Intraoperative pulmonary embolism and intracardiac thrombosis complicating liver transplantation: a systematic review.

BACKGROUND: Pulmonary embolism (PE) and intracardiac thrombosis (ICT) are rare but potentially lethal complications during orthotopic liver transplantation (OLT). METHODS: We aimed to review clinical and pathological correlates of PE and ICT in patients undergoing OLT. A systematic review of the literature was conducted using MEDLINE and ISI Web of Science. RESULTS: Seventy-four cases of intraoperative PE and/or ICT were identified; PE alone in 32 patients (43%) and a combination of PE and ICT in 42 patients (57%). Most frequent clinical symptoms included systemic hypotension and concomitant rising pulmonary artery pressure, often leading to complete circulatory collapse. PE and ICT occurred in every stage of the operation and were reported equally in patients with or without the use of venovenous bypass or antifibrinolytics. A large variety of putative risk factors have been suggested in the literature, including the use of pulmonary artery catheters or certain blood products. Nineteen patients underwent urgent thrombectomy or thrombolysis. Overall mortality was 68% (50/74) and 41 patients (82%) died intraoperatively. CONCLUSION: Mortality was significantly higher in patients with an isolated PE, compared to patients with a combination of PE and ICT (91% and 50%, respectively; P < 0.001). Intraoperative PE and ICT during OLT appear to have multiple etiologies and may occur unexpectedly at any time during the procedure.

Primary hepatic carcinoid tumor presenting as Cushing's syndrome.

Hepatic carcinoid tumors are very uncommon; most are clinically non-functional and very few present with the symptoms of carcinoid syndrome. ACTH-producing carcinoid tumors most commonly originate in the lung or thymus and present insidiously with bronchospasm and/or chest mass. Occasionally, ectopic ACTH syndromes have been reported in association with pancreatic islet cell tumors, medullary thyroid cancer, pheochromocytoma, small-cell lung carcinoma, and rarely, ovarian and prostate tumors. We report here a patient with an ectopic ACTH-secreting primary hepatic carcinoid tumor who presented with cushingoid appearance, profound proximal muscle weakness, severe lower extremity edema, and markedly elevated urinary free cortisol. ACTH levels were in the low normal range. A solitary vascular hepatic lesion was found on magnetic resonance imaging, which was isodense with the surrounding liver on octreotide scan and photopenic on an 18-fluorodeoxyglucose (18FDG)-positron emission tomography (PET) scan. Following surgical resection of the hepatic tumor, histopathology confirmed an ACTH-secreting neuroendocrine tumor (NET), the patient had complete resolution of hypercortisolemic symptoms and remains in remission, now 4 yr after hepatic tumor resection. This case reports the first ACTH-secreting primary hepatic NET presenting as ectopic Cushing's syndrome. Interesting aspects of this case include the presence of a pituitary incidentaloma, the low normal ACTH, and photopenia on 18FDG-PET imaging.

Abdominal compartment syndrome secondary to retroperitoneal hematoma as a complication of ERCP after liver transplantation.

Endoscopic retrograde cholangiopancreatography (ERCP) is frequently employed in the management of postoperative biliary complications in the liver transplant patient. Bleeding after ERCP most commonly presents as gastrointestinal bleeding and often can be managed with repeat endoscopy. ERCP can also be complicated by retroperitoneal hematoma, which in rare cases can lead to hemodynamic compromise due to relentless hemorrhage or from secondary abdominal compartment syndrome. We describe the first reported case of post-ERCP retroperitoneal hematoma in a liver transplant recipient that led to abdominal compartment syndrome and shock liver. We will present the case, discuss management, and review the complications of ERCP in the liver transplant recipient. Close post-procedure monitoring, rapid detection, and low threshold for decompressive laparotomy are keys to the successful management of the liver transplant recipient experiencing expanding retroperitoneal hematoma after ERCP.

Liver transplantation for cholangiocellular carcinoma: analysis of a single-center experience and review of the literature.

Cholangiocellular carcinoma (CCC) is a biliary malignancy that frequently presents in advanced unresectable stages. The role of liver transplantation (LT) as a surgical modality is unclear. The goal of this study is to evaluate outcomes of patients with CCC undergoing LT. A retrospective analysis of all patients undergoing LT was undertaken. Only those patients with the pathological diagnosis of CCC were included on the study. Patients were divided into two groups based on primary tumor location: extrahepatic (EH)-CCC and intrahepatic (IH)-CCC. The Kaplan-Meier method was used to calculate overall and recurrence-free survival. Log-rank analysis was used to determine the significance of prognostic variables. Twenty-five patients were identified: 9 patients with EH-CCC (5 patients, Klatskin-type; 2 patients, the middle third; and 2 patients, the distal third) and 16 patients with IH-CCC. Mean age was 47.1 +/- 10.6 years. There were 14 men and 11 women. Tumor stage was local (stages I and II; n = 9) or advanced (stages III and IV; n = 16). Overall and disease-free survival rates were 71% and 67% at 1 year and 35% and 32% at 3 years, respectively. Analysis of variables showed statistically significant improved outcomes (P < .05) for the absence of contiguous organ invasion at LT, small tumor size, and single tumor foci. This study indicates that early survival after LT for CCC is acceptable. Three-year disease-free survival is achieved in approximately 30% of patients. These outcomes can be improved by applying strict selection criteria based on prognostic variables identified in this study.

Transmission of hepatitis B infection from hepatitis B core antibody--positive liver allografts is prevented by lamivudine therapy.

Donor shortage has led to the use of hepatitis B core antibody (anti-HBc)--positive (anti-HBc(+)) liver allografts for patients in need of relatively urgent orthotopic liver transplantation (OLT). Because anti-HBc(+) allografts transmit hepatitis B virus (HBV) infection at a high rate, effective prophylaxis is required. We assessed the effectiveness of lamivudine in preventing HBV transmission by anti-HBc(+) allografts. Between March 1996 and March 2000 at Cedars-Sinai Medical Center (Los Angeles, CA), 15 of 169 patients (8.9%) received liver allografts from anti-HBc(+) donors. Six patients were hepatitis B surface antigen (HBsAg)(+) (group 1), and 9 patients were HBsAg negative (HBsAg(-); group 2) before OLT. All patients were administered lamivudine, 100 or 150 mg/d, orally after OLT. Patients who were HBsAg(+) before OLT also were administered hepatitis B immunoglobulin (HBIG) prophylaxis. Hepatitis B serological tests were performed on all patients, and HBV DNA was determined in liver tissues in 10 patients. All 15 patients remained HBsAg(-) at their last follow-up 2 to 40 months (mean, 17 months) post-OLT. All patients in group 1 had antibody to HBsAg (anti-HBs) titers greater than 250 mIU/mL post-OLT (mean follow-up, 20 months; range, 7 to 40 months). Of the 2 patients in group 1 who underwent liver biopsy after OLT, 1 patient had detectable hepatic HBV DNA despite being anti-HBs(+) and HBsAg(-). Among the patients in group 2, none acquired anti-HBc or HBsAg. Hepatic HBV DNA was undetectable in the 7 patients in group 2 who underwent liver biopsy after OLT. Anti-HBc(+) allografts can be safely used in patients who undergo OLT for chronic hepatitis B and susceptible transplant recipients if prophylaxis with combination HBIG and lamivudine or lamividine alone is administered after OLT, respectively. However, more data are needed to determine the efficacy of lamivudine monotherapy in preventing transmission of HBV infection from anti-HBc(+) liver allografts to susceptible recipients.

Portal-Systemic shunts reduce asialoglycoprotein receptor density in rats.

UNLABELLED: The clinical usefulness of quantitative functional imaging techniques that use asialoglycoprotein receptor (ASGP-R) binding is based on the correlation between ASGP-R density and hepatic functional reserve. Portal-systemic shunting (PSS) is common in patients with cirrhosis and portal hypertension-the same group that is most frequently considered for such imaging. PSS occurs spontaneously through collateral vessels and from the creation of surgical shunts or placement of transjugular intrahepatic portal-systemic shunts (TIPS). Understanding the physiologic relationship between PSS and ASGP-R activity may aid in the interpretation of quantitative clinical imaging. This study was conducted to determine the relationship between PSS and ASGP-R density in the absence of parenchymal disease. METHODS: Sprague-Dawley rats with end-to-side portal-systemic shunts and sham-operated control rats were imaged with 99mTC-diethylenetriaminepentaacetic acid galactosyl-neoglycoalbumin. Pharmacokinetic modeling of the liver and heart time-activity data was used to measure ASGP-R concentration, as well as hepatic plasma volume and flow. RESULTS: The mean ASGP-R density (nmol/g of liver) was significantly decreased in the shunted rats. Blood ammonia was significantly elevated, whereas hepatic plasma flow, alkaline phosphatase, alanine aminotransferase, and aspartate aminotransferase levels were unaltered. Liver histology was normal in both groups. CONCLUSION: A significant change in the ASGP-R density occurs with PSS in the absence of parenchymal disease. PSS appears to be an independent variable affecting ASGP-R activity. This could prove clinically important during interpretation of quantitative imaging from patients with varying degrees of PSS based on underlying disease or the presence of a surgical shunt or TIPS device.

The pathophysiology, diagnosis, and management of acute hepatic encephalopathy.

Acute hepatic encephalopathy is a disorder linked between the 2 most complex organs of the body and is clearly an integral aspect of acute liver failure. Its presence defines fulminant hepatic failure and its progression reflects the prognosis. For the scientist, the pathophysiology of this syndrome is a fascinating and active area of research, bridging numerous independent disciplines in new and creative ways. For the clinician, acute hepatic encephalopathy invokes its due respect as a challenging aspect of the syndrome of fulminant liver failure.

Metabolic activity of cultured rat brainstem, hippocampal and spinal cord slices.

The use of cultured brain slices has become an accepted technique for the ex vivo analysis of neural mechanisms, yet the viability of this preparation is not routinely measured. The tetrazolium dye 3-(4, 5-dimethlythiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) is reduced by active mitochondria to an insoluble purple precipitate which accumulates within living cells and is easily visualized with bright field or phase contrast microscopy. In this study, the MTT assay was used to assess the viability of cultured brainstem, hippocampal and spinal cord slices (150-300 micrometer) from 0 to 22 day-old neonatal rats at post-explant time points ranging from 2 to 29 days. After 2 weeks, 180-300 micrometer cultured slices from 4-13 day old rats remained 90-100% viable. Those from 0-1 day old rats had similar viability but displayed peripheral tissue outgrowth. Slices from older 18-22 day rats were no longer viable after 10-14 days. After 4 weeks, the thicker (300 micrometer) slices of hippocampus and spinal cord retained 75-89% viability, in contrast to the 50-74% viability of the brainstem. Thinner brainstem and hippocampal slices (150-220 micrometer) slices were less than 50% viable at 4 weeks. Morphologic characteristics of the brain regions gradually degenerated over the 4-week culture period. Slice viability was markedly influenced by tissue thickness, donor age and brain region. Use of the MTT assay provides an inexpensive and expeditious means to assess a significant functional parameter of regional slice viability under variable conditions and enhances the feasibility of this preparation for functional studies, such as those concerned with genetic and protein expression within circumscribed areas of the brain.

Transplantation in the hepatitis B patient and current therapies to prevent recurrence.

Hepatitis B is the sixth most common indication for liver transplantation in the United States, accounting for about 7% of all transplants among adults. Transplantation for hepatitis B is especially problematic because the virus is not eradicated and there is great potential for reinfection that can lead to graft failure or death. This risk is higher still in patients with active viral replication and chronic liver disease. Treatment with short-term hepatitis B immune globulin (HBIG) delays reinfection of the allograft, but only long-term treatment with HBIG has led to a decline in the reinfection rate. Combination therapy using HBIG with nucleoside analogues will likely become the standard of care to maintain stable serum titers of protective anti-HBs antibody and to prevent posttransplantation reinfection.

Induction of peroxiredoxins in transplanted livers and demonstration of their in vitro cytoprotection activity.

Peroxiredoxin (Prx)-I and -II belong to a new class of antioxidants. Here, we report that they are induced by ischemia/reperfusion (I/R) in transplanted livers. Hypothesizing that Prxs are induced to protect liver from oxidative damage, we transduced these human genes into murine NIH-3T3 cells. The overexpressed Prxs made the cells more resistant to t-butylhydroperoxide-induced apoptosis. These results indicate that Prx-I and Prx-II are induced by the transplantation process and can protect cells against oxidant damage in tissue culture. Thus, proper genetic manipulations of Prxs may be useful in increasing the success rate of organ transplantation.

Intracranial pressure during liver transplantation for fulminant hepatic failure.

During orthotopic liver transplantation (OLT) for fulminant hepatic failure (FHF), some patients develop cerebral injury secondary to intracranial hypertension. We monitored intracranial pressure (ICP) and cerebral perfusion pressure (CPP) before and during OLT in 12 FHF patients undergoing transplantation. All four patients who had normal ICP preoperatively maintained normal ICP/CPP throughout OLT. During OLT, four of the eight patients with pretransplant intracranial hypertension had six episodes of ICP increase. These episodes of intracranial hypertension occurred during failing liver dissection (n=3) and graft reperfusion (n=3). At the end of the anhepatic phase, the ICP was lower than the preoperative ICP in all patients, and was below 15 mmHg in all but one patient. These data suggest that in FHF patients who develop intracranial hypertension before OLT, dissection of the native liver and graft reperfusion are associated with a risk of brain injury resulting from intracranial hypertension and cerebral hypoperfusion.

Outcomes from nonemergent orthotopic liver transplantation: is postoperative care becoming routine?

The outcome of surgical intensive care unit (SICU) care after nonemergent orthotopic liver transplantation (OLTX) was evaluated in 168 consecutive patients over a 6-year period (1/90-12/95). Prospective data collected included age, first and last SICU day Simplified Acute Physiology Score and Quantitative Therapeutic Intervention System Score, SICU length of stay (LOS), and mortality. The patient population was 61 per cent male and 39 per cent female, with ages ranging from 20 to 75 years. A total of four patients died in the SICU, for a mortality of 2.4 per cent. Over the study period, SICU LOS decreased by 21 per cent, from 3.9 +/- 0.7 to 3.1 +/- 0.3 days (P < 0.05). Although no difference in admission severity of illness was observed over the study period, there was an increase in the intensity of intervention performed on admission to the SICU. Over the study period, there was no difference in severity of illness or intensity of intervention upon discharge to floor care. The decreased SICU LOS did not adversely affect patient mortality or severity of illness upon SICU discharge during the 6-year period. With intensified SICU intervention, nonemergent orthotopic liver transplantation patients can have a shorter SICU LOS without adverse effects on outcome.

In situ splitting of the cadaveric liver for transplantation.

BACKGROUND: The shortage of cadaveric donor livers is the rate-limiting step in clinical liver transplantation. Split liver transplantation provides a means to expand the cadaveric donor pool. However, this concept has not reached its full potential because of inferior patient and graft survival and high complication rates when traditional ex vivo split techniques are used. Therefore we sought to evaluate the safety, applicability, and effectiveness of a new technique for split liver transplantation. METHODS: This study consists of 15 in situ split liver procurements, which resulted in 28 liver transplants. In situ splitting of selected livers from hemodynamically stable cadaveric donors was performed at the donor hospital without any additional work-up or equipment being needed. In situ liver splitting is accomplished in a manner identical to the living-donor procurement. This technique for liver splitting results in a left lateral segment graft (segments 2 and 3) and a right trisegmental graft (segments 1 and 4-8). This procedure required the use of the donor hospital operating room for an additional 1.5-2.5 hr and did not interfere with the procurement of 30 kidneys, 12 hearts, 7 lungs, and 9 pancreata from these same donors. RESULTS: The 6-month and 1-year actuarial patient survival rates were 92% and 92%, respectively, while the 6-month and 1-year actuarial graft survival rates were 86% and 86%, respectively. The 6-month and 1-year actuarial patient survival rate of patients who received a left lateral segment graft was 100% and 100%, respectively, while those who received a right trisegmental graft had 6-month and 1-year rates of 86% and 86%, respectively. The actuarial death-censored graft survival rates at 6 months and 1 year were 80% and 80%, respectively, for the left lateral segment grafts, and 93% and 93%, respectively, for the right trisegmental grafts. Alograft and patient survival was independent of United Network for Organ Sharing status at the time of liver transplantation. No patient developed a biliary stricture, required re-exploration for intra-abdominal hemorrhage, or suffered from portal vein, hepatic vein, or hepatic artery thrombosis CONCLUSIONS: In situ split liver transplantation can be accomplished without complications and provides results that are superior to those obtained previously with ex vivo methods. It abolishes ex vivo benching and prolonged ischemia times and provides two optimal grafts with hemostasis accomplished. This technique decreases pediatric waiting time and allows adult recipients to receive right-sided grafts safely. In situ splitting is the method of choice for expanding the cadaveric liver donor pool.

The impact of microsurgical hepatic arterial reconstruction on the outcome of liver transplantation for congenital biliary atresia.

BACKGROUND: Hepatic artery thrombosis (HAT) after liver transplantation for biliary atresia (BA) is a serious complication that most often leads to retransplantation (re-OLT). The purpose of the present study was: (1) to identify risk factors associated with HAT and (2) to analyze the impact of recently introduced microsurgical hepatic arterial reconstruction (MHR) on the incidence of HAT, subsequent need for re-OLT, and patient survival. METHODS: A retrospective review of 194 patients transplanted for BA was performed. One hundred and sixty-six patients (group 1) underwent conventional arterial reconstruction and 28 (group 2) had MHR. RESULTS: Actuarial survival for patients with HAT was significantly worse than for patients without HAT at 1, 2, and 5 years (71%, 61%, and 57% versus 85%, 85%, and 85%, P = 0.0007). Stepwise logistic regression analysis revealed that the risk of HAT correlated best with the type of arterial reconstruction (P = 0.007) followed by pretransplant bilirubin concentration (P = 0.04) and the number of acute rejection episodes (P = 0.03). In group 1, 32 patients developed HAT (19%), and of these, 18 underwent re-OLT for HAT. No patient in group 2 developed HAT (P = 0.006 versus group 1). One-year actuarial patient survival was 81% in group 1 and 100% in group 2 (P = 0.02). CONCLUSIONS: In OLT for BA, (1) the predominant risk factor for HAT is the technique of arterial reconstruction, and (2) MHR markedly reduces the incidence of HAT and the need for re-OLT while improving patient survival.

Rapid en bloc technique for pancreas-liver procurement. Improved early liver function.

It is our experience that warm dissection in the porta hepatis as well as extensive organ mobilization during combined pancreas-liver procurements may cause posttransplant dysfunction of the liver. To avoid this, we recently utilized a rapid en bloc procurement technique with minimal warm dissection and division of the liver and pancreas ex vivo. Fifteen procurements were performed using this rapid en bloc technique; seventeen procurements involved extensive dissection followed by sequential in situ procurement of the liver and pancreas grafts. The control group consisted of 15 age-matched patients who received livers when no pancreas was harvested. Dissection time was 157 +/- 13 min (mean +/- SEM) in the in situ group, 78 +/- 3 min in the en bloc group (P<0.02), and 51 +/- 6 min in the liver only group (P<0.02). There was no difference in donor age, cold ischemia time, or recipient United Network for Organ Sharing status. Pancreata obtained using the en bloc technique all had immediate function and there were no episodes of acute pancreatitis. Early liver graft function, as assessed by lactate dehydrogenase, serum glutamic oxaloacetic transaminase, serum glutamic pyruvic transaminase, and total bilirubin levels, was significantly lower in the en bloc and liver only group when compared with the in situ group. The total hospital stay was also significantly lower in these groups. We conclude that the rapid en bloc technique decreases operative time during the donor operation. Procurement-related injury to the liver graft is minimized without compromising pancreas graft function.

Hepatitis C. A clinical update.

Hepatitis C virus is now known to be the causative agent for at least 90% of non-A, non-B hepatitis cases. In the few years since its characterization, much has been learned about this virus and the scope of its disease. It now appears that close to 100% of infections may become chronic, with delayed but potentially devastating consequences. The treatment options for hepatitis C remain limited and less than satisfactory. A vaccine seems to be a distant goal, but other strategies for treatment may be closer. For now, the best option remains prevention.

Transjugular intrahepatic portosystemic shunts: impact on liver transplantation.

This study was designed to evaluate the impact of transjugular intrahepatic portosystemic shunts (TIPS) on liver transplantation. Historically, the complications of portal hypertension have been temporized with sclerotherapy or surgical portosystemic shunts. In patients whose liver disease progressed, liver transplantation has been used as definitive treatment. More recently, TIPS is being used increasingly for the management of the complications of portal hypertension. The impact of this new modality on liver transplantation is evaluated. The records of 135 adult patients undergoing liver transplantation at University of California at Los Angeles between October 1992 and June 1993 were reviewed. Twenty-three patients had received at least one shunt before transplantation. The TIPS procedure complicated the operative course of 5 patients (22%). In 2 patients the TIPS had been placed cephalad, making placement of the suprahepatic vena caval clamp difficult. In 2 other patients, the shunt had been placed caudad, extending in the extrahepatic portal vein. In all 4 of these patients, the intima had been damaged at the area of the subsequent anastomosis. In the fifth patient, the bile duct had been perforated during the placement of the shunt, causing diffuse bile peritonitis, which was sterile, and the transplantation was performed. The average intraoperative blood loss for these 5 patients was 13 U. There was no significant decrease in intraoperative blood loss for all patients with a TIPS when compared with 112 adults who underwent liver transplantation during the same period (11 U v 10.5 U). The TIPS stent did not improve objective intraoperative parameters as compared with liver transplant recipients without TIPS. The indications for TIPS must be carefully weighed against the potential risks of increasing the technical difficulty of the transplantation and jeopardizing the candidacy of some liver transplantation candidates. Liver transplantation is not facilitated by TIPS insertion and therefore should not be used to justify TIPS placement.

One thousand liver transplants. The lessons learned.

OBJECTIVE: To evaluate the first 1000 liver transplants performed at UCLA Medical Center to determine factors responsible for improved results. SUMMARY BACKGROUND DATA: Liver transplant has evolved impressively since the first case was performed in 1963. The 1980s have highlighted this progress with the development of better organ preservation, standardization of operative procedure, improved immunosuppressive agents, and better understanding of patient selection. METHODS: The first 100 consecutive liver transplants (group 1) performed from February 1984 through October 1986 were compared with the last 200 (group 2) performed between September 1991 and June 1992. An analysis was made of donor use; changes in patient candidacy; patient care variables; morbidity and mortality; survival data; and hospital resource use. RESULTS: In group 1, 31% of donors were refused because of medical unsuitability compared with 4% in group 2 (p < 0.0001). In group 1, alcoholic patients comprised 1% of liver transplant candidates compared with 20% group 2 (p < 0.0001). High-risk patients (United Network for Organ Sharing criteria 4) only comprised 11% of patients in group 1 compared with 37% in group 2 (p < 0.0001). Operative time (7.6 hours compared with 5.4 hours), packed cell replacement (17 units compared with 9.5 units), intensive care unit stay (10 days compared with 5 days), and hospital stay (50 days compared with 31 days) were all significantly improved (p < 0.05). In group 1, the 1-year survival rate was 73% and improved to 88% in group 2 (p < 0.0001). CONCLUSIONS: Despite unfavorable donor characteristics (obesity, cause of death, age, hypotension), most organs function well and should not be refused based on history alone. The older and high-risk patient (renal failure, ventilator dependence, portal vein pathology, and so on) is routinely transplanted with good success. Despite liberalization of both donor and recipient criteria, patient survival after liver transplant is improved, use of hospital resources is maximized, and cost reduction is achieved.