The sustainability of transplantation surgery (TS) relies on the ability to attract and retain the next generation of surgeons. This study aims to assess how surgical residents perceive TS as a career pathway in Germany, and to identify barriers in choosing TS as a career. An anonymous 30-item online survey was distributed to surgical residents at all transplant centers registered with the Deutsche Stiftung Organtransplantation (DSO, German Organ Procurement Organization). Quantitative data were analyzed using SPSS (version 29), free-text responses underwent thematic content analysis. Sixty-eight complete surveys were analyzed. TS was considered by 25% of respondents as a subspecialty training. Transplant-specific education was occasional or absent, though desired by >80%. Motivators included personal interest, patient care, and career development, while barriers were structural: lack of defined fellowship programs and limited autonomy during residency. Structured fellowship programs (46%), mentorship (27%) and enhanced operative autonomy (25%) were identified as key factors to encourage recruitment of surgeons in their early career stages. Surgical residents in their early career stages in Germany regard TS as an appealing career option. A structured training framework is a perceived unmet need to enhance recruitment to TS. Transplantation surgery, workforce sustainability, medical education
Introduction Sodium-glucose co-transporter 2 inhibitors (SGLT2i) have gained significant attention in clinical research due to their diverse therapeutic effects. The aim of this retrospective study was to analyze the nephroprotective effects of SGLT2i on kidney function in patients experiencing renal insufficiency after liver transplantation. Methods A retrospective study was conducted comparing 43 liver transplant recipients with chronic kidney disease treated with dapagliflozin and 43 controls, who attended the LMU University Hospital between 2020 and 2023. Changes in estimated glomerular filtration rate (eGFR), urinary albumin-to-creatinine ratio (UACR), liver parameters, and safety outcomes were assessed. Results Dapagliflozin administration was associated with preservation of renal function demonstrated by stable eGFR values (p=0.05), while the control cohort experienced significant deterioration in kidney function (p=0.03). The nephroprotective effect persisted in patients with severely reduced baseline GFR (≤30 ml/min; p=0.08). Moreover, dapagliflozin significantly reduced UACR (p=0.04), with enhanced renal protection observed in patients with severe albuminuria, diabetes (p=0.08), and those receiving calcineurin inhibitor therapy (p=0.12). The incidence of transient eGFR decline (>10% decrease within 4 weeks, followed by recovery) was observed in 9 patients (20.9%) treated with dapagliflozin, while sustained progressive kidney dysfunction (>10% eGFR decline persisting at final follow-up) occurred significantly more frequently in controls (46.5%; p=0.001). One urinary tract infection was documented in the dapagliflozin group during the observation period. No treatment discontinuations due to serious adverse events occurred. Conclusion Dapagliflozin improves renal outcomes in liver transplant recipients with chronic kidney disease and has a favorable safety profile. Prospective trials are needed to confirm these findings.
The Model for End-Stage Liver Disease (MELD) score has been the primary allocation tool in the Eurotransplant region. However, certain patient groups remain disadvantaged. As diagnostic and therapeutic means evolve, regular revision of allocation criteria is necessary. Infectious diseases can lead to acute organ dysfunction and transient increases in MELD scores, whereas uncontrolled infections represent a contraindication to transplantation. In this retrospective study, we investigated peak-MELD scores, defined as a transient increase of at least five MELD points within 1 month, and evaluated their association with infections and liver transplantation outcomes. Among 109 patients listed for liver transplantation at LMU University Hospital between 2019 and 2022, 11% experienced a peak-MELD trajectory. It was associated with a significantly lower transplantation rate independent of baseline characteristics (HR = 0.37; 95% CI [0.15, 0.92]; p = 0.03). Patients with peak-MELD scores underwent more frequent waitlist status changes (median 2.50 vs. 0.00; p < 0.001), with infections representing the predominant cause of these changes (median 33.33% vs. 0.00%; p = 0.002). In this small single-center study, our findings suggest that a transient MELD increase associated with infectious complications may reflect a clinically vulnerable disease trajectory linked to reduced access to transplantation. Larger multicenter studies are needed to validate these findings and to further evaluate the implications of MELD fluctuations on waitlist outcome. At present, clinicians may consider dynamic disease courses when assessing liver transplantation urgency in patients with cirrhosis.
Abstract Background Liver dysfunction is associated with a rebalanced but fragile hemostatic system, in which alterations in coagulation factor synthesis and activity contribute to both bleeding and thrombotic risks. During liver transplantation, this fragile equilibrium is further challenged by major physiological stress. This study aimed to characterize the phase-specific intraoperative dynamics of coagulation factors V, VIII, and XIII (FV, FVIII, and FXIII) to better understand hemostatic modulation and its clinical implications during liver transplantation. Methods A subset of 17 liver transplant recipients receiving transfusion support without administration of recombinant FVIII or FXIII was analyzed. Measurements were obtained at three defined intraoperative time points: T1 anesthesia induction, T2 end of anhepatic phase, T3 end of surgery. Activities of FV, FVIII, and FXIII were quantified and analyzed for temporal trends. Results All three coagulation factors declined during surgery. FV was already markedly reduced at T1 (37% (22/55)) and further decreased to 26% at T3 ((19/34); p = 0.0309). FVIII showed supranormal levels at T1 (193% (160/254) and declined to near-normal levels at T3 (109% ((67/143); p < 0.0001). FXIII remained close to the lower limit of normal (T1: 68% (50/85)); T3: (63% (55/78)) without significant change. Conclusion This prospective analysis reveals distinct, phase-specific trajectories of FV, FVIII, and FXIII during liver transplantation. Understanding these differential patterns may help identify critical periods of hemostatic vulnerability and guide individualized factor-specific therapeutic interventions to optimize perioperative coagulation management in liver transplant recipients. Trial registration German Clinical Trials Register (DRKS00032827).
Colorectal cancer remains a major challenge for the global health care system. Many patients with colorectal cancer develop liver metastases (CRLM), and a certain proportion of these patients are neither eligible for surgical nor interventional treatment. Liver transplantation (LT) could be a curative treatment option for these patients. This narrative review was based on a targeted literature search of the National Library of medicine (PubMED) to identify current publications investigating LT as a treatment option for patients with CRLM without local treatment options. The search term “colorectal AND liver transplantation” was used, and only original articles of the last ten years were included. Additionally, the ClinicalTrials.gov registry was screened for ongoing clinical trials in this field. A total of 6 studies were identified, along with 21 active clinical trials. LT was associated with higher survival rates compared to standard of care, e.g., 73.3
Background: A substantial number of viable donor livers are discarded due to the donor's underlying malignancy. Concurrently, patients with certain liver malignancies - such as unresectable colorectal cancer liver metastases (CRC-LM), unresectable intrahepatic or perihilar cholangiocarcinoma (iCCC/phCCC), or unresectable hepatocellular carcinoma (HCC) responding to immunotherapy - often face poor survival outcomes and are deemed ineligible for potentially curative liver transplantation. In this context, a rational risk-benefit analysis suggests that transplanting an organ with a theoretical risk of tumor transmission may be justifiable for these patients facing otherwise short-term fatal outcomes. Methods: The TRANSMIT study is a compassionate use exploratory study aimed at assessing the utility and safety of using donor organs from individuals with a current or past history of cancer for liver transplantation in patients with liver malignancies (CRC-LM, i/phCCC, HCC) who are not eligible for regular organ allocation. The study will evaluate the utilization rate of donor organs that would otherwise be discarded, overall survival, progression-free survival, and tumor transmission rates at one and three years, stratified by indication. Discussion: Donor organs from individuals with a current or past history of cancer may represent a valuable and safe resource for expanding the limited donor pool, particularly for patients who lack access to standard organ allocation.
BACKGROUND:End-stage liver disease induces a precarious hemostatic equilibrium, named rebalanced hemostasis. Liver transplantation additionally causes profound disturbances in the hemostatic balance. Hyperfibrinolysis poses a relevant impairment to the coagulation process during liver transplantation. During surgery, the hemostatic management is guided by viscoelastic monitoring systems. The aim of this prospective, observational study was to evaluate the incidence of hyperfibrinolysis during liver transplantation using different viscoelastic assays, namely an ecarin-based test and a tissue factor-based test. METHODS:Blood sampling was done at five measurement time points during liver transplantation (T1 induction of general anesthesia, T2 start of anhepatic phase, T3 end of anhepatic phase, T4 10 min after reperfusion, T5 end of surgery). Viscoelastic testing included ClotPro assays EX-test, FIB-test, AP-test, and ECA-test. Hyperfibrinolysis was defined as a maximum lysis of at least 15%. Lysis detection time (LDT) served as an indicator for the velocity of lysis, marking the time point when less than 85% of the clot are extant. RESULTS:Thirty transplantation surgeries were included. A total of 150 viscoelastic measurements have been performed. The ECA-test detected hyperfibrinolysis significantly more often (31 [21%] vs. 22 [15%] out of 150, p = 0.039) and in a higher number of patients than the EX-test. The ECA-test revealed hyperfibrinolysis significantly earlier compared to the EX-test (median LDT 2100 s [1500/2900] vs. 3300 s [2400/3800], p < 0.001). CONCLUSION:This study demonstrates higher sensitivity of the ecarin-test than the tissue-factor-test in monitoring hyperfibrinolysis, with more frequent and earlier detection of this coagulopathy. TRIAL REGISTRATION:German Clinical Trials Register: DRKS00032827.
Hypothermic oxygenated machine perfusion (HOPE) has become an integral technique to enhance donor graft function in liver transplantation (LiTx). This study compares early posttransplant outcomes of mono-HOPE (portal vein perfusion only) versus dual- HOPE (both portal vein and hepatic artery perfusion). A retrospective analysis was conducted on 183 LiTx recipients, with 90 receiving mono-HOPE and 93 receiving dual-HOPE grafts. Propensity Score Matching (PSM) was applied, resulting in a matched cohort of 146 patients. Primary outcomes included one-year patient and graft survival, and non-anastomotic biliary strictures (NAS). Secondary outcomes included hospital length of stay (HLS). One-year patient survival was 81.7% in the mono-HOPE and 81.7% in the dual-HOPE group, and overall survival did not differ (p = 0.990). One-year death-censored graft survival was similarly comparable (91.2% vs. 93.3%, p = 0.893). NAS were observed in 10.96% in the mono-HOPE and 8.22% in the dual-HOPE group (p = 0.574). The median HLS was 29 days for both groups. Results suggest that dual-HOPE did not significantly improve patient or graft survival, nor did it reduce NAS or HLS compared to mono-HOPE. Assuming that larger cohorts and long-term follow-up data confirm this, additional cannulation of the hepatic artery during machine perfusion in hypothermic conditions may not be beneficial.
Background:Recent retrospective studies suggest a role for distinct microbiota in the perioperative morbidity and mortality of pancreatic head resections.Objective:We aimed to prospectively investigate the microbial colonization of critical operative sites of pancreatic head resections to identify microbial stratification factors for surgical and long-term oncologic outcomes.Methods:Prospective biomarker study applying 16S rRNA sequencing and microbial culturing to samples collected from various sites of the gastrointestinal tract and surgical sites of patients during pancreatic head resections at a German single high-volume pancreatic center.Results:A total of 101 patients were included {38 noncancer, 63 cancer patients [50 pancreatic ductal adenocarcinoma (PDAC) patients]} in the study. In a first data analysis series, 16S rRNA sequencing data were utilized from 96 patients to assess associations of microbiome profiles with clinical parameters and outcomes. In general, microbiome composition varied according to sampling site, cancer, age or preoperative endoscopic retrograde cholangiopancreatography (ERCP) intervention, notably for the bile microbiome. In the PDAC subcohort, the compositional variance of the bile or periampullary microbiome was significantly associated with postoperative complications such as intensive care unit admission; on a taxonomic level we observed Enterococcus spp. to be significantly more abundant in patients developing deep or organ-space surgical site infections (SSI). Elevated Enterococcus relative abundances in the upper gastrointestinal tract, in turn, were associated with 6 months mortality rates. In a second step, we focused on microbiological cultures collected from bile aspirates during surgery and investigated associations with perioperative complications and long-term survival. Notably, Enterococcus spp. were among the most prevalent pathobiont isolates observed in cancer patient bile specimens that were associated with severe SSIs, and thereby elevated mortality rates up to 24 months. Clinically relevant postoperative pancreatic fistulas or severe SSI were found as other major variables determining short-term mortality in this cancer patient cohort. In the context of adverse microbiological factors, a preoperative ERCP was also observed to segregate long-term survival, and it appeared to interact with the presence of Enterococcus spp. as highest mortality rates were observed in PDAC patients with both preoperative ERCP and presence of E. faecalis in bile aspirates.Conclusions:The presence of Enterococcus spp. in bile ducts of PDAC patients undergoing pancreatic surgery represents a significant risk factor for perioperative infections and, thereby, elevated postoperative and long-term mortality. This finding supports previous data on the use of the antibiotic drug piperacillin-tazobactam as appropriate perioperative antibiotic prophylaxis for preventing adverse outcomes after pancreatoduodenectomy.
This case report details the clinical course of a 35-year-old patient with decompensated liver cirrhosis due to primary sclerosing cholangitis awaiting liver transplantation. The patient developed recurrent candidemia due to biliary candidiasis complicated by endotipsitis, leading to repeated hospitalizations and an eventual diagnosis of tricuspid valve Candida endocarditis. In the setting of active Candida infection and severe acute-on-chronic liver failure and lacking other suitable alternatives for infection control, an interdisciplinary team of hepatologists, transplant surgeons, and cardiologists decided to proceed with liver transplantation during a window of opportunity with repeat negative blood cultures. The patient experienced an unremarkable posttransplant recovery despite having repeated positive-result blood cultures for Candida albicans and underwent successful tricuspid valve replacement 5 months later. Our goal is to underscore the critical role of multidisciplinary collaboration in managing high-risk transplant candidates, highlighting in particular the potential benefits of liver transplantation in infection-induced acute-on-chronic liver failure, where full recovery from complex infections might not be possible before transplantation in a setting of severe cirrhosis-associated immune deficiency.
Acute intermittent porphyria is a rare inborn disease of porphyrin metabolism which can cause severe abdominal pain attacks and neurological symptoms. Here, we report a patient with a 20-year history of severe chronic manifestations of acute intermittent porphyria that led to end-stage renal disease and liver function impairment. Since only transplants can cure both disease manifestations, a combined liver and renal transplantation was performed. The patient recovered so well that she delivered a very low birth extreme premature baby 16 months later which developed normally over the next 5 years. Our case represents the third case in the literature with a successful combined liver/renal transplantation of a patient with acute porphyria. Thus, transplantation seems to be a viable backup option, should novel therapies such as siRNA treatment with givosiran fail.
Background.Liver transplantation (LT) remains the most effective treatment for patients with hepatocellular carcinoma (HCC), offering 5-y recurrence rates as low as 15%. Recent advances in organ preservation, particularly hypothermic oxygenated machine perfusion (HOPE), have demonstrated the ability to attenuate ischemia-reperfusion injury (IRI). However, whether HOPE can reduce HCC recurrence rates by mitigating IRI remains an open question. In this study, we aimed to compare oncological outcomes after LT for HCC with and without the use of HOPE.Methods.We conducted a retrospective cohort study including 137 patients who underwent LT for HCC with grafts from donation after brain death. Risk factors for HCC recurrence were analyzed using Cox regression. To assess the impact of HOPE on oncological outcomes, propensity score matching was used to adjust for baseline differences.Results.Cox regression identified Milan Criteria status as a significant predictor of HCC recurrence. Among the 32 patients in the HOPE group, no HCC recurrence was observed over a median follow-up of 2.11 y. In contrast, within the control group of 105 patients, 8 (7.6%) experienced recurrence within 2 y posttransplantation. Although this translated into a significant difference in time-to-recurrence after propensity score matching, recurrence-free survival and overall survival did not differ significantly.Conclusions.Our findings suggest that HOPE treatment of donation after brain death liver grafts may reduce early HCC recurrence after LT. Although only nonsignificant trends were observed in recurrence-free survival and overall survival within the first 2 y posttransplant, these results underscore the potential of HOPE to influence oncological outcomes. Long-term follow-up, prospective randomized controlled trials, and basic research are warranted to further elucidate the role of HOPE and IRI.
BACKGROUND:Living kidney donation is a crucial option for addressing the global organ shortage and providing kidney transplantation for patients suffering from end-stage kidney disease. Ensuring donor safety necessitates a comprehensive preoperative assessment of kidney anatomy and function. This study evaluates the relationship between kidney volumes derived from deep learning-based MRI volumetry, intraoperative kidney volume measurements, split renal function measured by renal scintigraphy, and post-donation eGFR. Deep learning-based MRI volumetry is hypothesized to be a reliable method with good correlation. METHODS:This retrospective study analyzed 178 living kidney donors. Deep learning MRI volumetry-based kidney volumes were compared with intraoperative volumes of the explanted donor kidneys obtained using the water displacement method. Additionally, MRI-based volume ratios were compared with scintigraphy-based split renal function ratios to determine their ability to predict the kidney with poorer renal function and post-donation eGFR. RESULTS:Deep learning-based MRI volumetry strongly correlated with intraoperatively measured kidney volumes (Pearson's correlation; r = 0.7671; p < 0.0001), confirming its precision in volume estimation. Although MRI-based kidney volume ratios demonstrated only a moderate correlation with scintigraphy-based split renal function ratios (r = 0.4798), MRI volumetry correlated with 1-year post-donation eGFR. It tended to be better than renal scintigraphy (r = 0.6829 versus r = 0.6191). CONCLUSION:Deep learning-based MRI volumetry is a reliable, non-invasive tool for estimating kidney volumes in living donors, offering a radiation-free alternative for preoperative assessment. While it differs from renal scintigraphy in evaluating split renal function ratios, its correlation with post-donation eGFR tends to be better, supporting its potential role in living kidney donor assessment.
To develop and validate an integrated model that combines CT-based radiomics and imaging biomarkers with clinical variables to predict recurrence and recurrence-free survival in patients with HCC following liver transplantation (LT), this 2-center retrospective study includes 123 patients with HCC who underwent LT between 2007 and 2021. Radiomic features (RFs) were extracted from baseline CT liver tumor volume. Feature selection was performed using the Least Absolute Shrinkage and Selection Operator (LASSO) regression method with 10-fold cross-validation in the training cohort (n=48) to build a predictive radiomics signature for HCC recurrence. Combined diagnostic models were built based on the radiomics signature supplemented with imaging features beyond the Milan criteria, the AFP (alpha-fetoprotein) model, and Metroticket 2.0 before LT using multivariate logistic regression. Receiver operating characteristic analyses were performed in both internal (n=22) and external (n=53) validation cohorts, and patients were stratified into either high-risk or low-risk groups for HCC recurrence. Kaplan-Meier analysis was performed to analyze recurrence-free survival. LASSO and multivariate regression analysis revealed 4 independent predictors associated with an increased risk of HCC recurrence: radiomics signature of 5 RF, peritumoral enhancement, satellite nodules, and no bridging therapies. For the prediction of tumor recurrence, the highest AUC of the final integrated models combining clinical variables, non-radiomics imaging features, and radiomics was 0.990 and 0.900 for the internal and external validation sets, respectively, outperforming the Milan and clinical stand-alone models. In all integrated models, the high-risk groups had a shorter recurrence-free survival than the corresponding low-risk group. CT-based radiomics and imaging parameters beyond the Milan criteria representing aggressive behavior, along with the history of bridging therapies, show potential for predicting HCC recurrence after LT.