Prognostic role of the Donor Risk Index, the Eurotransplant Donor Risk Index, and the Balance of Risk score on graft loss after liver transplantation.

This study aimed to identify cutoff values for donor risk index (DRI), Eurotransplant (ET)-DRI, and balance of risk (BAR) scores that predict the risk of liver graft loss. MEDLINE and Web of Science databases were searched systematically and unrestrictedly. Graft loss odds ratios and 95% confidence intervals were assessed by meta-analyses using Mantel-Haenszel tests with a random-effects model. Cutoff values for predicting graft loss at 3 months, 1 year, and 3 years were analyzed for each of the scores. Measures of calibration and discrimination used in studies validating the DRI and the ET-DRI were summarized. DRI ≥ 1.4 (six studies, n = 35 580 patients) and ET-DRI ≥ 1.4 (four studies, n = 11 666 patients) were associated with the highest risk of graft loss at all time points. BAR > 18 was associated with the highest risk of 3-month and 1-year graft loss (n = 6499 patients). A DRI cutoff of 1.8 and an ET-DRI cutoff of 1.7 were estimated using a summary receiver operator characteristic curve, but the sensitivity and specificity of these cutoff values were low. A DRI and ET-DRI score ≥ 1.4 and a BAR score > 18 have a negative influence on graft survival, but these cutoff values are not well suited for predicting graft loss.

Oral Preconditioning of Donors After Brain Death With Calcineurin Inhibitors vs. Inhibitors of Mammalian Target for Rapamycin in Pig Kidney Transplantation.

Background: The systemic inflammatory cascade triggered in donors after brain death enhances the ischemia-reperfusion injury after organ transplantation. Intravenous steroids are routinely used in the intensive care units for the donor preconditioning. Immunosuppressive medications could be potentially used for this purpose as well. Data regarding donor preconditioning with calcineurin inhibitors or inhibitors of mammalian target for Rapamycin is limited. The aim of this project is to investigate the effects of (oral) donor preconditioning with a calcineurin inhibitor (Cyclosporine) vs. an inhibitor of mammalian target for Rapamycin (Everolimus) compared to the conventional administration of steroid in the setting of donation after brain death in porcine renal transplantation. Methods: Six hours after the induction of brain death, German landrace donor pigs (33.2 ± 3.9 kg) were randomly preconditioned with either Cyclosporine (n = 9) or Everolimus (n = 9) administered via nasogastric tube with a repeated dose just before organ procurement. Control donors received intravenous Methylprednisolone (n = 8). Kidneys were procured, cold-stored in Histidine-Tryptophane-Ketoglutarate solution at 4°C and transplanted in nephrectomized recipients after a mean cold ischemia time of 18 h. No post-transplant immunosuppression was given to avoid confounding bias. Blood samples were obtained at 4 h post reperfusion and daily until postoperative day 5 for complete blood count, blood urea nitrogen, creatinine, and electrolytes. Graft protocol biopsies were performed 4 h after reperfusion to assess early histological and immunohistochemical changes. Results: There was no difference in the hemodynamic parameters, hemoglobin/hematocrit and electrolytes between the groups. Serum blood urea nitrogen and creatinine peaked on postoperative day 1 in all groups and went back to the preoperative levels at the conclusion of the study on postoperative day 5. Histological assessment of the kidney grafts revealed no significant differences between the groups. TNF-α expression was significantly lower in the study groups compared with Methylprednisolone group (p = 0.01) Immunohistochemistry staining for cytochrome c showed no difference between the groups. Conclusion: Oral preconditioning with Cyclosporine or Everolimus is feasible in donation after brain death pig kidney transplantation and reduces the expression of TNF-α. Future studies are needed to further delineate the role of oral donor preconditioning against ischemia-reperfusion injury.

Expanding pancreas donor pool by evaluation of unallocated organs after brain death: Study protocol clinical trial (SPIRIT Compliant).

BACKGROUND: Pancreas graft quality directly affects morbidity and mortality rates after pancreas transplantation (PTx). The criteria for pancreas graft allocation are restricted, which has decreased the number of available organs. Suitable pancreatic allografts are selected based on donor demographics, medical history, and the transplant surgeon's assessment of organ quality during procurement. Quality is assessed based on macroscopic appearance, which is biased by individual experience and personal skills. Therefore, we aim to assess the histopathological quality of unallocated pancreas organs to determine how many unallocated organs are potentially of suitable quality for PTx. METHODS AND ANALYSIS: This is a multicenter cross-sectional explorative study. The demographic data and medical history of donor and cause of rejection of the allocation of graft will be recorded. Organs of included donors will be explanted and macroscopic features such as weight, color, size, and stiffness will be recorded by 2 independent transplant surgeons. A tissue sample of the organ will be fixed for further microscopic assessments. Histopathologic assessments will be performed as soon as a biopsy can be obtained. We will evaluate up to 100 pancreata in this study. RESULT: This study will evaluate the histopathological quality of unallocated pancreas organs from brain-dead donors to determine how many of these unallocated organs were potentially suitable for transplantation based on a histopathologic evaluation of organ quality. CONCLUSION: The comprehensive findings of this study could help to increase the pancreas graft pool, overcome organ shortage, reduce the waiting time, and also increase the number of PTx in the future. Registration number: ClinicalTrials.gov: NCT04127266.

Meta-analysis of the efficacy of preoperative biliary drainage in patients undergoing liver resection for perihilar cholangiocarcinoma.

PURPOSE: A systematic review was performed to evaluate the effect of preoperative biliary drainage (PBD) on outcomes after liver resection in perihilar cholangiocarcinoma (PHCC) patients. METHOD: MEDLINE and Web of Science were searched up to March 2019. All studies assessing morbidity, mortality, or recurrence in patients who received PBD and hepatectomy for PHCC were included. Mantel-Haenszel tests with a random-effects model were used for meta-analysis. RESULTS: Sixteen studies involving 2162 patients were included. PBD was associated with higher major morbidity odds ratio [OR] = 1.51; 95 % confidence interval [CI] = 1.14-2.00). Selecting patients for PBD based on simple selection criteria was associated with significantly higher major morbidity (OR = 1.57; 95 % CI = 1.10-2.25). In contrast, selecting patients for PBD according to strict criteria resulted in lower major morbidity compared with patients without PBD (OR = 0.51; 95 % CI = 0.18-1.42). PBD did not influence mortality (OR = 1.06; 95 % CI = 0.70-1.61). Tumor recurrence was significantly higher in the PBD group (OR = 2.07; 95 % CI = 1.38-3.11). To decrease PBD-related complications, the duration between PBD and hepatectomy should be shorter than two weeks. Most reports described PBD on the future liver remnant side. CONCLUSIONS: Routine PBD cannot be recommended but it may be useful in highly selected patients suffering from cholangitis, malnutrition, and long lasting jaundice, for whom an extended hepatectomy is planned. However, However, routine PBD cannot be recommended due to higher morbidity rate after hepatectomy clear patient selection criteria can be defined for PBD in future multicenter randomized controlled studies.

Comparative Analysis of the Discriminatory Performance of Different Well-Known Risk Assessment Scores for Extended Hepatectomy.

The aim of this study was to assess and compare the discriminatory performance of well-known risk assessment scores in predicting mortality risk after extended hepatectomy (EH). A series of 250 patients who underwent EH (≥5 segments resection) were evaluated. Aspartate aminotransferase-to-platelet ratio index (APRI), albumin to bilirubin (ALBI) grade, predictive score developed by Breitenstein et al., liver fibrosis (FIB-4) index, and Heidelberg reference lines charting were used to compute cut-off values, and the sensitivity and specificity of each risk assessment score for predicting mortality were also calculated. Major morbidity and 90-day mortality after EH increased with increasing risk scores. APRI (86%), ALBI (86%), Heidelberg score (81%), and FIB-4 index (79%) had the highest sensitivity for 90-day mortality. However, only the FIB-4 index and Heidelberg score had an acceptable specificity (70% and 65%, respectively). A two-stage risk assessment strategy (Heidelberg-FIB-4 model) with a sensitivity of 70% and a specificity 86% for 90-day mortality was proposed. There is no single specific risk assessment score for patients who undergo EH. A two-stage screening strategy using Heidelberg score and FIB-4 index was proposed to predict mortality after major liver resection.

Interdisciplinary approach allows minimally invasive, nerve-sparing removal of retroperitoneal peripheral nerve sheath tumors.

PURPOSE: En bloc resection of retroperitoneal peripheral nerve sheath tumors (PNST) is advocated by a variety of surgical disciplines. Yet, microsurgical, nerve-sparing tumor resection might be better suited to improve symptoms and maintain neurological function, especially in cases where patients present with preoperative neurological deficits. However, neurosurgeons, versed in nerve-sparing techniques to remove PNST, are generally unfamiliar with the visceral approaches to retroperitoneal PNST. METHODS: We retrospectively evaluate a series of 16 patients suffering from retroperitoneal PNST. Patients were treated by a unique interdisciplinary approach, combining the visceral surgeon's skills to navigate the complex anatomy of the retroperitoneal space and the neurosurgeon's familiarity with microsurgical, nerve-sparing tumor removal. Specifically, we assess whether our interdisciplinary approach is suited to improve preoperative symptoms and maintain neurological function and study whether oncological outcome, surgical morbidity, and operative times are comparable to those reported for "classical" retroperitoneal PNST resection. In addition, we study two cases of suspected PNST that were diagnosed as malignant peripheral nerve sheath tumors (MPNST) after surgery. RESULTS: Total macroscopic tumor resection was achieved in 14/16 PNST patients. Mean intraoperative blood loss was 680.6 ml (95% CI, 194.3-1167.0 ml) and mean operative time was 162.5 min (95% CI, 121.6-203.4 min). We did not record any major postoperative surgical or neurological complications. A total of 8/11 patients with preoperative pain symptoms reported long-lasting improvement of their symptoms. In terms of oncological outcome, all patients that had been subjected to total tumor removal and for whom follow-up was available, were tumor-free after a mean follow-up of 761.9 days (95% CI, 97.6-1426.0 days). One of the two MPNST patients, who presented with tumor progress 15 months after initial surgery, was subjected to radical re-resection. CONCLUSIONS: Interdisciplinary, nerve-sparing removal of retroperitoneal PNST is well suited to improve preoperative symptoms and maintain neurological function, while achieving an oncological outcome and a surgical morbidity similar to previously reported results for radical retroperitoneal PNST resection. Radical re-resection was feasible in a patient with post hoc MPNST diagnosis.

Ex Situ Liver Machine Perfusion as an Emerging Graft Protective Strategy in Clinical Liver Transplantation: the Dawn of a New Era.

The disparity between the number of available donor livers and patients awaiting a liver transplant has led transplant centers to accept suboptimal livers. There has been no universally accepted tool to predict the posttransplant function of these organs to safely increase the donor pool, protect these livers against ischemia-reperfusion injury, or improve their quality before implantation. Ex situ liver machine preservation has emerged as a promising novel graft protective strategy in the field of liver transplantation, with remarkable ongoing research and evolving clinical trials within Europe and the United States. This technology has been shown to be safe and feasible in the clinical liver transplantation field, has shown to reduce liver ischemia-reperfusion injury, and has shown to decrease the graft discard rate compared with conventional static cold storage. This review focuses on the current status of ex situ machine preservation in clinical liver transplantation, describing the most important technical aspects with the emphasis on the findings of the most recent clinical studies.