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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.

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.

Introduction: Liver transplantation (LT) is potentially curative for patients with cirrhosis and hepatocellular carcinoma (HCC). However, this procedure is usually reserved for patients with early tumor stages or after successful downstaging with local regional therapies (LRT). In patients with locally advanced HCC current guidelines recommend locoregional and palliative systemic therapies for tumor stages Barcelona Clinic Liver Cancer (BCLC) B and C respectively. Case report: In this article we describe a 63 –year-old male patient with locally advanced hepatocellular carcinoma (BCLC C) and hepatitis C associated cirrhosis. Following systemic treatment with the immune checkpoint inhibitor atezolizumab and the anti-VEGF antibody bevacizumab significant downstaging to a tumor stage within the Milan criteria was achieved after which liver transplantation was successfully performed. Conclusion: As more effective systemic therapies become available, liver transplantation and potential curative treatment could become feasible for selected patients with locally advanced HCC.

Background Normothermic machine perfusion (NMP) bears the potential for significant prolongation of liver preservation before transplantation. Although safety and feasibility have been recently published, no data are available describing the significant challenges of establishing NMP programs outside clinical studies. We herein present our experience and propose a multidisciplinary approach for liver NMP in the clinical routine. Methods In February 2018, liver NMP was introduced for routine use in marginal organs, logistic challenges, and complex recipients at our institution. In a multidisciplinary effort among transplant coordinators, perfusionists, transplant surgeons, anesthesia, nurses, blood bank as well as laboratory staff, a clinical routine was established and 34 NMP cases were performed without critical incidents or organ loss. Results Nine livers were discarded due to poor organ quality and function observed during NMP. Twenty-five livers were successfully transplanted after preservation of up to 38 h. The extended criteria donors rate was 100% and 92% in discarded and transplanted livers, respectively. Nighttime procedures and parallel transplantations were eventually omitted. Graft and patient survival was 88% at 20 mo. No cholangiopathy was observed despite the use of extended criteria donor organs in 92% of cases. Conclusions NMP in a multidisciplinary approach enables a safe prolongation of liver preservation and overnight organ care. A first field test of NMP indicates safety and benefit of this approach.

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-1β, 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.

Normothermic machine perfusion (NMP) allows for ex vivo viability and functional assessment prior to liver transplantation (LT). Hyperspectral imaging represents a suitable, non-invasive method to evaluate tissue morphology and organ perfusion during NMP. Liver allografts were subjected to NMP prior to LT. Serial image acquisition of oxygen saturation levels (StO2), organ hemoglobin (THI), near-infrared perfusion (NIR) and tissue water indices (TWI) through hyperspectral imaging was performed during static cold storage, at 1h, 6h, 12h and at the end of NMP. The readouts were correlated with perfusate parameters at equivalent time points. Twenty-one deceased donor livers were included in the study. Seven (33.0%) were discarded due to poor organ function during NMP. StO2 (p < 0.001), THI (p < 0.001) and NIR (p = 0.002) significantly augmented, from static cold storage (pre-NMP) to NMP end, while TWI dropped (p = 0.005) during the observational period. At 12–24h, a significantly higher hemoglobin concentration (THI) in the superficial tissue layers was seen in discarded, compared to transplanted livers (p = 0.036). Lactate values at 12h NMP correlated negatively with NIR perfusion index between 12 and 24h NMP and with the delta NIR perfusion index between 1 and 24h (rs = −0.883, p = 0.008 for both). Furthermore, NIR and TWI correlated with lactate clearance and pH. This study provides first evidence of feasibility of hyperspectral imaging as a potentially helpful contact-free organ viability assessment tool during liver NMP.

Normothermic machine perfusion (NMP) has become a clinically established tool to preserve livers in a near-physiological environment. However, little is known about the predictive value of perfusate parameters toward the outcomes after transplantation.Fifty-five consecutive NMP livers between 2018 and 2019 were included. All of the livers were perfused on the OrganOx metra device according to an institutional protocol. Transplant and perfusion data were collected prospectively.Forty-five livers were transplanted after NMP. Five livers stem from donors after circulatory death and 31 (68.9%) from extended criteria donors. Mean (SD) cold ischemia time was 6.4 (2.3) h; mean (SD) total preservation time was 21.4 (7.1) h. Early allograft dysfunction (EAD) occurred in 13 of 45 (28.9%) patients. Perfusate aspartate aminotransferase (P = 0.008), alanine aminotransferase (P = 0.006), lactate dehydrogenase (P = 0.007) and their development over time, alkaline phosphatase (P = 0.013), and sodium (P = 0.016) correlated with EAD. Number of perfusate platelets correlated with cold ischemia time duration and were indicative for the occurrence of EAD. Moreover, von Willebrand Factor antigen was significantly higher in perfusates of EAD livers (P 0.001), and Δ von Willebrand factor antigen correlated with EAD. Although perfusate lactate and glucose had no predictive value, EAD was more likely to occur in livers with lower perfusate pH (P = 0.008). ΔPerfusate alkaline phosphatase, Δperfusate aspartate aminotransferase, Δperfusate alanine aminotransferase, and Δperfusate lactate dehydrogenase correlated closely with model for early allograft function but not liver graft assessment following transplantation risk score. Bile parameters correlated with extended criteria donor and donor risk index.Biomarker assessment during NMP may help to predict EAD after liver transplantation. The increase of transaminases and lactate dehydrogenase over time as well as platelets and vWF antigen are important factors indicative for EAD.

Liver transplantation (LT) survival rates have continued to improve over the last decades, mostly due to the reduction of mortality early after transplantation. The advancement is facilitating a liberalization of access to LT, with more patients with higher risk profiles being added to the waiting list. At the same time, the persisting organ shortage fosters strategies to rescue organs of high-risk donors. This is facilitated by novel technologies such as machine perfusion. Owing to these developments, reconsideration of the current and emerging endpoints for the assessment of the efficacy of existing and new therapies is warranted. While conventional early endpoints in LT have focused on the damage induced to the parenchyma, the fate of the bile duct and the recurrence of the underlying disease have a stronger impact on the long-term outcome. In light of this evolving landscape, we here attempt to reflect on the appropriateness of the currently used endpoints in the field of LT trials.

Chronic immunosuppression is associated with an increased risk of malignancy. The main objective of this study is to evaluate the incidence and effect of post-transplant malignancies (PTMs) following pancreas transplantation. The 348 first pancreas transplants performed between 1985 and 2015 were retrospectively analyzed in this study. Incidences of PTMs, as well as patient and graft survival, were evaluated. Out of 348 patients, 71 (20.4%) developed a PTM. Median time to diagnosis was 130 months. Thirty-six patients (50.7%) developed skin cancers (four patients with melanoma, 32 with NMSCs). Solid organ malignancy occurred in 25 (35.2%), hematologic malignancy in ten patients (14.1%). Affected patients were transplanted earlier [2000 (IQR 1993−2004) vs. 2003 (IQR 1999−2008), p &lt, 0.001]. No differences in induction therapy were seen, both groups demonstrated comparable patient and graft survival. Pancreas transplant recipients with solid organ and hematologic malignancies had a three- and six-fold increased hazard of death compared to those with skin cancers [aHR 3.04 (IQR 1.17–7.91), p = 0.023, aHR 6.07 (IQR 1.87–19.71), p = 0.003]. PTMs affect every fifth patient following pancreas transplantation. Skin cancers are the most common malignancies accounting for 50% of all PTMs. These results underscore the importance of close dermatologic follow-up.

In contrast to well-published data with acceptable long-term results in large cohorts of single renal transplant recipients aged >65 y (lit.), combined pancreas-kidney transplantation in recipients >50 y is discussed controversially. Some groups have identified older recipients as a high-risk group, demonstrating decreased patient and graft survival in this population.1-4 Nevertheless, several centers have reported results for pancreatic transplantation in older patients as being comparable to those for younger recipients with the age cutoff ranging from 50 to 60 y.5-10 At our center, we have long-term experience with a total of 655 pancreas transplants performed between 1979 and August 2020, whereby 21 recipients were over 60 y of age; the oldest was age 69 and in remarkably good general condition with good mental adherence and a strong wish to undergo simultaneous kidney-pancreas transplantation (SPK). We retrospectively analyzed patient, pancreas, and kidney graft survival, graft function, and complications at month 38 posttransplant.

Summary Donor cardiac arrest and cardiopulmonary resuscitation (CACPR) has been considered critically because of concerns over hypoperfusion and mechanical trauma to the donor organs. We retrospectively analyzed 371 first simultaneous pancreas–kidney transplants performed at the Medical University of Innsbruck between 1997 and 2017. We evaluated short‐ and long‐term outcomes from recipients of organs from donors with and without a history of CACPR. A total of 63 recipients received a pancreas and kidney graft from a CACPR donor. At 1, and 5‐years, patient survival was similar with 98.3%, and 96.5% in the CACPR and 97.0%, and 90.2% in the non‐CACPR group (log rank P = 0.652). Death‐censored pancreas graft survival was superior in the CACPR group with 98.3%, and 91.4% compared to 86.3%, and 77.4% (log rank P = 0.028) in the non‐CACPR group, which remained statistically significant even after adjustment [aHR 0.49 (95% CI 0.24–0.98), P = 0.044]. Similar relative risks for postoperative complications Clavien Dindo > 3a, pancreatitis, abscess, immunologic complications, delayed pancreas graft function, and relative length of stay were observed for both groups. Donors with a history of CACPR are, in the current practice, safe for transplantation. Stringent donor selection and short CPR durations may allow for outcomes surpassing those of donors without CACPR.

BACKGROUND Sarcopenia is an established risk factor predicting survival in chronically ill and trauma patients. We herein examine the assessment and clinical implication of sarcopenia in liver transplantation (LT). METHODS Computerized tomography scans from 172 patients waitlisted for LT were analyzed by applying 6 morphometric muscle scores, including 2 density indices (psoas density [PD] and skeletal muscle density [SMD]) and 4 scores based on muscle area (total psoas area, psoas muscle index, skeletal muscle area, and skeletal muscle index). RESULTS The prevalence of sarcopenia in our cohort ranged from 7.0% to 37.8%, depending on the score applied. Only sarcopenia as defined by the density indices PD and SMD (but not total psoas area, psoas muscle index, skeletal muscle area, or skeletal muscle index) revealed clinical relevance since it correlates significantly with postoperative complications (≥Grade III, Clavien-Dindo classification) and sepsis. Furthermore, sarcopenia predicted inferior patient and graft survival, with low muscle density (PD

The aim of our prospective clinical trial was to test a tissue staining technique (real-time confocal analysis [RTCA]) as a rapid assessment tool for donor kidney quality and function in human kidney transplantation.Tools for objective graft tissue viability assessment before kidney transplantation are lacking. RTCA has recently been established and tested in a pilot study using rodent kidneys.RTCA was performed in kidney biopsies stained with SYTO16/PI and WGA. A score between -3 (100% nonviable) and +3 (100% viable) describes the sum of viable cells divided by the number of nonviable cells per examined area (glomerulus, proximal, and distal tubules). The primary study endpoint was the delayed graft function (DGF).Seventy-one kidney transplant recipients were transplanted. The median recipient and donor age were 58.5 and 57 years, respectively. Cold ischemia time was 13.6 ± 4.7 hours; anastomosis time was 30.8 ± 8.7 minutes (mean ± SD). Overall, 23 (33.8%) patients developed DGF. The RTCA score was significantly lower in kidneys developing DGF -0.43 ± 1.78 versus no DGF 0.91 ± 2.17, P = 0.01. The Remuzzi score did not differ between DGF and no DGF, P = 0.13. Remuzzi score and RTCA score correlate inversely significantly; P = 0.004. In the multivariate analysis, solely RTCA score was revealed as a significant independent factor predicting DGF; P = 0.015, Wald = 5.95, odds ratio = 0.72, 95% confidence interval = 0.55 to 0.94.Our data demonstrate that RTCA is feasible and clinically meaningful. The RTCA score predicts DGF and is a valid option to be applied in renal transplantation.

Despite technical advances in surgical resection and postoperative management of the pancreas, surgical procedures of the pancreas are associated with a high rate of complications, resulting in a relevant morbidity and mortality. Early diagnosis and management of complications associated with pancreas surgery is mandatory, favoring a multidisciplinary approach. Interventional radiology offers minimal invasive techniques to manage post-surgical complications. These procedures are highlighted in this review, including percutaneous drainage of fluid collections, percutaneous transhepatic biliary interventions, arterial embolisation and fistula embolisation. Post-surgical complications of pancreatic surgery are effectively managed by radiological procedures, offering a feasible and safe treatment with low morbidity rates. Accurate patient selection is key to an effective management of clinical situations where these interventions represent the first line approach. Radiologic procedures allow for minimal invasive treatment of postoperative complications after pancreatic surgery, reducing the time of hospitalization and the time of recovery.

Graft vasculopathy is the main feature of chronic rejection in organ transplantation, with oxidative stress being a major trigger. Inflammation-associated prooxidant processes may be controlled by antioxidants; however, interference with redox-regulated mechanisms is a complex endeavor. An essential feature of the cellular immune response is the acceleration of tryptophan (Trp) breakdown, leading to the formation of several bioactive catabolites. Long-term activation of this immunobiochemical pathway contributes to the establishment of a tolerogenic environment, thereby supporting allograft survival. Herein, the impact of the antioxidant sodium sulfite on the development of graft vasculopathy was assessed in murine aortic transplantation. Allogeneic (BALB/c to C57BL/6) heterotopic murine aortic transplantations were performed. Animals were left untreated or were treated with 10 μl of 0.1 M, of 0.01 M sodium sulfite, or of 0.1 M sodium sulfate, intraperitoneally once/day, until postoperative day (POD) 100. Grafts were assessed by histology, immunohistochemistry, and adhesion molecule gene expression. Serum concentrations of tryptophan and its catabolite kynurenine (Kyn) were measured. On day 100, graft vasculopathy was significantly increased upon treatment with 0.1 M sodium sulfite, compared to allogeneic untreated controls (p=0.004), which correlated with a significant increase ofα-smooth-muscle-actin, Vcam-1, and P-selectin. Serum Kyn concentrations increased in the allogeneic control group over time (p<0.05,POD≥50), while low-dose sodium sulfite treatment (0.01 M) treatment resulted in a decrease in Kyn levels over time (p<0.05,POD≥10), compared to the respective baselines (p<0.05). Longitudinal analysis of serum metabolite concentrations in the different treatment groups further identified an overall effect of sodium sulfite on Kyn concentrations. Antioxidative treatment may result in ambivalent consequences. Our data reveal that an excess of antioxidants like sodium sulfite can aggravate allograft vasculopathy, which further highlights the challenges associated with interventions that interfere with the complex interplay of redox-regulated inflammatory processes.

Despite clear advances in decreasing postoperative mortality below 4% after pancreatic resections in experienced centres, specific morbidity according to standardized definitions still remains high. While some recent multicentre studies have reported on complications after pancreatic surgery in Austria, detailed outcome data from single high-volume centres over longer time-periods are scarce. This study provides an in-depth picture of patient characteristics, indications, morbidity and mortality after pancreatic surgery in an Austrian tertiary referral centre. All patients undergoing curative intent resection between 2010 and 2017 at the Medical University of Innsbruck were evaluated. Patient characteristics and procedural details, overall and specific complications including postoperative pancreatic fistula (POPF), delayed gastric emptying (DGE) and post-pancreatectomy haemorrhage (PPH) rates according to accepted definitions are reported. Outcomes after pancreatic head resections, distal pancreatectomy and other types of resections are compared. Factors associated with severe and overall morbidity are evaluated by logistic regression modelling. A total of 343 patients underwent pancreatic resection, at a median of 64 years (53% males). Most common indications were pancreatic or bile-duct carcinoma (52%), benign/precursor lesions (22%) and neuroendocrine tumours (11%). The 90-day mortality was 2%; 90-day overall/severe morbidity was 66.2%/22.4%. POPF grade B/C occurred in 19.3%, PPH in 17.5% and DGE in 14.3%. Male gender was associated with severe morbidity, body mass index and procedures other than distal resections with overall morbidity. POPF and PPH were major causes for relaparotomy. Pancreatic resections in our centre are performed with low mortality, although morbidity still represents a relevant clinical problem, especially POPF and PPH.

BACKGROUND Early biliary complications (EBC) constitute a burden after pediatric liver transplantation frequently requiring immediate therapy. We aimed to assess the impact of EBC on short- and long-term patient and graft survival as well as post-transplant morbidity. METHODS We analyzed 121 pediatric liver transplantations performed between 1984 and 2019 at the Medical University of Innsbruck for the occurrence of early (

High alpha-fetoprotein levels after liver transplantation in hepatoblastoma: Does it matter?Hetzer Benjamin, M.D.1, Oberhuber Rupert, M.D.2, Entenmann Andreas, M.D.1, Schneeberger Stefan, M.D.2, Crazzolara Roman, M.D.1,*1Department of Pediatrics I, Medical University of Innsbruck, Innsbruck, Austria2Department of Visceral, Transplant and Thoracic Surgery, Medical University of Innsbruck, Innsbruck, Austria*Correspondence to:Roman Crazzolara, M.D., Department of Pediatrics, Anichstrasse 35, 6020 Innsbruck, Austria; Tel.: 0043-512-504-23600; Fax: 0043-512-504-24934; Email: roman.crazzolara@i-med.ac.at

BACKGROUND In an experimental murine liver clamping model, we aimed to investigate the efficacy of real-time confocal microscopy (RCM) in assessing viability of steatotic livers in comparison to standard assessment tools, including histopathological evaluation. METHODS C57Bl/6 mice were subjected to a methionine-choline-deficient diet causing nonalcoholic fatty liver disease or to Lieber DeCarli diet causing ethanol-induced liver injury. Untreated animals served as controls. Liver biopsies were analyzed following challenge with 45 min of warm ischemia time and either 4 h of reperfusion or 24 h of cold storage. Organ quality assessment was performed at defined time points by RCM, histological staining, measurement of serum alanine aminotransferase activity, and expression analyses of proinflammatory cytokines. Additionally, survival analysis was performed. RESULTS Cold as well as warm ischemia time resulted in a significant decrease in cell viability when compared with naive livers as well as nonischemic-challenged steatotic livers (P

The coronavirus disease 2019 (COVID-19) pandemic has changed life on a global scale. The numbers of transplantations have plummeted as a result of fear of disease transmission, recipient coronavirus disease 2019 infection, priority shift, and resource limitations. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) complicates transplantation because donor testing, (re)allocation of limited resources, and recipient testing may exceed permissible ischemia times. Normothermic machine perfusion (NMP) helps safely prolong liver preservation up to 38 hours. Additional time is essential under the current circumstances. Here we present the case of a 29-year-old liver transplant recipient in whom prolonged liver preservation required for SARS-CoV-2 screening was accomplished through NMP. Donor and recipient test results for SARS-CoV-2 were negative, and intensive care unit capacity was eventually available. The surgical procedure and postoperative course were uneventful. NMP can extend preservation times in liver transplantation while awaiting SARS-CoV-2 test results and available intensive care unit capacity.

Hypothermic machine perfusion (HMP) has been introduced as an alternative to static cold storage (SCS) in kidney transplantation, but its true benefit in the clinical routine remains incompletely understood. The aim of this study was to assess the effect of HMP vs. SCS in kidney transplantation. All kidney transplants performed between 08/2015 and 12/2019 (n = 347) were propensity score (PS) matched for cold ischemia time (CIT), extended criteria donor (ECD), gender mismatch, cytomegalovirus (CMV) mismatch, re-transplantation and Eurotransplant (ET) senior program. A total of 103 HMP and 103 SCS instances fitted the matching criteria. Prior to PS matching, the CIT was longer in the HMP group (17.5 h vs. 13.3 h, p &lt, 0.001), while the delayed graft function (DGF) rates were 29.8% and 32.3% in HMP and SCS, respectively. In the PS matched groups, the DGF rate was 64.1% in SCS vs. 31.1% following HMP: equivalent to a 51.5% reduction of the DGF rate (OR 0.485, 95% CI 0.318&ndash, 0.740). DGF was associated with decreased 1- and 3-year graft survival (100% and 96.3% vs. 90.8% and 86.7%, p = 0.001 and p = 0.008) or a 4.1-fold increased risk of graft failure (HR = 4.108, 95% CI: 1.336&ndash, 12.631, p = 0.014). HMP significantly reduces DGF in kidney transplantation. DGF remains a strong predictor of graft survival.

Retrospective analysis of the long-term results of a randomized controlled trial comparing alemtuzumab (ALEM) and antithymocyte globulin (ATG) as induction therapy in simultaneous pancreas-kidney transplantation (SPK) to address individualized long-term immunosuppression. Between 2006 and 2010 a total of 30 SPKs were randomized to treatment with ALEM plus tacrolimus (TAC) monotherapy (Group A, n=14) versus ATG induction plus TAC, mycophenolate mofetil (MMF) and steroids (Group B, n=16), followed by individualized long-term immunosuppression. We here present the long-term results for graft survival, graft function, and major complications. The 9-year patient survival rates in Groups A and Group B were 92.9% and 86.7% respectively; pancreas graft survival was 75.0% and 65.0% respectively; renal graft survival was 83.1% and 93.8% respectively. Long-term graft function was excellent with a creatinine of 1.5 mg/dL and 1.4 mg/dL, fasting glycemia of 104 mg/dL and 102 mg/dL, hemoglobin (Hb) A1c of 5.4 g% and 5.6 g% in Group A and Group B, respectively. Major complications were comparable in both groups. Good long-term results for patient, pancreas graft and kidney graft survival were achieved in both groups with individually adapted maintenance immunosuppression. ALEM is a valid induction therapy.

While both living donation and donation after circulatory death provide alternative opportunities for organ transplantation, donation after donor brain death (BD) still represents the major source for solid transplants. Unfortunately, the irreversible loss of brain function is known to induce multiple pathophysiological changes, including hemodynamic as well as hormonal modifications, finally leading to a systemic inflammatory response. Models that allow a systematic investigation of these effects in vivo are scarce. We present a murine model of BD induction, which could aid investigations into the devastating effects of BD on allograft quality. After implementing intra-arterial blood pressure measurement via the common carotid artery and reliable ventilation via a tracheostomy, BD is induced by steadily increasing intracranial pressure using a balloon catheter. Four hours after BD induction, organs may be harvested for analysis or for further transplantation procedures. Our strategy enables the comprehensive analysis of donor BD in a murine model, therefore allowing an in-depth understanding of BD-related effects in solid organ transplantation and potentially paving the way to optimized organ preconditioning.

Primary focal segmental glomerulosclerosis (FSGS) recurs in up to 55% of patients after kidney transplantation. Herein we report the successful management of recurrent FSGS. A 5‐year‐old boy with primary FSGS received a deceased donor renal transplant. Immediate and fulminant recurrence of FSGS caused anuric graft failure that was resistant to plasmapheresis and rituximab. After exclusion of structural or immunologic damage to the kidney by repeated biopsies, the allograft was retrieved from the first recipient on day 27 and transplanted into a 52‐year‐old second recipient who had vascular nephropathy. Immediately after retransplantation, the allograft regained function with excellent graft function persistent now at 3 years after transplant. After 2 years on hemodialysis, the boy was listed for kidney retransplantation. To prevent FSGS recurrence, pretreatment with ofatumumab was performed. Nephrotic range proteinuria still occurred after the second transplantation, which responded, however, to daily plasma exchange in combination with ofatumumab. At 8 months after kidney retransplantation graft function is good. The clinical course supports the hypothesis of a circulating permeability factor in the pathogenesis of FSGS. Successful ofatumumab pretreatment implicates a key role of B cells. Herein we provide a description of successful management of kidney failure by FSGS, carefully avoiding waste of organs., Successful management of recurrent primary focal segmental glomerulosclerosis after kidney transplantation includes retransplantation of an allograft that failed in the first recipient due to disease recurrence into a second recipient and ofatumumab pretreatment before kidney retransplantation in the patient with fulminant recurrence of focal segmental glomerulosclerosis in the first graft.

Background: Heart failure (HF) survival has improved, and nowadays, many patients with HF die of noncardiac causes, including cancer. Our aim was to investigate whether a causal relationship exists between HF and the development of cancer. Methods: HF was induced by inflicting large anterior myocardial infarction in APC min mice, which are prone to developing precancerous intestinal tumors, and tumor growth was measured. In addition, to rule out hemodynamic impairment, a heterotopic heart transplantation model was used in which an infarcted or sham-operated heart was transplanted into a recipient mouse while the native heart was left in situ. After 6 weeks, tumor number, volume, and proliferation were quantified. Candidate secreted proteins were selected because they were previously associated both with (colon) tumor growth and with myocardial production in post–myocardial infarction proteomic studies. Myocardial gene expression levels of these selected candidates were analyzed, as well as their proliferative effects on HT-29 (colon cancer) cells. We validated these candidates by measuring them in plasma of healthy subjects and patients with HF. Finally, we associated the relation between cardiac specific and inflammatory biomarkers and new-onset cancer in a large, prospective general population cohort. Results: The presence of failing hearts, both native and heterotopically transplanted, resulted in significantly increased intestinal tumor load of 2.4-fold in APC min mice (all P P =0.002 and P =0.016, respectively). We identified several proteins (including serpinA3 and A1, fibronectin, ceruloplasmin, and paraoxonase 1) that were elevated in human patients with chronic HF (n=101) compared with healthy subjects (n=180; P Conclusions: We demonstrate that the presence of HF is associated with enhanced tumor growth and that this is independent of hemodynamic impairment and could be caused by cardiac excreted factors. A diagnosis of HF may therefore be considered a risk factor for incident cancer.

Summary Background Owing to remarkable improvements of surgical techniques and associated specialities, liver surgery has become the standard of care for hepatocellular carcinoma and cholangiocarcinoma. Although applied with much greater safety, hepatic resections for primary liver tumours remain challenging and need to be integrated in a complex multidisciplinary treatment approach. Methods This literature review gives an update on the recent developments regarding basics of open and laparoscopic liver surgery and surgical strategies for primary liver tumours. Results Single-centre reports and multicentre registries mainly from Asia and Europe dominate the surgical literature on primary liver tumours, but the numbers of randomized trials are slowly increasing. Perioperative outcomes of open liver surgery for hepatocellular and cholangiocellular carcinoma have vastly improved over the last decades, accompanied by some progress in terms of oncological outcome. The laparoscopic approach is increasingly being applied in many centres, even for patients with underlying liver disease, and may result in decreased morbidity. Liver transplantation represents a cornerstone in the treatment of early hepatocellular carcinoma and is indispensable to achieve long-term survival. In contrast, resection remains the gold standard for cholangiocarcinoma in most countries, but interventional techniques are on the rise. Conclusion Liver surgery for primary tumours is complex, with a need for high expertise in a multidisciplinary team to achieve acceptable outcomes. Technical developments and clinical stratification tools have optimized individual care, but further improvements in oncological survival will likely require enhanced pre- and postoperative systemic and local treatment options.

Mitochondria sense changes resulting from the ischemia and subsequent reperfusion of an organ and mitochondrial reactive oxygen species (ROS) production initiates a series of events, which over time result in the development of full-fledged ischemia-reperfusion injury (IRI), severely affecting graft function and survival after transplantation. ROS activate the innate immune system, regulate cell death, impair mitochondrial and cellular performance and hence organ function. Arresting the development of IRI before the onset of ROS production is currently not feasible and clinicians are faced with limiting the consequences. Ex vivo machine perfusion has opened the possibility to ameliorate or antagonize the development of IRI and may be particularly beneficial for extended criteria donor organs. The molecular events occurring during machine perfusion remain incompletely understood. Accumulation of succinate and depletion of adenosine triphosphate (ATP) have been considered key mechanisms in the initiation; however, a plethora of molecular events contribute to the final tissue damage. Here we discuss how understanding mitochondrial dysfunction linked to IRI may help to develop novel strategies for the prevention of ROS-initiated damage in the evolving era of machine perfusion.