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.

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 for Human Kidney Transplantation: First North American Results.

BACKGROUND: Normothermic ex vivo kidney perfusion (NEVKP) has shown promising results for preservation, assessment, and reconditioning of kidney allografts in preclinical studies. Here, we report the first North American safety and feasibility study of deceased donor kidneys grafts transplanted following preservation with NEVKP. METHODS: Outcomes of 13 human kidney grafts that received 1 to 3 h of NEVKP after being transported in an anoxic hypothermic machine perfusion device were compared with a matched control group of 26 grafts that were preserved with anoxic hypothermic machine perfusion alone. RESULTS: Grafts were perfused for a median of 171 min (range, 44-275 min). The delayed graft function rate in NEVKP versus control patients was 30.8% versus 46.2% ( P = 0.51). During the 1-y follow-up, no differences in postoperative graft function, measured by serum creatinine, necessity for dialysis, and urine production, were found between the study group and the control group. There were no differences in 1 y posttransplantation graft or patient survival between the 2 groups. CONCLUSIONS: Our study demonstrates the safety and feasibility of NEVKP for human deceased donor kidney transplantation. Further studies are warranted to explore how this technology can minimize cold ischemia, improve posttransplant graft function, and assess and repair expanded criteria kidney grafts.

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.

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).

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.

Prolonged warm ischemia time leads to severe renal dysfunction of donation-after-cardiac death kidney grafts.

Kidney transplantation with grafts procured after donation-after-cardiac death (DCD) has led to an increase in incidence of delayed graft function (DGF). It is thought that the warm ischemic (WI) insult encountered during DCD procurement is the cause of this finding, although few studies have been designed to definitely demonstrate this causation in a transplantation setting. Here, we use a large animal renal transplantation model to study the effects of prolonged WI during procurement on post-transplantation renal function. Kidneys from 30 kg-Yorkshire pigs were procured following increasing WI times of 0 min (Heart-Beating Donor), 30 min, 60 min, 90 min, and 120 min (n = 3-6 per group) to mimic DCD. Following 8 h of static cold storage and autotransplantation, animals were followed for 7-days. Significant renal dysfunction (SRD), resembling clinical DGF, was defined as the development of oliguria < 500 mL in 24 h from POD3-4 along with POD4 serum potassium > 6.0 mmol/L. Increasing WI times resulted in incremental elevation of post-operative serum creatinine that peaked later. DCD120min grafts had the highest and latest elevation of serum creatinine compared to all groups (POD5: 19.0 ± 1.1 mg/dL, p < 0.05). All surviving animals in this group had POD4 24 h urine output < 500 cc (mean 235 ± 172 mL) and elevated serum potassium (7.2 ± 1.1 mmol/L). Only animals in the DCD120min group fulfilled our criteria of SRD (p = 0.003), and their renal function improved by POD7 with 24 h urine output > 500 mL and POD7 serum potassium < 6.0 mmol/L distinguishing this state from primary non-function. In a transplantation survival model, this work demonstrates that prolonging WI time similar to that which occurs in DCD conditions contributes to the development of SRD that resembles clinical DGF.

Prolonged Normothermic Ex Vivo Kidney Perfusion Is Superior to Cold Nonoxygenated and Oxygenated Machine Perfusion for the Preservation of DCD Porcine Kidney Grafts.

The increased usage of marginal grafts has triggered interest in perfused kidney preservation to minimize graft injury. We used a donation after circulatory death (DCD) porcine kidney autotransplantation model to compare 3 of the most frequently used ex vivo kidney perfusion techniques: nonoxygenated hypothermic machine perfusion (non-oxHMP), oxygenated hypothermic machine perfusion (oxHMP), and normothermic ex vivo kidney perfusion (NEVKP). METHODS: Following 30 min of warm ischemia, grafts were retrieved and preserved with either 16 h of non-oxHMP, oxHMP, or NEVKP (n = 5 per group). After contralateral nephrectomy, grafts were autotransplanted and animals were followed for 8 d. Kidney function and injury markers were compared between groups. RESULTS: NEVKP demonstrated a significant reduction in preservation injury compared with either cold preservation method. Grafts preserved by NEVKP showed superior function with lower peak serum creatinine (NEVKP versus non-oxHMP versus oxHMP: 3.66 ± 1.33 mg/dL, 8.82 ± 3.17 mg/dL, and 9.02 ± 5.5 mg/dL) and more rapid recovery. The NEVKP group demonstrated significantly increased creatinine clearance on postoperative day 3 compared with the cold perfused groups. Tubular injury scores on postoperative day 8 were similar in all groups. CONCLUSIONS: Addition of oxygen during HMP did not reduce preservation injury of DCD kidney grafts. Grafts preserved with prolonged NEVKP demonstrated superior initial graft function compared with grafts preserved with non-oxHMP or oxHMP in a model of pig DCD kidney transplantation.

Transcriptome Analysis of Kidney Grafts Subjected to Normothermic Ex Vivo Perfusion Demonstrates an Enrichment of Mitochondrial Metabolism Genes.

Normothermic ex vivo kidney perfusion (NEVKP) has demonstrated superior outcomes for donation-after-cardiovascular death grafts compared with static cold storage (SCS). To determine the mechanisms responsible for this, we performed an unbiased genome-wide microarray analysis. METHODS: Kidneys from 30-kg Yorkshire pigs were subjected to 30 min of warm ischemia followed by 8 h of NEVKP or SCS, or no storage, before autotransplantation. mRNA expression was analyzed on renal biopsies on postoperative day 3. Gene set enrichment analysis was performed using hallmark gene sets, Gene Ontology, and pathway analysis. RESULTS: The gene expression profile of NEVKP-stored grafts closely resembled no storage kidneys. Gene set enrichment analysis demonstrated enrichment of fatty acid metabolism and oxidative phosphorylation following NEVKP, whereas SCS-enriched gene sets were related to mitosis, cell cycle checkpoint, and reactive oxygen species (q < 0.05). Pathway analysis demonstrated enrichment of lipid oxidation/metabolism, the Krebs cycle, and pyruvate metabolism in NEVKP compared with SCS (q < 0.05). Comparison of our findings with external data sets of renal ischemia-reperfusion injury revealed that SCS-stored grafts demonstrated similar gene expression profiles to ischemia-reperfusion injury, whereas the profile of NEVKP-stored grafts resembled recovered kidneys. CONCLUSIONS: Increased transcripts of key mitochondrial metabolic pathways following NEVKP storage may account for improved donation-after-cardiovascular death graft function, compared with SCS, which promoted expression of genes typically perturbed during IRI.

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.

Normothermic Ex Situ Liver Perfusion Enhances Mitochondrial Function of DCD Grafts as Evidenced by High-throughput Metabolomics.

BACKGROUND: Normothermic ex situ liver perfusion (NEsLP) reduces reperfusion injury of donation after circulatory death (DCD) grafts and optimizes graft function. The goal of our study was to elucidate how NEsLP impacts global metabolism in DCD grafts using high-throughput metabolomics. METHODS: Pig livers were preserved by 2 different techniques: static cold storage and NEsLP. Grafts obtained from heart-beating donors were compared with donation after circulatory death (DCD) grafts with either 30 minutes (DCD30) or 60 minutes (DCD60) ischemia time. Liver tissues were collected at the end of preservation period (T0) with either cold storage or NEsLP (n = 5 per group). Grafts were transplanted into recipient pigs and a second liver biopsy was collected 2 hours following liver transplantation (T1). Snap-frozen tissue was processed and analyzed by Sciex 6600 Q-TOF high-resolution mass spectrometer. Data analysis was performed using MetaboAnalyst 4.0 software. RESULTS: Prolonged ischemia resulted in 38 out of 81 metabolites being differentially abundant over time. Mitochondrial metabolism was significantly affected, with disruption in oxidative phosphorylation capacity i.e the Warburg effect (P = 3.62E-03) and urea cycle (P = 7.95E-0.4). NEsLP resulted in improved mitochondrial metabolism and glycolysis (4.20E-02) oxidation of branched chain fatty acids (P = 4.07E-02). CONCLUSIONS: This unbiased, high-throughput metabolomics study reveals that mitochondrial function is globally rescued with NEsLP, associated with improvement in DCD graft function. NEsLP is able to rescue DCD grafts, improving their metabolic function to that of livers not exposed to DCD procurement.

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.

Significant Dysfunction of Kidney Grafts Exposed to Prolonged Warm Ischemia Is Minimized Through Normothermic Ex Vivo Kidney Perfusion.

Normothermic ex vivo kidney perfusion (NEVKP) is an emerging technique for renal graft preservation. We investigated whether NEVKP could improve early function of severely injured grafts and reduce the incidence of significant renal dysfunction (SRD) similar to delayed graft function in a model of donation after circulatory death. METHODS: Kidneys from 30-kg Yorkshire pigs were removed following 120 minutes of warm ischemia (WI). These grafts were then preserved in static cold storage (SCS, n = 6) or subjected to NEVKP (n = 5) for 8 hours before heterotopic autotransplantation. SRD was defined as postoperative day (POD) 4 oliguria <500 mL/24 h with serum K +> 6.0 mmol/L. RESULTS: All 4 surviving animals with 120 minutes WI grafts stored with SCS developed SRD, compared with 1/5 in the NEVKP group (P = 0.02). The NEVKP group, when compared with SCS, also demonstrated significantly decreased serum creatinine peak values (1118.51 ± 206.90 µmol/L versus 1675.56 ± 98.15 µmol/L; P = 0.002) and higher creatinine clearance (POD4: 9.05 ± 6.97 mL/min versus 0.89 ± 0.56 mL/min; P = 0.05). By POD7, serum creatinine was not significantly different than baseline in the NEVKP (431.49 ± 492.50 µmol/L versus 90.19 ± 14.15 µmol/L, respectively; P = 0.20) but remained elevated following SCS (1189.25 ± 309.47 µmol/L versus 97.26 ± 29.18 µmol/L, respectively; P < 0.01). Histology demonstrated significantly decreased tubular injury scores compared with SCS grafts (P = 0.03). CONCLUSIONS: Kidney grafts subjected to 120 minutes WI before retrieval showed significant improvement in function, prevention of SRD, and decreased injury following 8 hours of NEVKP.

Normothermic Ex Vivo Liver Perfusion Prevents Intrahepatic Platelet Sequestration After Liver Transplantation.

BACKGROUND: The detrimental role of platelets in sinusoidal endothelial cell (SEC) injury during liver transplantation (LT) has been previously addressed after static cold storage (SCS), however, it is currently unknown after normothermic ex vivo liver perfusion (NEVLP). METHODS: Pig LT was performed with livers from heart-beating donors or donation after circulatory death (DCD) donors subjected to SCS or NEVLP (n = 5/group). RESULTS: All pigs except for 1 (DCD-SCS-group) survived 4 days. The heart-beating donor- and DCD-NEVLP-groups showed significantly lower aspartate transaminase-levels compared with the SCS-groups 3 hours post-LT (P = 0.006), on postoperative day (POD) 2 (P = 0.005), POD3 (P = 0.007), and on POD4 (P = 0.012). Post-LT total platelet count recovered faster in the NEVLP than in the SCS-groups at 12 hours (P = 0.023) and 24 hours (P = 0.0038). Intrahepatic sequestration of platelets was significantly higher in the SCS-groups 3 hours postreperfusion and correlated with severity of SEC injury. In both SCS-groups, levels of tumor growth factor-ß were higher 3 hours post-LT, on POD1 and on POD3. Moreover, platelet factor 4 levels and platelet-derived extracellular vesicles were increased in the SCS-groups. Hyaluronic acid levels were significantly higher in the SCS-groups, indicating a higher grade of endothelial cell dysfunction. Platelet inhibition achieved by pretreatment with clopidogrel (n = 3) partly reversed the detrimental effects on SEC injury and therefore provided further evidence of the important role of platelets in ischemia/reperfusion injury and SEC injury. CONCLUSIONS: Normothermic perfusion of liver grafts before transplantation effectively reduced platelet aggregation and SEC injury, which translated into an improved posttransplant organ function.

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.

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.