Normothermic Liver Machine Perfusion and Successful Transplantation of Split Liver Grafts: From Proof of Concept to Clinical Implementation.

BACKGROUND: Normothermic liver machine perfusion (NLMP) is advancing the field of liver transplantation (LT). Beyond improved preservation and organ assessment, NLMP helps to increase organ utilization. We herein address the feasibility and merit of NLMP in split liver transplantation (SLT) to postpone the transplantation of the second split graft to the following day. METHODS: We analyzed the perfusion characteristics and outcomes of all consecutive adult recipients who underwent SLT following NLMP from February 1, 2018, to June 30, 2023. The primary endpoint was 90-d graft and patient survival. Secondary endpoints were posttransplant complications and 90-d morbidity. RESULTS: Three right and 3 extended right SLT following NLMP have been performed. NLMP was uneventful in all cases. Perfusion characteristics differed according to graft volume. Mean perfusion time was 17:00 h (±05:13) and bile production ranged between 8 and 21 mL/h. All split grafts fulfilled predefined center viability criteria during NLMP and were transplanted on the following day. The 90-d graft and patient survival rate was 100%. Three patients (50%) required an early relaparotomy, and 2 patients (33.3%) developed biliary complications. The 90-d morbidity as recorded by the comprehensive complication index was 62.7 (±24.7). CONCLUSION: NLMP of split liver grafts is technically feasible and safe. Through prolongation of preservation time, NLMP allows to safely postpone transplantation of the second split liver graft to the next day.

The Predictive Value of Graft Viability and Bioenergetics Testing Towards the Outcome in Liver Transplantation.

Donor organ biomarkers with sufficient predictive value in liver transplantation (LT) are lacking. We herein evaluate liver viability and mitochondrial bioenergetics for their predictive capacity towards the outcome in LT. We enrolled 43 consecutive patients undergoing LT. Liver biopsy samples taken upon arrival after static cold storage were assessed by histology, real-time confocal imaging analysis (RTCA), and high-resolution respirometry (HRR) for mitochondrial respiration of tissue homogenates. Early allograft dysfunction (EAD) served as primary endpoint. HRR data were analysed with a focus on the efficacy of ATP production or P-L control efficiency, calculated as 1-L/P from the capacity of oxidative phosphorylation P and non-phosphorylating respiration L. Twenty-two recipients experienced EAD. Pre-transplant histology was not predictive of EAD. The mean RTCA score was significantly lower in the EAD cohort (-0.75 ± 2.27) compared to the IF cohort (0.70 ± 2.08; p = 0.01), indicating decreased cell viability. P-L control efficiency was predictive of EAD (0.76 ± 0.06 in IF vs. 0.70 ± 0.08 in EAD-livers; p = 0.02) and correlated with the RTCA score. Both RTCA and P-L control efficiency in biopsy samples taken during cold storage have predictive capacity towards the outcome in LT. Therefore, RTCA and HRR should be considered for risk stratification, viability assessment, and bioenergetic testing in liver transplantation.

The impact and relevance of techniques and fluids on lung injury in machine perfusion of lungs.

Primary graft dysfunction (PGD) is a common complication after lung transplantation. A plethora of contributing factors are known and assessment of donor lung function prior to organ retrieval is mandatory for determination of lung quality. Specialized centers increasingly perform ex vivo lung perfusion (EVLP) to further assess lung functionality and improve and extend lung preservation with the aim to increase lung utilization. EVLP can be performed following different protocols. The impact of the individual EVLP parameters on PGD development, organ function and postoperative outcome remains to be fully investigated. The variables relate to the engineering and function of the respective perfusion devices, such as the type of pump used, functional, like ventilation modes or physiological (e.g. perfusion solutions). This review reflects on the individual technical and fluid components relevant to EVLP and their respective impact on inflammatory response and outcome. We discuss key components of EVLP protocols and options for further improvement of EVLP in regard to PGD. This review offers an overview of available options for centers establishing an EVLP program and for researchers looking for ways to adapt existing protocols.

Impact of citrulline substitution on clinical outcome after liver transplantation in carbamoyl phosphate synthetase 1 and ornithine transcarbamylase deficiency.

Carbamoyl phosphate synthetase 1 (CPS1) and ornithine transcarbamylase (OTC) deficiencies are rare urea cycle disorders, which can lead to life-threatening hyperammonemia. Liver transplantation (LT) provides a cure and offers an alternative to medical treatment and life-long dietary restrictions with permanent impending risk of hyperammonemia. Nevertheless, in most patients, metabolic aberrations persist after LT, especially low plasma citrulline levels, with questionable clinical impact. So far, little is known about these alterations and there is no consensus, whether l-citrulline substitution after LT improves patients' symptoms and outcomes. In this multicentre, retrospective, observational study of 24 patients who underwent LT for CPS1 (n = 11) or OTC (n = 13) deficiency, 25% did not receive l-citrulline or arginine substitution. Correlation analysis revealed no correlation between substitution dosage and citrulline levels (CPS1, p = 0.8 and OTC, p = 1). Arginine levels after liver transplantation were normal after LT independent of citrulline substitution. Native liver survival had no impact on mental impairment (p = 0.67). Regression analysis showed no correlation between l-citrulline substitution and failure to thrive (p = 0.611) or neurological outcome (p = 0.701). Peak ammonia had a significant effect on mental impairment (p = 0.017). Peak plasma ammonia levels correlate with mental impairment after LT in CPS1 and OTC deficiency. Growth and intellectual impairment after LT are not significantly associated with l-citrulline substitution.

Recent outcomes of liver transplantation for Budd-Chiari syndrome: A study of the European Liver Transplant Registry (ELTR) and affiliated centers.

BACKGROUND AND AIMS: Management of Budd-Chiari syndrome (BCS) has improved over the last decades. The main aim was to evaluate the contemporary post-liver transplantant (post-LT) outcomes in Europe. APPROACH AND RESULTS: Data from all patients who underwent transplantation from 1976 to 2020 was obtained from the European Liver Transplant Registry (ELTR). Patients < 16 years with secondary BCS or HCC were excluded. Patient survival (PS) and graft survival (GS) before and after 2000 were compared. Multivariate Cox regression analysis identified predictors of PS and GS after 2000. Supplemental data was requested from all ELTR-affiliated centers and received from 44. In all, 808 patients underwent transplantation between 2000 and 2020. One-, 5- and 10-year PS was 84%, 77%, and 68%, and GS was 79%, 70%, and 62%, respectively. Both significantly improved compared to outcomes before 2000 ( p < 0.001). Median follow-up was 50 months and retransplantation rate was 12%. Recipient age (aHR:1.04,95%CI:1.02-1.06) and MELD score (aHR:1.04,95%CI:1.01-1.06), especially above 30, were associated with worse PS, while male sex had better outcomes (aHR:0.63,95%CI:0.41-0.96). Donor age was associated with worse PS (aHR:1.01,95%CI:1.00-1.03) and GS (aHR:1.02,95%CI:1.01-1.03). In 353 patients (44%) with supplemental data, 33% had myeloproliferative neoplasm, 20% underwent TIPS pre-LT, and 85% used anticoagulation post-LT. Post-LT anticoagulation was associated with improved PS (aHR:0.29,95%CI:0.16-0.54) and GS (aHR:0.48,95%CI:0.29-0.81). Hepatic artery thrombosis and portal vein thrombosis (PVT) occurred in 9% and 7%, while recurrent BCS was rare (3%). CONCLUSIONS: LT for BCS results in excellent patient- and graft-survival. Older recipient or donor age and higher MELD are associated with poorer outcomes, while long-term anticoagulation improves both patient and graft outcomes.

The BAR Score Predicts and Stratifies Outcomes Following Liver Retransplantation: Insights From a Retrospective Cohort Study.

Liver retransplantation (reLT) yields poorer outcomes than primary liver transplantation, necessitating careful patient selection to avoid futile reLT. We conducted a retrospective analysis to assess reLT outcomes and identify associated risk factors. All adult patients who underwent a first reLT at the Medical University of Innsbruck from 2000 to 2021 (N = 111) were included. Graft- and patient survival were assessed via Kaplan-Meier plots and log-rank tests. Uni- and multivariate analyses were performed to identify independent predictors of graft loss. Five-year graft- and patient survival rates were 64.9% and 67.6%, respectively. The balance of risk (BAR) score was found to correlate with and be predictive of graft loss and patient death. The BAR score also predicted sepsis (AUC 0.676) and major complications (AUC 0.720). Multivariate Cox regression analysis identified sepsis [HR 5.179 (95% CI 2.575-10.417), p < 0.001] as the most significant independent risk factor for graft loss. At a cutoff of 18 points, the 5 year graft survival rate fell below 50%. The BAR score, a simple and easy to use score available at the time of organ acceptance, predicts and stratifies clinically relevant outcomes following reLT and may aid in clinical decision-making.

Handheld hyperspectral imaging as a tool for the post-mortem interval estimation of human skeletal remains.

In forensic medicine, estimating human skeletal remains' post-mortem interval (PMI) can be challenging. Following death, bones undergo a series of chemical and physical transformations due to their interactions with the surrounding environment. Post-mortem changes have been assessed using various methods, but estimating the PMI of skeletal remains could still be improved. We propose a new methodology with handheld hyperspectral imaging (HSI) system based on the first results from 104 human skeletal remains with PMIs ranging between 1 day and 2000 years. To differentiate between forensic and archaeological bone material, the Convolutional Neural Network analyzed 65.000 distinct diagnostic spectra: the classification accuracy was 0.58, 0.62, 0.73, 0.81, and 0.98 for PMIs of 0 week-2 weeks, 2 weeks-6 months, 6 months-1 year, 1 year-10 years, and >100 years, respectively. In conclusion, HSI can be used in forensic medicine to distinguish bone materials >100 years old from those <10 years old with an accuracy of 98%. The model has adequate predictive performance, and handheld HSI could serve as a novel approach to objectively and accurately determine the PMI of human skeletal remains.

Transplant oncology - Current indications and strategies to advance the field.

Liver transplantation (LT) was originally described by Starzl as a promising strategy to treat primary malignancies of the liver. Confronted with high recurrence rates, indications drifted towards non-oncologic liver diseases with LT finally evolving from a high-risk surgery to an almost routine surgical procedure. Continuously improving outcomes following LT and evolving oncological treatment strategies have driven renewed interest in transplant oncology. This is not only reflected by constant refinements to the criteria for LT in patients with HCC, but especially by efforts to expand indications to other primary and secondary liver malignancies. With new patient-centred oncological treatments on the rise and new technologies to expand the donor pool, the field has the chance to come full circle. In this review, we focus on the concept of transplant oncology, current indications, as well as technical and ethical aspects in the context of donor organs as precious resources.

Post-pancreatectomy acute pancreatitis after pancreatoduodenectomy: Analysis of a clinically-relevant complication in a single-center retrospective study.

BACKGROUND: /Objectives: This study aimed to evaluate the frequency, clinical impact, and risk factors of post-pancreatectomy acute pancreatitis (PPAP) after pancreatoduodenectomy (PD) according to the definition proposed by the International Study Group for Pancreatic Surgery (ISGPS). METHODS: patients undergoing PD between 2010 and 2021 were retrospectively analyzed. PPAP was defined according to the ISGPS criteria, including elevated serum amylase for 48 h and concurring pancreatitis alterations on a CT scan. RESULTS: 272 patients were finally included in the study. PPAP occurred in 40 (14.7 %) patients, and it was significantly related to higher rates of clinically-relevant postoperative pancreatic fistula (CR-POPF) (p < 0.001), post-pancreatectomy hemorrhage (PPH) (p < 0.001) and major complications (Clavien-Dindo ≥ 3a) (p < 0.001). Moreover, PPAP in the absence of CR-POPF (n = 18) was significantly related to longer hospital stay (p < 0.001), PPH (p < 0.001), major complications (Clavien-Dindo≥ 3a, p = 0.001) and higher intensive care unit costs (p = 0.029) compared to patients not developing PPAP. In the univariable and multivariable analysis, the duct size (p = 0.004) and high-risk pathologies (p = 0.004) but not intraoperative bleeding (p = 0.066) represented independent risk factors for PPAP. In the same analysis, patients receiving a bridging therapy with low molecular-weight heparin showed significantly lower rates of PPAP (p = 0.045). CONCLUSIONS: PPAP represents a relevant complication after PD. Its risk factors are similar to those for CR-POPF, while anticoagulants could represent a possible prevention strategy.

Prediction of Biliary Complications After Human Liver Transplantation Using Hyperspectral Imaging and Convolutional Neural Networks: A Proof-of-concept Study.

BACKGROUND: Biliary complications (BCs) negatively impact the outcome after liver transplantation. We herein tested whether hyperspectral imaging (HSI) generated data from bile ducts (BD) on reperfusion and machine learning techniques for data readout may serve as a novel approach for predicting BC. METHODS: Tissue-specific data from 136 HSI liver images were integrated into a convolutional neural network (CNN). Fourteen patients undergoing liver transplantation after normothermic machine preservation served as a validation cohort. Assessment of oxygen saturation, organ hemoglobin, and tissue water levels through HSI was performed after completing the biliary anastomosis. Resected BD segments were analyzed by immunohistochemistry and real-time confocal microscopy. RESULTS: Immunohistochemistry and real-time confocal microscopy revealed mild (grade I: 1%-40%) BD damage in 8 patients and moderate (grade II: 40%-80%) injury in 1 patient. Donor and recipient data alone had no predictive capacity toward BC. Deep learning-based analysis of HSI data resulted in >90% accuracy of automated detection of BD. The CNN-based analysis yielded a correct classification in 72% and 69% for BC/no BC. The combination of HSI with donor and recipient factors showed 94% accuracy in predicting BC. CONCLUSIONS: Deep learning-based modeling using CNN of HSI-based tissue property data represents a noninvasive technique for predicting postoperative BC.

Rescue Allocation Modes in Eurotransplant Kidney Transplantation: Recipient Oriented Extended Allocation Versus Competitive Rescue Allocation-A Retrospective Multicenter Outcome Analysis.

BACKGROUND: Whenever the kidney standard allocation (SA) algorithms according to the Eurotransplant (ET) Kidney Allocation System or the Eurotransplant Senior Program fail, rescue allocation (RA) is initiated. There are 2 procedurally different modes of RA: recipient oriented extended allocation (REAL) and competitive rescue allocation (CRA). The objective of this study was to evaluate the association of patient survival and graft failure with RA mode and whether or not it varied across the different ET countries. METHODS: The ET database was retrospectively analyzed for donor and recipient clinical and demographic characteristics in association with graft outcomes of deceased donor renal transplantation (DDRT) across all ET countries and centers from 2014 to 2021 using Cox proportional hazards methods. RESULTS: Seventeen thousand six hundred seventy-nine renal transplantations were included (SA 15 658 [89%], REAL 860 [4.9%], and CRA 1161 [6.6%]). In CRA, donors were older, cold ischemia times were longer, and HLA matches were worse in comparison with REAL and especially SA. Multivariable analyses showed comparable graft and recipient survival between SA and REAL; however, CRA was associated with shorter graft survival. Germany performed 76% of all DDRTs after REAL and CRA and the latter mode reduced waiting times by up to 2.9 y. CONCLUSIONS: REAL and CRA are used differently in the ET countries according to national donor rates. Both RA schemes optimize graft utilization, lead to acceptable outcomes, and help to stabilize national DDRT programs, especially in Germany.

Sarcopenia and Mediastinal Adipose Tissue as a Prognostic Marker for Short- and Long-Term Outcomes after Primary Surgical Treatment for Lung Cancer.

Surgical resection remains the gold standard of treatment for early-stage lung cancer. Several risk models exist to predict postoperative morbidity and mortality. Psoas muscle sarcopenia has already successfully been used for morbidity prediction in lung transplantation and is not yet included in the available risk scores for pulmonary resections. We hypothesized that the skeletal muscle index and mediastinal adipose tissue might also have an impact on postoperative outcomes after primary surgery for primary lung cancer. The institutional database was queried for patients with primary lung cancer who were treated with primary lobectomy or segmentectomy between February 2009 and November 2018. In total, 311 patients were included for analysis. Patients receiving neo-/adjuvant chemotherapy or with a positive nodal status were excluded to rule out any morbidity or mortality due to (neo-)adjuvant treatment. Sarcopenia was defined as a skeletal muscle index of <34.4 cm2/m2 for women and <45.4 cm2/m2 for men. Mediastinal adipose tissue was defined with a radiodensity of -150 to -30 Hounsfield units. Sarcopenia was diagnosed in 78 (25.1%) of the 311 patients. Male patients were significantly more likely to suffer from sarcopenia (31.5% vs. 18.1%, p = 0.009). Comorbidities, lung function, tumour histology, pathologic tumour staging, mediastinal adipose tissue and age did not differ between groups with or without sarcopenia. Sarcopenic patients had a significantly longer length of stay, with 13.0 days vs. 9.5 (p = 0.003), and a higher rate of any postoperative complications (59.0% vs. 44.6%, p = 0.036). There was no difference in recurrence rate. Five-year overall survival was significantly better in the patient cohort without sarcopenia (75.6% vs. 64.5%, p = 0.044). Mediastinal adipose tissue showed no significant impact on length of stay, postoperative complications, recurrence rate, morbidity or survival. Sarcopenia, quantified with the skeletal muscle index, is shown to be a risk factor for postoperative morbidity and reduced survival in primary lung cancer. Efforts should be taken to pre-emptively screen for sarcopenia and start countermeasures (e.g., physical prehabilitation, protein-rich nutrition, etc.) during the preoperative workup phase.

Interleukin-6 Levels During Normothermic Machine Perfusion Impact Postreperfusion Hemodynamics of Liver Graft Recipients: A Prospective Single-center Observational Study.

BACKGROUND: Hemodynamic instability after liver graft reperfusion increases recipient morbidity after liver transplantation. The etiologies of hemodynamic disturbances appear to be multifactorial and are poorly understood. Normothermic machine perfusion (NMP) provides an opportunity to analyze graft quality prior to transplantation. In the present study, we aim to investigate the influence of interleukin-6 (IL-6) levels during NMP on postreperfusion hemodynamics of the recipient. METHODS: Consecutive NMP-liver transplants at a single-center were prospectively analyzed. Perfusate samples were collected at the beginning, after 6 h, and at the end of perfusion and analyzed for IL-6 levels. Mean arterial pressure (MAP) and catecholamine consumption during surgery were recorded. IL-6 levels at the end of NMP were correlated to donor and perfusion characteristics as well as changes in MAP and catecholamine requirements during the anhepatic and reperfusion phase. RESULTS: IL-6 perfusate measurements were assessed in 77 livers undergoing NMP and transplantation. Donor age, sex, cold ischemic time, and NMP time did not correlate with IL-6 levels. Perfusates of donation after circulatory death grafts showed higher IL-6 levels at the end of NMP than donation after brain death grafts. However, IL-6 levels at the end of NMP correlated with catecholamine requirements and MAP in the reperfusion phase. Per log10 increase in IL-6 levels, an increase of 42% points in administered catecholamine dose was observed, despite MAP being decreased by 3.6% points compared to baseline values. CONCLUSIONS: IL-6 levels may be a predictor for recipient hemodynamic instability during liver reperfusion. Larger studies are needed to confirm this finding.

48 h Normothermic Machine Perfusion With Urine Recirculation for Discarded Human Kidney Grafts.

Normothermic machine perfusion (NMP) has reshaped organ preservation in recent years. In this preclinical study, prolonged normothermic perfusions of discarded human kidney grafts were performed in order to investigate perfusion dynamics and identify potential quality and assessment indicators. Five human discarded kidney grafts were perfused normothermically (37°C) for 48 h using the Kidney Assist device with a red-blood-cell based perfusate with urine recirculation. Perfusion dynamics, perfusate and urine composition as well as injury markers were measured and analyzed. Donor age ranged from 41 to 68 years. All but one kidney were from brain dead donors. Perfusions were performed successfully for 48 h with all discarded kidneys. Median arterial flow ranged from 405 to 841 mL/min. All kidneys excreted urine until the end of perfusion (median 0.43 mL/min at the end of perfusion). While sodium levels were consistently lower in urine compared to perfusate samples, this was only seen for chloride and potassium in kidney KTX 2. Lactate, AST, LDH as well as pro-inflammatory cytokines increased over time, especially in kidneys KTX 3 and 4. Ex vivo normothermic perfusion is able to identify patterns of perfusion, biological function, and changes in inflammatory markers in heterogenous discarded kidney grafts.

Diverticulitis with coloenteric fistula mimicking gangrenous appendicitis with perityphlitic abscess. An uncommon presentation of a common disease - A case report.

INTRODUCTION: Diverticulitis is a common gastrointestinal disease usually presenting with a typical clinical picture depending on the stage of the disease. In complicated cases, the clinical presentation may be untypical, thus delaying diagnosis and treatment. PRESENTATION OF CASE: We present a case of a young patient who was initially treated for obscure intraabdominal abscesses presumably due to gangrenous appendicitis; however, intraoperative exploration revealed a normal appendix and a coloenteric fistula resulting from an unknown and untreated perforated diverticulitis. DISCUSSION: A patient with a perityphlitic abscess was initially managed with primary non-operative management (NOM) in accordance with the current Jerusalem guidelines, but surgery was eventually necessary due to failure of NOM. Intraoperative findings revealed a sigmoido-ileal fistula, a rare but potentially detectable complication of diverticulitis through colonoscopy. This case highlights the challenges in diagnosing and treating common surgical diseases with uncommon clinical presentations, emphasizing the importance of a detailed patient history and not relying solely on imaging studies. CONCLUSION: Intraabdominal abscesses require prompt treatment with non-operative management, while intestinal fistulae associated with diverticulitis are a rare consequence of chronic inflammation, often asymptomatic and often detected incidentally during surgery. In most cases simple fistulous tract resection is usually sufficient as first line therapy.

Bioenergetic and Cytokine Profiling May Help to Rescue More DCD Livers for Transplantation.

The majority of organs used for liver transplantation come from brain-dead donors (DBD). In order to overcome the organ shortage, increasingly donation after circulatory death (DCD) organs are also considered. Since normothermic machine perfusion (NMP) restores metabolic activity and allows for in-depth assessment of organ quality and function prior to transplantation, such organs may benefit from NMP. We herein compare the bioenergetic performance through a comprehensive evaluation of mitochondria by high-resolution respirometry in tissue biopsies and the inflammatory response in DBD and DCD livers during NMP. While livers were indistinguishable by perfusate biomarker assessment and histology, our findings revealed a greater impairment of mitochondrial function in DCD livers after static cold storage compared to DBD livers. During subsequent NMPs, DCD organs recovered and eventually showed a similar performance as DBD livers. Cytokine expression analysis showed no differences in the early phase of NMP, while towards the end of NMP, significantly elevated levels of IL-1ß, IL-5 and IL-6 were found in the perfusate of DCD livers. Based on our results, we find it worthwhile to reconsider more DCD organs for transplantation to further extend the donor pool. Therefore, donor organ quality criteria must be developed, which may include an assessment of bioenergetic function and cytokine quantification.

A paired-kidney allocation study found superior survival with HLA-DR compatible kidney transplants in the Eurotransplant Senior Program.

The Eurotransplant Senior Program (ESP) has expedited the chance for elderly patients with kidney failure to receive a timely transplant. This current study evaluated survival parameters of kidneys donated after brain death with or without matching for HLA-DR antigens. This cohort study evaluated the period within ESP with paired allocation of 675 kidneys from donors 65 years and older to transplant candidates 65 years and older, the first kidney to 341 patients within the Eurotransplant Senior DR-compatible Program and 334 contralateral kidneys without (ESP) HLA-DR antigen matching. We used Kaplan-Meier estimates and competing risk analysis to assess all cause mortality and kidney graft failure, respectively. The log-rank test and Cox proportional hazards regression were used for comparisons. Within ESP, matching for HLA-DR antigens was associated with a significantly lower five-year risk of mortality (hazard ratio 0.71; 95% confidence interval 0.53-0.95) and significantly lower cause-specific hazards for kidney graft failure and return to dialysis at one year (0.55; 0.35-0.87) and five years (0.73; 0.53-0.99) post-transplant. Allocation based on HLA-DR matching resulted in longer cold ischemia (mean difference 1.00 hours; 95% confidence interval: 0.32-1.68) and kidney offers with a significantly shorter median dialysis vintage of 2.4 versus 4.1 yrs. in ESP without matching. Thus, our allocation based on HLA-DR matching improved five-year patient and kidney allograft survival. Hence, our paired allocation study suggests a superior outcome of HLA-DR matching in the context of old-for-old kidney transplantation.

Single Center, Propensity Score Matching Analysis of Different Reconstruction Techniques following Pancreatoduodenectomy.

BACKGROUND: Pancreatoduodenectomy is still hampered by significant morbidity. So far, there is no universally accepted technique aimed at minimizing postoperative complications. Herein, we compare three different reconstruction techniques. METHODS: This is a retrospective study of a prospectively maintained database including 283 patients operated between January 2010 and December 2020. Three reconstruction techniques were compared: (1) the Neuhaus-style telescope pancreatojejunostomy, (2) the pancreatogastrostomy, and (3) the modified Blumgart-style, duct-to-mucosa pancreatojejunostomy. The primary endpoint consisted in determining the rates of clinically relevant postoperative pancreatic fistulas (CR-POPF); the secondary endpoints included 90 days morbidity and mortality rates. A propensity score matching analysis was used. RESULTS: Rates of CR-POPF did not differ significantly between the groups (Neuhaus-style pancreatojejunostomy 16%, pancreatogastrostomy 17%, modified Blumgart-style pancreatojejunostomy 15%), neither in the unmatched nor in the matched analysis (p = 0.993 and p = 0.901, respectively). Similarly, no significant differences could be observed with regard to major morbidity (unmatched p = 0.596, matched p = 0.188) and mortality rates (unmatched p = 0.371, matched p = 0.209) within the first 90 days following surgery. Propensity-score matching analyses revealed, however, a higher occurrence of post-pancreatectomy hemorrhage after pancreatogastrostomy (p = 0.015). CONCLUSION: Similar CR-POPF rates suggest no crucial role of the applied reconstruction technique. Increased incidence of intraluminal post-pancreatectomy hemorrhages following pancreatogastrostomy demands awareness for meticulous hemostasis.

The influence of liver transplantation on the interplay between gut microbiome and bile acid homeostasis in children with biliary atresia.

BACKGROUND: Biliary atresia (BA) causes neonatal cholestasis and rapidly progresses into cirrhosis if left untreated. Kasai portoenterostomy may delay cirrhosis. BA remains among the most common indications for liver transplantation (LT) during childhood. Liver function and gut microbiome are interconnected. Disturbed liver function and enterohepatic signaling influence microbial diversity. We, herein, investigate the impact of LT and reestablishment of bile flow on gut microbiome-bile acid homeostasis in children with BA before (pre, n = 10), 3 months (post3m, n = 12), 12 months (post12m, n = 9), and more than 24 months (post24 + m, n = 12) after LT. METHODS: We analyzed the intestinal microbiome of BA patients before and after LT by 16S-rRNA-sequencing and bioinformatics analyses, and serum primary and secondary bile acid levels. RESULTS: The gut microbiome in BA patients exhibits a markedly reduced alpha diversity in pre (p = 0.015) and post3m group (p = 0.044), and approximated healthy control groups at later timepoints post12m (p = 1.0) and post24 + m (p = 0.74). Beta diversity analysis showed overall community structure similarities of pre and post3m (p = 0.675), but both differed from the post24 + m (p < 0.001). Longitudinal analysis of the composition of the gut microbiome revealed the Klebsiella genus to show increased abundance in the post24 + m group compared with an age-matched control (p = 0.029). Secondary bile acid production increased 2+ years after LT (p = 0.03). Multivariable associations of microbial communities and clinical metadata reveal several significant associations of microbial genera with tacrolimus and mycophenolate mofetil-based immunosuppressive regimens. CONCLUSIONS: In children with BA, the gut microbiome shows strongly reduced diversity before and shortly after LT, and approximates healthy controls at later timepoints. Changes in diversity correlate with altered secondary bile acid synthesis at 2+ years and with the selection of different immunosuppressants.

Liver Transplantation in Recipients With a Positive Crossmatch: A Retrospective Single-Center Match-Pair Analysis.

A positive crossmatch (XM+) is considered a contraindication to solid abdominal organ transplantation except liver transplantation (LT). Conflicting reports exist regarding the effects of XM+ on post-transplant outcomes. The goal of this retrospective single-center analysis is to evaluate the influence of XM+ on relevant outcome parameters such as survival, graft rejection, biliary and arterial complications. Forty-nine adult patients undergoing LT with a XM+ between 2002 and 2017 were included. XM+ LT recipients were matched 1:2 with crossmatch negative (XM-) LT recipients based on the balance of risk (BAR) score. Patient and graft survival were compared using Kaplan-Meier survival analysis and the log-rank test. Comparative analysis of clinical outcomes in XM+ and XM- groups were conducted. Patient and graft survival were similar in XM+ and XM- patients. Rejection episodes did not differ either. Recipients with a strong XM+ were more likely to develop a PCR+ CMV infection. A XM+ was not associated with a higher incidence of biliary or arterial complications. Donor age, cold ischemia time, PCR+ CMV infection and a rejection episode were associated with the occurrence of ischemic type biliary lesions. A XM+ has no effects on patient and graft survival or other relevant outcome parameters following LT.