Size Matching Deceased Donor Livers: The Tampa General Measurement System.

BACKGROUND: No reliable or standardized system exists for measuring the size of deceased donor livers to determine whether they will fit appropriately into intended recipients. METHODS: This retrospective, single-center study evaluated the efficacy of Tampa General Hospital's size-matching protocol for consecutive, deceased donor liver transplantations between October 2021 and November 2022. Our protocol uses cross-sectional imaging at the time of organ offer to compare the donor's right hepatic lobe size with the recipient's right hepatic fossa. Outcomes were analyzed, including large-for-size syndrome, small-for-size syndrome, early allograft dysfunction, primary nonfunction, graft survival, and patient survival. RESULTS: We included 171 patients in the study. The donor liver physically fit in all the patients except one whose pretransplant imaging was outdated. One patient (0.6%) had large-for-size syndrome, none had small-for-size syndrome, 15 (10%) had early allograft dysfunction, and none had primary nonfunction. There were 11 (7%) patient deaths and 11 (7%) graft failures. CONCLUSION: Our measurement system is fast and effective. It reliably predicts whether the donor liver will fit in the intended recipient and is associated with low rates of early allograft dysfunction.

The sex disparity in liver transplantation.

PURPOSE OF THE REVIEW: This review describes the sex disparity in liver transplantation (LT) and explains its underlying causes. RECENT FINDINGS: There is a small but persistent sex disparity in transplant rate and waitlist mortality that disappears once women are listed as Status 1. Allocation systems that could replace the Model for End Stage Liver Disease (MELD)-Na with scores less reliant on serum creatine and muscle mass have the potential to alleviate part of the sex disparity. Women perform worse on frailty assessments and are more likely to have nonalcoholic steatohepatitis (NASH). A diagnosis of NASH is compounding risk factor for frailty. SUMMARY: Women remain disadvantaged in their access to LT despite multiple evolutions of the allocation system. An allocation system that relies less heavily on serum creatinine could partially alleviate the sex disparity. As NASH becomes more prevalent and frailty becomes more important in listing decisions, we may also need to carefully consider differences in the manifestations of frailty between the genders.

COVID-19 and transplantation-Data censoring.

During the early wave of the COVID-19 pandemic, the Scientific Registry of Transplant Recipients (SRTR) designated a "black out" period between March 12, 2020, and June 12, 2020, for transplant outcomes reporting. We discuss the implications and potential bias it has introduced as it may selectively favor the outcomes for certain regions and harm other regions due to varied effects of different waves of COVID-19 infections across the United States.

Optimal Timing of Administration of Direct-acting Antivirals for Patients With Hepatitis C-associated Hepatocellular Carcinoma Undergoing Liver Transplantation.

OBJECTIVE: To investigate the optimal timing of direct acting antiviral (DAA) administration in patients with hepatitis C-associated hepatocellular carcinoma (HCC) undergoing liver transplantation (LT). SUMMARY OF BACKGROUND DATA: In patients with hepatitis C (HCV) associated HCC undergoing LT, the optimal timing of direct-acting antivirals (DAA) administration to achieve sustained virologic response (SVR) and improved oncologic outcomes remains a topic of much debate. METHODS: The United States HCC LT Consortium (2015-2019) was reviewed for patients with primary HCV-associated HCC who underwent LT and received DAA therapy at 20 institutions. Primary outcomes were SVR and HCC recurrence-free survival (RFS). RESULTS: Of 857 patients, 725 were within Milan criteria. SVR was associated with improved 5-year RFS (92% vs 77%, P < 0.01). Patients who received DAAs pre-LT, 0-3 months post-LT, and ≥3 months post-LT had SVR rates of 91%, 92%, and 82%, and 5-year RFS of 93%, 94%, and 87%, respectively. Among 427 HCV treatment-naïve patients (no previous interferon therapy), patients who achieved SVR with DAAs had improved 5-year RFS (93% vs 76%, P < 0.01). Patients who received DAAs pre-LT, 0-3 months post-LT, and ≥3 months post-LT had SVR rates of 91%, 93%, and 78% (P < 0.01) and 5-year RFS of 93%, 100%, and 83% (P = 0.01). CONCLUSIONS: The optimal timing of DAA therapy appears to be 0 to 3 months after LT for HCV-associated HCC, given increased rates of SVR and improved RFS. Delayed administration after transplant should be avoided. A prospective randomized controlled trial is warranted to validate these results.

More Than Just Wait Time? Regional Differences in Liver Transplant Outcomes for Hepatocellular Carcinoma.

BACKGROUND: Regional allocation of deceased donor livers has led to variable wait times for hepatocellular carcinoma (HCC) patients on the liver transplant list. The purpose of our study was to evaluate how regional differences in wait time affect outcomes for HCC patients. METHODS: A retrospective, observational study was performed using the Organ Procurement and Transplantation Network database from February 27, 2002, to September 25, 2015. The cumulative incidences of transplant and waitlist death as well as intention-to-treat and posttransplant survival were evaluated for patients 18 years or older listed for deceased donor liver transplantation with stage II HCC exception points in each United Network for Organ Sharing region. A multivariable analysis of predictive factors for posttransplant survival was performed. RESULTS: Cumulative incidence of transplant decreased and cumulative incidence of waitlist death increased as regional wait time increased. Intention-to-treat survival decreased with increased regional wait time with long wait time regions 1, 5, and 9 having significantly lower intention-to-treat survival compared with many of the shorter wait time regions (P < 0.05). Wait time did not predict posttransplant survival. Significant predictive factors of posttransplant survival included alpha-fetoprotein, size of the largest tumor, number of tumors, age of the recipient, laboratory model for end-stage liver disease, donor risk index, period of transplantation, and region (P < 0.05). CONCLUSIONS: Wait time inequality affects waitlist mortality and intention-to-treat survival but does not affect posttransplant survival. Posttransplant survival is predicted by tumor biology, graft quality, recipient age, underlying liver function, and region. Regional environments of HCC care seem to drive posttransplant survival.

Pancreaticoduodenectomy in the surgical management of primary retroperitoneal sarcoma.

BACKGROUND: In retroperitoneal sarcoma (RPS), the optimal extent of resection must balance adequate disease control with potential for morbidity. We sought to study the frequency and outcomes after a Whipple procedure or pancreaticoduodenectomy (PD) in patients undergoing resection for primary RPS. METHODS: Participating referral centers within the Trans-Atlantic Retroperitoneal Sarcoma Working Group provided retrospective data from January 2007 to December 2016 for patients with primary RPS who underwent PD along with the total number of consecutive resections done during the same time period. Data from participating centers were combined for analysis. RESULTS: In total, 29 patients underwent PD among 2068 resections performed for primary RPS (1.4%). The predominant histologic subtypes were liposarcoma and leiomyosarcoma. All PD patients underwent concomitant resection of additional organs (median: 2, range: 1-5), including 13 patients (45%) who also received vena cava resection. Definitive evidence of microscopic invasion of the duodenum or pancreas was seen in 84% of patients. Postoperatively, 10 patients (34%) had major complications including 8 (28%) that developed a clinically-significant pancreatic leak. One postoperative death (3.4%) occurred. With a median follow-up of 4.8 years, 19 patients (66%) developed disease recurrence. The patterns of recurrence were dependent on histologic subtype. CONCLUSION: Although infrequent, when PD is done for primary RPS, resection of additional organs is often required and major complication rates are moderate. The recurrence rate is overall high and the pattern of recurrence is dictated by histologic subtype.

Balanced blood product transfusion during liver transplantation.

INTRODUCTION: This study was conducted to determine whether an intra-operative ratio of at least 1:1:2 of fresh frozen plasma (FFP):platelets (PLTs):packed red blood cells (pRBCs) improves outcomes in orthotopic liver transplantation (OLT). METHODS: A single-center, retrospective study of deceased donor OLT recipients (MELD ≥15) requiring intra-operative pRBC transfusion (years 2013-2016). Patients were grouped into those receiving an intra-operative ratio of ≥1:1:2 of FFP:PLTs:pRBCs vs ratios <1:1:2. RESULTS: Patients in ≥1:1:2 group (n = 150) and patients in <1:1:2 group (n = 80) were matched for baseline characteristics (P > .05). Patients in the ≥1:1:2 group had lower pRBC and intra-operative blood product requirements (11 ± 0.5 vs 19 ± 1.4 units, P < .001, and 33 ± 1.3 vs 43 ± 3.3 units, P = .006, respectively), improved 1-month mortality (0 vs 8%, P = .002), improved 1-year survival (P = .004), less intra-operative cardiac arrest (3% vs 10%, P = .03), and shorter operating room time (389 ± 7.2 vs 431 ± 17.2 minutes, P = .03). After multivariate adjustment for baseline and intra-operative variables, balanced blood product transfusion (BBPT) was significantly associated with less intra-operative pRBC transfusion (95% confidence interval: 0.60-0.72). CONCLUSION: Balanced blood product transfusion is associated with reduced transfusion requirements in OLT.

Invasive fungal infections following liver transplantation.

PURPOSE OF REVIEW: The review outlines the microbiology, presentation, prophylactic strategies, resistance patterns, and consequences of invasive fungal infections (IFIs) in orthotopic liver transplantation (OLT) recipients. RECENT FINDINGS: There has been an increase in the proportion of non-albicans Candida causing IFIs. The biomarkers galactomannan and ß-D-glucan should not be routinely used in the diagnosis of IFIs in OLT recipients due to their limited accuracy. Echinocandins have emerged as noninferior to fluconazole and other prophylactic regimens. Their broad spectrum of activity and side-effect profile are appealing; however, the development of echinocandin resistance, especially in Candida glabrata has been highlighted as one of their limitations. SUMMARY: A significant decline in IFIs but an increase in IFIs caused by non-albicans Candida species has been observed in the model for end-stage liver disease era. Diagnostic tools remain limited. Studies continue to support antifungal prophylaxis individualized to recipient risk with echinocandins now established as an additional option for antifungal prophylaxis. The appropriate duration of antifungal prophylaxis remains ill-defined with some studies advocating targeted therapy based on clinical status and others more prolonged therapy beyond the historically common 4 weeks. However, prolonged therapy with echinocandins can result in resistance.

Early Aggressive Hydration Hastens Clinical Improvement in Mild Acute Pancreatitis.

OBJECTIVES: Early aggressive intravenous hydration is recommended for acute pancreatitis treatment although randomized trials have not documented benefit. We performed a randomized trial of aggressive vs. standard hydration in the initial management of mild acute pancreatitis. METHODS: Sixty patients with acute pancreatitis without systemic inflammatory response syndrome (SIRS) or organ failure were randomized within 4 h of diagnosis to aggressive (20 ml/kg bolus followed by 3 ml/kg/h) vs. standard (10 ml/kg bolus followed by 1.5 mg/kg/h) hydration with Lactated Ringer's solution. Patients were assessed at 12-h intervals. At each interval, in both groups, if hematocrit, blood urea nitrogen (BUN), or creatinine was increased, a bolus of 20 ml/kg followed by 3 ml/kg/h was given; if labs were decreased and epigastric pain was decreased (measured on 0-10 visual analog scale), hydration was then given at 1.5 ml/kg/h and clear liquid diet was started. The primary endpoint, clinical improvement within 36 h, was defined as the combination of decreased hematocrit, BUN, and creatinine; improved pain; and tolerance of oral diet. RESULTS: The mean age of the patients was 45 years and only 14 (23%) had comorbidities. A higher proportion of patients treated with aggressive vs. standard hydration showed clinical improvement at 36 h: 70 vs. 42% (P=0.03). The rate of clinical improvement was greater with aggressive vs. standard hydration by Cox regression analysis: adjusted hazard ratio=2.32, 95% confidence interval 1.21-4.45. Persistent SIRS occurred less commonly with aggressive hydration (7.4 vs. 21.1%; adjusted odds ratio (OR)=0.12, 0.02-0.94) as did hemoconcentration (11.1 vs. 36.4%, adjusted OR=0.08, 0.01-0.49). No patients developed signs of volume overload. CONCLUSIONS: Early aggressive intravenous hydration with Lactated Ringer's solution hastens clinical improvement in patients with mild acute pancreatitis.

Antibody-mediated rejection: what is the clinical relevance?

PURPOSE OF REVIEW: The review outlines the diagnosis, clinical implications, and treatment strategies for acute and chronic antibody-mediated rejection (AMR) after orthotopic liver transplantation (OLT). RECENT FINDINGS: A combination of clinical work-up, histopathology, C4d staining, and donor-specific antibody (DSA) should be used to diagnose AMR. The differential diagnosis for idiopathic fibrosis now includes chronic AMR. Characterization of pathogenic DSA continues to progress. De-novo and persistent DSA, particularly of the IgG3 subtype, are associated with inferior long-term outcomes.The liver allograft may confer long-term immunologic benefits to the kidney allograft after simultaneous liver-kidney transplant.The more widespread use of rituximab has improved outcomes in ABO-incompatible OLT.Although larger long-term studies of treatment options are needed, compliance with tacrolimus-based immunosuppression and transfusion minimization are agreed upon preventive strategies. SUMMARY: AMR has evolved into an established pathology in OLT recipients. Acute AMR may lead to early graft loss whereas chronic AMR results in progressive fibrosis if unrecognized. DSAs, likely in the setting of predisposing environmental factors, appear to play a role in T cell-mediated rejection and long-term graft outcomes.

Blood Conservation Strategies and Liver Transplantation Transfusion-Free Techniques Derived from Jehovah's Witness Surgical Cohorts.

Red blood cell and component transfusions are a frequent and widely accepted accompaniment of surgical procedures. Although the risk of specific disease transmission via allogeneic blood transfusions (ABT) is very low, the occurrence of transfusion related immune modulation (TRIM) still remains a ubiquitous concern. Recent studies have shown that ABT are linked to increased morbidity and mortality across various specialties, with negative outcomes directly correlated to number of transfusions. Blood conservation methods are therefore necessary to reduce ABT. Acute normo-volemic hemodilution (ANH) along with pre-operative blood augmentation and intraoperative cell salvage are blood conservation techniques utilized in tertiary and even quaternary (transplantation) surgery in Jehovah's Witnesses with excellent outcomes. The many hematologic complications such as anemia, thrombocytopenia and coagulopathies that occur with liver transplantation present a significant barrier when trying to avoid ABT. Despite this, living donor liver transplantation (LDLT) has been successfully performed in a transfusion-free environment, providing valuable insight into the possibilities of limiting ABT and its associated risks in all patients.

Cardiophrenic lymph nodes in liver transplant candidates with hepatocellular carcinoma: imaging characteristics and post-transplant outcomes.

BACKGROUND: No guidelines exist for the management of cardiophrenic lymph nodes in patients with hepatocellular carcinoma (HCC) being evaluated for liver transplantation. METHODS: One hundred and seventy-eight patients with HCC listed for liver transplant received both pre-transplant computed tomography (CT) and follow-up CT scans. Enlarged cardiophrenic lymph nodes on CT were characterized and followed on subsequent scans; lymph node outcomes were assigned to "reduced" and "not reduced" categories. Tumor and patient characteristics were also recorded. RESULTS: Seventy-one of one hundred and seventy-eight patients (39.9%) had at least one cardiophrenic lymph node larger than 8 mm in diameter on pre-transplant CT. One hundred and sixty-six total lymph nodes were characterized. Six lymph nodes (3.6%) in two patients increased in size on follow-up imaging; all six cardiophrenic lymph nodes were presumed to represent metastases. There was a statistically significant reduction in lymph node size in patients who were transplanted vs. those who were not transplanted. Furthermore, a statistically significant association was found between increasing Model for End-Stage Liver Disease score and lymph node size reduction. There were no significant differences in post-transplant survival between patients with different lymph node outcomes. CONCLUSION: In the absence of metastatic disease in other sites, these lymph nodes are probably reactive; further workup is likely not necessary.

Can ultrasound common bile duct diameter predict common bile duct stones in the setting of acute cholecystitis?

BACKGROUND: Our aim is assessment of ultrasound (US) common bile duct (CBD) diameter to predict the presence of CBD stones in acute cholecystitis (AC). METHODS: A retrospective review from 2007 to 2011 with codes for ultrasound, magnetic resonance cholangiopancreatography (MRCP), endoscopic retrograde cholangiopancreatography, and AC was conducted. RESULTS: The incidence of CBD stones was 1.8%. Two hundred forty eight individuals had US+MRCP+ERCP+AC, of which 48 had CBD stones and 200 did not have CBD stones. US CBD diameter range was 3.6 to 19 mm. Ninety percent of MRCPs were negative, and it delayed care by 2.9 days. Mean CBD diameter was narrower in those negative for CBD stones (5.8 vs 7.08; P = .0043). Groups based on diameter ranges <6, 6 to 9.9, and ≥10 mm demonstrated 14%, 14%, and 39% CBD stones, respectively. CONCLUSIONS: US CBD diameter is not sufficient to identify patients at significant risk for CBD stones. MRCP delayed care by 2.9 days. Intraoperative cholangiography may be more effective, based on the low risk of CBD stones in AC.

Outcomes after liver transplantation in patients achieving a model for end-stage liver disease score of 40 or higher.

BACKGROUND: Patients with Model for End-Stage Liver Disease (MELD) scores of 40 or higher are at high risk for liver transplantation. In some regions, the organ donor shortage has resulted in a substantial increase in the number of patients who underwent transplantation with MELD scores of 40 or higher. The objective of this study was to characterize the outcomes of liver transplantation in these patients. METHODS: A single-center retrospective study evaluating the outcome of liver transplantation in 38 consecutive patients achieving a MELD score of 40 or higher from January 1, 2006, to November 30, 2010, was conducted. Patient and graft survivals and independent risk factors for postoperative death or graft loss were determined. RESULTS: Kaplan-Meier-based 1-, 2-, and 3-year patient survival rates were 89%, 82%, and 77% with 1-, 2-, and 3-year graft survival rates of 84%, 75%, and 70.3%, respectively. One of three recipients was on a vasopressor before transplantation, and 13% were mechanically ventilated. Renal replacement therapy was used before operation in 90% of the recipients. Postoperative length of stay averaged 38 days. There was a 42% incidence of postoperative bacteremia and an 18% incidence of bile duct stricture within 6 months. Univariate analysis identified admission-to-transplantation time and recipient diabetes as risk factors for graft failure and patient death. Multivariate analysis confirmed recipient diabetes as a risk factor for patient survival and admission-to-transplantation time of more than 15 days as a risk factor for graft survival. CONCLUSIONS: Acceptable outcomes are achievable after liver transplantation in patients with MELD scores of 40 or higher but come at high pretransplantation and posttransplantation resource utilization.

Pancreas transplantation.

SPK transplant is the definitive treatment of type 1 diabetes combined with end-stage renal disease. Long-term graft function can lead to improvement in diabetes-related complications and, in patients younger than 50 years, can lead to improved overall survival. PAK transplant and PA transplant do not result in similar improvements in patient survival, but with appropriate patient selection, they can improve quality of life by rendering patients insulin-free. Pancreas transplant is associated with more surgical complications and higher perioperative morbidity and mortality than KTA. Therefore, careful donor and recipient selection along with meticulous surgical technique are mandatory for optimal outcomes.

Human monocytes as intermediaries between allogeneic endothelial cells and allospecific T cells: a role for direct scavenger receptor-mediated endothelial membrane uptake in the initiation of alloimmunity.

Recipient monocytes, T cells, and donor endothelial cells (ECs) are recognized as critical components of allograft rejection. We have recently shown that human monocytes infiltrate vascularized allografts before clinical rejection and have thus hypothesized that monocytes, rather than costimulation-poor ECs, initiate an alloimmune response. However, the nature of the interactions between ECs, monocytes, and T cells has been incompletely defined. Specifically, it is not clear whether these cells interact in a hierarchical manner, nor is it apparent what constitutes an interaction. We therefore studied human ECs, monocytes, and T cells in various isolated in vitro combinations to define the salient features of their contact and to determine whether their interactions were sequential in nature. We find that T cells proliferate poorly to allogeneic ECs and autologous monocytes but well to autologous monocytes following allogeneic EC contact. We show that monocytes gain their stimulatory capacity by phagocytizing allogeneic but not autologous EC membranes in a process governed by scavenger receptors. This process facilitates the subsequent presentation of intact donor HLA molecules to T cells (semidirect presentation). Moreover, monocytes are receptive to T cell help only after exposure to ECs and require CD4+ T cells to optimally express costimulatory molecules and foster Ag presentation. Our results indicate that monocytes engage allogeneic ECs through scavenger receptors and are then primed to facilitate T cell activation in a codependent manner. This reciprocal codependence allows for monocytes to serve as a regulated bridge between the allograft and T cells.

Induction of transplantation tolerance in non-human primate preclinical models.

Short-term outcomes following organ transplantation have improved considerably since the availability of cyclosporine ushered in the modern era of immunosuppression. In spite of this, many of the current limitations to progress in the field are directly related to the existing practice of relatively non-specific immunosuppression. These include increased risks of opportunistic infection and cancer, and toxicity associated with long-term immunosuppressive drug exposure. In addition, long-term graft loss continues to result in part from a failure to adequately control the anti-donor immune response. The development of a safe and reliable means of inducing tolerance would ameliorate these issues and improve the lives of transplant recipients, yet given the improving clinical standard of care, the translation of new therapies has become appropriately more cautious and dependent on increasingly predictive preclinical models. While convenient and easy to use, rodent tolerance models have not to date been reliably capable of predicting a therapy's potential efficacy in humans. Non-human primates possess an immune system that more closely approximates that found in humans, and have served as a more rigorous preclinical testing ground for novel therapies. Prior to clinical adaptation therefore, tolerance regimens should be vetted in non-human primates to ensure that there is sufficient potential for efficacy to justify the risk of its application.