Portable hypothermic oxygenated machine perfusion for organ preservation in liver transplantation: A randomized, open-label, clinical trial.

BACKGROUND AND AIMS: In liver transplantation, cold preservation induces ischemia, resulting in significant reperfusion injury. Hypothermic oxygenated machine perfusion (HMP-O 2 ) has shown benefits compared to static cold storage (SCS) by limiting ischemia-reperfusion injury. This study reports outcomes using a novel portable HMP-O 2 device in the first US randomized control trial. APPROACH AND RESULTS: The PILOT trial (NCT03484455) was a multicenter, randomized, open-label, noninferiority trial, with participants randomized to HMP-O 2 or SCS. HMP-O 2 livers were preserved using the Lifeport Liver Transporter and Vasosol perfusion solution. The primary outcome was early allograft dysfunction. Noninferiority margin was 7.5%. From April 3, 2019, to July 12, 2022, 179 patients were randomized to HMP-O 2 (n=90) or SCS (n=89). The per-protocol cohort included 63 HMP-O 2 and 73 SCS. Early allograft dysfunction occurred in 11.1% HMP-O 2 (N=7) and 16.4% SCS (N=12). The risk difference between HMP-O 2 and SCS was -5.33% (one-sided 95% upper confidence limit of 5.81%), establishing noninferiority. The risk of graft failure as predicted by Liver Graft Assessment Following Transplant score at seven days (L-GrAFT 7 ) was lower with HMP-O 2 [median (IQR) 3.4% (2.4-6.5) vs. 4.5% (2.9-9.4), p =0.024]. Primary nonfunction occurred in 2.2% of all SCS (n=3, p =0.10). Biliary strictures occurred in 16.4% SCS (n=12) and 6.3% (n=4) HMP-O 2 ( p =0.18). Nonanastomotic biliary strictures occurred only in SCS (n=4). CONCLUSIONS: HMP-O 2 demonstrates safety and noninferior efficacy for liver graft preservation in comparison to SCS. Early allograft failure by L-GrAFT 7 was lower in HMP-O 2 , suggesting improved early clinical function. Recipients of HMP-O 2 livers also demonstrated a lower incidence of primary nonfunction and biliary strictures, although this difference did not reach significance.

Kidney transplant in pediatric gut transplant recipients - Technical challenges and outcomes.

BACKGROUND: There is limited data in the literature about pediatric kidney transplant (KT) following gut transplant (GT). The purpose of this study is to highlight the technical challenges and outcomes of KT in pediatric gut recipients who developed kidney failure (KF). METHODS: A retrospective single-center study of pediatric GT recipients from January 2000 to December 2019 was performed. In total, 14 (7%) out of 206 pediatric GT recipients developed KF and were listed for KT. Ten patients underwent kidney after gut transplant (KAGT), three patients underwent simultaneous kidney and re-do gut transplant (SKAGT), and one patient died on the KT waitlist. RESULTS: 1-, 5-, and 10-year kidney graft survival was 100%, 91%, and 78%, respectively. 1-, 5-, and 10-year GT graft survival was 100%, 77%, and 77%, respectively. 1-, 5-, and 10-year patient survival was 100%, 91%, and 91%, respectively. CONCLUSION: Despite the technical complexity, KAGT and SKAGT for pediatric GT recipients that develop KF can be performed with favorable outcomes.

Predictors of survival following liver transplantation for pediatric hepatoblastoma and hepatocellular carcinoma: Experience from the Society of Pediatric Liver Transplantation (SPLIT).

Management of unresectable pediatric hepatoblastoma (HB) and hepatocellular carcinoma (HCC) remains challenging. The Society of Pediatric Liver Transplantation (SPLIT) database was used to study survival predictors in pediatric liver transplantation (LT) for HB and HCC. Event-free survival (EFS), associated risk factors, and postoperative complications were studied in children requiring LT for HB/HCC at 16 SPLIT centers. Three-year EFS was 81% for HB (n = 157) and 62% for HCC (n = 18) transplants. Of HB transplants, 6.9% were PRETEXT II and 15.3% were POST-TEXT I/II. Tumor extent did not impact survival (p = NS). Salvage (n = 13) and primary HB transplants had similar 3-year EFS (62% versus 78%, p = NS). Among HCC transplants, 3-year EFS was poorer in older patients (38% in ≥8-year-olds vs 86% <8-year-olds) and those with larger tumors (48% for those beyond versus 83% within Milan criteria, p = NS). Risk of infection (HR 1.5, 95% CI 1.1-2.2, p = .02) and renal injury (HR 2.4, 95% CI 1.7-3.3, p < .001) were higher in malignant versus nonmalignant LT. Survival is favorable for pediatric HB and HCC LT, including outcomes after salvage transplant. Unexpected numbers of LTs occurred in PRE/POST-TEXT I/II tumors. Judicious patient selection is critical to distinguish tumors that are potentially resectable; simultaneously, we must advocate for patients with unresectable malignancies to receive organs.

Hypothermic machine perfusion for liver graft preservation.

PURPOSE OF REVIEW: Ex-vivo machine perfusion has emerged as a promising alternative to static cold storage (SCS) for preservation of liver grafts over the last decade. This review describes the mechanistic benefits associated with hypothermic machine perfusion (HMP) for preservation of liver grafts and highlights clinical outcomes of liver transplantation using HMP technology. RECENT FINDINGS: Over the last decade, several single-centre studies have shown decreased biliary complications, decreased early allograft dysfunction (EAD) rates and improved patient survival in liver transplant recipients after application of HMP for liver graft preservation. This has led to initiation of prospective, multicentre, randomized controlled trials (RCTs) in both Europe and North America focused on clinical outcomes in liver transplant recipients using HMP-preserved liver grafts. In addition, recent single-centre studies have shown the utility of perfusate biomarker analysis during HMP in predicting EAD after liver transplantation. SUMMARY: HMP technology has potential to increase the available donor liver organ pool for liver transplant recipients and improve clinical outcomes after liver transplantation. Broader clinical application of HMP in resuscitation and preservation of liver grafts is anticipated over the next decade once regulatory, logistical and financial challenges are overcome.

Current outcomes after pediatric and adult intestinal transplantation.

PURPOSE OF REVIEW: In this article, we will review the outcomes of patients with intestinal transplant (ITx) with a focus on factors affecting long-term graft and patient survival. RECENT FINDINGS: The most recent International Intestinal Transplant Registry reports a 1-, 5-, and 10-year graft survival of 71%, 50%, and 41% respectively, for ITx grafts transplanted since 2000. Over the past decades, significant improvements have been achieved in short-term graft and patient outcomes for ITx recipients. The improvement in short-term outcomes may be related to the focused treatment of antihuman leukocyte antigen antibodies, the use of induction immunotherapy protocols, refinements in surgical techniques, establishment of dedicated ITx units, and improved postoperative management.However, long-term graft and patient outcomes for ITx recipients remain stagnant. Issues impairing long-term outcomes of ITx include the challenges in the diagnosis and treatment of chronic rejection and antibody-mediated rejection, progressive decline in renal function, and long-term infectious and malignancy risks especially related to cytomegalovirus, Epstein-Barr virus and posttransplant lymphoproliferative disorder after ITx. SUMMARY: Addressing and preventing early and late complications is the key to improving short-term and long-term outcomes after ITx.

Maximizing the Donor Potential for Patients with Acute-on-Chronic Liver Failure Listed for Liver Transplant.

Owing to inherent limitations of static cold storage, marginal liver grafts from donors after circulatory death and extended criteria donors after brain death are prone to be discarded secondary to the increased risk of severe early allograft dysfunction and ischemic cholangiopathy. Marginal liver grafts resuscitated with hypothermic machine perfusion and normothermic machine perfusion demonstrate lower degree of ischemia-reperfusion injury and have decreased risk of severe early allograft dysfunction and ischemic cholangiopathy. Marginal grafts preserved by ex vivo machine perfusion technology can be used to rescue patients with acute-on-chronic liver failure who are underserved by the current deceased donor liver allocation system.

Pre-transplant Biomarkers of Immune Dysfunction Improve Risk Assessment of Post-transplant Mortality Compared to Conventional Clinical Risk Scores.

Introduction: There is a critical need to accurately stratify liver transplant (LT) candidates' risk of post-LT mortality prior to LT to optimize patient selection and avoid futility. Here, we compare previously described pre-LT clinical risk scores with the recently developed Liver Immune Frailty Index (LIFI) for prediction of post-LT mortality. LIFI measures immune dysregulation based on pre-LT plasma HCV IgG, MMP3 and Fractalkine. LIFI accurately predicts post-LT mortality, with LIFI-low corresponding to 1.4% 1-year post-LT mortality compared with 58.3% for LIFI-high (C-statistic=0.85). Methods: LIFI was compared to MELD, MELD-Na, MELD 3.0, D-MELD, MELD-GRAIL, MELD-GRAIL-Na, UCLA-FRS, BAR, SOFT, P-SOFT, and LDRI scores on 289 LT recipients based on waitlist data at the time of LT. Survival, hazard of early post-LT death, and discrimination power (C-statistic) were assessed. Results: LIFI showed superior discrimination (highest C-statistic) for post-LT mortality when compared to all other risk scores, irrespective of biologic MELD. On univariate analysis, the LIFI showed a significant correlation with mortality 6-months, as well as 1-, 3-, and 5-years. No other pre-LT scoring system significantly correlated with post-LT mortality. On bivariate adjusted analysis, African American race (p<0.05) and pre-LT cardiovascular disease (p=0.053) were associated with early- and long-term post-LT mortality. Patients who died within 1-yr following LT had a significantly higher incidence of infections, including 30-day and 90-day incidence of any infection, pneumonia, abdominal infections, and UTI (p<0.05). Conclusions: LIFI, which measures pre-LT biomarkers of immune dysfunction, more accurately predicts risk of post-LT futility compared with current clinical predictive models. Pre-LT assessment of immune dysregulation may be critical in predicting mortality after LT and may optimize selection of candidates with lowest risk of futile outcomes.

Liver Transplantation in Patients With Pretransplant Aspergillus Colonization: Is It Safe to Proceed?

BACKGROUND: Patients with end-stage liver disease and pretransplant Aspergillus colonization are problematic for determining liver transplant candidacy and timing of transplantation because of concerns for posttransplant invasive aspergillosis. METHODS: We performed a retrospective review of the medical and laboratory records of all adult patients (aged ≥18 y) who underwent liver transplantation with pretransplant Aspergillus colonization at the Ronald Reagan University of California, Los Angeles, Medical Center from January 1, 2010, to December 31, 2015. RESULTS: A total of 27 patients who had Aspergillus colonization (respiratory tract 26, biliary tract 1) before liver transplantation were identified. Pretransplant characteristics included previous liver transplant (11 of 27, 40.7%), dialysis (22 of 27, 81.5%), corticosteroid therapy (12 of 27, 44.4%), intensive care unit stay (27 of 27, 100%), and median model for end-stage liver disease score of 39. Only 22.2% (6 of 27) received pretransplant antifungal agents (median duration, 5 d), whereas 100% (27 of 27) received posttransplant antifungal prophylaxis (voriconazole 81.4%, 22 of 27; echinocandin 14.8%, 4 of 27; voriconazole plus echinocandin 3.7%, 1 of 27) for median duration of 85 d. Posttransplant invasive fungal infection occurred in 14.8% (4 of 27; aspergillosis 3, mucormycosis 1). Both 6-month and 12-month survival were 66.7% (18 of 27), but only 1 death was due to fungal infection. Other causes of death were liver graft failure, intraabdominal complications, and malignancy. CONCLUSIONS: A substantial number of patients with pretransplant Aspergillus colonization can still undergo successful liver transplantation if they are otherwise suitable candidates and receive appropriate antifungal prophylaxis. Posttransplant outcome in these patients is determined mostly by noninfectious complications and not fungal infection. Pretransplant Aspergillus colonization alone should not necessarily preclude or delay liver transplantation.

Subarachnoid Contrast Hyperdensity Following Pelvic Trauma Mimicking Diffuse Subarachnoid Hemorrhage.

We present a case of a 54-year-old male who was involved in a motorcycle accident. His head computed tomography (CT) scan on arrival at our Level 1 institution was positive for hyperdensity suspicious for subarachnoid hemorrhage (SAH). Spine CT showed anterior compression fractures of T7-T9 vertebral bodies along with the presence of contrast within the subarachnoid space in the thoracic and lumbar spine, raising suspicion for a dural tear. CT of the chest, abdomen, and pelvis revealed open book pelvic fracture, left sacral ala fracture extending into the left sacroiliac joint and S1 neural foramen, coccygeal fracture, and extraperitoneal bladder rupture. This rare case report highlights the possibility of a spinal meningeal tear in severe pelvic trauma with concomitant bladder injury as a pathway of contrast entry into the normally impermeable cerebrospinal fluid (CSF) space mimicking traumatic subarachnoid hemorrhage.

Drug-Induced Autoimmune Hepatitis From Hydralazine Leading to Acute Liver Failure and Liver Transplantation.

We describe a woman with no previous liver disease who developed drug-induced autoimmune hepatitis from hydralazine prescribed to her for hypertension. Despite the discontinuation of the medication, she developed acute liver failure and subsequently underwent successful liver transplantation. She survived and had a good clinical outcome.

Combined Endoscopic and Laparoscopic Management of Postcholecystectomy Mirizzi Syndrome from a Remnant Cystic Duct Stone: Case Report and Review of the Literature.

Mirizzi syndrome has been defined in the literature as common bile duct obstruction resulting from calculi within Hartmann's pouch or cystic duct. We present a case of a 78-year-old female, who developed postcholecystectomy Mirizzi syndrome from a remnant cystic duct stone. Diagnosis of postcholecystectomy Mirizzi syndrome was made on endoscopic retrograde cholangiography (ERCP) performed postoperatively. The patient was treated with a novel strategy by combining advanced endoscopic and laparoscopic techniques in three stages as follows: Stage 1 (initial presentation): endoscopic sphincterotomy with common bile duct stent placement; Stage 2 (6 weeks after Stage 1): laparoscopic ultrasonography to locate the remnant cystic duct calculi followed by laparoscopic retrieval of the calculi and intracorporeal closure of cystic duct stump; Stage 3 (6 weeks after Stage 2): endoscopic removal of common bile duct stent along with performance of completion endoscopic retrograde cholangiogram. In addition, we have performed an extensive review of the various endoscopic and laparoscopic management techniques described in the literature for the treatment of postcholecystectomy syndrome occurring from retained cystic duct stones.

Leiomyosarcoma of the Inferior Vena Cava - Radical Resection, Vascular Reconstruction and Challenges: A Case Report and Review of Relevant Literature.

Leiomyosarcomas of the inferior Vena Cava (IVC) are rare soft tissue sarcomas accounting for only 0.5% of all soft tissue sarcomas in adults with fewer than 300 cases reported. Extraluminal tumor growth along the adventitia of the IVC seems to be the common presentation. Intraluminal tumor growth is rare. The origin of the tumor is divided into three levels in relation to the hepatic and renal veins. The presentations and surgical modalities vary accordingly. Retroperitoneal tumors are often not diagnosed until the disease is at an advanced stage with large tumor growth and involvement of surrounding structures. This is partly because of the nonspecific clinical presentation as well as absence of early symptoms. Most patients present with abdominal or flank pain. Symptoms vary according to the dimensions of the tumor, growth pattern and localization of the tumor. Radical en bloc resection of the affected venous segment remains the only therapeutic option associated with prolonged survival. The goals of surgical management of these tumors include the achievement of local tumor control, maintenance of caval flow, and the prevention of recurrence. The involvement of renal or hepatic veins determines the strategy for vascular reconstruction. Reconstruction of the IVC is not always required, because gradual occlusion of the IVC allows the development of venous collaterals. However, when pararenal leiomyosarcoma of the IVC is present, reconstruction of the IVC and the renal vein is necessary to prevent transient or permanent renal dysfunction. Recent study has shown that radical surgery combined with adjuvant multimodal therapy has improved the cumulative survival rate. We report a case of IVC leiomyosarcoma in a young healthy woman along with details of its diagnostic workup and discussion of the surgical options and reconstruction of caval continuity.

Traumatic injury causing intraperitoneal hemorrhage of an occult pheochromocytoma.

Pheochromocytoma is a rare catecholamine-secreting tumor derived from chromaffin cells. The diagnosis is usually suggested by classic history in a symptomatic patient, presence of a strong family history in a patient, or discovery of an incidental mass on imaging in an asymptomatic patient. Traumatic hemorrhage into an occult pheochromocytoma presenting as hypovolemic shock is a rare presentation of pheochromocytoma. We report a case of a 48-year-old female, who presented in hypovolemic shock due to unilateral adrenal hemorrhage secondary to a fall from horse. Computed tomographic imaging revealed that the source of the hypovolemic shock was hemorrhagic right adrenal mass with active extravasation. The patient underwent emergent selective arterial embolization of right superior adrenal artery and a small adrenal branch from the right renal artery to control the hemorrhage. The patient subsequently progressed to sepsis and MODS, needing multiple surgical procedures and a protracted recovery in the ICU. In the ICU, the patient suffered from rapid cyclic fluctuation of her systolic blood pressure and was subsequently diagnosed with pheochromocytoma secondary to traumatic hemorrhage. We discuss this rare case along with the presentation and diagnostic workup of this critically ill patient with a previously undiagnosed pheochromocytoma.