Mercedes Susan Mandell

Adult living donor liver transplantation using a right hepatic lobe

BACKGROUND Living donor liver transplantation has gained wide acceptance as an alternative for children with end-stage liver disease. The standard left lateral segment used in this operation does not provide adequate parenchymal mass to broaden its application to larger children or adults. METHODS We report two cases of adult to adult living donor liver transplantation using a right hepatic lobe in patients with chronic liver disease. RESULTS Both recipients experienced excellent initial graft function and have normal liver function 4 and 9 months postoperatively. Both donors are alive and well and returned to normal life 4 weeks postoperatively. CONCLUSIONS Our initial experience suggests that this technique is a safe and reliable option for adults with chronic end-stage liver disease. A conservative application of this procedure in the adult population could significantly reduce the mortality on the adult waiting list.

Signaling through hepatocellular A2B adenosine receptors dampens ischemia and reperfusion injury of the liver

Ischemia and reperfusion significantly contributes to the morbidity and mortality of liver surgery and transplantation. Based on studies showing a critical role for adenosine signaling in mediating tissue adaptation during hypoxia, we hypothesized that signaling events through adenosine receptors (ADORA1, ADORA2A, ADORA2B, or ADORA3) attenuates hepatic ischemia and reperfusion injury. Initial screening studies of human liver biopsies obtained during hepatic transplantation demonstrated a selective and robust induction of ADORA2B transcript and protein following ischemia and reperfusion. Subsequent exposure of gene-targeted mice for each individual adenosine receptor to liver ischemia and reperfusion revealed a selective role for the Adora2b in liver protection. Moreover, treatment of wild-type mice with an Adora2b-selective antagonist resulted in enhanced liver injury, whereas Adora2b-agonist treatment was associated with attenuated hepatic injury in wild-type, but not in Adora2b−/− mice. Subsequent studies in mice with Adora2b deletion in different tissues—including vascular endothelia, myeloid cells, and hepatocytes—revealed a surprising role for hepatocellular-specific Adora2b signaling in attenuating nuclear factor NF-κB activation and thereby mediating liver protection from ischemia and reperfusion injury. These studies provide a unique role for hepatocellular-specific Adora2b signaling in liver protection during ischemia and reperfusion injury.

Choledochoduodenostomy is a Safe Alternative to Roux-en-Y Choledochojejunostomy for Biliary Reconstruction in Liver Transplantation

IntroductionBile duct reconstruction during liver transplantation is usually performed by a duct-to-duct anastomosis or a Roux-en-Y choledochojejunostomy (CDJ). Direct anastomosis of the bile duct to the duodenum (choledochoduodenostomy—CDD) is another option for biliary reconstruction. This technique has been used with good outcome for the treatment of choledochal cysts, ampullary stenosis, and major bile duct injuries; however, there is little published experience with CDD in liver transplantation. We provide preliminary evidence that CDD is a safe technique for biliary anastomosis in liver transplant recipients.MethodsFrom September 2000 to August 2007 a total of 619 adult first-time cadaveric or living donor liver transplants were performed at the University of Colorado Health and Science Center. Bile duct repair was performed by direct end-to-end anastomosis in 466 patients and by choledocoenterostomy in the remaining 153 patients, 82 of whom were cadaveric recipients. The cadaveric choledocoenterostomy patients were divided into two groups: CDD in 25 and CDJ in 57 recipients.ResultsThere were no significant differences in the 1-year patient or graft survival between the cadaveric groups. The 1-year patient survival was 100% in the CDD group and 97.1% in the CDJ group. The CDD group did not experience more surgical complications compared to the CDJ group.ConclusionsCholedochoduodenostomy is a safe alternative to CDJ biliary anastomosis when a duct-to-duct anastomosis cannot be performed. There is no significant difference in mortality, graft survival, or biliary complications. In addition, CDD offers the advantage of postoperative access to the billiary system by endoscopy and avoids complications associated with the CDJ bowel anastomosis.

The clinical value of early extubation.

Purpose of reviewThe trend to extubate patients as soon as possible following large and complex surgery is supported by a large body of evidence showing early extubation is safe and saves money. However, the use of early extubation in liver transplant recipients is still debated. This review will explore the reasons why there is still resistance to the use of early extubation in liver transplantation. Recent findingsStudies show the majority of liver transplant recipients can be extubated immediately after surgery. A multiinstitutional study addressed the safety of immediate postoperative intubation and confirmed that the rate of complications and reintubation was similar to the very low rate observed in recovery room patients. Investigators, however, cannot agree on what patient or donor factors predict successful extubation. These variables seem to differ between institutions. SummaryThere is robust evidence to support the use of immediate postoperative ventilation in liver transplant recipients. There is no evidence, however, to show that routine ventilation of all transplant recipients provides outcomes that are as good as those documented in extubated patients. It is probably time to turn the evidentiary tables around and ask proponents of routine ventilation to prove that they have done no harm and that they meet the new minimal performance standards established by immediate postoperative extubation.

Hepaticoduodenostomy Is an Alternative to Roux-en-Y Hepaticojejunostomy for Biliary Reconstruction in Live Donor Liver Transplantation

Introduction. A Roux-en-Y hepaticojejunostomy (HJ) is usually performed during live donor liver transplantation (LDLT) when a duct-to-duct reconstruction is not possible. However, direct anastomosis of the bile duct to the duodenum (hepaticoduodenostomy [HD]) is an alternative technique for biliary repair that has been previously used for conventional biliary surgery and at our center for cadaveric liver transplant. We provide the first evidence that HD is an alternative technique for biliary reconstruction in LDLT. Methods. We performed a total of 71 LDLT between 2002 and 2008. An end-to-end anastomosis was used in 30 patients. Forty-one patients had a biliary enteric anastomosis in which seven were reconstructed with an HD. Accessory ducts were fashioned into a common duct or implanted into the duodenum separately. Results. There were no patient deaths or retransplants in a follow-up period that ranged from 90 to 771 days after surgery. One patient was diagnosed with cholangitis that responded to intravenous antibiotics and removal of the stent by endoscopy. Conclusions. This preliminary case series suggests that that HD is a feasible alternative to HJ biliary anastomosis when a duct-to-duct anastomosis cannot be performed. HD offers the possible advantage of simple postoperative access to the biliary system by endoscopy and avoids complications caused by HJ bowel anastomosis.

Cardiac risk evaluation for abdominal transplantation.

Purpose of reviewCardiovascular disease has emerged as a leading cause of perioperative morbidity and mortality in renal and liver transplant patients. There is no consensus on how to diagnose cardiac disease in transplant patients. Further, there is significant disagreement in the literature regarding the use of routine screening methods to detect disease. This review will explore published observations on cardiac complications in renal and liver transplant patients to try and determine why investigators hold such divergent opinions. Recent findingsThe prevalence of cardiac disease is greater in renal and liver transplant patients than in the general public. Complications of cardiac disease play a large role in early mortality and graft loss in the postoperative period. While the presence of risk factors seems to predict coronary disease in renal disease, these factors do not perform as well in liver disease. Noninvasive stress testing for coronary artery disease seems to have low sensitivity in both transplant populations. However, the measurement of cardiac troponin seems to be of some value in predicting early mortality. SummaryPhysicians have not identified an effective yet cost-effective way to screen transplant patients for cardiac disease. Therefore, the first step in creating widely accepted protocols demand that physicians decide what predictive power that screening tests should have in this unique population.

Social and Financial Outcomes of Living Liver Donation: A Prospective Investigation Within the Adult-to-Adult Living Donor Liver Transplantation Cohort Study 2 (A2ALL-2)

Because results from single‐center (mostly kidney) donor studies demonstrate interpersonal relationship and financial strains for some donors, we conducted a liver donor study involving nine centers within the Adult‐to‐Adult Living Donor Liver Transplantation Cohort Study 2 (A2ALL‐2) consortium. Among other initiatives, A2ALL‐2 examined the nature of these outcomes following donation. Using validated measures, donors were prospectively surveyed before donation and at 3, 6, 12, and 24 mo after donation. Repeated‐measures regression models were used to examine social relationship and financial outcomes over time and to identify relevant predictors. Of 297 eligible donors, 271 (91%) consented and were interviewed at least once. Relationship changes were positive overall across postdonation time points, with nearly one‐third reporting improved donor family and spousal or partner relationships and >50% reporting improved recipient relationships. The majority of donors, however, reported cumulative out‐of‐pocket medical and nonmedical expenses, which were judged burdensome by 44% of donors. Lower income predicted burdensome donation costs. Those who anticipated financial concerns and who held nonprofessional positions before donation were more likely to experience adverse financial outcomes. These data support the need for initiatives to reduce financial burden.

Choledochoduodenostomy in pediatric liver transplantation.

Campsen J, Zimmerman MA, Narkewicz MR, Sokol RJ, Mandell MS, Kam I, Dovel D, Karrer FM. Choledochoduodenostomy in pediatric liver transplantation. Pediatr Transplantation 2011: 15: 237–239.

Use of a Hanging-weight System for Liver Ischemia in Mice

Acute liver injury due to ischemia can occur during several clinical procedures e.g. liver transplantation, hepatic tumor resection or trauma repair and can result in liver failure which has a high mortality rate1-2. Therefore murine studies of hepatic ischemia have become an important field of research by providing the opportunity to utilize pharmacological and genetic studies3-9. Specifically, conditional mice with tissue specific deletion of a gene (cre, flox system) provide insights into the role of proteins in particular tissues10-13 . Because of the technical difficulty associated with manually clamping the portal triad in mice, we performed a systematic evaluation using a hanging-weight system for portal triad occlusion which has been previously described3. By using a hanging-weight system we place a suture around the left branch of the portal triad without causing any damage to the hepatic lobes, since also the finest clamps available can cause hepatic tissue damage because of the close location of liver tissue to the vessels. Furthermore, the right branch of the hepatic triad is still perfused thus no intestinal congestion occurs with this technique as blood flow to the right hepatic lobes is preserved. Furthermore, the portal triad is only manipulated once throughout the entire surgical procedure. As a result, procedures like pre-conditioning, with short times of ischemia and reperfusion, can be easily performed. Systematic evaluation of this model by performing different ischemia and reperfusion times revealed a close correlation of hepatic ischemia time with liver damage as measured by alanine (ALT) and aspartate (AST) aminotransferase serum levels3,9. Taken together, these studies confirm highly reproducible liver injury when using the hanging-weight system for hepatic ischemia and intermittent reperfusion. Thus, this technique might be useful for other investigators interested in liver ischemia studies in mice. Therefore the video clip provides a detailed step-by-step description of this technique.

Pulmonary Complications of Liver Disease

Liver disease affects the function of all other organ systems, and cirrhosis can be thought of as a systemic disease that produces multisystem organ failure as a principal cause of death. The lung is particularly sensitive to changes in hepatic function and respiratory failure is a common complication of advanced liver disease. Historically, while physicians recognized an association between lung and liver disease, this association was considered to be rare. But more recent studies have shown that symptoms such as hypoxemia at rest occur in at least 27–33 % of liver transplant candidates [1]. Hypoxemia is caused by a wide variety of diseases. Some pulmonary diseases occur more commonly in patients with liver disease than in the general population. These pulmonary defects can affect the perioperative management of patients and may influence the decision to proceed with transplantation. This chapter will present an overview of the changes in lung mechanics and gas exchange that occur in patients with liver disease and cover some of the more common causes of pulmonary disease in cirrhotic patients.