The role of T-tubes and abdominal drains on short-term outcomes in liver transplantation - A systematic review of the literature and expert panel recommendations.

BACKGROUND: This systematic review and expert panel recommendation aims to answer the question regarding the routine use of T-tubes or abdominal drains to better manage complications and thereby improve outcomes after liver transplantation. METHODS: Systematic review following PRISMA guidelines and recommendations using the GRADE approach derived from an international expert panel to assess the potential risks and benefits of T-tubes and intra-abdominal drainage in liver transplantation (CRD42021243036). RESULTS: Of the 2996 screened records, 33 studies were included in the systematic review, of which 29 (six RCTs) assessed the use of T-tubes and four regarding surgical drains. Although some studies reported less strictures when using a T-tube, there was a trend toward more biliary complications with T-tubes, mainly related to biliary leakage. Due to the small number of studies, there was a paucity of evidence on the effect of abdominal drains with no clear benefit for or against the use of drainage. However, one study investigating the open vs. closed circuit drains found a significantly higher incidence of intra-abdominal infections when open-circuit drains were used. CONCLUSIONS: Due to the potential risk of biliary leakage and infections, the routine intraoperative insertion of T-tubes is not recommended (Level of Evidence moderate - very low; grade of recommendation strong). However, a T-tube can be considered in cases at risk for biliary stenosis. Due to the scant evidence on abdominal drainage, no change in clinical practice in individual centers is recommended. (Level of Evidence very low; weak recommendation).

Procalcitonin in early allograft dysfunction after orthotopic liver transplantation: a retrospective single centre study.

BACKGROUND: Ischemia-reperfusion injury (IRI) is the pathophysiological hallmark of hepatic dysfunction after orthotopic liver transplantation (OLT). Related to IRI, early allograft dysfunction (EAD) after OLT affects short- and long-term outcome. During inflammatory states, the liver seems to be the main source of procalcitonin (PCT), which has been shown to increase independently of bacterial infection. This study investigates the association of PCT, IRI and EAD as well as the predictive value of PCT during the first postoperative week in terms of short- and long-term outcome after OLT. METHODS: Patients ≥ 18 years undergoing OLT between January 2016 and April 2020 at the University Hospital of Zurich were eligible for this retrospective study. Patients with incomplete PCT data on postoperative days (POD) 1 + 2 or combined liver-kidney transplantation were excluded. The PCT course during the first postoperative week, its association with EAD, defined by the criteria of Olthoff, and IRI, defined as aminotransferase level > 2000 IU/L within 2 PODs, were analysed. Finally, 90-day as well as 12-month graft and patient survival were assessed. RESULTS: Of 234 patients undergoing OLT, 110 patients were included. Overall, EAD and IRI patients had significantly higher median PCT values on POD 2 [31.3 (9.7-53.8) mcg/l vs. 11.1 (5.3-25.0) mcg/l; p < 0.001 and 27.7 (9.7-51.9) mcg/l vs. 11.5 (5.5-25.2) mcg/l; p < 0.001] and impaired 90-day graft survival (79.2% vs. 95.2%; p = 0.01 and 80.4% vs. 93.8%; p = 0.033). IRI patients with PCT < 15 mcg/l on POD 2 had reduced 90-day graft and patient survival (57.9% vs. 93.8%; p = 0.001 and 68.4% vs. 93.8%; p = 0.008) as well as impaired 12-month graft and patient survival (57.9% vs. 96.3%; p = 0.001 and 68.4% vs. 96.3%; p = 0.008), while the outcome of IRI patients with PCT > 15 mcg/l on POD 2 was comparable to that of patients without IRI/EAD. CONCLUSION: Generally, PCT is increased in the early postoperative phase after OLT. Patients with EAD and IRI have a significantly increased PCT maximum on POD 2, and impaired 90-day graft survival. PCT measurement may have potential as an additional outcome predictor in the early phase after OLT, as in our subanalysis of IRI patients, PCT values < 15 mcg/l were associated with impaired outcome.

Hypothermic Oxygenated Liver Perfusion (HOPE) Prevents Tumor Recurrence in Liver Transplantation From Donation After Circulatory Death.

OBJECTIVE: The aim of this study was to investigate tumor recurrence after liver transplantation for hepatocellular carcinoma (HCC), with and without hypothermic oxygenated liver perfusion (HOPE) before transplantation. PATIENTS AND METHODS: We analyzed all liver recipients with HCC, transplanted between January 2012 and September 2019 with donation after circulatory death (DCD) livers after previous end-ischemic HOPE-treatment (n = 70, Center A). Tumor parameters and key confounders were compared to consecutive recipients with HCC, transplanted during the same observation period with an unperfused DBD liver (n = 70). In a next step, we analyzed unperfused DCD (n = 70) and DBD liver recipients (n = 70), transplanted for HCC at an external center (Center B). RESULTS: Tumor parameters were not significantly different between HOPE-treated DCD and unperfused DBD liver recipients at Center A. One-third of patients were outside established tumor thresholds, for example, Milan criteria, in both groups. Despite no difference in tumor load, we found a 4-fold higher tumor recurrence rate in unperfused DBD livers (25.7%, 18/70), compared to only 5.7% (n = 4/70) recipients with tumor recurrence in the HOPE-treated DCD cohort (P = 0.002) in Center A. The tumor recurrence rate was also twice higher in unperfused DCD and DBD recipients at the external Center B, despite significant less cases outside Milan. HOPE-treatment of DCD livers resulted therefore in a 5-year tumor-free survival of 92% in HCC recipients, compared to 73%, 82.7%, and 81.2% in patients receiving unperfused DBD or DCD livers, from both centers. CONCLUSION: We suggest that a simple machine liver perfusion approach appears advantageous to protect from HCC recurrence after liver transplantation, despite extended tumor criteria.

Effect of time to surgery in resectable pancreatic cancer: a systematic review and meta-analysis.

PURPOSE: Achieving surgical resection is essential if patients with pancreatic ductal adenocarcinoma (PDAC) have a chance for cure. The objective of this study was to evaluate the effect of time to surgery on resection rates in patients with resectable PDAC. METHODS: A systematic literature search was performed to identify studies reporting times to surgery and resection rates. Meta-regression models were then produced to assess the relationship between time to surgery and resection rates, using both intra- and inter-study comparisons. RESULTS: A total of 21 studies were included, comprising n = 2171 patients, with a pooled resection rate of 76%. Intra-study meta-analysis of the five studies that reported comparisons between patients with vs. without preoperative biliary drainage (PBD) or with long vs. short delays to surgery found earlier surgery to be associated with a significantly higher rate of resection (pooled odds ratio 1.93, 95% CI: 1.25-2.97, P = 0.003). Inter-study meta-regression across all studies found a tendency for resection rates to decline with increasing time from CT or ERCP to surgery (gradient - 0.13 log-odds per week, 95% CI - 0.28, 0.03, P = 0.100), although this did not reach statistical significance, in part due to considerable heterogeneity between studies. CONCLUSION: Pathways to reduce the time to surgery, primarily by avoiding PBD, demonstrate significantly greater resection rates. Early surgery, including avoidance of PBD, not only provides patients with the benefit of avoiding harm associated with PBD but also with a greater chance of undergoing resection.

Recurrence patterns of pancreatic cancer after pancreatoduodenectomy: systematic review and a single-centre retrospective study.

BACKGROUND: Positive margins in pancreatoduodenectomy (PD) for pancreatic cancer, specifically the superior mesenteric artery (SMA) margin, are associated with worse outcomes. Local therapies targeting these margins could impact on recurrence. This study analysed recurrence-patterns to identify whether strategies to control local disease could have a meaningful impact. METHODS: (I) Systematic review to define recurrence patterns and resection margin status. (II) Additional retrospective study of PD performed at our centre. RESULTS: In the systematic review, 23/617 evaluated studies were included (n = 3815). Local recurrence was observed in 7-69%. SMA margin (6 studies) was positive in 15-35%. In the retrospective study (n = 204), local recurrence was more frequently observed with a positive SMA margin (66 vs.45%; p = 0.005). Furthermore, in a multivariate cox-proportional hazard model, only a positive SMA margin was associated with disease recurrence (HR 1.615; 95%CI 1.127-2.315; p = 0.009). Interestingly, median overall survival was 20 months and similar for patients who developed local only, metastases only or simultaneous recurrence (p = 0.124). CONCLUSION: Local recurrence of pancreatic cancer is common and associated with similar mortality rates as those who present with simultaneous or metastatic recurrence. Involvement of the SMA margin is an independent predictor for disease progression and should be the target of future adjuvant local therapies.

Outcomes of DCD liver transplantation using organs treated by hypothermic oxygenated perfusion before implantation.

BACKGROUND & AIMS: Donation after circulatory death (DCD) liver transplantation is known for potentially worse outcomes because of higher rates of graft non-function or irreversible cholangiopathy. The impact of machine liver perfusion techniques on these complications remains elusive. We aimed to provide data on 5-year outcomes in patients receiving DCD liver transplants, after donor organs had been treated by hypothermic oxygenated perfusion (HOPE). METHODS: Fifty HOPE-treated DCD liver transplants performed in Zurich between 2012 and 3/2017 were matched with 50 primary donation after brain death (DBD) liver transplants, and with 50 untreated DCD liver transplants in Birmingham. Match factors focussed on short cold ischaemia, comparable recipient age and low recipient laboratory model for end-stage liver disease scores. Primary endpoints were post-transplant complications, and non-tumour-related patient death or graft loss. RESULTS: Despite extended donor warm ischaemia, HOPE-treated DCD liver transplants achieved similar overall graft survival, compared to standard DBD liver transplants. Particularly, graft loss due to any non-tumour-related causes occurred in 8% (4/50) of cases. In contrast, untreated DCD livers resulted in non-tumour-related graft failure in one-third (16/50) of cases (p = 0.005), despite significantly (p <0.001) shorter functional donor warm ischaemia. Five-year graft survival, censored for tumour death, was 94% for HOPE-treated DCD liver transplants vs. 78% in untreated DCD liver transplants (p = 0.024). CONCLUSIONS: The 5-year outcomes of HOPE-treated DCD liver transplants were similar to those of DBD primary transplants and superior to those of untreated DCD liver transplants, despite much higher risk. These results suggest that a simple end-ischaemic perfusion approach is very effective and may open the field for safe utilisation of extended DCD liver grafts. LAY SUMMARY: Machine perfusion techniques are currently being introduced into the clinic, with the aim of optimising injured grafts prior to implantation. While short-term effects of machine liver perfusion have been frequently reported in terms of hepatocellular enzyme release and early graft function, the long-term benefit on irreversible graft loss has been unclear. Herein, we report on 5-year graft survival in donation after cardiac death livers, treated either by conventional cold storage, or by 1-2 h of hypothermic oxygenated perfusion (HOPE) after cold storage. Graft loss was significantly less in HOPE-treated livers, despite longer donor warm ischaemia times. Therefore, HOPE after cold storage appears to be a simple and effective method to treat high-risk livers before implantation.

Benchmarks in Pancreatic Surgery: A Novel Tool for Unbiased Outcome Comparisons.

OBJECTIVE: To use the concept of benchmarking to establish robust and standardized outcome references after pancreatico-duodenectomy (PD). BACKGROUND: Best achievable results after PD are unknown. Consequently, outcome comparisons among different cohorts, centers or with novel surgical techniques remain speculative. METHODS: This multicenter study analyzes consecutive patients (2012-2015) undergoing PD in 23 international expert centers in pancreas surgery. Outcomes in patients without significant comorbidities and major vascular resection (benchmark cases) were analyzed to establish 20 outcome benchmarks for PD. These benchmarks were tested in a cohort with a poorer preoperative physical status (ASA class ≥3) and a cohort treated by minimally invasive approaches. RESULTS: Two thousand three hundred seventy-five (38%) low-risk cases out of a total of 6186 PDs were analyzed, disclosing low in-hospital mortality (≤1.6%) but high morbidity, with a 73% benchmark morbidity rate cumulated within 6 months following surgery. Benchmark cutoffs for pancreatic fistulas (B-C), severe complications (≥ grade 3), and failure-to-rescue rate were 19%, 30%, and 9%, respectively. The ASA ≥3 cohort showed comparable morbidity but a higher in hospital-mortality (3% vs 1.6%) and failure-to-rescue rate (16% vs 9%) than the benchmarks. The proportion of benchmark cases performed varied greatly across centers and continents for both open (9%-93%) and minimally invasive (11%-62%) PD. Centers operating mostly on complex PD cases disclosed better results than those with a majority of low-risk cases. CONCLUSION: The proposed outcome benchmarks for PD, established in a large-scale international patient cohort and tested in 2 different cohorts, may allow for meaningful comparisons between different patient cohorts, centers, countries, and surgical techniques.

Chronic Kidney Disease After Liver Transplantation: Impact of Extended Criteria Grafts.

The use of extended criteria donor (ECD) grafts has been associated with acute kidney injury (AKI) after liver transplantation. However, the relation between graft quality and development of chronic kidney disease (CKD) remains unknown. Therefore, the aim of this study was to analyze the impact of ECD grafts for CKD after liver transplantation. All patients (2007-2015) transplanted for end-stage liver disease at our center were assessed. Longterm kidney function was divided into 4 groups: no CKD (estimated glomerular filtration rate [eGFR], ≥60 mL/minute/1.73 m2 ), mild CKD (eGFR, 30-59 mL/minute/1.73 m2 ), severe CKD (eGFR, 15-29 mL/minute/1.73 m2 ), and end-stage renal disease (ESRD). Marginal donation after brain death (DBD) grafts (donor age, >70 years; body mass index, >35 kg/m2 ; cold storage, >12 hours) and donation after circulatory death (DCD) grafts were considered ECD grafts. Overall, 926 patients were included, and 43% received an ECD graft (15% marginal DBD; 28% DCD). After 5 years, 35% developed CKD; severe CKD and ESRD occurred in only 2% and 1%, respectively. CKD rates were comparable for all 3 graft groups (standard group, 36%; marginal DBD group, 29%; DCD group, 35%; standard versus marginal DBD groups, P = 0.16; standard versus DCD group, P = 0.80). None of the ECD criteria were identified as independent risk factors in a Cox regression model for CKD. Risk factors included recipient age, female sex, and preoperative kidney function. Furthermore, recipients who had severe acute kidney injury (AKI; Kidney Disease: Improving Global Outcomes stages 2 and 3) had a 1.8-fold increased risk for CKD. Longterm kidney function of recipients with severe AKI depended on the recovery of kidney function in the first postoperative week. In conclusion, there is no direct relation between the use of ECD grafts and CKD after liver transplantation. However, caution should be taken in recipients who experience severe AKI, regardless of graft type.

Retrieval Practice or Overall Donor and Recipient Risk: What Impacts on Outcomes After Donation After Circulatory Death Liver Transplantation in the United Kingdom?

Parameters of retrieval surgery are meticulously documented in the United Kingdom, where up to 40% of livers are donation after circulatory death (DCD) donations. This retrospective analysis focuses on outcomes after transplantation of DCD livers, retrieved by different UK centers between 2011 and 2016. Donor and recipient risk factors and the donor retrieval technique were assessed. A total of 236 DCD livers from 9 retrieval centers with a median UK DCD risk score of 5 (low risk) to 7 points (high risk) were compared. The majority used University of Wisconsin solution for aortic flush with a median hepatectomy time of 27-44 minutes. The overall liver injury rate appeared relatively high (27.1%) with an observed tendency toward more retrieval injuries from centers performing a quicker hepatectomy. Among all included risk factors, the UK DCD risk score remained the best predictor for overall graft loss in the multivariate analysis (P < 0.001). In high-risk and futile donor-recipient combinations, the occurrence of liver retrieval injuries had negative impact on graft survival (P = 0.023). Expectedly, more ischemic cholangiopathies (P = 0.003) were found in livers transplanted with a higher cumulative donor-recipient risk. Although more biliary complications with subsequent graft loss were found in high-risk donor-recipient combinations, the impact of the standardized national retrieval practice on outcomes after DCD liver transplantation was minimal.

Future liver remnant portal or hepatic vein reconstruction at stage I of ALPPS-How far can we push the boundaries?

Preservation of the future liver remnant (FLR) vascular integrity has always been considered crucial to achieving successful liver growths after major hepatectomies. Most surgeons appeared therefore reluctant to combine stage I of associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) with vascular reconstructions. Here we describe a case series, where we combine parenchymal transection and venous in- or outflow reconstruction of the FLR at stage I of ALPPS. In addition, the cold flush of the FLR or delayed portal vein embolization is applied in selected cases.

The AKI Prediction Score: a new prediction model for acute kidney injury after liver transplantation.

BACKGROUND: Acute kidney injury (AKI) is a frequent complication after liver transplantation. Although numerous risk factors for AKI have been identified, their cumulative impact remains unclear. Our aim was therefore to design a new model to predict post-transplant AKI. METHODS: Risk analysis was performed in patients undergoing liver transplantation in two centres (n = 1230). A model to predict severe AKI was calculated, based on weight of donor and recipient risk factors in a multivariable regression analysis according to the Framingham risk-scheme. RESULTS: Overall, 34% developed severe AKI, including 18% requiring postoperative renal replacement therapy (RRT). Five factors were identified as strongest predictors: donor and recipient BMI, DCD grafts, FFP requirements, and recipient warm ischemia time, leading to a range of 0-25 score points with an AUC of 0.70. Three risk classes were identified: low, intermediate and high-risk. Severe AKI was less frequently observed if recipients with an intermediate or high-risk were treated with a renal-sparing immunosuppression regimen (29 vs. 45%; p = 0.007). CONCLUSION: The AKI Prediction Score is a new instrument to identify recipients at risk for severe post-transplant AKI. This score is readily available at end of the transplant procedure, as a tool to timely decide on the use of kidney-sparing immunosuppression and early RRT.

The UK DCD Risk Score: A new proposal to define futility in donation-after-circulatory-death liver transplantation.

BACKGROUND & AIMS: Primary non-function and ischaemic cholangiopathy are the most feared complications following donation-after-circulatory-death (DCD) liver transplantation. The aim of this study was to design a new score on risk assessment in liver-transplantation DCD based on donor-and-recipient parameters. METHODS: Using the UK national DCD database, a risk analysis was performed in adult recipients of DCD liver grafts in the UK between 2000 and 2015 (n = 1,153). A new risk score was calculated (UK DCD Risk Score) on the basis of a regression analysis. This is validated using the United Network for Organ Sharing database (n = 1,617) and our own DCD liver-transplant database (n = 315). Finally, the new score was compared with two other available prediction systems: the DCD risk scores from the University of California, Los Angeles and King's College Hospital, London. RESULTS: The following seven strongest predictors of DCD graft survival were identified: functional donor warm ischaemia, cold ischaemia, recipient model for end-stage liver disease, recipient age, donor age, previous orthotopic liver transplantation, and donor body mass index. A combination of these risk factors (UK DCD risk model) stratified the best recipients in terms of graft survival in the entire UK DCD database, as well as in the United Network for Organ Sharing and in our own DCD population. Importantly, the UK DCD Risk Score significantly predicted graft loss caused by primary non-function or ischaemic cholangiopathy in the futile group (>10 score points). The new prediction model demonstrated a better C statistic of 0.79 compared to the two other available systems (0.71 and 0.64, respectively). CONCLUSIONS: The UK DCD Risk Score is a reliable tool to detect high-risk and futile combinations of donor-and-recipient factors in DCD liver transplantation. It is simple to use and offers a great potential for making better decisions on which DCD graft should be rejected or may benefit from functional assessment and further optimization by machine perfusion. LAY SUMMARY: In this study, we provide a new prediction model for graft loss in donation-after-circulatory-death (DCD) liver transplantation. Based on UK national data, the new UK DCD Risk Score involves the following seven clinically relevant risk factors: donor age, donor body mass index, functional donor warm ischaemia, cold storage, recipient age, recipient laboratory model for end-stage liver disease, and retransplantation. Three risk classes were defined: low risk (0-5 points), high risk (6-10 points), and futile (>10 points). This new model stratified best in terms of graft survival compared to other available models. Futile combinations (>10 points) achieved an only very limited 1- and 5-year graft survival of 37% and less than 20%, respectively. In contrast, an excellent graft survival has been shown in low-risk combinations (≤5 points). The new model is easy to calculate at the time of liver acceptance. It may help to decide which risk combination will benefit from additional graft treatment, or which DCD liver should be declined for a certain recipient.

Impact of donor age in donation after circulatory death liver transplantation: Is the cutoff "60" still of relevance?

Advanced donor age has been identified as a risk factor when combined with donor warm ischemia time (WIT), eg, in donation after circulatory death (DCD). In several countries, DCD livers older than 60 years are not considered suitable due to concerns related to poor graft function and development of ischemic cholangiopathy. In this study, we evaluate outcomes after DCD liver transplantation using grafts from donors older than 60 years. We analyzed outcomes after DCD liver transplantation (n = 315), comparing donors > 60 years (n = 93) and donors ≤ 60 years (n = 222) from our center between 2005 and 2015. End points included graft function and complications and patient and graft survival. Multivariate risk analysis was performed to define further key factors that predicted inferior outcome. Donor age at the cutoff 60 years failed to stratify patient and graft survival. The rate of vascular, biliary, and overall complications was comparably low in both cohorts, and the median comprehensive complication index was 42.7 points, independent from the donor age. Second, donor body mass index (BMI) above a threshold of 25 kg/m2 significantly impacted on graft and patient survival at any donor age, whereas donor WIT and cold ischemia times were not predictive for graft loss. In conclusion, older DCD donors can be successfully used for liver transplantation with good longterm outcomes when further risk factors are limited. Additional risk is transmitted by an increased donor BMI regardless of donor age. Liver Transplantation 24 352-362 2018 AASLD.

Onset of Donor Warm Ischemia Time in Donation After Circulatory Death Liver Transplantation: Hypotension or Hypoxia?

The aim of this study was to investigate the impact of hypoxia and hypotension during the agonal phase of donor warm ischemia time (DWIT) on hepatic ischemia/reperfusion injury (IRI) and complications in donation after circulatory death (DCD) liver transplantation. A retrospective single-center study of 93 DCD liver transplants (Maastricht type III) was performed. DWIT was divided into 2 periods: the agonal phase (from withdrawal of treatment [WoT] until circulatory arrest) and the asystolic phase (circulatory arrest until cold perfusion). A drop to <80% in peripheral oxygenation (SpO2 ) was considered as hypoxia in the agonal phase (SpO2 -agonal) and a drop to <50 mm Hg as hypotension in the agonal phase (SBP-agonal). Peak postoperative aspartate transaminase level >3000 U/L was considered as severe hepatic IRI. SpO2 dropped within 2 minutes after WoT <80%, whereas the systolic blood pressure dropped to <50 mm Hg after 9 minutes, resulting in a longer SpO2 -agonal (13 minutes) than SBP-agonal (6 minutes). In multiple logistic regression analysis, only duration of SpO2 -agonal was associated with severe hepatic IRI (P = 0.006) and not SBP-agonal (P = 0.32). Also, recipients with long SpO2 -agonal (>13 minutes) had more complications with a higher Comprehensive Complication Index during hospital admission (43.0 versus 32.0; P = 0.002) and 90-day graft loss (26% versus 6%; P = 0.01), compared with recipients with a short SpO2 -agonal (≤13 minutes). Furthermore, Cox proportional hazard modeling identified a long SpO2 -agonal as a risk factor for longterm graft loss (hazard ratio, 3.30; 95% confidence interval, 1.15-9.48; P = 0.03). In conclusion, the onset of hypoxia during the agonal phase is related to the severity of hepatic IRI and postoperative complications. Therefore, SpO2 <80% should be considered as the start of functional DWIT in DCD liver transplantation.

Comparison of Postoperative Outcomes Between Donation After Circulatory Death and Donation After Brain Death Liver Transplantation Using the Comprehensive Complication Index.

OBJECTIVE: To test the total burden of complications in the early postoperative period after liver transplantation (LT) between donation after circulatory death (DCD) and donation after brain death (DBD) grafts with the novel Comprehensive Complication Index (CCI). BACKGROUND: LT is complex surgery and the increasing use of high-risk grafts is pressuring current postoperative outcomes. DCD grafts in particular are associated with ischemic-type biliary lesions (ITBL) with subsequent impaired graft survival rates. METHODS: Retrospective single-center study of all LT since the start of DCD program (2001-2015). CCI (at hospital discharge and after 6 months) was the result of all complications weighted by their Clavien-Dindo grade. A multiple logistic regression model was used to identify factors associated with a complex postoperative course (CCI at 6 months >60). RESULTS: In total, 441 cases were included: 115 DCD and 326 DBD grafts. Median in-hospital CCI was comparable for both groups (DCD 38.2; DBD 36.7; P = 0.429). Six-month postoperative median CCI was significantly higher for DCD grafts (53.4 vs 47.2; P = 0.041). Moreover, more DCD recipients underwent retransplantation for ITBL in this period (4% vs 1%; P = 0.031). Logistic regression identified recipient BMI (P = 0.046), recipient warm ischemia time (odds ratio, OR, 1.032; 95% CI, 1.008-1.056; P = 0.008), and DCD graft (OR 3.913; 95% CI 1.200-12.767; P = 0.024) as risk factors for a CCI >60. CONCLUSIONS: This analysis shows a comparable complication rate during the index hospital stay for DCD and DBD LT, but the CCI increases significantly for DCD recipients in 6 months after transplantation. Reduction of biliary complications, especially ITBL, is needed to improve the outcomes for DCD grafts.

The postreperfusion syndrome is associated with acute kidney injury following donation after brain death liver transplantation.

Acute kidney injury (AKI) is frequently observed after donation after brain death (DBD) liver transplantation (LT) and associated with impaired recipient survival and chronic kidney disease. Hepatic ischemia/reperfusion injury (IRI) is suggested to be an important factor in this process. The postreperfusion syndrome (PRS) is the first manifestation of severe hepatic IRI directly after reperfusion. We performed a retrospective study on the relation between hepatic IRI and PRS and their impact on AKI in 155 DBD LT recipients. Severity of hepatic IRI was measured by peak postoperative AST levels and PRS was defined as >30% decrease in MAP ≥1 min within 5 min after reperfusion. AKI was observed in 39% of the recipients. AKI was significantly more observed in recipients with PRS (53% vs. 32%; P = 0.013). Median peak AST level was higher in recipients with PRS (1388 vs. 771 U/l; P < 0.001). Decrease in MAP after reperfusion correlated well with both severity of AKI (P = 0.012) and hepatic IRI (P < 0.001). Multiple logistic regression identified PRS as an independent factor for postoperative AKI (OR 2.28; 95% CI 1.06-4.99; P = 0.035). In conclusion, PRS reflects severe hepatic IRI and predicts AKI after DBD LT. PRS immediately after reperfusion is an early warning sign and creates opportunities to preserve postoperative renal function.

Aberrant p53 protein expression is associated with an increased risk of neoplastic progression in patients with Barrett's oesophagus.

OBJECTIVE: The value of surveillance for patients with Barrett's oesophagus (BO) is under discussion given the overall low incidence of neoplastic progression and lack of discriminative tests for risk stratification. Histological diagnosis of low-grade dysplasia (LGD) is the only accepted predictor for progression to date, but has a low predictive value. The aim of this study was therefore to evaluate the value of p53 immunohistochemistry for predicting neoplastic progression in patients with BO. DESIGN: We conducted a case-control study within a prospective cohort of 720 patients with BO. Patients who developed high-grade dysplasia (HGD) or oesophageal adenocarcinoma (OAC) were classified as cases and patients without neoplastic progression were classified as controls. P53 protein expression was determined by immunohistochemistry in more than 12 000 biopsies from 635 patients and was scored independently by two expert pathologists who were blinded to long-term outcome. RESULTS: During follow-up, 49 (8%) patients developed HGD or OAC. P53 overexpression was associated with an increased risk of neoplastic progression in patients with BO after adjusting for age, gender, Barrett length and oesophagitis (adjusted relative risks (RR(a)) 5.6; 95% CI 3.1 to 10.3), but the risk was even higher with loss of p53 expression (RR(a) 14.0; 95% CI 5.3 to 37.2). The positive predictive value for neoplastic progression increased from 15% with histological diagnosis of LGD to 33% with LGD and concurrent aberrant p53 expression. CONCLUSIONS: Aberrant p53 protein expression is associated with an increased risk of neoplastic progression in patients with BO and appears to be a more powerful predictor of neoplastic progression than histological diagnosis of LGD.

Value of α-methylacyl-CoA racemase immunochemistry for predicting neoplastic progression in Barrett's oesophagus.

AIM: To investigate the value of α-methylacyl-CoA racemase (AMACR) immunohistochemistry for predicting neoplastic progression in Barrett's oesophagus (BO). METHODS AND RESULTS: We conducted a case-control study within a prospective cohort of 720 BO patients. Patients who developed high-grade dysplasia or oesophageal adenocarcinoma were classified as cases, and patients without neoplastic progression as controls. AMACR expression was determined by immunohistochemistry in 12 127 biopsies from 635 patients, and was scored independently by two expert pathologists. Relative risks adjusted for age, gender, BO length and oesophagitis (RR(a)) were calculated in log-linear models. During a median follow-up of 6.6 years, 49 patients (8%) developed high-grade dysplasia or oesophageal adenocarcinoma. Although mild AMACR expression was associated with a trend towards an increased risk of neoplastic progression (RR(a) 1.6, 95% CI 0.9-3.1), the risk was especially elevated with strong AMACR expression (RR(a) 4.8, 95% CI 1.9-12.6). The positive predictive value of strong AMACR expression was slightly higher than that of low-grade dysplasia (22% versus 15%); the negative predictive value was slightly lower (91% versus 93%). CONCLUSIONS: Strong AMACR expression is associated with an increased risk of neoplastic progression in BO. However, AMACR expression appears to be a less powerful predictor for neoplastic progression than low-grade dysplasia.