Indocyanine green fluorescence quantification during normothermic ex situ perfusion for the assessment of porcine liver grafts after circulatory death.

Current graft evaluation during normothermic ex situ liver perfusion lacks real-time parameters for predicting posttransplant hepatocyte and biliary function. Indocyanine green (ICG) imaging has been widely used in liver surgery, enabling the visualization of hepatic uptake and excretion through bile using near-infrared light. In this research, porcine livers under various ischemic conditions were examined during a 5-hour normothermic ex situ liver perfusion procedure, introducing ICG at 1 hour through the hepatic artery. These conditions included livers from heart-beating donors, donation after circulatory death (DCD) with warm ischemic durations of 60 minutes (DCD60) and 120 minutes (DCD120), as well as interventions utilizing tissue plasminogen activator in DCD120 cases (each n = 5). Distinct hepatic fluorescence patterns correlated with different degrees of ischemic injury ( p = 0.01). Low ICG uptake in the parenchyma (less than 40% of maximum intensity) was more prevalent in DCD120 (21.4%) compared to heart-beating donors (6.2%, p = 0.06) and DCD60 (3.0%, p = 0.02). Moreover, ICG clearance from 60 minutes to 240 minutes was significantly higher in heart-beating donors (69.3%) than in DCD60 (17.5%, p < 0.001) and DCD120 (32.1%, p = 0.01). Furthermore, thrombolytic intervention using tissue plasminogen activator in DCD120 resulted in noteworthy outcomes, including significantly reduced ALP levels ( p = 0.04) and improved ICG clearance ( p = 0.02) with a trend toward mitigating fibrin deposition similar to DCD60, as well as enhancements in bile production ( p = 0.09). In conclusion, ICG fluorescence imaging during normothermic ex situ liver perfusion provides real-time classification of hepatic vascular and biliary injuries, offering valuable insights for the more accurate selection and postintervention evaluation of marginal livers in transplantation.

Intraoperative hemodialysis with supra- and infradiaphragmatic catheters for liver transplantation.

PURPOSE: The benefits of intraoperative dialysis during orthotopic liver transplantation remain controversial. In patients with anuric renal failure and portopulmonary hypertension, maintaining venous return during caval clamping and unclamping along with minimizing fluid overload is critical to avoiding right ventricular strain and failure. CLINICAL FEATURES: We present the case of a 54-yr-old female who underwent orthotopic liver transplantation for alcohol-related liver disease with acute decompensation including severe hepatorenal syndrome (anuric requiring dialysis), probable hepatopulmonary syndrome, moderate pulmonary hypertension (right ventricular systolic pressure, 44 mm Hg), hepatic encephalopathy (grade 2), and esophageal varices. Prior to incision, pulmonary arterial pressures were 48/28 (mean, 35) mm Hg with a central venous pressure of 30 mm Hg, cardiac output of 7.4 L·min-1, and pulmonary vascular resistance of 98 dynes·sec·cm-5. In the context of right ventricular strain and volume overload observed on transthoracic echocardiography, we inserted an additional dialysis catheter into the right femoral vein. We initiated dialysis using the two catheters as a circuit (femoral line to the dialysis machine; blood was reinjected via the subclavian line) acting as a limited venovenous bypass, allowing right ventricular offloading and hemodialysis throughout the case. We removed 4.5 L via hemodialysis during the surgery, while avoiding acidosis, hyperkalemia, and sodium shifts. The patient tolerated reperfusion adequately despite pre-existing right ventricular dilation and dysfunction. CONCLUSION: We report on the use two hemodialysis catheters in a patient undergoing orthotopic liver transplantation as a circuit for simultaneous anuric hepatorenal syndrome and moderate pulmonary hypertension with right ventricular dilation and dysfunction. We believe this technique was instrumental in the patient's successful transplant.

RéSUMé: OBJECTIF: Les avantages de la dialyse peropératoire pendant une transplantation hépatique orthotopique demeurent controversés. Chez la patientèle atteinte d'insuffisance rénale anurique et d'hypertension portopulmonaire, il est essentiel de maintenir le retour veineux pendant le clampage et le déclampage de la veine cave ainsi que de minimiser la surcharge hydrique, afin d'éviter la déformation et l'insuffisance ventriculaires droites. CARACTéRISTIQUES CLINIQUES : Nous présentons le cas d'une femme de 54 ans qui a bénéficié d'une transplantation hépatique orthotopique pour une maladie hépatique liée à l'alcool avec une décompensation aiguë comprenant un syndrome hépatorénal sévère (anurie nécessitant une dialyse), un syndrome hépatopulmonaire probable, une hypertension pulmonaire modérée (pression systolique ventriculaire droite, 44 mm Hg), une encéphalopathie hépatique (grade 2) et des varices œsophagiennes. Avant l'incision, les pressions artérielles pulmonaires étaient de 48/28 (moyenne, 35) mm Hg avec une pression veineuse centrale de 30 mm Hg, un débit cardiaque de 7,4 L·min−1 et une résistance vasculaire pulmonaire de 98 dynes·sec·cm−5. Dans le contexte de la déformation ventriculaire et de la surcharge volémique droites observées à l'échocardiographie transthoracique, nous avons inséré un cathéter de dialyse supplémentaire dans la veine fémorale droite. Nous avons amorcé la dialyse en créant un circuit avec les deux cathéters (ligne fémorale en direction de l'appareil de dialyse; sang réinjecté via la ligne sous-clavière) agissant comme un pontage veino-veineux limité, permettant la décharge du ventricule droit et l'hémodialyse tout au long du cas. Nous avons retiré 4,5 L par hémodialyse pendant la chirurgie, tout en évitant l'acidose, l'hyperkaliémie et les changements en sodium plasmatique. La patiente a toléré la reperfusion de manière adéquate malgré la dilatation et le dysfonctionnement préexistants du ventricule droit. CONCLUSION: Nous rapportons l'utilisation de deux cathéters d'hémodialyse pour créer un circuit chez une patiente bénéficiant d'une transplantation hépatique orthotopique pour le traitement d'un syndrome hépatorénal anurique simultané à une hypertension pulmonaire modérée avec dilatation et dysfonctionnement du ventricule droit. Nous pensons que cette technique a joué un rôle déterminant dans la réussite de la greffe chez la patiente.

Normothermic ex situ pancreas perfusion for the preservation of porcine pancreas grafts.

Pancreas transplantation improves and extends the life of patients with insulin-dependent diabetes. Pancreata from extended criteria donors have been increasingly used due to the scarcity of available grafts. Normothermic ex situ pancreas perfusion (NESPP) can keep grafts metabolically active, potentially allowing for assessment and organ repair, and could improve outcomes of marginal grafts. A novel NESPP technique was developed and tested. Porcine pancreata were removed after a short period of warm ischemia and subjected to 6 h of NESPP. Perfusion parameters, potential graft assessment markers and graft injury were measured. Next, pancreata subjected to 3 h of NESPP were transplanted and animals were followed for up to 3 days. Graft function and injury post-transplantation were evaluated. Using this novel system of perfusion, pancreata were perfused for an extended period of time with minimal edema. Histology at the end of perfusion showed intact islet cells with only mild signs of tissue injury. NESPP transplanted grafts showed immediate function after transplantation, with glucose levels in normal range. NESPP maintains a physiologic environment and excellent graft function without causing significant graft injury. Porcine pancreas transplantation is feasible and allows for in vivo graft assessment of pancreas function and injury after NESPP.

Superior Long-Term Outcomes of Adult Living Donor Liver Transplantation: A Cumulative Single-Center Cohort Study With 20 Years of Follow-Up.

Living donor liver transplantation (LDLT) is an attractive alternative to deceased donor liver transplantation (DDLT). Although both modalities have similar short-term outcomes, long-term outcomes are not well studied. We compared the 20-year outcomes of 668 adults who received LDLT with1596 DDLTs at the largest liver transplantation (LT) program in Canada. Recipients of LDLT were significantly younger and more often male than DDLT recipients (P < 0.001). Autoimmune diseases were more frequent in LDLT, whereas viral hepatitis and alcohol-related liver disease were more frequent in DDLT. LDLT recipients had lower Model for End-Stage Liver Disease scores (P = 0.008), spent less time on the waiting list (P < 0.001), and were less often inpatients at the time of LT (P < 0.001). In a nonadjusted analysis, 1-year, 10-year, and 20-year patient survival rates were significantly higher in LDLT (93%, 74%, and 56%, respectively) versus DDLT (91%, 67%, and 46%, respectively; log-rank P = 0.02) as were graft survival rates LDLT (91%, 67%, and 50%, respectively) versus (90%, 65%, and 44.3%, respectively, for DDLT; log-rank P = 0.31). After multivariable adjustment, LDLT and DDLT were associated with a similar hazard of patient and graft survival. Our data of 20 years of follow-up of LDLT from a single, large Western center demonstrates excellent long-term outcomes for recipients of LDLT.

The feasibility of endoscopic submucosal dissection for colorectal lesions larger than 10 cm.

BACKGROUND: Although endoscopic submucosal dissection (ESD) enables en bloc removal of colorectal neoplasms, its effectiveness for larger lesions (≥ 10 cm in diameter) is undetermined. We aimed to investigate the feasibility and safety of ESD for colorectal lesions ≥ 10 cm wide. METHODS: This retrospective study included 3591 consecutive colorectal lesions managed with ESD from June 2012 through December 2020. Clinicopathological characteristics and treatment outcomes were compared between lesions ≥ 10 cm wide and lesions 5-10 cm wide. RESULTS: There were 50 patients in the ≥ 10 cm group and 270 patients in the 5-10 cm group. Among patients in the ≥ 10 cm group, lesions were most often in the rectum (50.0%), and the laterally spreading tumor-granular nodular mixed type (LST-G-M) was most prevalent (41/50, 82%). Although patients in the ≥ 10 cm group a longer mean ESD procedure time (186.0 vs. 94.4 min, p < 0.001), the dissection speed was significantly higher in this group (0.50 vs. 0.41 cm2/min, p = 0.003). The en bloc and curative resection rates were comparable between the ≥ 10 cm and 5-10 cm groups (100% vs. 99.6% and 86.0% vs. 88.5%, respectively). Although the stenosis rate was higher in the ≥ 10 cm group (4% vs. 0%), the delayed bleeding and perforation rates were similar between the two groups. CONCLUSIONS: ESD for colorectal lesions ≥ 10 cm wide is feasible and curative, even though it is associated with higher technical difficulty and longer procedure times compared with ESD for smaller lesions (Number: UMIN 000044313).

Endoscopic submucosal dissection of large pedunculated polyps with wide stalks: a retrospective multicenter study.

BACKGROUND: Endoscopic resection of large pedunculated colorectal polyps is technically difficult, especially when the polyp is large and has such a thick stalk that it is either too difficult or impossible to resect prophylactically by a conventional snare. Here, we evaluated the feasibility of ESD for large pedunculated polyps with wide stalks. METHODS: 29 patients with large pedunculated polyps that were not resectable by polypectomy or endoscopic mucosal resection were enrolled in the study. RESULTS: En bloc resection was achieved in 28/29 polyps. One suspended case was due to severe fibrosis with muscle retraction signs. The mean diameter of the 29 polyp heads was 39.7 (standard deviation 6.9) mm. Submucosal fibrosis was present in 16 polyps (9 mild; 7 severe). The stalks of severely fibrotic polyps were significantly thicker than those of polyps with no or mild fibrosis. The curative resection rate was 85.7 % without severe complications. CONCLUSIONS: ESD is feasible for the removal of large pedunculated polyps with wide stalks when conventional snare resection is difficult or impossible.

Impact of obesity in colorectal endoscopic submucosal dissection: single-center retrospective cohort study.

BACKGROUND: When performing colorectal endoscopic submucosal dissection (ESD) in obese patients, technically difficult cases are sometimes experienced because of difficulty with the insertion of the colonoscope, poor scope maneuverability, or an abundance of fat tissue in the submucosal layer. Since the association between obesity and colorectal ESD has not been investigated, we evaluated the clinical impact of obesity in patients who underwent colorectal ESD. METHODS: We retrospectively reviewed 535 patients who underwent colorectal ESD between April 2012 and February 2019. Patients were divided into three groups based on their body mass index (BMI): a control group (BMI < 25 kg/m2), an overweight group (25 kg/m2 ≤ BMI < 30 kg/m2), and an obese group (BMI ≥ 30 kg/m2), and the short-term clinical outcomes were analyzed to assess the safety and difficulty of colorectal ESD. RESULTS: No significant difference in the procedure times, en bloc resection rates, pathological diagnoses, or complications were seen among the groups. While the amount of sedative per body weight was significantly lower in the group with a higher BMI (flunitrazepam: 1.75 × 10-2 [1.27 × 10-2-2.34 × 10-2] mg/kg vs. 1.48 × 10-2 [1.08 × 10-2-2.03 × 10-2] mg/kg vs. 1.16 × 10-2 [0.98 × 10-2-1.54 × 10-2] mg/kg, P < 0.001; pethidine: 0.63 [0.55-0.72] mg/kg vs. 0.50 [0.46-0.56] mg/kg vs. 0.39 [0.32-0.45] mg/kg, P < 0.001), a reduction in percutaneous arterial oxygen saturation occurred significantly more frequently in the group with a higher BMI (123 [30.2%] vs. 43 [43.9%] vs. 10 [55.6%], P = 0.005). When the procedures were performed by trainees, the number of cases that required a procedure time of longer than 90 min was significantly larger in the group with a higher BMI (27 [10.8%] vs. 14 [21.9%] vs. 3 [25.0%], P = 0.033). CONCLUSIONS: This study showed that colorectal ESD could be performed safely and effectively in obese patients. However, ESD in obese patients requires attention, particularly to changes in respiratory conditions.

Predictive Factors of Mild and Severe Fibrosis in Colorectal Endoscopic Submucosal Dissection.

BACKGROUND AND STUDY AIMS: Varying degrees of fibrosis in colorectal endoscopic submucosal dissection (ESD) make the procedure difficult. Consensus on the predictive factors of fibrosis degree (mild or severe) has not been established. We conducted a study to identify the predictive factors and to examine the feasibility of ESD for fibrotic lesions. PATIENTS AND METHODS: We included 518 patients who had undergone ESD for 558 lesions from April 2012-September 2018. Patients were classified into fibrosis or no-fibrosis groups, and logistic regression analysis was performed to identify predictive factors of fibrosis. Subgroup analyses were performed for fibrosis degree. RESULTS: The total incidence of fibrosis was 21.1% (mild: 14.1%; severe: 7.1%). Although the curative resection rate (free margin: invasion depth less than 1000 µm: no lymphatic invasion, vascular involvement) was lower in the fibrosis group compared with the control (80.7% vs. 97.6%), neither the en bloc resection rate (99.1% vs. 100%) nor incidence of perforation (0.9% vs. 0.2%) differed between the two groups. Multivariate analysis revealed that a cecal location, preoperative biopsy, straddling fold, laterally spreading tumor-non-granular-pseudo-depressed (LST-NG-PD) type were predictive of mild fibrosis. The presence of a straddling fold and a protruded lesion were independent predictive factors of severe fibrosis. CONCLUSIONS: We identified the predictive factors of mild and severe fibrosis. It is preferable that a more experienced physician performs ESD for the lesions with F2 fibrosis.

Clinical characteristic of esophageal cancer without lugol-voiding lesions in the background esophagus.

Lugol chromoendoscopy is useful for the detection of early esophageal squamous cell cancer (ESCC). Multiple lugol-voiding lesions (LVLs) on lugol chromoendoscopy are associated with a very high risk of multiple cancers arising in the esophagus. Due to the widespread use of narrow band image technology in many institutions, esophageal cancer without LVLs in the background esophagus is sometimes detected. This retrospective study aims to clarify the clinical characteristic of esophageal cancer without LVLs in the background esophagus. A total of 191 consecutive patients with 204 ESCCs had undergone endoscopic submucosal dissection (ESD) from 2011 and 2014. Amongst these lesions, the number of LVLs in the background esophagus per endoscopic view was counted excluding main lesion, and the grading was divided into no LVLs ESCC (nL-ESCC) group and LVLs ESCC (L-ESCC) group. This study evaluated the clinical characteristics and the cumulative incidence of metachronous ESCC after ESD in both groups. Thirty-six patients with 36 lesions and 155 patients with 168 lesions were separated into the nL-ESCC group and L-ESCC group, respectively. On multivariate analysis, the nL-ESCC group was found to be more common in females, who were non-drinkers, or with erosive esophagitis. During follow-up periods, the cumulative incidence of metachronous ESCC at 3-years was 14.4% and 0.00% in the L-ESCC and nL-ESCC groups, respectively (P < 0.01). Our study showed that esophageal cancer without LVLs in the background esophagus was mostly occurred in females, who were non-drinkers, or with erosive esophagitis, which are uncommon features of ESCC.

Predictor parameters of liver viability during porcine normothermic ex situ liver perfusion in a model of liver transplantation with marginal grafts.

Normothermic ex situ liver perfusion (NEsLP) offers the opportunity to assess biomarkers of graft function and injury. We investigated NEsLP parameters (biomarkers and markers) for the assessment of liver viability in a porcine transplantation model. Grafts from heart-beating donors (HBD), and from donors with 30 minutes (donation after cardiac death [DCD]30'), 70 minutes (DCD70'), and 120 minutes (DCD120') of warm ischemia were studied. The HBD, DCD30', and DCD70'-groups had 100% survival. In contrast, 70% developed primary nonfunction (PNF) and died in the DCD120'-group. Hepatocellular function during NEsLP showed low lactate (≤1.1 mmol/L) in all the groups except the DCD120'-group (>2 mmol/L) at 4 hours of perfusion (P = .04). The fold-urea increase was significantly lower in the DCD120'-group (≤0.4) compared to the other groups (≥0.65) (P = .01). As for cholangiocyte function, bile/perfusate glucose ratio was significantly lower (<0.6) in all the groups except the DCD120'-group (≥0.9) after 3 hours of perfusion (<0.01). Bile/perfusate Na+ ratio was significantly higher (≥1.2) after 3 hours of perfusion in all the groups except for the DCD120'-group (≤1) (P < .01). Three hours after transplantation, the DCD120'-group had a significantly higher international normalized ratio (>5) compared to the rest of the groups (≤1.9) (P = .02). Rocuronium levels were higher at all the time-points in the animals that developed PNF during NEsLP and after transplantation. This study demonstrates that biomarkers and markers of hepatocellular and cholangiocyte function during NEsLP correlate with the degree of ischemic injury and posttransplant function.

Delayed Bleeding After Colorectal Endoscopic Submucosal Dissection: When Is Emergency Colonoscopy Needed?

BACKGROUND: Endoscopic submucosal dissection (ESD) is an effective treatment for early-colorectal cancer. Although delayed bleeding is a serious potential complication, there is no consensus on the optimal protocol to determine which cases require emergency colonoscopy. AIMS: This study aimed to assess the risk factors for delayed bleeding after ESD and evaluate the "watch and wait" strategy for delayed bleeding. The "watch and wait" strategy was used for delayed bleeding, unless the shock index was ≥ 1 and/or a moderate amount of hematochezia occurred more than five occurrences. METHODS: This study included 404 patients who had undergone endoscopic resection for 439 lesions between April 2012 and February 2018. Patients were classified into the bleeding group or the no-bleeding group to investigate the risk factors for delayed bleeding, and to assess the necessity of emergency colonoscopy. RESULTS: Twenty-seven patients into the bleeding group and 412 into the no-bleeding group were classified. However, no case required emergency colonoscopy for hemostasis under "watch and wait strategy." Multivariate analysis revealed the risk factors for bleeding were rectal lesion (OR 5.547, 95% CI 1.456-21.130; P = 0.012) and lesion size ≥ 40 mm (OR 3.967, 95% CI 1.003-15.696; P = 0.05). CONCLUSIONS: Risk factors for delayed bleeding are rectal lesions and lesion size ≥ 40 mm. This watch and wait strategy resulted in no requirements for emergency colonoscopy or blood transfusion, and no serious conditions caused by delayed bleeding.

Hydrogen Flush After Cold Storage as a New End-Ischemic Ex Vivo Treatment for Liver Grafts Against Ischemia/Reperfusion Injury.

Cold storage (CS) remains the gold standard for organ preservation worldwide, although it is inevitably associated with ischemia/reperfusion injury (IRI). Molecular hydrogen (H2 ) is well known to have antioxidative properties. However, its unfavorable features, ie, inflammability, low solubility, and high tissue/substance permeability, have hampered its clinical application. To overcome such obstacles, we developed a novel reconditioning method for donor organs named hydrogen flush after cold storage (HyFACS), which is just an end-ischemic H2 flush directly to donor organs ex vivo, and, herein, we report its therapeutic impact against hepatic IRI. Whole liver grafts were retrieved from Wistar rats. After 24-hour CS in UW solution, livers were cold-flushed with H2 solution (1.0 ppm) via the portal vein (PV), the hepatic artery (HA), or both (PV + HA). Functional integrity and morphological damages were then evaluated by 2-hour oxygenated reperfusion at 37°C. HyFACS significantly lowered portal venous pressure, transaminase, and high mobility group box protein 1 release compared with vehicle-treated controls (P < 0.01). Hyaluronic acid clearance was significantly higher in the HyFACS-PV and -PV + HA groups when compared with the others (P < 0.01), demonstrating the efficacy of the PV route to maintain the sinusoidal endothelia. In contrast, bile production and lactate dehydrogenase leakage therein were both significantly improved in HyFACS-HA and -PV + HA (P < 0.01), representing the superiority of the arterial route to attenuate biliary damage. Electron microscopy consistently revealed that sinusoidal ultrastructures were well maintained by portal HyFACS, while microvilli in bile canaliculi were well preserved by arterial flush. As an underlying mechanism, HyFACS significantly lowered oxidative damages, thus improving the glutathione/glutathione disulfide ratio in liver tissue. In conclusion, HyFACS significantly protected liver grafts from IRI by ameliorating oxidative damage upon reperfusion in the characteristic manner with its route of administration. Given its safety, simplicity, and cost-effectiveness, end-ischemic HyFACS may be a novel pretransplant conditioning for cold-stored donor organs.

A case of neuroendocrine carcinoma in the hepatic hilar lymph nodes concomitant with an adenocarcinoma of the gallbladder.

BACKGROUND: Neuroendocrine tumors (NETs) are rare especially in the gallbladder. They have not been elucidated in the pathogenesis, clinicopathological characteristics, and treatment options. CASE PRESENTATION: We present a 76-year-old woman with a gallbladder tumor and hepatic hilar lymph node swelling. The lymph node biopsy demonstrated neuroendocrine carcinoma (NEC). We performed cholecystectomy, hepatic hilar lymphadenectomy, extrahepatic biliary duct resection, and hepaticojejunostomy prior to chemotherapy. Pathological examination revealed the gallbladder mass was an adenocarcinoma invading to the muscular layer without any NEC components, whereas the hepatic hilar lymph nodes were filled with high-grade NEC cells with negligible area of adenocarcinoma. The patient received general chemotherapy consisting of carboplatin and etoposide, but a recurrence in the para-aortic lymph nodes occurred 4 months after surgery. CONCLUSIONS: We report a rare case of NEC of the hepatic hilar lymph nodes that were concomitant with an adenocarcinoma of the gallbladder. High-grade NEC generally has an aggressive behavior and an optimal treatment strategy should be chosen for each patient.

[Hepatic resection for local recurrence after radiofrequency ablation therapy for colorectal liver metastases].

Patients who underwent hepatic resection of locally recurrent tumors after radiofrequency ablation(RFA)for colorectal liver metastases (CRLM) were retrospectively investigated. Among 12 patients who underwent RFA as first-line treatment for CRLM, 7 experienced local recurrence, 5 of whom (6 nodules) underwent hepatic resection. The mean diameter (range) of the tumors was 9.5(5-16) mm, and they were located at S2, S7 (adjacent to the right hepatic vein), S5/6 (between the root of the anterior and the posterior Glisson's pedicle), S1r (right paracaval portion), S6, and S3. No local recurrence was observed after hepatic resection. In conclusion, hepatic resection must be the initial therapeutic strategy for CRLM, and the indication for RFA must be considered carefully.

Long-Term Outcomes of Recipients of Liver Transplants from Living Donors Treated with a Very Low-Calorie Diet.

The increasing prevalence of steatotic liver disease (SLD) in potential living donors is concerning, as it limits donor's availability amid rising demand. OPTIFAST very low-calorie diet (VLCD), a meal replacement product, effectively reduces weight and hepatic steatosis before transplantation. However, data on the outcomes of recipients of VLCD-treated donors are lacking. We conducted a single-center, retrospective study on 199 living donor liver transplant recipients at Toronto General Hospital, Canada, between January 2015 and January 2020. We compared the 1-year posttransplant outcomes between recipients who received organs from donors treated with VLCD (N = 34) for either weight loss or steatosis reduction, with those who did not require treatment (N = 165). Our analysis revealed no statistically significant differences in the rates of postoperative complications (23% vs 32.4%, p=0.3) or intensive care unit stays (70.9% vs 70.6%, p=1) between recipients of non-VLCD and VLCD grafts. Following adjusted multivariate logistic regression, receipt of VLCD grafts was not associated with increased hospital length of stay. In addition, one-year mortality did not differ between the two groups (4.2% non-VLCD recipients vs 2.9% VLCD recipients, p=0.6). OPTIFAST VLCD treatment for liver donors demonstrates positive and safe outcomes in recipients, expanding the pool of potential living donors for increased organ availability.

Combining Oxygenated Cold Perfusion With Normothermic Ex Vivo Perfusion Improves the Outcome of Donation After Circulatory Death Porcine Kidney Transplantation.

BACKGROUND: Ex vivo machine perfusion is a novel preservation technique for storing and assessing marginal kidney grafts. All ex vivo perfusion techniques have advantages and shortcomings. The current study analyzed whether a combination of oxygenated hypothermic machine perfusion (oxHMP) followed by a short period of normothermic ex vivo kidney perfusion (NEVKP) could combine the advantages of both techniques. METHODS: Porcine kidneys were exposed to 30 min of warm ischemia followed by perfusion. Kidneys underwent either 16-h NEVKP or 16-h oxHMP. The third group was exposed to 16-h oxHMP followed by 3-h NEVKP (oxHMP + NEVKP group). After contralateral nephrectomy, grafts were autotransplanted and animals were followed up for 8 d. RESULTS: All animals survived the follow-up period. Grafts preserved by continuous NEVKP showed improved function with lower peak serum creatinine and more rapid recovery compared with the other 2 groups. Urine neutrophil gelatinase-associated lipocalin, a marker of kidney injury, was found to be significantly lowered on postoperative day 3 in the oxHMP + NEVKP group compared with the other 2 groups. CONCLUSIONS: A short period of NEVKP after oxHMP provides comparable short-term outcomes to prolonged NEVKP and is superior to oxHMP alone. A combination of oxHMP with end-ischemic NEVKP could be an attractive, practical strategy to combine the advantages of both preservation techniques.

Normothermic ex vivo kidney perfusion preserves mitochondrial and graft function after warm ischemia and is further enhanced by AP39.

We previously reported that normothermic ex vivo kidney  perfusion (NEVKP) is superior in terms of organ protection compared to static cold storage (SCS), which is still the standard method of organ preservation, but the mechanisms are incompletely understood. We used a large animal kidney autotransplant model to evaluate mitochondrial function during organ preservation and after kidney transplantation, utilizing live cells extracted from fresh kidney tissue. Male porcine kidneys stored under normothermic perfusion showed preserved mitochondrial function and higher ATP levels compared to kidneys stored at 4 °C (SCS). Mitochondrial respiration and ATP levels were further enhanced when AP39, a mitochondria-targeted hydrogen sulfide donor, was administered during warm perfusion. Correspondingly, the combination of NEVKP and AP39 was associated with decreased oxidative stress and inflammation, and with improved graft function after transplantation. In conclusion, our findings suggest that the organ-protective effects of normothermic perfusion are mediated by maintenance of mitochondrial function and enhanced by AP39 administration. Activation of mitochondrial function through the combination of AP39 and normothermic perfusion could represent a new therapeutic strategy for long-term renal preservation.