PURPOSE OF REVIEW:This review synthesizes advanced preclinical and clinical studies published over the past 18 months evaluating mesenchymal stromal cells (MSCs) and MSC-derived products in kidney diseases. We focused on the translational relevance of MSC-based therapies against ischemia-reperfusion injury (IRI) and toxic acute kidney injury (AKI), as well as chronic kidney disease (CKD) progression in diabetic kidney disease (DKD) and lupus nephritis (LN). RECENT FINDINGS:The renoprotective effects of MSC-based therapies are highly dependent on the timing of administration and the local pathological microenvironment. In IRI and AKI, therapeutic efficacy is confined to specific exposure windows and is driven by early modulation of mitochondrial dysfunction, inflammation and cell death. In DKD, MSCs from multiple sources consistently improve albuminuria, renal function and structural damage through anti-inflammatory, antifibrotic, autophagy-restoring and ferroptosis-inhibiting mechanisms. This nephroprotection appears to be largely independent of the glycaemic control. In LN, immune-contextual conditioning critically shapes the phenotypes of MSCs and MSC-derived extracellular vesicles (EVs), with optimized or engineered products outperforming the naïve approaches. In contrast, hypertension-related kidney disease illustrates how chronic ischemia and vascular remodelling limit MSC efficacy unless the underlying hemodynamic stress is corrected. SUMMARY:Across diverse settings of acute and chronic kidney injury, MSC-based therapies act primarily as modulators of early pathogenic cascades rather than curative interventions for advanced damage. Their efficacy critically depends on timing, disease context and micro-environmental conditioning. Increasingly, cell-free strategies based on EVs offer scalable and potentially safer alternatives, supporting the translational development of context-adapted and combinatorial strategies.

20 Background: Liver transplantation (LTx) for unresectable colorectal liver metastases (uCLM) has gained renewed interest following the 2024 TransMet trial, which provided prospective, randomized evidence supporting its role in selected patients. This increased demand for LTx in Belgium despite the absence of a national protocol in this early adoption phase. Given the modest number of patients transplanted in TransMet (38), SECA-I (21) and SECA-II (15), and the heterogeneity in selection criteria, we retrospectively collected and analyzed all Belgian LTx cases for uCLM to date. Although performed without a uniform protocol, this national, multi-center cohort provides a timely snapshot of clinical practice prior to launching a standardized national framework. Our aim was to consolidate real-world data to inform future practice and to contribute to the international policy making on this emerging LTx indication. Methods: This multicenter retrospective study included all LTx cases for uCLM performed across all six accredited Belgian LTx centers. Patient selection followed local protocols that varied. In all cases, CLM were classified as permanently unresectable and there was no prior extrahepatic disease. Results: Between June 2016 and August 2025, 29 patients underwent LTx for uCLM in Belgium. Median age was 56 years (IQR 50–61), with 69% male. Primary tumors were mostly left-sided (79%). All tumors were MSS; 86% were RAS/BRAF wild type, 7% had a KRAS - and 7% a BRAF mutation. Prior to LTx, patients received a median of 22 chemotherapy cycles (IQR 16–28), in up to two lines of treatment. The first line consisted of a doublet (62%) or triplet (38%) regimen; 93% received targeted therapy. Serious adverse events after LTx occurred in 62%, including three acute rejections and one intraoperative death; no re-transplantations were performed. Median follow-up was 20.5 months (IQR 7.0–35.3). Recurrence occurred in 38%, mainly pulmonary (73%) and peritoneal (27%), with median time to recurrence 6.3 months (IQR 5.3–6.7). 2-year progression-free survival (PFS) was 35.7% (95% CI 12.8–64.9) among 14 patients eligible for analysis; 1-year PFS was 47.6% (95% CI 25.7–70.2) among 21 patients. 2-year overall survival (OS) was 53.3% (95% CI 43.3–74.1) among 15 patients eligible for analysis; 1-year OS was 68.2% (95% CI 45.6–85.8) among 22 patients. Conclusions: LTx for uCLM is feasible in Belgian practice, with encouraging short-term outcomes despite heterogeneous selection criteria and short follow-up. However recurrence was high despite the limited timeframe, though no hepatic recurrences were observed. These retrospective findings should be interpreted cautiously but support further uptake of LTx in clinical practice, while emphasizing the importance of a standardized national protocol for patient selection to improve long-term outcomes.

Enhanced recovery programs (ERPs) improve short-term outcomes after liver surgery (LS), but their impact on survival remains uncertain. This study evaluated the association between ERP compliance and survival in a large multicenter cohort. This prospective European multicenter cohort included adults undergoing elective LS between 2016 and 2024 in 10 centers implementing Enhanced Recovery After Surgery (ERAS)-consistent ERPs. Compliance was defined as the proportion of 21 fulfilled items with high compliance (≥70

BACKGROUND:Liver transplantation for hepatocellular carcinoma (HCC) is highly transfusion-demanding, and intraoperative cell salvage is used to limit allogeneic blood exposure. This study aimed to assess the oncologic safety of transfusion of irradiated-only autologous red blood cells during liver transplantation for HCC. METHODS:This single-center retrospective cohort included all patients who underwent liver transplantation for HCC between 2010 and 2022. Among the 135 patients, 97 received autologous transfusion of irradiated red blood cells collected through intraoperative cell salvage; the remaining 38 did not. No leukocyte depletion filters were used. The primary outcome was HCC recurrence; secondary outcomes were overall survival and transfusion requirements. RESULTS:The median follow-up time was 9.7 y. HCC recurrence occurred in 15.5% of patients in the autotransfusion group compared with 21.1% in the nonautotransfusion group ( P  = 0.44). Kaplan-Meier analyses revealed no significant differences in recurrence-free or overall survivals between the 2 groups. Multivariable Cox regression adjusted for the Model for End-Stage Liver Disease score, tumor burden, Milan criteria, and microvascular invasion revealed that autotransfusion was not associated with recurrence or mortality. Patients in the autotransfusion group had significantly higher exposure to allogeneic blood products. CONCLUSIONS:Intraoperative autotransfusion of irradiated red blood cells without leukocyte depletion filters appears oncologically safe during liver transplantation for HCC, although the single-center, retrospective design and small control group warrant cautious interpretation and confirmation in larger multicenter studies. As tertiary transplant centers already use blood irradiators for immunocompromised patients, these findings support irradiation as a practical alternative to filtration.

BACKGROUND The Pringle manoeuvre, which involves intermittent clamping of the hepatic pedicle, is a common surgical strategy employed to reduce blood loss during liver resection. Although its impact on intra-operative glucose levels has been documented, its contribution to postoperative hyperglycaemia remained an untested hypothesis. OBJECTIVES The primary aim of this study was to determine whether hepatic vascular clamping was associated with increased postoperative hyperglycaemia within 24 h after liver surgery. Secondary aims included examining the association between postoperative hyperglycaemia and infectious complications and length of hospital stay. DESIGN A retrospective observational cohort study. SETTING Single tertiary university hospital. The study period extended from January 2020 to June 2022. PATIENTS The study sample comprised 163 adult patients who underwent elective liver resection. Patients were grouped according to the intra-operative use of the Pringle manoeuvre: 107 patients underwent clamping (Pringle group), while 56 patients did not undergo clamping (No-Pringle group). No patients were excluded, and data were complete for all individuals included. MAIN OUTCOME MEASURES The primary outcome was the occurrence of postoperative hyperglycaemia, defined as blood glucose at least 10.0 mmol l −1 (180 mg dl −1 ) within 24 h after surgery. Secondary outcomes included postoperative infectious complications and length of hospital stay. RESULTS Postoperative hyperglycaemia occurred in 55.1% of patients in the Pringle group compared to 23.2% in the No-Pringle group ( P < 0.001). Hepatic clamping was independently associated with postoperative hyperglycaemia (adjusted odds ratio 2.91, 95% confidence interval 1.06 to 8.92). As secondary findings, a higher incidence of postoperative infections was observed in the Pringle group (23.4 vs. 5.4%, P = 0.007), and the median hospital length of stay was longer (4 [2 to 8] vs. 2 [1 to 6] days, P = 0.003). CONCLUSIONS The Pringle manoeuvre was associated with increased postoperative hyperglycaemia within 24 h after liver surgery. These findings underscore the necessity for proactive intra-operative and postoperative glucose control strategies as an integral component of peri-operative management in hepatic surgery.

INTRODUCTION:Ischemia-reperfusion injury remains a critical determinant of graft outcomes in kidney transplantation, contributing to delayed graft function and reduced long-term survival. Machine perfusion has emerged as a dynamic preservation strategy offering a therapeutic window to condition organs prior to implantation. The integration of stem cells and extracellular vesicles (EVs), known for their immunomodulatory and cytoprotective properties, into perfusion protocols represents a novel and potentially synergistic approach. However, the evidence base remains limited and heterogeneous. METHODS:This systematic review and meta-analysis evaluated the therapeutic potential of stem cell-based interventions during machine perfusion, following PRISMA guidelines. PubMed, Embase, and Scopus were searched for experimental studies using stem cells or EVs during hypothermic or normothermic machine perfusion in animal or discarded human kidneys. Outcomes included renal function, injury biomarkers, inflammation, and histology. RESULTS:Nine studies were included, seven in meta-analysis. Several reported reductions in inflammatory cytokines (IL-6, IL-1β) and biomarkers (NGAL) following stem cell or EV administration. However, meta-analysis showed no significant effects on creatinine clearance (SMD: 0.00; 95% CI: -0.54 to 0.55), urine output (SMD: 0.54; 95% CI: -0.46 to 1.55), or NGAL (SMD: -1.68; 95% CI: -5.60 to 2.25). Stem cell retention was limited, mechanisms of action remain incompletely understood, and only one study assessed post-transplant function. CONCLUSION:Despite potential immunomodulatory and cytoprotective effects, consistent functional benefits were not demonstrated. Standardized studies incorporating transplant models and long-term outcomes are needed to clarify therapeutic potential and optimize delivery strategies.

Older adults undergoing major abdominal, cardiac, or vascular surgery are highly vulnerable to postoperative complications, prolonged hospitalisation, functional decline, and mortality. Sarcopenia and frailty reduce physiological reserve, underscoring the potential role of prehabilitation in improving resilience to surgical stress and postoperative outcomes. To evaluate the effects of exercise-based prehabilitation, alone or combined with nutritional, psychological, or educational components, on postoperative outcomes, including complications, length of stay, readmissions, mortality, quality of life, and economic indicators, as well as on body composition, functional reserve, and biological markers, in adults aged ≥ 65 years undergoing major abdominal, cardiac, or vascular surgery. Medline, Scopus and EMBASE were searched for Randomised Controlled trials assessing prehabilitation programmes in older adults undergoing major abdominal, cardiac or vascular surgery. Data on study characteristics, interventions, outcomes, and methodological quality were extracted and synthesized narratively. Nine studies (n = 36–182; mean/median age 68–82) were included. Interventions lasted 2–6 weeks and involved exercise alone or multimodal programmes, delivered in-person, remotely, or via hybrid approaches. Vascular surgery studies showed modest reductions in complications and hospital stay, whereas abdominal surgery studies generally reported no significant improvements, except for isolated reductions in severe complications or gains in functional reserve. No studies involving cardiac surgery were identified. Prehabilitation in older adults remains understudied, especially in frail patients, the oldest old, and cardiac surgery. Robust trials are needed to assess individualized, multimodal, sarcopenia-targeted interventions and to integrate biological markers to clarify underlying mechanisms.

Initialement appliquée à la chirurgie colorectale, la réhabilitation améliorée s’étend aujourd’hui à une multitude de disciplines chirurgicales dont récemment la transplantation hépatique à la suite de la publication en 2022 et 2023 de deux consensus internationaux qui totalisent environ 80 recommandations evidence-based, couvrant les phases pré-, péri- et postopératoire. Ainsi, après transplantation hépatique la réhabilitation améliorée diminue la morbidité postopératoire, raccourcit les durées de séjours en soins intensifs et intra-hospitalières sans accroître les taux de réadmissions. Cette mise au point synthétise les recommandations dans ce domaine. Elle discute l’intérêt scientifique et clinique de ces items, en incluant des publications pertinentes qui ont été publiées depuis. L’objectif ultime de cette mise au point est de favoriser l’implémentation institutionnelle de ces items au travers de protocoles multidisciplinaires standardisés. Ces parcours de réhabilitation améliorée atténuent le stress chirurgical, accélèrent la récupération fonctionnelle et génèrent des économies médico-économiques substantielles, avec un objectif de compliance maximalisés par des audit annuels que les sociétés savantes devraient bientôt pouvoir proposer.

Kidney transplantation from donation after circulatory death (DCD) donors is increasingly used but remains associated with warm ischemic injury. Normothermic machine perfusion (NMP) enables functional assessment and therapeutic interventions. Mesenchymal stromal cells (MSCs) display immunomodulatory and regenerative properties, yet their translational efficacy during NMP remains unclear. In a porcine model, six pairs of kidneys subjected to 30 min of warm ischemia followed by 3 h of static cold storage underwent 6 h of NMP. In each pair, one kidney randomly received an intra-arterial injection of placebo, while the contralateral kidney received 10 million clinical-grade human bone marrow-derived MSCs (hMSCs). Perfusion characteristics, glomerular filtration, tissue injury, and inflammatory markers were assessed. hMSC infusion during NMP was technically feasible and hemodynamically well tolerated, with no adverse effects on perfusion stability. Perfusion parameters, urine output, and creatinine/iohexol clearance showed no significant differences between groups. NGAL and cytokines levels increased during perfusion, but hMSCs did not alter their dynamics. Intra-arterial delivery of clinical grade hMSCs during NMP was safe but did not improve renal function or reduce histological injury. These results highlight the challenges of achieving MSC engraftment during ex situ perfusion and highlight the need for refined strategies such as repeated dosing, prolonged perfusion, or extracellular vesicle therapy. Despite the negative findings, this study presents a highly translational large-animal model, supporting further investigation of MSC-based therapies in human kidneys discarded for transplantation.

Hepatocellular carcinoma (HCC) is the most common primary hepatic tumour and represents a major diagnostic challenge. Conventional imaging, mainly based on computed tomography (CT) and magnetic resonance imaging (MRI), has some limitations, particularly in characterizing atypical and small lesions. Molecular imaging with [18F]Fluoro-2-deoxy-d-glucose, by positron emission tomography associated with computed tomography ([18F]FDG PET/CT), suffers from variable sensitivity depending on tumour differentiation. Recently, PET/CT imaging with prostate-specific membrane antigen (PSMA) showed growing interest in non prostatic tumours, especially in HCC due to its affinity for tumoural vascular endothelium. A case report illustrates the value of PSMA PET/CT in the staging and therapeutic management of HCC.

BACKGROUND:Normothermic Machine Perfusion (NMP) is essential in renal transplantation to improve organ viability before transplantation. This study presents a proof of concept for simultaneous ex situ perfusion of paired porcine kidneys using exogenous creatinine and iohexol clearances to assess renal function, with the primary objective of examining intra-individual differences. METHODS:Five kidney pairs (n = 10) were harvested from pigs, preserved at 4°C for 3 h, and subjected to 6-h NMP. Each pair was perfused with a solution containing red blood cells, and perfusion parameters were monitored continuously. Biochemical parameters were assessed using hourly perfusate and urine samples. Kidney function was evaluated using creatinine, which was introduced during the priming procedure. RESULTS:No significant differences were observed between paired kidneys in terms of perfusion and biochemical parameters. Both kidneys maintained stable mean arterial pressures (67.40 ± 12.08 mmHg for right vs. 71.50 ± 4.36 mmHg for left) and flows (68.90 ± 38.61 mL/min vs. 54.00 ± 26.08 mL/min), with consistent electrolyte balance and pH levels. The high inter-individual variability in perfusion and biochemical parameters underscores the importance of paired comparisons. CONCLUSIONS:This pig model of simultaneous NMP of paired kidneys demonstrates that the intra-individual variance is low, which makes it possible to test treatments prior to kidney transplantation using one kidney as a valid comparator of the other.

OBJECTIVE:To analyze the effectiveness of prophylactic mesh augmentation (PMA) of the abdominal wall following open aortic aneurysm repair as compared to primary sutured (PS) closure in preventing incisional hernia (IH) formation by performing an individual patient-data meta-analysis (IPDMA). BACKGROUND:IH is a prevalent complication after abdominal surgery, especially in high-risk groups. PMA of the abdominal wall has been studied as a preventive measure for IH formation, but strong recommendations are lacking. METHODS:A systematic literature search was conducted till September 23, 2024, to identify randomized controlled trials (RCTs) that compared PMA with PS after open AAA surgery. Lead authors of eligible studies were asked to share individual patient-data. A one-stage analysis was performed, and Cox regression analyses were used to assess time-to-event outcomes. RESULTS:Five randomized trials with a total of 493 patients were included. Intention to treat analysis revealed that PMA was associated with a significantly lower risk of IH [hazard ratio of 0.25 (95% CI: 0.12-0.50)] as compared with PS closure. Three-year incisional hernia rates were 13.2% and 39.6%, respectively, with a number needed to treat of 3.7. The effect was similar for onlay and retro-rectus PMA. PMA resulted in longer operative time (mean 27 min) and more seroma formation (especially onlay PMA) but did not increase the risk of surgical site infection. CONCLUSIONS:PMA after elective open abdominal aortic aneurysm surgery is proven to be an effective measure to reduce IH formation and should be considered in future guidelines as a standard of care.

BACKGROUND AND AIMS:Patients with a history of metabolic and bariatric surgery (MBS) are susceptible to developing alcohol use disorder. Outcome after transplantation for alcohol-related liver disease (ALD) has not been studied in-depth. METHODS:We included adult patients who underwent a liver transplantation (LT) in Belgium between 1 January 2013 and 31 December 2022 for ALD. We captured all patients with a history of MBS prior to developing ALD, and included non-MBS patients for comparison. RESULTS:We identified 39 patients who underwent MBS before developing ALD, and included 443 non-MBS patients with an LT for ALD as controls. The median time between MBS and diagnosis of severe liver disease was 7.2 years. MBS patients were 9 years younger at the time of transplantation (p < 0.001). Pre-LT hepatocellular carcinoma was more prevalent in the non-MBS group (p < 0.001), while severe bacterial infections occurred more frequently in those with prior MBS. Importantly, patients with MBS had a lower survival after LT in age- and sex-adjusted Cox regression analysis (HR 2.205, p = 0.023). Liver disease was listed in 70.0% versus 13.3% of patients as the main cause of death. Liver-related mortality was linked to alcohol use relapse post-LT, with significantly more MBS patients experiencing relapse (30.8% vs. 13.3%, p = 0.003). CONCLUSION:Following MBS, excessive alcohol use can progress to end-stage ALD and need for LT. These patients present at a younger age, with more signs of hepatic decompensation, and can be at a higher risk for post-LT mortality, especially liver-related death.