Robotic versus open mini-incision living donor nephrectomy: Single centre experience.

BACKGROUND: Robotic surgery is associated with less tissue manipulation and earlier recovery with minimal incision. The aim of this study was to compare the short-term clinical outcomes between robotic-assisted donor nephrectomy (RDN) and open mini-incision donor nephrectomy (ODN). METHODS: From 2016 to 2019, 141 cases involving RDN were analysed. Patient outcomes were compared with those of 191 patients who underwent ODN from 2010 to 2015. Demographics, operation factors, perioperative outcomes, and complications were retrospectively reviewed. RESULTS: The RDN group presented with less blood loss than the ODN group (p = 0.023). The length of hospital stay was significantly shorter in the RDN group than in the ODN group (p < 0.005). The overall rate of complications was low and there was no significant difference in complication rates between the groups. CONCLUSION: The robotic approach has benefits over the traditional open approach, including shorter length of hospital stay and reduced intraoperative blood loss.

Successful Opioid Minimization Following Kidney Transplant: A Quality Improvement Initiative.

Opioid use after kidney transplant has been associated with an increased risk of death and graft loss. Several transplant centers have reported reductions in opioid use using multimodal analgesia and education. This study evaluated the impact of an opioid minimization protocol on inpatient opioid use and opioid prescribing on discharge. This was a single-center, retrospective study of adult kidney recipients transplanted from October 2021 to July 2022. Patients on chronic opioids prior to transplant were excluded. The protocol included an intra-operative ultrasound-guided lateral transversus abdominis plane (TAP) block combined with scheduled non-opioid analgesics and tramadol as needed. Acetaminophen 1000 mg and gabapentin 300 mg were given 1 hour prior to the procedure and continued three times daily after transplant. The gabapentin dose was reduced for patients with renal impairment. Additional analgesics including opioids could be added for uncontrolled pain. We hypothesized the protocol would decrease total inpatient morphine milligram equivalents (MMEs) and opioid prescribing on discharge. Fifty-nine post-protocol patients were compared to 52 pre-protocol patients. After the protocol, there was a significant decrease in total inpatient MMEs per day administered and no patient-controlled analgesia (PCA) devices were required. In alignment with the protocol, there was a significant increase in the use of TAP blocks, acetaminophen, gabapentin, and lidocaine patches. While opioid use was lowest in post-protocol patients who received TAP blocks, significant reductions in MMEs per day were still seen in those post-protocol who did not receive TAP blocks. Opioid prescribing at the time of discharge decreased significantly after protocol. No difference was seen in patient-reported pain scores, return to operating room, readmission within 30 days, or length of stay. The use of scheduled acetaminophen and gabapentin with or without a TAP block allowed the elimination of PCA devices and led to significant minimizations in both inpatient opioid use and opioid prescribing on discharge.

Reduced metabolic flexibility is a predictor of weight gain among liver transplant recipients.

Metabolic flexibility is the ability to match biofuel availability to utilization and is inversely associated with increased metabolic burden among liver transplant (LT) recipients. The present study evaluated the impact of metabolic flexibility on weight gain following LT. LT recipients were enrolled prospectively (n = 47) and followed for 6 months. Metabolic flexibility was measured using whole-room calorimetry and is expressed as a respiratory quotient (RQ). Peak RQ represents maximal carbohydrate metabolism and occurs in the post-prandial state, while trough RQ represents maximal fatty acid metabolism occurring in the fasted state. The clinical, metabolic, and laboratory characteristics of the study cohort of lost weight (n = 14) and gained weight (n = 33) were similar at baseline. Patients who lost weight were more likely to reach maximal RQ (maximal carbohydrate oxidation) early and rapidly transitioned to trough RQ (maximal fatty acid oxidation). In contrast, patients who gained weight had delayed time to peak RQ and trough RQ. In multivariate modeling, time to peak RQ (ß-coefficient 0.509, p = 0.01), time from peak RQ to trough RQ (ß-coefficient 0.634, p = 0.006), and interaction between time to peak RQ to trough RQ and fasting RQ (ß-coefficient 0.447, p = 0.02) directly correlated with the severity of weight gain. No statistically significant relationship between peak RQ, trough RQ, and weight change was demonstrated. Inefficient transition between biofuels (carbohydrates and fatty acids) is associated with weight gain in LT recipients that is independent of clinical metabolic risk. These data offer novel insight into the physiology of obesity after LT with the potential to develop new diagnostics and therapeutics.

Prospective observational study to validate a next-generation sequencing blood RNA signature to predict early kidney transplant rejection.

The objective of this study was to validate the performance of Tutivia, a peripheral blood gene expression signature, in predicting early acute rejection (AR) post-kidney transplant. Recipients of living or deceased donor kidney transplants were enrolled in a nonrandomized, prospective, global, and observational study (NCT04727788). The main outcome was validation of the area under the curve (AUC) of Tutivia vs serum creatinine at biopsy alone, or Tutivia + serum creatinine at biopsy. Of the 151 kidney transplant recipients, the mean cohort age was 53 years old, and 64% were male. There were 71% (107/151) surveillance/protocol biopsies and 29% (44/151) for-cause biopsies, with a 31% (47/151) overall rejection rate. Tutivia (AUC 0.69 [95% CI: 0.59-0.77]) and AUC of Tutivia + creatinine at biopsy (0.68 [95% CI: 0.59-0.77]) were greater than the AUC of creatinine at biopsy alone (0.51.4 [95% CI: 0.43-0.60]). Applying a model cut-off of 50 (scale 0-100) generated a high- and low-risk category for AR with a negative predictive value of 0.79 (95% CI: 0.71-0.86), a positive predictive value of 0.60 (95% CI: 0.45-0.74), and an odds ratio of 5.74 (95% CI: 2.63-12.54). Tutivia represents a validated noninvasive approach for clinicians to accurately predict early AR, beyond the current standard of care.

Right versus left fully robotic live donor nephrectomy and open kidney transplantation: Does the laterality of the donor kidney really matter?

Objective: Robotic-assisted live donor nephrectomy (LDN) is being gradually adopted across transplant centers. The left donor kidney is preferred over right due to anatomical factors and ease of procurement. We aimed to study donor and recipient outcomes after robotic procurement and subsequent open implantation of right and left kidneys. Methods: All fully robotic LDNs and their corresponding open kidney transplants performed at our center between February 2016 and December 2021 were retrospectively analyzed. Results: Out of 196 robotic LDN (49 [right] vs. 147 [left]), 10 (5.1%) donors had intra-operative events (6.1% [right] vs. 4.8% [left], p=0.71). None of the LDN required conversion to open surgery. The operative times were comparable for the two groups. Nausea (13.3%) was the most common post-operative complication. There was no mortality in either LDN group. Herein, we report our outcomes on 156 recipients (39 right and 117 left allografts) excluding robotic implants, exports, and pediatric recipients. There were no significant differences between right and left kidney recipients with respect to 1-year post-transplant patient survival (100.0% vs. 98.1%, p=0.45) or graft survival (93.9% vs. 97.1%, p=0.11), or delayed graft function (7.7% vs. 5.1%, p=0.55). Conclusion: Non-hand-assisted robotic live donor nephrectomies can be safely performed with excellent outcomes. Right LDN was not associated with higher incidence of complications compared to left LDN. Open implantation of robotically procured right renal allografts was not associated with higher risk of recipient complications.

Domino Liver Transplantation for Unresectable Colon Cancer Liver Metastasis From a Donor With Heterozygous Familial Hyperlipidemia: A Case Report.

Liver transplantation (LT) is a potential curative treatment for unresectable colorectal cancer liver metastasis (CRLM). Familial hypercholesterolemia (FH) is an inherited condition characterized by elevated low-density lipoprotein cholesterol (LDL-C) levels. Liver transplantation is offered for selected cases, and an explanted liver can be used as a domino graft. We report the first report of domino LT for unresectable CRLM using a liver from a patient with heterozygous FH. The domino donor was a 30-year-old female with a history of heterozygous FH. She had failed medical therapies for FH, including plasmapheresis; therefore, she underwent living donor LT as a treatment for FH. The explanted liver was transplanted to the domino recipient. She has been doing well with normal LDL-C levels. The domino recipient was a 44-year-old female with a history of stage 4 sigmoid cancer with liver metastases, for which she underwent laparoscopic sigmoid colectomy and right hepatectomy. She developed unresectable lesions in the remnant left lobe, which were controlled well with chemotherapy; therefore, she underwent domino LT. She is doing well without recurrence at the 31-month follow-up. Domino LT from a donor with heterozygous FH is feasible for strictly selected patients with unresectable CRLM.

Hepatobiliary mucinous cystic neoplasms and mimics.

This review will provide an overview of hepatobiliary mucinous cystic neoplasms and their mimics such as complex appearing benign cysts, intraductal papillary neoplasm of bile ducts, choledochal cysts, infectious cysts, and other cystic neoplasms. Preoperative imaging, particularly abdominal MRI with MRCP, plays a key role in differentiating these entities which differ widely in management. Familiarity with the differentiating imaging features of mucinous cystic neoplasms and their mimics allows radiologists to provide management-guiding reports.

Performance of Vibration-Controlled Transient Elastography and Clinical Prediction Models In Liver Transplant Recipients.

Hepatic fibrosis is a strong predictor of clinical outcomes following liver transplantation (LT).1 Despite the centrality of hepatic fibrosis in clinical outcomes, the published literature with noninvasive fibrosis assessment in LT recipients is limited and liver biopsy, despite its invasive nature, remains the reference standard. Vibration-controlled transient elastography (VCTE) and clinical prediction models (CPM) are point-of-care tests that can provide noninvasive assessment of hepatic fibrosis2-4; however, the data comparing the diagnostic performance of VCTE and CPM in LT recipients are lacking. The current study evaluated the diagnostic performance of VCTE and CPM in LT recipients using best practices in regulatory sciences for biomarker development.

Radiologic findings of biliary complications post liver transplantation.

Liver transplantation is a potentially curative treatment for patients with acute liver failure, end-stage liver disease, and primary hepatic malignancy. Despite tremendous advancements in surgical techniques and immunosuppressive management, there remains a high rate of post-transplant complications, with one of the main complications being biliary complications. In addition to anastomotic leak and stricture, numerous additional biliary complications are encountered, including ischemic cholangiopathy due to the sole arterial supply of the bile ducts, recurrence of primary biliary disease, infections, biliary obstruction from stones, cast, or hemobilia, and less commonly cystic duct remnant mucocele, vanishing duct syndrome, duct discrepancy and kinking, post-transplant lymphoproliferative disorder, retained stent, and ampullary dysfunction. This article presents an overview of biliary anatomy and surgical techniques in liver transplantation, followed by a detailed review of post-transplant biliary complications with their corresponding imaging findings on multiple modalities with emphasis on magnetic resonance imaging and MR cholangiopancreatography.

Evaluation of liver stiffness measurement-based scores in liver transplantation recipients.

Combining bioclinical parameters with liver stiffness measurement (LSM) has improved the diagnostic performance of vibration-controlled transient elastography (VCTE) for detection of advanced fibrosis in patients with chronic liver disease. However, this approach has not yet been tested in liver transplantation (LT) recipients. Thus, the aim of this study was to evaluate the diagnostic performance of combining LSM-based scores with LSM alone for the detection of advanced fibrosis in LT recipients. Adult LT recipients with a liver biopsy, VCTE, and clinical data necessary to construct LSM-based fibrosis models (FibroScan-AST [FAST], AGILE-3+, and AGILE-4) were included ( n = 132). The diagnostic statistics for advanced fibrosis (fibrosis stage 0-2 vs. 3-4) were determined by optimal cut-off using the Youden index. The area under the receiver operating characteristic curve (AUROC) for LSM was 0.94 (95% confidence interval [95% CI], 0.89-0.99), FAST was 0.65 (95% CI, 0.50-0.79), AGILE-3+ was 0.90 (95% CI, 0.83-0.97), and AGILE-4 was 0.90 (95% CI, 0.83-0.97). No statistically significant differences were noted between the AUROC of LSM versus LSM-based scores. The false-positive rates for AGILE-3+ and AGILE-4 were 14.5% and 11.8% compared with 8.3% for LSM alone. The false-positive rates in LSM-based scores were higher among patients with diabetes mellitus, higher AST levels, and lower platelet counts. The LSM-based scores did not improve the diagnostic performance of LSM alone in LT recipients for the detection of advanced fibrosis. This lack of improvement in diagnostic performance results from the impact of immunosuppression on bioclinical profile and underscores the importance of developing LSM-based scores that are specific to LT patients.

Imaging of fibropolycystic liver disease.

Fibropolycystic liver diseases (FLDs) make up a rare spectrum of heritable hepatobiliary diseases resulting from congenital ductal plate malformations (DPMs) due to the dysfunction of proteins expressed on the primary cilia of cholangiocytes. The embryonic development of the ductal plate is key to understanding this spectrum of diseases. In particular, DPMs can result in various degrees of intrahepatic duct involvement and a wide spectrum of cholangiopathies, including congenital hepatic fibrosis, Caroli disease, polycystic liver disease, and Von Meyenberg complexes. The most common clinical manifestations of FLDs are portal hypertension, cholestasis, cholangitis, and (in rare cases) cholangiocarcinoma. This article reviews recent updates in the pathophysiology, imaging, and clinical management of FLDs.

Xenotransplantation: A New Era.

Organ allotransplantation has now reached an impassable ceiling inherent to the limited supply of human donor organs. In the United States, there are currently over 100,000 individuals on the national transplant waiting list awaiting a kidney, heart, and/or liver transplant. This is in contrast with only a fraction of them receiving a living or deceased donor allograft. Given the morbidity, mortality, costs, or absence of supportive treatments, xenotransplant has the potential to address the critical shortage in organ grafts. Last decade research efforts focused on creation of donor organs from pigs with various genes edited out using CRISPR technologies and utilizing non-human primates for trial. Three groups in the United States have recently moved forward with trials in human subjects and obtained initial successful results with pig-to-human heart and kidney xenotransplantation. This review serves as a brief discussion of the recent progress in xenotransplantation research, particularly as it concerns utilization of porcine heart, renal, and liver xenografts in clinical practice.

Glomerular filtration rate early after liver transplantation independently predicts atherosclerotic events.

Cardiovascular disease (CVD) is an important cause of mortality among liver transplantation (LT) recipients; however, the data on CVD risk stratification following LT are limited. Thus, the primary aim of this study was to evaluate the association between decline in renal function early after LT and atherosclerotic events. This retrospective study included all patients receiving LT between 2007 and 2019. Early renal function was quantified as estimated glomerular filtration rate (GFR) 6 months after LT. The primary endpoint for the study was a composite atherosclerotic cardiovascular event of three-point major adverse cardiovascular events (MACEs), which includes nonfatal myocardial infarction (MI), nonfatal stroke, or death from CVD. A total of 553 LT recipients met entry criteria. After a median follow-up of 74 months (interquartile range 46-111), 94 (17%) LT recipients died and CVD-associated death occurred in 20 patients. MACE-3 occurred in 66 (12%) patients, with nonfatal MI being the most common event (n = 30). A strong inverse relationship between early GFR and MACE-3 was noted in unadjusted analysis with hazard ratio (HR) 0.96 (95% confidence interval [CI] 0.95-0.98; p = 0.0001) and remained significant even after accounting for age, sex, coronary artery disease, diabetes mellitus, hypertension, calcineurin inhibitor use, and Framingham Risk Score (FRS; HR 0.96, 95% CI 0.95-0.97; p = 0.0001 per unit increase in GFR). Furthermore, an independent interaction between GFR, FRS, and likelihood of developing an MACE-3 was noted. GFR 6 months following LT is a strong predictor of developing atherosclerotic events. This relationship is independent of traditional CVD risk stratification models (e.g. FRS) and thus has the potential to be incorporated into CVD risk assessment after LT but requires further validation.

Differential fuel utilization in liver transplant recipients and its relationship with non-alcoholic fatty liver disease.

Metabolic flexibility is the ability to match biofuel availability to utilization. Reduced metabolic flexibility, or lower fatty acid (FA) oxidation in the fasted state, is associated with obesity. The present study evaluated metabolic flexibility after liver transplantation (LT). METHODS: Patients receiving LT for non-alcoholic steatohepatitis (NASH) (n = 35) and non-NASH (n = 10) were enrolled. NASH was chosen as these patients are at the highest risk of metabolic complications. Metabolic flexibility was measured using whole-body calorimetry and expressed as respiratory quotient (RQ), which ranges from 0.7 (pure FA oxidation) to 1.0 is (carbohydrate oxidation). RESULTS: The two cohorts were similar except for a higher prevalence of obesity and diabetes in the NASH cohort. Post-prandially, RQ increased in both cohorts (i.e. greater carbohydrate utilization) but peak RQ and time at peak RQ was higher in the NASH cohort. Fasting RQ in NASH was significantly higher (0.845 vs. 0.772, p < .001), indicative of impaired FA utilization. In subgroup analysis of the NASH cohort, body mass index but not liver fat content (MRI-PDFF) was an independent predictor of fasting RQ. In NASH, fasting RQ inversely correlated with fat-free muscle volume and directly with visceral adipose tissue. CONCLUSION: Reduced metabolic flexibility in patients transplanted for NASH cirrhosis may precede the development of non-alcoholic fatty liver disease after LT.

Early laboratory values after liver transplantation are associated with anastomotic biliary strictures.

BACKGROUNDS/AIMS: The aim of this study was to evaluate longitudinal changes of post-liver transplantation (LT) biliary anatomy and to assess the association of increased laboratory values after LT with the development of post-LT anastomotic biliary stricture (ABS). METHODS: Adult deceased donor LT recipients from 2008 and 2019 were evaluated. ABS was defined after blinded review of endoscopic cholangiograms. Controls were patients who underwent LT for hepatocellular carcinoma who did not have any clinical or biochemical concerns for ABS. RESULTS: Of 534 patients who underwent LT, 57 patients had ABS and 57 patients served as controls. On MRI, ABS patients had a narrower anastomosis (2.47 ± 1.32 mm vs. 3.38 ± 1.05 mm; p < 0.01) and wider bile duct at 1-cm proximal to the anastomosis (6.73 ± 2.45 mm vs. 5.66 ± 1.95 mm; p = 0.01) than controls. Association between labs at day 7 and ABS formation was as follows: aspartate aminotransferase hazard ratio (HR): 1.014; 95% confidence interval (CI): 1.008-1.020, p = 0.001; total bilirubin HR: 1.292, 95% CI: 1.100-1.517, p = 0.002; and conjugated bilirubin HR: 1.467, 95% CI: 1.216-1.768, p = 0.001. Corresponding analysis results for day 28 were alanine aminotransferase HR: 1.004, 95% CI: 1.002-1.006, p = 0.001; alkaline phosphatase HR: 1.005, 95% CI: 1.003-1.007, p = 0.001; total bilirubin HR: 1.233, 95% CI: 1.110-1.369, p = 0.001; and conjugated bilirubin HR: 1.272, 95% CI: 1.126-1.437, p = 0.001. CONCLUSIONS: Elevation of laboratory values early after LT is associated with ABS formation.

Impact of Portable Normothermic Blood-Based Machine Perfusion on Outcomes of Liver Transplant: The OCS Liver PROTECT Randomized Clinical Trial.

IMPORTANCE: Ischemic cold storage (ICS) of livers for transplant is associated with serious posttransplant complications and underuse of liver allografts. OBJECTIVE: To determine whether portable normothermic machine perfusion preservation of livers obtained from deceased donors using the Organ Care System (OCS) Liver ameliorates early allograft dysfunction (EAD) and ischemic biliary complications (IBCs). DESIGN, SETTING, AND PARTICIPANTS: This multicenter randomized clinical trial (International Randomized Trial to Evaluate the Effectiveness of the Portable Organ Care System Liver for Preserving and Assessing Donor Livers for Transplantation) was conducted between November 2016 and October 2019 at 20 US liver transplant programs. The trial compared outcomes for 300 recipients of livers preserved using either OCS (n = 153) or ICS (n = 147). Participants were actively listed for liver transplant on the United Network of Organ Sharing national waiting list. INTERVENTIONS: Transplants were performed for recipients randomly assigned to receive donor livers preserved by either conventional ICS or the OCS Liver initiated at the donor hospital. MAIN OUTCOMES AND MEASURES: The primary effectiveness end point was incidence of EAD. Secondary end points included OCS Liver ex vivo assessment capability of donor allografts, extent of reperfusion syndrome, incidence of IBC at 6 and 12 months, and overall recipient survival after transplant. The primary safety end point was the number of liver graft-related severe adverse events within 30 days after transplant. RESULTS: Of 293 patients in the per-protocol population, the primary analysis population for effectiveness, 151 were in the OCS Liver group (mean [SD] age, 57.1 [10.3] years; 102 [67%] men), and 142 were in the ICS group (mean SD age, 58.6 [10.0] years; 100 [68%] men). The primary effectiveness end point was met by a significant decrease in EAD (27 of 150 [18%] vs 44 of 141 [31%]; P = .01). The OCS Liver preserved livers had significant reduction in histopathologic evidence of ischemia-reperfusion injury after reperfusion (eg, less moderate to severe lobular inflammation: 9 of 150 [6%] for OCS Liver vs 18 of 141 [13%] for ICS; P = .004). The OCS Liver resulted in significantly higher use of livers from donors after cardiac death (28 of 55 [51%] for the OCS Liver vs 13 of 51 [26%] for ICS; P = .007). The OCS Liver was also associated with significant reduction in incidence of IBC 6 months (1.3% vs 8.5%; P = .02) and 12 months (2.6% vs 9.9%; P = .02) after transplant. CONCLUSIONS AND RELEVANCE: This multicenter randomized clinical trial provides the first indication, to our knowledge, that normothermic machine perfusion preservation of deceased donor livers reduces both posttransplant EAD and IBC. Use of the OCS Liver also resulted in increased use of livers from donors after cardiac death. Together these findings indicate that OCS Liver preservation is associated with superior posttransplant outcomes and increased donor liver use. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02522871.

Correlation of Donor-derived Cell-free DNA With Histology and Molecular Diagnoses of Kidney Transplant Biopsies.

BACKGROUND: Circulating donor-derived cell-free DNA (cfDNA), a minimally invasive diagnostic tool for kidney transplant rejection, was validated using traditional histology. The molecular microscope diagnostic system (MMDx) tissue gene expression platform may provide increased precision to traditional histology. METHODS: In this single-center prospective study of 208 biopsies (median = 5.8 mo) posttransplant, we report on the calibration of cfDNA with simultaneous biopsy assessments using MMDx and histology by area under the curve (AUC) analyses for optimal criterion, as well as for, previously published cfDNA cutoffs ≤ 0.21% to "rule-out" rejection and ≥1% to "rule-in" rejection. RESULTS: There were significant discrepancies between histology and MMDx, with MMDx identifying more antibody-mediated rejection (65; 31%) than histology (43; 21%); the opposite was true for T cell-mediated rejection [TCMR; histology: 27 (13%) versus MMDx: 13 (6%)]. Most of the TCMR discrepancies were seen for histologic borderline/1A TCMR. AUC for cfDNA and prediction of rejection were slightly better with MMDx (AUC = 0.80; 95% CI: 0.74-0.86) versus histology (AUC = 0.75; 95% CI: 0.69-0.81). A cfDNA ≤ 0.21% had similar sensitivity (~91%) to "rule-out" rejection by histology and MMDx. Specificity was slightly higher with MMDx (92%) compared with histology (85%) to "rule-in" rejection using cfDNA criterion ≥1%. Strong positive quantitative correlations were observed between cfDNA scores and molecular acute kidney injury for both "rejection" and "nonrejection" biopsies. CONCLUSIONS: Molecular diagnostics using tissue gene expression and blood-based donor-derived cell-free DNA may add precision to some cases of traditional histology. The positive correlation of cfDNA with molecular acute kidney injury suggests a dose-dependent association with tissue injury irrespective of rejection characteristics.