J Endourol. 2023 Oct;37(10):1129-1138 doi: 10.1089/end.2023.0224.
Background: Patients who have undergone renal transplant may have a concomitant benign prostatic hyperplasia (BPH), a condition that can potentially hinder the recovery of the renal graft and necessitate surgical intervention. However, endoscopic treatment of BPH should be performed carefully because of the associated perioperative risks. We aimed to systematically assess the factors affecting surgical indications and perioperative outcomes of BPH surgical treatment in renal transplantation (RT) recipients. Methods: A systematic literature search was performed on January 28, 2023, using Scopus, PubMed, and EMBASE with no date limit. Preclinical and animal studies, reviews, letters to the editor, case reports, and meeting abstracts were excluded. Results: Eighteen articles were accepted and included. Clinical BPH has a high incidence rate after RT, particularly in elderly men. Secondary events associated with BPH, such as acute urinary retention and urinary tract infections, can lead to a gradual decline of renal graft function and patient survival. BPH procedure can prevent these events and guarantee improvements in serum creatinine levels, voiding parameters, and lower urinary tract symptoms. When the urine culture is negative, the endoscopic procedure of the prostate may be performed within 1 month of the initial procedure, particularly in older patients, more prone to develop voiding dysfunction. Alternatively, a transurethral incision of the prostate may be recommended for patients with smaller prostates who wish to preserve ejaculatory function. Data on comparative BPH surgical procedures are lacking. Conclusions: BPH procedure should be offered in RT recipients who develop bladder outlet obstruction owing to BPH. Endoscopic treatment should be performed after a few weeks from RT to avoid further graft deterioration. |
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Eur J Surg Oncol. 2023 Oct;49(10):106922 doi: 10.1016/j.ejso.2023.04.021.
INTRODUCTION:
Colon cancer in ulcerative colitis patients with liver transplant (UCCOLT) due to primary sclerosing cholangitis carries significant treatment challenges. Aim of this literature search is to review management strategies and provide a framework to facilitate the decisional process in this clinical setting. METHODS:PRISMA-compliant systematic search was followed by critical expert commentary of the results and development of a surgical management algorithm. Endpoints included surgical management, operative strategies, functional and survival outcomes. Technical and strategics aspects with particular regard to the choice of reconstruction were evaluated to tentatively develop an integrated algorithm. RESULTS:Ten studies reporting treatment of 20 UCCOLT patients were identified after screening. Nine patients underwent proctocolectomy and end-ileostomy (PC) and eleven had restorative ileal pouch-anal anastomosis (IPAA). Reported results for perioperative outcomes, oncological outcomes, and graft loss were comparable for both procedures. There were no reports of subtotal colectomies and ileo-rectal anastomosis (IRA). CONCLUSIONS:Literature in the field is scarce and decision-making is particularly complex. PC and IPAA have been reported with good results. Nevertheless, IRA may also be considered in UCCOLT patients in selected cases, reducing the risks of sepsis, OLT and pouch failure; furthermore, in young patients, it has the advantage of preserving fertility or sexual function. The proposed treatment algorithm may represent a valuable support in guiding surgical strategy. |
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Cochrane Database Syst Rev. 2023 Sep 12;9(9):CD014685 doi: 10.1002/14651858.CD014685.pub2.
BACKGROUND:
Liver transplantation is the only chance of cure for people with end-stage liver disease and some people with advanced liver cancers or acute liver failure. The increasing prevalence of these conditions drives demand and necessitates the increasing use of donated livers which have traditionally been considered suboptimal. Several novel machine perfusion preservation technologies have been developed, which attempt to ameliorate some of the deleterious effects of ischaemia reperfusion injury. Machine perfusion technology aims to improve organ quality, thereby improving outcomes in recipients of suboptimal livers when compared to traditional static cold storage (SCS; ice box). OBJECTIVES:To evaluate the effects of different methods of machine perfusion (including hypothermic oxygenated machine perfusion (HOPE), normothermic machine perfusion (NMP), controlled oxygenated rewarming, and normothermic regional perfusion) versus each other or versus static cold storage (SCS) in people undergoing liver transplantation. SEARCH METHODS:We used standard, extensive Cochrane search methods. The latest search date was 10 January 2023. SELECTION CRITERIA:We included randomised clinical trials which compared different methods of machine perfusion, either with each other or with SCS. Studies comparing HOPE via both hepatic artery and portal vein, or via portal vein only, were grouped. The protocol detailed that we also planned to include quasi-randomised studies to assess treatment harms. DATA COLLECTION AND ANALYSIS:We used standard Cochrane methods. Our primary outcomes were 1. overall participant survival, 2. quality of life, and 3. serious adverse events. Secondary outcomes were 4. graft survival, 5. ischaemic biliary complications, 6. primary non-function of the graft, 7. early allograft function, 8. non-serious adverse events, 9. transplant utilisation, and 10. transaminase release during the first week post-transplant. We assessed bias using Cochrane's RoB 2 tool and used GRADE to assess certainty of evidence. MAIN RESULTS:We included seven randomised trials (1024 transplant recipients from 1301 randomised/included livers). All trials were parallel two-group trials; four compared HOPE versus SCS, and three compared NMP versus SCS. No trials used normothermic regional perfusion. When compared with SCS, it was uncertain whether overall participant survival was improved with either HOPE (hazard ratio (HR) 0.91, 95% confidence interval (CI) 0.42 to 1.98; P = 0.81, I2 = 0%; 4 trials, 482 recipients; low-certainty evidence due to imprecision because of low number of events) or NMP (HR 1.08, 95% CI 0.31 to 3.80; P = 0.90; 1 trial, 222 recipients; very low-certainty evidence due to imprecision and risk of bias). No trials reported quality of life. When compared with SCS alone, HOPE was associated with improvement in the following clinically relevant outcomes: graft survival (HR 0.45, 95% CI 0.23 to 0.87; P = 0.02, I2 = 0%; 4 trials, 482 recipients; high-certainty evidence), serious adverse events in extended criteria DBD liver transplants (OR 0.45, 95% CI 0.22 to 0.91; P = 0.03, I2 = 0%; 2 trials, 156 participants; moderate-certainty evidence) and clinically significant ischaemic cholangiopathy in recipients of DCD livers (OR 0.31, 95% CI 0.11 to 0.92; P = 0.03; 1 trial, 156 recipients; high-certainty evidence). In contrast, NMP was not associated with improvement in any of these clinically relevant outcomes. NMP was associated with improved utilisation compared with SCS (one trial found a 50% lower rate of organ discard; P = 0.008), but the reasons underlying this effect are unknown. We identified 11 ongoing studies investigating machine perfusion technologies. AUTHORS' CONCLUSIONS:In situations where the decision has been made to transplant a liver donated after circulatory death or donated following brain death, end-ischaemic HOPE will provide superior clinically relevant outcomes compared with SCS alone. Specifically, graft survival is improved (high-certainty evidence), serious adverse events are reduced (moderate-certainty evidence), and in donors after circulatory death, clinically relevant ischaemic biliary complications are reduced (high-certainty evidence). There is no good evidence that NMP has the same benefits over SCS in terms of these clinically relevant outcomes. NMP does appear to improve utilisation of grafts that would otherwise be discarded with SCS; however, the reasons for this, and whether this effect is specific to NMP, is not clear. Further studies into NMP viability criteria and utilisation, as well as head-to-head trials with other perfusion technologies are needed. In the setting of donation following circulatory death transplantation, further trials are needed to assess the effect of these ex situ machine perfusion methods against, or in combination with, normothermic regional perfusion. |
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Hepatology. 2023 Sep 1;78(3):835-846 doi: 10.1097/HEP.0000000000000363.
BACKGROUND AND AIMS:
Acute cellular rejection (ACR) is a frequent complication after liver transplantation. By reducing ischemia and graft damage, dynamic preservation techniques may diminish ACR. We performed a systematic review to assess the effect of currently tested organ perfusion (OP) approaches versus static cold storage (SCS) on post-transplant ACR-rates. APPROACH AND RESULTS:A systematic search of Medline, Embase, Cochrane Library, and Web of Science was conducted. Studies reporting ACR-rates between OP and SCS and comprising at least 10 liver transplants performed with either hypothermic oxygenated perfusion (HOPE), normothermic machine perfusion, or normothermic regional perfusion were included. Studies with mixed perfusion approaches were excluded. Eight studies were identified (226 patients in OP and 330 in SCS). Six studies were on HOPE, one on normothermic machine perfusion, and one on normothermic regional perfusion. At meta-analysis, OP was associated with a reduction in ACR compared with SCS [OR: 0.55 (95% CI, 0.33-0.91), p =0.02]. This effect remained significant when considering HOPE alone [OR: 0.54 (95% CI, 0.29-1), p =0.05], in a subgroup analysis of studies including only grafts from donation after cardiac death [OR: 0.43 (0.20-0.91) p =0.03], and in HOPE studies with only donation after cardiac death grafts [OR: 0.37 (0.14-1), p =0.05]. CONCLUSIONS:Dynamic OP techniques are associated with a reduction in ACR after liver transplantation compared with SCS. PROSPERO registration: CRD42022348356. |
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J Hepatol. 2023 Sep;79(3):e114-e116 doi: 10.1016/j.jhep.2023.03.009.
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J Hepatol. 2023 Aug;79(2):394-402 doi: 10.1016/j.jhep.2023.04.010.
CET Conclusion
Expert Review
BACKGROUND & AIMS:
Ischemia-reperfusion injury (IRI) has thus far been considered as an inevitable component of organ transplantation, compromising outcomes, and limiting organ availability. Ischemia-free organ transplantation is a novel approach designed to avoid IRI, with the potential to improve outcomes. METHODS:In this randomized-controlled clinical trial, recipients of livers from donors after brain death were randomly assigned to receive either an ischemia-free or a 'conventional' transplant. The primary endpoint was the incidence of early allograft dysfunction. Secondary endpoints included complications related to graft IRI. RESULTS:Out of 68 randomized patients, 65 underwent transplants and were included in the analysis. 32 patients received ischemia-free liver transplantation (IFLT), and 33 received conventional liver transplantation (CLT). Early allograft dysfunction occurred in two recipients (6%) randomized to IFLT and in eight (24%) randomized to CLT (difference -18%; 95% CI -35% to -1%; p = 0.044). Post-reperfusion syndrome occurred in three recipients (9%) randomized to IFLT and in 21 (64%) randomized to CLT (difference -54%; 95% CI -74% to -35%; p <0.001). Non-anastomotic biliary strictures diagnosed with protocol magnetic resonance cholangiopancreatography at 12 months were observed in two recipients (8%) randomized to IFLT and in nine (36%) randomized to CLT (difference, -28%; 95% CI -50% to -7%; p = 0.014). The comprehensive complication index at 1 year after transplantation was 30.48 (95% CI 23.25-37.71) in the IFLT group vs. 42.14 (95% CI 35.01-49.26) in the CLT group (difference -11.66; 95% CI -21.81 to -1.51; p = 0.025). CONCLUSIONS:Among patients with end-stage liver disease, IFLT significantly reduced complications related to IRI compared to a conventional approach. CLINICAL TRIAL REGISTRATION:chictr.org. ChiCTR1900021158. IMPACT AND IMPLICATIONS:Ischemia-reperfusion injury has thus far been considered as an inevitable event in organ transplantation, compromising outcomes and limiting organ availability. Ischemia-free liver transplantation is a novel approach of transplanting donor livers without interruption of blood supply. We showed that in patients with end-stage liver disease, ischemia-free liver transplantation, compared with a conventional approach, led to reduced complications related to ischemia-reperfusion injury in this randomized trial. This new approach is expected to change the current practice in organ transplantation, improving transplant outcomes, increasing organ utilization, while providing a clinical model to delineate the impact of organ injury on alloimmunity. |
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Transpl Int. 2023 Jul 19;36:11374 doi: 10.3389/ti.2023.11374.
The advent of Machine Perfusion (MP) as a superior form of preservation and assessment for cold storage of both high-risk kidney's and the liver presents opportunities in the field of beta-cell replacement. It is yet unknown whether such techniques, when applied to the pancreas, can increase the pool of suitable donor organs as well as ameliorating the effects of ischemia incurred during the retrieval process. Recent experimental models of pancreatic MP appear promising. Applications of MP to the pancreas, needs refinement regarding perfusion protocols and organ viability assessment criteria. To address the "Role of pancreas machine perfusion to increase the donor pool for beta cell replacement," the European Society for Organ Transplantation (ESOT) assembled a dedicated working group comprising of experts to review literature pertaining to the role of MP as a method of improving donor pancreas quality as well as quantity available for transplant, and to develop guidelines founded on evidence-based reviews in experimental and clinical settings. These were subsequently refined during the Consensus Conference when this took place in Prague. |
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HPB (Oxford). 2023 Jul;25(7):732-746 doi: 10.1016/j.hpb.2023.02.017.
BACKGROUND:
In conventional orthotopic liver transplantation (OLT), the recipient's retrohepatic inferior vena cava (IVC) is completely clamped and replaced with the donor IVC. The piggyback technique has been used to preserve venous return, either via an end-to-side or standard piggyback (SPB), or via a side-to-side or modified piggyback (MPB) anastomosis, using a venous cuff from the recipient hepatic veins with partially clamping and preserves the recipient's inferior vena cava. However, whether these piggyback techniques improve the efficacy of OLT is unclear. To address the low quality of the available evidence, we performed a meta-analysis to compare the efficacy of conventional, MPB, and SPB techniques. METHODS:Literature was searched in Medline and Web of Science databases for relevant articles published until 2021 without any time restriction. A Bayesian network meta-analysis was performed to compare the intra- and postoperative outcomes of conventional OLT, MPB, and SPB techniques. RESULTS:Forty studies were included, comprising 10,238 patients. MPB and SPB had significantly shorter operation times and fewer transfusions of red blood cell and fresh frozen plasma than conventional techniques. However, there were no differences between MPB and SPB in operation time and blood product transfusion. There were also no differences in primary non-function, retransplantation, portal vein thrombosis, acute kidney injury, renal dysfunction, venous outflow complications, length of hospital and intensive care unit stay, 90-day mortality rate, and graft survival between the three techniques. CONCLUSION:MBP and SBP techniques reduce the operation time and need for blood transfusion compared with conventional OLT, but postoperative outcomes are similar. This indicates that all techniques can be implemented based on the experience and policy of the transplant center. |
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PLoS One. 2023 Jun 23;18(6):e0287713 doi: 10.1371/journal.pone.0287713.
CET Conclusion
Hypothermic machine perfusion (HMP) provides preservation superior to cold storage and may allow for organ assessment prior to transplantation. Since flavin mononucleotide (FMN) in perfusate has been proposed as a biomarker of organ quality during HMP of donor livers, the aim of this study was to validate FMN as a biomarker for organ quality in the context of HMP preserved kidneys. Perfusate samples (n = 422) from the paired randomised controlled COPE-COMPARE-trial, comparing HMP with oxygenation (HMPO2) versus standard HMP in kidneys, were used. Fluorescence intensity (FI) was assessed using fluorescence spectroscopy (excitation 450nm; emission 500-600nm) and validated by fluorospectrophotometer and targeted liquid chromatography mass spectrometry (LC-MS/MS). Fluorescence intensity (FI)(ex450;em500-600) increased over time during machine perfusion in both groups (p<0.0001). This increase was similar for both groups (p = 0.83). No correlation, however, was found between FI(ex450;em500-600) and post-transplant outcomes, including day 5 or 7 serum creatinine (p = 0.11; p = 0.16), immediate graft function (p = 0.91), creatinine clearance and biopsy-proven rejection at one year (p = 0.14; p = 0.59). LC-MS/MS validation experiments of samples detected FMN in only one perfusate sample, whilst the majority of samples with the highest fluorescence (n = 37/38, 97.4%) remained negative. In the context of clinical kidney HMP, fluorescence spectroscopy unfortunately appears to be not specific and probably unsuitable for FMN. This study shows that FMN does not classify as a clinically relevant predictive biomarker of kidney graft function after transplantation. |
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N Engl J Med. 2023 Jun 8;388(23):2121-2131 doi: 10.1056/NEJMoa2212438.
CET Conclusion
BACKGROUND:
Data showing the efficacy and safety of the transplantation of hearts obtained from donors after circulatory death as compared with hearts obtained from donors after brain death are limited. METHODS:We conducted a randomized, noninferiority trial in which adult candidates for heart transplantation were assigned in a 3:1 ratio to receive a heart after the circulatory death of the donor or a heart from a donor after brain death if that heart was available first (circulatory-death group) or to receive only a heart that had been preserved with the use of traditional cold storage after the brain death of the donor (brain-death group). The primary end point was the risk-adjusted survival at 6 months in the as-treated circulatory-death group as compared with the brain-death group. The primary safety end point was serious adverse events associated with the heart graft at 30 days after transplantation. RESULTS:A total of 180 patients underwent transplantation; 90 (assigned to the circulatory-death group) received a heart donated after circulatory death and 90 (regardless of group assignment) received a heart donated after brain death. A total of 166 transplant recipients were included in the as-treated primary analysis (80 who received a heart from a circulatory-death donor and 86 who received a heart from a brain-death donor). The risk-adjusted 6-month survival in the as-treated population was 94% (95% confidence interval [CI], 88 to 99) among recipients of a heart from a circulatory-death donor, as compared with 90% (95% CI, 84 to 97) among recipients of a heart from a brain-death donor (least-squares mean difference, -3 percentage points; 90% CI, -10 to 3; P<0.001 for noninferiority [margin, 20 percentage points]). There were no substantial between-group differences in the mean per-patient number of serious adverse events associated with the heart graft at 30 days after transplantation. CONCLUSIONS:In this trial, risk-adjusted survival at 6 months after transplantation with a donor heart that had been reanimated and assessed with the use of extracorporeal nonischemic perfusion after circulatory death was not inferior to that after standard-care transplantation with a donor heart that had been preserved with the use of cold storage after brain death. (Funded by TransMedics; ClinicalTrials.gov number, NCT03831048.). |