British Transplantation Society guidelines on abdominal organ transplantation from deceased donors after circulatory death.

The British Transplantation Society (BTS) 'Guideline on transplantation from deceased donors after circulatory death' has recently been updated and this manuscript summarises the relevant recommendations in abdominal organ transplantation from Donation after Circulatory Death (DCD) donors, encompassing the chapters on liver, kidney, pancreas and islet cell transplantation.

N-acetylcysteine: a novel approach to methaemoglobinaemia in normothermic liver machine perfusion.

Extended duration of normothermic machine perfusion (NMP) provides opportunities to resuscitate suboptimal donor livers. This intervention requires adequate oxygen delivery typically provided by a blood-based perfusion solution. Methaemoglobin (MetHb) results from the oxidation of iron within haemoglobin and represents a serious problem in perfusions lasting > 24 h. We explored the effects of anti-oxidant, N-acetylcysteine (NAC) on the accumulation of methaemoglobin. NMP was performed on nine human donor livers declined for transplantation: three were perfused without NAC (no-NAC group), and six organs perfused with an initial NAC bolus, followed by continuous infusion (NAC group), with hourly methaemoglobin perfusate measurements. In-vitro experiments examined the impact of NAC (3 mg) on red cells (30 ml) in the absence of liver tissue. The no-NAC group sustained perfusions for an average of 96 (range 87-102) h, universally developing methaemoglobinaemia (≥ 2%) observed after an average of 45 h, with subsequent steep rise. The NAC group was perfused for an average of 148 (range 90-184) h. Only 2 livers developed methaemoglobinaemia (peak MetHb of 6%), with an average onset of 116.5 h. Addition of NAC efficiently limits formation and accumulation of methaemoglobin during NMP, and allows the significant extension of perfusion duration.

Early postoperative risk stratification in patients with pancreatic fistula after pancreaticoduodenectomy.

BACKGROUND: Early stratification of postoperative pancreatic fistula according to severity and/or need for invasive intervention may improve outcomes after pancreaticoduodenectomy. This study aimed to identify the early postoperative variables that may predict postoperative pancreatic fistula severity. METHODS: All patients diagnosed with biochemical leak and clinically relevant-postoperative pancreatic fistula based on drain fluid amylase >300 U/L on the fifth postoperative day after pancreaticoduodenectomy were identified from a consecutive cohort from Birmingham, UK. Demographics, intraoperative parameters, and postoperative laboratory results on postoperative days 1 through 7 were retrospectively extracted. Independent predictors of clinically relevant-postoperative pancreatic fistula were identified using multivariable binary logistic regression and converted into a risk score, which was applied to an external cohort from Verona, Italy. RESULTS: The Birmingham cohort had 187 patients diagnosed with postoperative pancreatic fistula (biochemical leak: 99, clinically relevant: 88). In clinically relevant-postoperative pancreatic fistula patients, the leak became clinically relevant at a median of 9 days (interquartile range: 6-13) after pancreaticoduodenectomy. Male sex (P = .002), drain fluid amylase-postoperative day 3 (P < .001), c-reactive protein postoperative day 3 (P < .001), and albumin-postoperative day 3 (P = .028) were found to be significant predictors of clinically relevant-postoperative pancreatic fistula on multivariable analysis. The multivariable model was converted into a risk score with an area under the receiver operating characteristic curve of 0.78 (standard error: 0.038). This score significantly predicted the need for invasive intervention (postoperative pancreatic fistula grades B3 and C) in the Verona cohort (n = 121; area under the receiver operating characteristic curve: 0.68; standard error = 0.06; P = .006) but did not predict clinically relevant-postoperative pancreatic fistula when grades B1 and B2 were included (area under the receiver operating characteristic curve 0.52; standard error = 0.07; P = .802). CONCLUSION: We developed a novel risk score based on early postoperative laboratory values that can accurately predict higher grades of clinically relevant-postoperative pancreatic fistula requiring invasive intervention. Early identification of severe postoperative pancreatic fistula may allow earlier intervention.

Machine perfusion and the prevention of ischemic type biliary lesions following liver transplant: What is the evidence?

The widespread uptake of different machine perfusion (MP) strategies for liver transplant has been driven by an effort to minimize graft injury. Damage to the cholangiocytes during the liver donation, preservation, or early posttransplant period may result in stricturing of the biliary tree and inadequate biliary drainage. This problem continues to trouble clinicians, and may have catastrophic consequences for the graft and patient. Ischemic injury, as a result of compromised hepatic artery flow, is a well-known cause of biliary strictures, sepsis, and graft failure. However, very similar lesions can appear with a patent hepatic artery and these are known as ischemic type biliary lesions (ITBL) that are attributed to microcirculatory dysfunction rather than main hepatic arterial compromise. Both the warm and cold ischemic period duration appear to influence the onset of ITBL. All of the commonly used MP techniques deliver oxygen to the graft cells, and therefore may minimize the cholangiocyte injury and subsequently reduce the incidence of ITBL. As clinical experience and published evidence grows for these modalities, the impact they have on ITBL rates is important to consider. In this review, the evidence for the three commonly used MP strategies (abdominal normothermic regional perfusion [A-NRP], hypothermic oxygenated perfusion [HOPE], and normothermic machine perfusion [NMP] for ITBL prevention has been critically reviewed. Inconsistencies with ITBL definitions used in trials, coupled with variations in techniques of MP, make interpretation challenging. Overall, the evidence suggests that both HOPE and A-NRP prevent ITBL in donated after circulatory death grafts compared to cold storage. The evidence for ITBL prevention in donor after brain death grafts with any MP technique is weak.

Liver Transplantation in Sexagenarian Patients Using Grafts From Uncontrolled Circulatory Death Versus Grafts From Brain Death Donation.

BACKGROUND: An increased number of older recipients underwent liver transplantation in recent years, and consequently needing to obtain more liver grafts. In order to increase this pool, in 2006, we initiated the use of livers from uncontrolled circulatory death (uDCD). We analyzed the use of uDCD livers in sexagenarian recipients and their effect on overall survival. METHODS: A retrospective and comparative study was performed among 4 groups according to recipient age (less or greater than 60 years) and donor type (donor brain death [DBD] or uDCD): Group A: DBD livers in recipients aged <60 years (n = 169); Group B: uDCD livers in recipients aged <60 years (n = 36); Group C: DBD livers in recipients aged >60 years (n = 96); and Group D: uDCD livers in recipients aged >60 years(n = 39). RESULTS: Intraoperative transfusion, biliary complications, primary non-function, acute rejection, chronic renal dysfunction, retransplantation, and mortality during follow-up (cardiovascular diseases in 3 patients, hepatitis C virus recurrence in 4 patients, and de novo malignancies in 3 patients) were significantly higher, and 5-year patient and graft survival was significantly lower in sexagenarian recipients. Bilirubin and packed red blood cells transfusion were risk factors for patient survival, whereas hepatocelular carcinoma, creatinine, and packed red blood cells transfusion were risk factors for patient survival. Recipient age (<60 years) was confirmed as protective factor for patient and graft survival, whereas the use of uDCD was not a risk factor for patient or graft survival. CONCLUSIONS: Use of a uDCD liver did not demonstrate as a risk factor for patient and graft survival, and recipient age (<60 years) was a protective factor for patient and graft survival.

Normothermic Machine Perfusion-Improving the Supply of Transplantable Livers for High-Risk Recipients.

The effectiveness of liver transplantation to cure numerous diseases, alleviate suffering, and improve patient survival has led to an ever increasing demand. Improvements in preoperative management, surgical technique, and postoperative care have allowed increasingly complicated and high-risk patients to be safely transplanted. As a result, many patients are safely transplanted in the modern era that would have been considered untransplantable in times gone by. Despite this, more gains are possible as the science behind transplantation is increasingly understood. Normothermic machine perfusion of liver grafts builds on these gains further by increasing the safe use of grafts with suboptimal features, through objective assessment of both hepatocyte and cholangiocyte function. This technology can minimize cold ischemia, but prolong total preservation time, with particular benefits for suboptimal grafts and surgically challenging recipients. In addition to more physiological and favorable preservation conditions for grafts with risk factors for poor outcome, the extended preservation time benefits operative logistics by allowing a careful explant and complicated vascular reconstruction when presented with challenging surgical scenarios. This technology represents a significant advancement in graft preservation techniques and the transplant community must continue to incorporate this technology to ensure the benefits of liver transplant are maximized.

Influence of middle hepatic vein resection during right or left hepatectomy on post hepatectomy outcomes.

Backgrounds/Aims: Middle hepatic vein (MHV) is usually preserved as a part of the right or left hepatectomy in order preserve the venous outflow of remnant liver. The aim of this study was to evaluate if resection of MHV could influence post-resection outcomes of standard right or left hepatectomy. Methods: Patients who underwent standard right or left hepatectomy between January 2015 and December 2019 were included. Anatomical remnant liver volumes were measured retrospectively using the Hermes workstation (Hermes Medical Solutions AB, Stockholm, Sweden). Uni- and multi-variate analyses were performed to assess the difference in outcomes of those with preservation of MHV and those without preservation. Results: A total of 144 patients were included. Right hepatectomy was performed for 114 (79.2%) and left hepatectomy was performed for 30 (20.8%) patients. MHV was resected for 13 (9.0%) in addition to the standard right or left hepatectomy. Median remnant liver volume was significantly higher in the MHV resected group (p < 0.01). There was no significant difference in serum level of bilirubin, international normalized ratio, alanine aminotransferase, creatinine on postoperative day 1, 3, 5, or 10, ≥ grade IIIa complications (p = 0.44), or 90-day mortality (p = 0.41). On multivariable analysis, resection of the MHV did not influence the incidence of post hepatectomy liver failure (p = 0.52). Conclusions: Resection of the MHV at standard right or left hepatectomy did not have a negative impact on postoperative outcomes of patients with adequate remnant liver volume.

Short series regarding uncontrolled donor after cardiac death: A call for caution.

The authors did not receive any funding for this work.

Validation of McCluskey Index for Massive Blood Transfusion Prediction in Liver Transplantation.

BACKGROUND: The McCluskey index has been used as a tool to predict massive bleeding (>6 red blood cells units) during orthotropic liver transplantation. The objective of this study is to verify its efficacy at our institution. MATERIALS AND METHODS: Between May 1998 and December 2017, we performed 1216 orthotropic liver transplantations, of which 1016 had sufficient data registered with respect to hemoderivative transfusion. We divided these patients into groups based on the original study of McCluskey. This study was approved by the ethical committee of our Institution and was performed in accordance with the Declaration of Helsinki. RESULTS: The mean Model for End-Stage Liver Disease score in the 4 groups was 7.5 (range, 7-8) for low risk; 13 (range, 3-32) for medium risk, 17 (range, 8-41) for high risk, and 25 (range, 11-36) for very high risk (P < .001). No significant differences were observed regarding body mass index or hospital stay. No differences have been found in the number of suboptimal donors among the groups. With respect to hemoderivative transfusions, we observed the following for red blood cells: 7 (range, 6-8) units for low risk; 5.5 (range, 0-74) for medium risk; 7 (range, 0-73) for high risk, and 12 (range, 5-30) for very high risk (P < .001) and transfusion of plasma: 12 (range, 10-15) units for low risk; 11 (range, 0-89) for medium risk; 14 (range, 0-76) for high risk, and 13 (range, 3-30) for very high risk (P = .001). CONCLUSIONS: The McCluskey index is a good indicator of the risk of hemorrhage and hence the necessity of transfusion.

Duodenopancreatectomía cefálica y tutorización externa del conducto de Wirsung. Resultados de una serie de 80 casos consecutivos / Pancreaticoduodenectomy and external Wirsung stenting: our outcomes in 80 cases

Introducción: Existe controversia respecto a la técnica ideal de reconstrucción pancreático-yeyunal posresección duodeno-pancreática. La tutorización externa del Wirsung se ha considerado por muchos autores como una técnica con menor incidencia de fístulas y morbimortalidad. Analizamos nuestra experiencia con esta técnica. Pacientes y métodos: Análisis retrospectivo de la morbimortalidad, de una serie de 80 pacientes consecutivos intervenidos, durante 6,5 años, por tumores pancreáticos cefálicos o periampulares realizando resección y pancreático-yeyunostomía con tutorización externa del Wirsung. Resultados: La edad media de los pacientes fue 68,3 ± 9 años y la tasa de resecabilidad del 78%. La consistencia del páncreas era blanda en 51,2% de pacientes y dura en 48,8%. Se preservó el píloro en 43,8%. El tumor más frecuente fue el adenocarcinoma (68,8%) y se consiguió un R0 en 70%. La fístula bioquímica se presentó en 11,2%, la fístula pancreática grado B en 12,5% y la C en 2,5%, mientras que la tasa de reintervención abdominal fue del 10%. La mediana de estancia hospitalaria fue de 16 días y la mortalidad postoperatoria y a 90 días fue del 2,5%. La tasa de retraso del vaciamiento gástrico fue del 36,3%, diabetes de novo del 12,5% e insuficiencia exocrina del 30%. La supervivencia a uno, tres y cinco años fue 80,2, 53,6 y 19,2%. Conclusiones: Aunque nuestras tasas de morbimortalidad con la tutorización externa del Wirsung son bajas, coincidiendo con series más amplias recientemente publicadas, se precisa un análisis comparativo con otras técnicas reconstructivas, con más casos, para elegir la mejor opción después de una duodenopancreatectomía cefálica. (AU)

Introduction: There is controversy regarding the ideal pancreaticojejunostomy technique after pancreaticoduodenectomy. Many authors consider the external Wirsung stenting technique to be associated with a low incidence of fistula, morbidity and mortality. We analyse our experience with this technique. Patients and methods: A retrospective analysis of the morbidity and mortality of a series of 80 consecutive patients who had been treated surgically over a 6.5-year period for pancreatic head or periampullary tumors, performing pancreaticoduodenectomy and pancreaticojejunostomy with external Wirsung duct stenting. Results: Mean patient age was 68.3 ± 9 years, and the resectability rate was 78%. The texture of the pancreas was soft in 51.2% of patients and hard in 48.8%. Pylorus-preserving resection was performed in 43.8%. Adenocarcinoma was the most frequent tumor (68.8%), and R0 was confirmed in 70% of patients. Biochemical fistula was observed in 11.2%, pancreatic fistula grade B in 12.5% and C in 2.5%, whereas the abdominal reoperation rate was 10%. Median postoperative hospital stay was 16 days, and postoperative and 90-day mortality was 2.5%. Delayed gastric emptying was observed in 36.3% of patients, de novo diabetes in 12.5%, and exocrine insufficiency in 3. Patient survival rates after 1, 3 and 5 years were 80.2, 53.6 and 19.2%, respectively. Conclusions: Although our low rates of postoperative complications and mortality using external Wirsung duct stenting coincides with other more numerous recent series, it is necessary to perform a comparative analysis with other techniques, including more cases, to choose the best reconstruction technique after pancreaticoduodenectomy. (AU)

Liver transplantation for hepatocellular carcinoma using grafts from uncontrolled circulatory death donation.

Controversy exists regarding whether the rate of hepatocellular carcinoma (HCC) recurrence after orthotopic liver transplantation (OLT) differs when using livers from donation after controlled circulatory death (DCD) versus livers from donation after brain death (DBD). The aim of this cohort study was to analyze rates of HCC recurrence, patient survival, and graft survival after OLT for HCC, comparing recipients of DBD livers (n = 103) with recipients of uncontrolled DCD livers (uDCD; n = 41). No significant differences in tumor size, tumor number, serum alpha-fetoprotein, proportion of patients within Milan criteria, or pre-OLT bridging therapies were identified between groups, although the waitlist period was significantly shorter in the uDCD group (p = 0.040). HCC recurrence was similar between groups. Patient survival was similar between groups, but graft survival was lower in the uDCD group. Multivariate analysis identified recipient age (p = 0.031), pre-OLT bridging therapy (p = 0.024), and HCC recurrence (p = 0.048) as independent risk factors for patient survival and pre-OLT transarterial chemoembolization (p = 0.045) as the single risk factor for HCC recurrence. In conclusion, similar patient survival and lower graft survival were observed in the uDCD group. However, the use of uDCD livers appears to be justified due to a shorter waitlist time, and lower waitlist dropout and HCC recurrence rates.

Pancreaticoduodenectomy and external Wirsung stenting: Our outcomes in 80 cases.

INTRODUCTION: There is controversy regarding the ideal pancreaticojejunostomy technique after pancreaticoduodenectomy. Many authors consider the external Wirsung stenting technique to be associated with a low incidence of fistula, morbidity and mortality. We analyse our experience with this technique. PATIENTS AND METHODS: A retrospective analysis of the morbidity and mortality of a series of 80 consecutive patients who had been treated surgically over a 6.5-year period for pancreatic head or periampullary tumors, performing pancreaticoduodenectomy and pancreaticojejunostomy with external Wirsung duct stenting. RESULTS: Mean patient age was 68.3 ± 9 years, and the resectability rate was 78%. The texture of the pancreas was soft in 51.2% of patients and hard in 48.8%. Pylorus-preserving resection was performed in 43.8%. Adenocarcinoma was the most frequent tumor (68.8%), and R0 was confirmed in 70% of patients. Biochemical fistula was observed in 11.2%, pancreatic fistula grade B in 12.5% and C in 2.5%, whereas the abdominal reoperation rate was 10%. Median postoperative hospital stay was 16 days, and postoperative and 90-day mortality was 2.5%. Delayed gastric emptying was observed in 36.3% of patients, de novo diabetes in 12.5%, and exocrine insufficiency in 3. Patient survival rates after 1, 3 and 5 years were 80.2%, 53.6% and 19.2%, respectively. CONCLUSIONS: Although our low rates of postoperative complications and mortality using external Wirsung duct stenting coincides with other more numerous recent series, it is necessary to perform a comparative analysis with other techniques, including more cases, to choose the best reconstruction technique after pancreaticoduodenectomy.

Incidence and risk factors of primary non-function after liver transplantation using grafts from uncontrolled donors after circulatory death.

BACKGROUND: Graft primary non-function (PNF) is the most severe complication after orthotopic liver transplantation (OLT) and is frequently associated with livers from uncontrolled circulatory death (uDCD). METHODS: We reviewed retrospectively the incidence, risk factors, and outcome of patients showing PNF after receiving uDCD liver grafts. The series comprises 75 OLT performed during 11 years. RESULTS: The incidence of PNF using uDCD livers was 8%. We compared patients who developed PNF (n = 6) vs. patients without PNF (n = 69). Mean pump flow of donors during normothermic regional perfusion (NRP) was significantly lower in PNF (p = .032). Day 1 post-OLT levels of transaminases and the incidence of renal complications and postoperative mortality were also significantly higher in the PNF group, but 5-year patient survival was similar in both groups (66.7% in PNF and 68.5% in non-PNF). All PNF patients underwent re-OLT, and 2 died. PNF incidence has decreased in the last 5-years. Binary logistic regression analysis confirmed final ALT value >4 times the normal value as risk factor for PNF, and median donor pump flow >3700 ml/min as protective effect. CONCLUSIONS: Adequate donor pump flow during NRP was a protective.

Biliary Complications After Liver Transplantation From Uncontrolled Donors After Circulatory Death: Incidence, Management, and Outcome.

The utilization of livers from donation after uncontrolled circulatory death (uDCD) increases the availability of liver grafts, but it is associated with a higher incidence of biliary complications (BCs) and lower graft survival than those organs donated after brain death. From January 2006 to December 2016, we performed 75 orthotopic liver transplantations (OLTs) using uDCD livers. To investigate the relationship of BCs with the use of uDCD OLT, we compared patients who developed BCs (23 patients) with those who did not (non-BC group, 43 patients) after excluding cases of hepatic artery thrombosis (a known cause of BC) and primary nonfunction. The groups had similar uDCD donor maintenance, donor and recipient characteristics, and perioperative morbidity/mortality rates, but we observed a higher rate of hepatocellular carcinoma and hepatitis C virus in the non-BC group. Percutaneous transhepatic biliary dilation, endoscopic retrograde cholangiopancreatography dilation, Roux-en-Y hepaticojejunostomy (HJ), a T-tube, and retransplantation were used for BC management. In the BC group, 1-, 3-, and 5-year patient survival rates were 91.3%, 69.6%, and 65.2%, respectively, versus 77.8%, 72.9%, and 72.9%, respectively, in the non-BC group (P = 0.89). However, 1-, 3-, and 5-year graft survival rates were 78.3%, 60.9%, and 56.5%, respectively, in the BC group versus 77.8%, 72.9%, and 72.9%, respectively, in the non-BC group (P = 0.38). Multivariate analysis did not indicate independent risk factors for BC development. In conclusion, patient and graft survival rates were generally lower in patients who developed BCs but not significantly so. These complications were managed in the majority of patients through radiological dilation, endoscopic dilation, or Roux-en-Y HJ. Retransplantation is necessary in rare cases after the failure of biliary dilation or surgical procedures.

Liver Transplantation Using Uncontrolled Donors After Circulatory Death: A 10-year Single-center Experience.

BACKGROUND: One method for increasing the donor pool for orthotopic liver transplantations (OLTs) is to use uncontrolled donation after circulation death (uDCDs). METHODS: From January 2006 to December 2016, we performed 75 OLTs using uDCD livers. The control group comprised a sample of 265 OLTs using livers of donations after brain death (DBDs). A comparative study was performed. RESULTS: Of 256 potential uDCD donors cannulated, 75 (29.3%) livers were accepted for OLT. The amount of hemoderivatives transfused was significantly higher in the uDCD group. The rate of primary nonfunction was also significantly higher (P = 0.031) in uDCD recipients (8%) than DBD recipients (1.5%). The overall rate of biliary complications was significantly higher (P = 0.001) in uDCD recipients (23 cases, 30.6%) than DBD recipients (28 cases, 10.6%). In the uDCD group, 1-, 3-, and 5-year patient survival rates were 82.7%, 73%, and 71.5%, respectively; in the DBD group, they were 89%, 83.7%, and 78.8%, respectively (P = 0.180). In the uDCD group, 1-, 3-, and 5-year graft survival rates were 73.3%, 65.1%, and 63.6%, respectively; in the DBD group, they were 87.1%, 81.9%, and 76.5%, respectively (P = 0.013). Multivariate analysis showed that independent risk factors for patient and graft survival were intraoperative transfusion of >6 units of packed red blood cell concentrates and recipients who were older than 60 years. CONCLUSIONS: Although graft survival is significantly lower using uDCD livers, 5-year patient survival in recipients of DBD and uDCD livers is similar. After careful selection, the livers of uDCD can be selectively used for OLT.

Utilidad del trasplante de la pared abdominal en el trasplante de órganos. Nuestra experiencia inicial / Abdominal wall transplantation in organ transplantation: Our experience

El cierre de la pared abdominal después del trasplante de órganos abdominales, especialmente en los casos de trasplante intestinal y multivisceral, sigue siendo un reto en muchos pacientes debido al importante número de intervenciones previas al trasplante, así como al edema de asas que dichos injertos presentan. Ante la imposibilidad de cierre primario y debido a las complicaciones en el uso de mallas, surge la opción del trasplante de la pared abdominal. Existen diversas opciones para dicho procedimiento, desde el empleo únicamente de la fascia no vascularizada hasta el trasplante de espesor completo de la pared abdominal. Revisamos la literatura en cuanto al uso de los injertos referidos y presentamos 2 casos de trasplante de fascia no vascularizada realizados en nuestra unidad de trasplante

Abdominal wall transplantation has been consolidated as an alternative to primary abdominal wall closure in intestinal and multiple organ transplant recipients. Given that it is feasible to obtain the visceral graft and the abdominal wall graft from the same donor, abdominal wall transplantation could offer satisfactory outcomes and be easily coordinated. Non-vascularized fascia is one of the alternatives for abdominal wall closure in transplantation. We report two cases of non-vascularized fascia transplantation in intestinal and multivisceral transplants, respectively. Both donors were young (23 and 18 years old). Both recipients had endured multiple previous surgeries, and no surgical alternatives for primary wall repair could be offered. In both cases, a complete abdominal wall flap was retrieved from the donor, however, due to the characteristics of the recipient's abdominal wall defect, only non-vascularized fascia was used after removing skin and subcutaneous cellular tissue from the graft. Abdominal wall transplantation is an option to consider for abdominal wall closure in patients with multiple previous surgeries and no alternatives for primary wall repair