intestine transplantation. More recently, apart from a clear definition of the classification of the procedures, progress has been more directed in a conservative direction such as the preservation of the native spleen with and without the pancreas in multivisceral transplants. SUMMARY: After achieving consistent satisfactory short-term results, the technical interest in intestinal transplantation is now moved to solutions that, in spite of a possible increased difficulty, may offer better opportunities of mid-term and long-term successes, both in terms of survival and quality of life.

The Relationship between Timing of Pretransplant Kidney Biopsy, Graft Loss, and Survival in Kidney Transplantation: An Italian Cohort Study.

INTRODUCTION: Kidney biopsy is performed to assess if an extended criteria graft can be used for transplantation. It may be performed before or after cross-clamping during organ procurement. This study aims to evaluate whether the timing of biopsy may modify cold ischemia times (CIT) and/or graft outcomes. METHODS: Kidney transplants performed in our center from January 2007 to December 2017 were analyzed. Grafts with preimplantation kidney biopsy were included. Biopsies were performed during surgical back table (ex situ kidney biopsy [ESKB]) until 2012 and since then before the aortic cross-clamping (in situ kidney biopsy [ISKB]). To overcome biases owing to different distributions, a propensity score model was developed. The study population consists in 322 patients, 115 ESKB, and 207 ISKB. RESULTS: CIT was significantly lower for ISKB (730 min ISKB vs. 840 min ESKB, p value = 0.001). In both crude (OR 0.27; 95% confidence interval, 95% CI 0.12-0.60; p value = 0.002) and adjusted analyses (OR 0.37; 95% CI 0.14-0.94; p value = 0.039), ISKB was associated with a reduced odd of graft loss when compared to ESKB. DISCUSSION/CONCLUSION: Performing preimplantation kidney biopsy during the recovery, prior to the aortic cross-clamping, may be a strategy to reduce CIT and improve transplant outcomes.

Double Single-Side Kidney Transplants With Bench Vascular Reconstruction: A Further Challenge Beyond the Marginality Without Future Preclusions.

BACKGROUND: Double kidney transplantation allows the use of marginal kidneys with a significant improvement in the recovery of renal function expected after transplantation, although with a greater anesthesiologic and surgical risk. One-sided positioning, more cautious in the event of functional exhaustion, can be complex due to vascular anomalies. MATERIALS AND METHODS: We report the case of 2 double unilateral kidney transplants with vascular reconstructions. The first is a double kidney transplant from a 83-year-old donor. Both kidneys (score 5) had 2 arteries and the arterial patch was not usable. A cryopreserved arterial graft was used for the packaging of an arterial axis with which a single T-L anastomosis was performed; the 2 veins were also joined with the packaging of a single anastomosis. The second case is a double kidney transplant from a cadaveric donor performed on a recipient suffering from severe diffuse atheromasia. The right kidney had 2 arteries and the left kidney had 3 arteries (both score 5). The aortic patches and veins of the 2 kidneys were joined together and a single arterial and venous anastomosis was performed. RESULTS: The course has been uneventful. In both cases there were no perioperative vascular complications. CONCLUSIONS: The use of marginal organs is an increasingly common reality. Bench vascular reconstructions can further increase donation resources, safely enhancing the transplantation of already marginal organs that would otherwise not be usable and allowing the contralateral vascular axis to be kept intact.

Hypothermic Oxygenated Perfusion Versus Static Cold Storage for Expanded Criteria Donors in Liver and Kidney Transplantation: Protocol for a Single-Center Randomized Controlled Trial.

BACKGROUND: Extended criteria donors (ECD) are widely utilized due to organ shortage, but they may increase the risk of graft dysfunction and poorer outcomes. Hypothermic oxygenated perfusion (HOPE) is a recent organ preservation strategy for marginal kidney and liver grafts, allowing a redirect from anaerobic metabolism to aerobic metabolism under hypothermic conditions and protecting grafts from oxidative species-related damage. These mechanisms may improve graft function and survival. OBJECTIVE: With this study, we will evaluate the benefit of end-ischemic HOPE on ECD grafts for livers and kidneys as compared to static cold storage (SCS). The aim of the study is to demonstrate the ability of HOPE to improve graft function and postoperative outcomes of ECD kidney and liver recipients. METHODS: This is an open-label, single-center randomized clinical trial with the aim of comparing HOPE with SCS in ECD kidney and liver transplantation. In the study protocol, which has been approved by the ethics committee, 220 patients (110 liver recipients and 110 kidney recipients) will be enrolled. Livers and kidneys assigned to the HOPE group undergo machine perfusion with cold Belzer solution (4-10°C) and continuous oxygenation (partial pressure of oxygen of 500-600 mm Hg). In the control group, livers and kidneys undergoing SCS are steeped in Celsior solution and stored on ice. Using the same perfusion machine for both liver and kidney grafts, organs are perfused from the start of the back-table procedure until implantation, without increasing the cold ischemia time. For each group, we will evaluate clinical outcomes, graft function tests, histologic findings, perfusate, and the number of allocated organs. Publication of the results is expected to begin in 2021. RESULTS: Dynamic preservation methods for organs from high-risk donors should improve graft dysfunction after transplantation. To date, we have recruited 108 participants. The study is ongoing, and recruitment of participants will continue until January 2020. CONCLUSIONS: The proposed preservation method should improve ECD graft function and consequently the postoperative patient outcomes. TRIAL REGISTRATION: ClinicalTrials.gov NCT03837197; https://clinicaltrials.gov/ct2/show/NCT03837197 ; Archived by WebCite® at http://www.webcitation.org/76fSutT3R. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/13922.

Impact of induction therapy on bacterial infections and long-term outcome in adult intestinal and multivisceral transplantation: a comparison of two different induction protocols: daclizumab vs. alemtuzumab.

INTRODUCTION: Induction therapy with daclizumab or alemtuzumab has been recently introduced for intestinal transplantation; however, the impact of such induction therapy on bacterial infections remains to be clarified. The purpose of this study was to evaluate the impact of induction therapy on the incidence of bacterial infections and long-term patient survival. PATIENTS AND METHODS: Over the past seven yr, we performed 39 intestinal (ITx) and multivisceral (MTVx) transplants in 38 adult patients. In the early period, daclizumab was used for induction, and tacrolimus and steroids were administered for maintenance [daclizumab and tacrolimus (DT) group; n = 11]. From 2002, we used alemtuzumab for induction, with low-dose tacrolimus maintenance [alemtuzumab and tacrolimus (AT) group; n = 23]. The incidence of bacterial infections and patient outcome were compared between the two groups. RESULTS: There were no significant differences in recipient and donor demographics, procedure (ITx vs. MTVx), and cold and warm ischemic time between the two groups. Within 30 d after ITx, bacterial infections were observed in seven patients (64%) in the DT and in 14 patients (64%) in the AT group. Between 30 and 180 d after ITx, a total of 17 episodes of bacterial infections were observed in the DT and 26 episodes in the AT group. Three patients in the DT and eight in the AT group died, and all of the deaths were related to infectious complications except one each in DT and AT. CONCLUSION: There was no difference in incidence of bacterial infections and long-term patient survival between the two groups.

[Kidney Transplant from donors after cardiac death (DCD): monocentric experience and literature review].

Kidney transplant from donor after circulatory death (DCD) represents a valid choice to increase the incidence of renal transplantation, presenting recipients' and grafts' survival rates comparable to those from brain dead donors (DBD). In January 2016, the Transplant Referral Center in the Emilia Romagna region has started a DCD program. In the present study we report on the first 30 months of the program as far as our own Center in Bologna is concerned, and we provide a comparison with DBD transplants performed over the same period. From January 2016 to September 2018, 16 kidney transplants from 10 DCD donors (5 SCD-DCD and 5 ECD-DCD) have been performed, with two graft-loss at 12 months of follow-up, both due to renal artery rupture caused by infectious arteritis with consequent transplantectomy. Two patients died due to sepsis. Seven (44%) delay graft function (DGF) have been reported. No differences have been found between DCD and DBD in terms of kidney function (serum creatinine and eGFR evaluated at discharge, 12 and 24 months of follow-up). Kidney from marginal donors (ECD-DCD or KDPI >65%) were associated with a higher rate of DGF and worst graft function at discharge. All the predicting factors that have been analysed, including Karpinsky Score, failed to show an association with serum creatinine and eGFR at 12 and 24 months of follow up.

Incidence and management of abdominal closure-related complications in adult intestinal transplantation.

BACKGROUND: We sought to determine the best strategy to overcome difficult abdominal wall closures in intestinal transplantation (ITx). METHODS: Among 38 adult recipients of 39 ITxs from deceased donors, the median number of previous laparotomies was 2.0 per patient, with a median donor-to-recipient body weight ratio of 1.1. Eight patients (21%) had full residual intestinal length before transplant. Abdominal wall closure after transplant was considered difficult in 15 (39.5%) patients (group A). To overcome size mismatching, we performed two graft reductions, five skin-only closures, one two-step abdominal wall closure, four prosthetic mesh closures, and three abdominal wall transplants. In the remaining 23 (60.5%) patients, a regular abdominal closure was performed (group B). RESULTS: Twelve patients (32%) experienced complications related to abdominal wall closure, 10 (67%) in group A and 2 (8.7%) in group B (P<0.0001). Abdominal closure-related mortality was 6.7% (1/15) and 4.3% (1/23), respectively (P=1.0). In group A, there were six incisional hernias (one of them after abdominal wall transplant), although all four patients with mesh experienced mesh infection. Two of them developed intestinal fistulae, leading to patient death in one case. In group B, one patient with unfavorable donor/recipient size matching had fatal vascular thrombosis of a multivisceral graft caused by compression after abdominal closure. CONCLUSIONS: A careful evaluation of abdominal cavity is necessary in candidates for ITx. In our experience, closure with mesh should be avoided because of the high rate of complications. Abdominal wall transplantation is a feasible option when a difficult abdominal wall closure is expected.

Intestinal failure in adults: Recommendations from the ESPEN expert groups.

BACKGROUND & AIMS: Intestinal failure (IF) is defined as "the reduction of gut function below the minimum necessary for the absorption of macronutrients and/or water and electrolytes, such that intravenous supplementation is required to maintain health and/or growth". Functionally, it may be classified as type I acute intestinal failure (AIF), type II prolonged AIF and type III chronic intestinal failure (CIF) The ESPEN Workshop on IF was held in Bologna, Italy, on 15-16 October 2017 and the aims of this document were to highlight the current state of the art and future directions for research in IF. METHODS: This paper represents the opinion of experts in the field, based on current evidence. It is not a formal review, but encompasses the current evidence, with emphasis on epidemiology, classification, diagnosis and management. RESULTS: IF is the rarest form of organ failure and can result from a variety of conditions that affect gastrointestinal anatomy and function adversely. Assessment, diagnosis, and short and long-term management involves a multidisciplinary team with diverse expertise in the field that aims to reduce complications, increase life expectancy and improve quality of life in patients. CONCLUSIONS: Both AIF and CIF are relatively rare conditions and most of the published work presents evidence from small, single-centre studies. Much remains to be investigated to improve the diagnosis and management of IF and future studies should rely on multidisciplinary, multicentre and multinational collaborations that gather data from large cohorts of patients. Emphasis should also be placed on partnership with patients, carers and government agencies in order to improve the quality of research that focuses on patient-centred outcomes that will help to improve both outcomes and quality of life in patients with this devastating condition.

Strategies to Restore Adenosine Triphosphate (ATP) Level After More than 20 Hours of Cold Ischemia Time in Human Marginal Kidney Grafts.

BACKGROUND The persisting organ shortage in the field of transplantation recommends the use of marginal kidneys which poorly tolerate ischemic damage. Adenosine triphosphate (ATP) depletion during cold ischemia time (CIT) is considered crucial for graft function. We tested different strategies of kidney perfusion before transplantation in the attempt to improve the technique. MATERIAL AND METHODS Twenty human discarded kidneys from donors after brain death and with at least 20 hours of CIT were randomized to the following experimental groups (treatment time three-hours at 4°C): a) static cold storage (CS); b) static cold hyperbaric oxygenation (Hyp); c) hypothermic perfusion (PE); d) hypothermic perfusion in hyperbaric oxygenation (PE-Hyp); and e) hypothermic oxygenated perfusion (PE-O2). RESULTS Histological results showed that perfusion with or without oxygen did not produce any endothelial damage. A depletion of ATP content following the preservation procedure was observed in CS, PE, and Hyp, while PE-Hyp and PE-O2 were associated with a net increase of ATP content with respect to baseline level. In addition, PE-Hyp was associated with a significant downregulation of endothelial isoform of nitric oxide synthase (eNOS) gene expression and of hypoxia inducible factor-1α (HIF-1α). CONCLUSIONS Hyperbaric or normobaric oxygenation with perfusion improves organ metabolic preservation compared to other methods. This approach may prevent the onset of delayed graft function, but clinical trials are needed to confirm this.