De novo hepatocellular carcinoma post-multivisceral transplantation in a child.

De novo hepatocellular carcinoma (HCC) post-transplantation in patients without viral hepatitis is extremely rare, with only three reported adult cases in the English literature. Here, we present a case of de novo HCC that developed in a 7-year-old female, who at 8 months of age received a liver, small bowel, spleen, and pancreas transplantation 6.5 years ago for gastroschisis and total parenteral nutrition (TPN)-related cirrhosis. The post-transplant course was complicated by Epstein-Barr virus (EBV) infection, post-transplant lymphoproliferative disease, and subsequent development of multifocal EBV-associated post-transplant smooth muscle tumors (EBV-PTSMT) in the small bowel 1 year and 10 months after transplantation, respectively. This was managed by reducing immunosuppression with rituximab and EBV-specific cytotoxic T-cell therapy. She was noted to have a new lesion in her transplanted liver graft 6.5 years post-transplantation that was diagnosed as HCC. The HCC was resected, and the patient remained clinically stable for 7 months. At that time, recurrence of the HCC was discovered on MRI. She passed away 6 months after. To the best of our knowledge, this is the first reported occurrence of de novo HCC post-transplantation in the pediatric population that is unrelated to viral hepatitis in either recipient or donor.

Effect of neoadjuvant chemotherapy on resectability of stage III and IV hepatoblastoma.

BACKGROUND: The potential for surgical resection of primary hepatoblastoma tumours was assessed at diagnosis, and after two and four cycles of neoadjuvant chemotherapy. METHODS: Available radiographic images for patients with stage III and IV hepatoblastoma diagnosed between 1991 and 2008 were reviewed. The extent of disease was determined at diagnosis using the PRETEXT staging system, and after two and four cycles of therapy by POST-TEXT staging. Tumour resectability based on radiographic studies was assessed independently by two surgeons with expertise in hepatic surgery who were blinded to treatment and clinical outcome. RESULTS: Radiographic images from 20 patients with hepatoblastoma were reviewed. Six of 20 tumours were downstaged after two cycles, and three additional tumours were downstaged following four cycles. All PRETEXT stage III and IV tumours were determined to be surgically unresectable at diagnosis. The number of tumours considered unresectable decreased from 16 of 20 at diagnosis to seven of 20 after two cycles, and to four of 20 after four cycles. Five of the seven tumours that were unresectable after two cycles, and all four tumours that were unresectable after four cycles would have qualified for liver transplant based on radiographic studies. CONCLUSION: The majority of stage III and IV hepatoblastomas achieved radiographic resectability after two cycles of chemotherapy. There may be an opportunity for earlier surgical intervention and potential for a reduction in chemotherapy in a considerable number of patients.

Simultaneous liver-kidney transplantation: a survey of US transplant centers.

Consensus recommendations have been published to help better define those patients who would benefit from simultaneous liver-kidney transplantation (SLK). We conducted a survey of transplant centers that perform SLK (n = 88, 65% response rate) to determine practice patterns in the United States. The majority of centers (73%) stated that they use dialysis duration whereas only 30% of centers use acute kidney injury duration as a criterion for determining need for SLK. Dialysis duration >4 weeks was used by 32% of centers, >6 weeks by 37% and >8 weeks by 32% of centers. Glomerular filtration rate (GFR) was estimated using the modified diet in renal disease (MDRD)-4 equation in roughly half of centers whereas the MDRD-6 equation was used by only 6%. In patients with chronic kidney disease, GFR < 40 mL/min was used by 24% of centers as a criterion for SLK transplants instead of the recommended threshold of < 30 mL/min. Regional differences in practices were also observed. This survey demonstrates significant variation in the criteria used for SLK among transplant centers, with few centers following the current published recommendations, and emphasizes the need for evidence-based guidelines and uniformity in studying renal dysfunction in liver transplant candidates.

Simultaneous liver-kidney transplantation summit: current state and future directions.

Although previous consensus recommendations have helped define patients who would benefit from simultaneous liver-kidney transplantation (SLK), there is a current need to reassess published guidelines for SLK because of continuing increase in proportion of liver transplant candidates with renal dysfunction and ongoing donor organ shortage. The purpose of this consensus meeting was to critically evaluate published and registry data regarding patient and renal outcomes following liver transplantation alone or SLK in liver transplant recipients with renal dysfunction. Modifications to the current guidelines for SLK and a research agenda were proposed.

Expanding the donor kidney pool: utility of renal allografts procured in a setting of uncontrolled cardiac death.

The chronic shortage of deceased kidney donors has led to increased utilization of donation after cardiac death (DCD) kidneys, the majority of which are procured in a controlled setting. The objective of this study is to evaluate transplantation outcomes from uncontrolled DCD (uDCD) donors and evaluate their utility as a source of donor kidneys. From January 1995 to December 2004, 75,865 kidney-alone transplants from donation after brain death (DBD) donors and 2136 transplants from DCD donors were reported to the United Network for Organ Sharing. Among the DCD transplants, 1814 were from controlled and 216 from uncontrolled DCD donors. The log-rank test was used to compare survival curves. The incidence of delayed graft function in controlled DCD (cDCD) was 42% and in uDCD kidneys was 51%, compared to only 24% in kidneys from DBD donors (p < 0.001). The overall graft and patient survival of DCD donors was similar to that of DBD donor kidneys (p = 0.66; p = 0.88). Despite longer donor warm and cold ischemic times, overall graft and patient survival of uDCD donors was comparable to that of cDCD donors (p = 0.65, p = 0.99). Concerted efforts should be focused on procurement of uDCD donors, which can provide another source of quality deceased donor kidneys.

Risk factors for graft survival after liver transplantation from donation after cardiac death donors: an analysis of OPTN/UNOS data.

Due to increasing use of allografts from donation after cardiac death (DCD) donors, we evaluated DCD liver transplants and impact of recipient and donor factors on graft survival. Liver transplants from DCD donors reported to UNOS were analyzed against donation after brain death (DBD) donor liver transplants performed between 1996 and 2003. We defined a recipient cumulative relative risk (RCRR) using significant risk factors identified from a Cox regression analysis: age; medical condition at transplantation; regraft status; dialysis received and serum creatinine. Graft survival from DCD donors (71% at 1 year and 60% at 3 years) were significantly inferior to DBD donors (80% at 1 year and 72% at 3 years, p < 0.001). Low-risk recipients (RCRR < or = 1.5) with low-risk DCD livers (DWIT < 30 min and CIT < 10 h, n = 226) achieved graft survival rates (81% and 67% at 1 and 3 years, respectively) not significantly different from recipients with DBD allografts (80% and 72% at 1 and 3 years, respectively, log-rank p = 0.23). Liver allografts from DCD donors may be used to increase the cadaveric donor pool, with favorable graft survival rates achieved when low-risk grafts are transplanted in a low-risk setting. Whether transplantation of these organs in low-risk recipients provides a survival benefit compared to the waiting list is unknown.

A comparison of sirolimus vs. calcineurin inhibitor-based immunosuppressive therapies in liver transplantation.

BACKGROUND: Sirolimus is a potent immunosuppressive agent whose role in liver transplantation has not been well-described. AIM: To evaluate the efficacy and side-effects of sirolimus-based immunosuppression in liver transplant patients. METHODS: Retrospective analysis of 185 patients who underwent orthotopic liver transplantation. Patients were divided into three groups: group SA, sirolimus alone (n = 28); group SC, sirolimus with calcineurin inhibitors (n =56) and group CNI, calcineurin inhibitors without sirolimus (n = 101). RESULTS: One-year patient and graft survival rates were 86.5% and 82.1% in group SA, 94.6% and 92.9% in group SC, and 83.2% and 75.2% in group CNI (P = N.S.). The rates of acute cellular rejection at 12 months were comparable among the three groups. At the time of transplantation, serum creatinine levels were significantly higher in group SA, but mean creatinine among the three groups at 1 month was similar. More patients in group SA required dialysis before orthotopic liver transplantation (group SA, 25%; group SC, 9%; group CNI, 5%; P = 0.008), but at 1 year, post-orthotopic liver transplantation dialysis rates were similar. CONCLUSIONS: Sirolimus given alone or in conjunction with calcineurin inhibitors appears to be an effective primary immunosuppressant regimen for orthotopic liver transplantation patients. Further studies to evaluate the efficacy and side-effect profile of sirolimus in liver transplant patients are warranted.

Iatrogenic pseudoaneurysms of the extrahepatic arterial vasculature: management and outcome.

BACKGROUND: Pseudoaneurysms of the extrahepatic arterial vasculature are relatively uncommon lesions following surgery and trauma. In this report we analyze the presentation, management and outcomes of these vascular lesions. Of the related surgical procedures, the reported incidence is highest following laparoscopic cholecystectomy. We hereby analyze the literature on this subject and report our experience, specifically with extrahepatic pseudoaneurysms, drawing an important distinction from intrahepatic pseudoaneurysms. METHODS: From September 1995 until July 2004, six patients, including three males and three females with a mean age of 67 years, were treated for seven extrahepatic arterial pseudoaneurysms. Patients were evaluated by endoscopy, ultrasound, computerized tomography, and angiography. Management included coil embolization or arterial ligation and/or hepatic resection. RESULTS: The mean pseudoaneurysm size was 4.9-cm (range 1.0-11.0-cm) and the locations included the right hepatic artery (n = 5), inferior pancreaticoduodenal artery (n = 1), and gastroduodenal artery (n = 1). All six patients had prior surgical or percutaneous procedures. Median latency period between the original procedure and treatment of pseudoaneurysm was 17 weeks (range one month-16 years). Clinical features ranged from the dramatic presentation of hypotension secondary to intraperitoneal aneurysmal rupture to the subtle presentation of obstructive jaundice secondary to pseudoaneurysm mass effect. The range of patient presentations created diagnostic challenges, proving that accurate diagnosis is made only by early consideration of pseudoaneurysm. Management was ligation of the right hepatic artery (n = 4) and embolization of the pseudoaneurysms (n = 2). Post-treatment sequelae included liver failure requiring liver transplant (n = 1), intrahepatic biloma requiring percutaneous drainage (n = 1) and cholangitis with right hepatic duct strictures requiring right lobectomy and biliary reconstruction (n = 1). These complications followed arterial ligation, with no complications resulting from embolization. All six patients are alive and well after a mean follow-up of 53 months. CONCLUSIONS: Our six patients demonstrate the diversity and unpredictability with which a pseudoaneurysm of the extrahepatic arterial vasculature may present in terms of initial symptoms, prior procedures, and the latency period between presentation and prior procedure. Through our experience and an analysis of the literature, we recommend a diagnostic and management approach for these patients.

Liver transplantation in cystic fibrosis.

Liver disease is the second most common cause of death in patients with cystic fibrosis (CF). Improvement in surgical techniques, medical management, and imaging modalities has broadened the range of options for treatment of these patients. Medical management with ursodeoxycholic acid and nutritional support may help decelerate the progression of liver disease. A timely evaluation of CF patients with liver involvement for transplantation is important. Such evaluation should not be delayed until signs of hepatic decompensation occur. Combined lung-liver transplant can be considered for patients with advanced pulmonary disease. Pretransplant management of portal hypertension with a portosystemic shunt procedure is an option for patients with well-preserved synthetic liver function. Improvement in lung function after liver transplantation and no significant risk of pulmonary infection with immunosuppressive therapy have been reported. Review of individual center experiences have shown satisfactory survival and improved quality of life for CF patients undergoing liver transplant.

Live-donor liver transplantation: the USC experience.

BACKGROUND: Liver transplantation is currently the standard of care for patients with end stage liver disease. However due to the cadaveric organ shortage, live donor liver transplantation (LDLT), has been recently introduced as a potential solution. We analyzed and support our initial experience with this procedure at USC. MATERIAL AND METHODS: From September 1998 until July 2000, a total of 27 patients underwent LDLT at USC University Hospital and Los Angeles Children's Hospital. There were 12 children with the median age of 10 months (4-114) and 15 adults with the median age of 56 years (35-65). The most common indication for transplantation was biliary atresia for children and hepatitis C for adults. RESULTS: All donors did well postoperatively; the median postoperative stay was five days (5-7) for left lateral segmentectomy and seven days (4-12) for lobar donation. None of the donors required blood transfusion, re-operation or postoperative invasive procedure. However, five of them (18%) experienced minor complications. The survival rate in pediatric patients was 100% and only one graft was lost at nine months due to rejection. Two adult recipients died in the postoperative period, one from graft non-function and one from necrotizing fascitis. 37% of adult recipients experienced postoperative complications, mainly related to biliary reconstruction. Also 26% of the recipients underwent reoperation for some of these complications. CONCLUSION: LDLT is an excellent alternative to cadaveric transplantation with excellent results in the pediatric population. However, in adult patients it still carries a significant complication rate and it should be used with caution.

Treatment of tacrolimus-related adverse effects by conversion to cyclosporine in liver transplant recipients.

When tacrolimus side effects persist despite dose reduction, conversion to cyclosporine-based immunosuppression (CyA) is necessary. We characterized tacrolimus side effects that warranted discontinuation of the drug, and outcomes after conversion. Of 388 liver recipients who received tacrolimus as primary immunosuppression, 70 required conversion to CyA. We recorded indication for conversion, whether conversion was early or late after transplantation, tacrolimus dose and trough blood level at conversion, and incidence of rejection after conversion. Conversion was early in 29 patients (41.4%) and late in 41 (58.6%). Indications for early conversion were neurotoxicity (20), (insulin-dependent) diabetes mellitus (IDDM) (5), nephrotoxicity (3), gastrointestinal (GI) toxicity (6), and cardiomyopathy (1), and for late conversion were neurotoxicity (15), IDDM (12), nephrotoxicity (3), GI toxicity (5), hepatotoxicity (6), post-transplant lmphoproliferate disease (PTLD) (2), cardiomyopathy (1), hemolytic anemia (1), and pruritus (1). All early-conversion patients showed improvement/resolution of symptoms. Among late-conversion patients, 37 (90.2%) had improvement/resolution; in 4 (9.8%), adverse effects persisted. The overall rejection rate was 30%. Sixty-two patients (88.6%) are alive with functioning grafts 686 +/- 362 days (range, 154-1433 days) after conversion. When tacrolimus side effects are unresponsive to dose reduction, conversion to CyA can be accomplished safely, with no increased risk of rejection and excellent long-term outcome.

Successful transplantation of pediatric en bloc kidneys with bilateral double ureters.

We report a case in which en bloc kidneys with bilateral double ureters from a 5-month-old donor were successfully transplanted into a 25-year-old recipient. No stents were used. There were no complications after the transplant. The patient remains well at more than 1.5 years post-transplantation with serum creatinine 1.2 mg/dl.

Development of an in situ isolated porcine liver perfusion model for tightly controlled physiologic and pharmacologic studies.

Several types of isolated perfused porcine liver models have been proposed for the study of hepatic assist, preservation injury, and specific physiologic or pharmacologic mechanisms. The development of a more general in situ isolated perfused model applicable to a broad range of studies is presented. This model eliminates or minimizes the shortcomings of previous models including ischemic injury prior to perfusion, limited range of vascular pressures and flows, nonphysiologic sources of portal and hepatic artery perfusion, and coupling of the liver to uncontrolled whole-body homeostatic mechanisms. Essentially the model as presented can be described as an autologous transplanted liver without preservation or ischemic injury, functioning within an adrenalectomized, cardiac output and temperature-controlled animal. Independent control of the dual hepatic vascular supply is maintained with pulsatile perfusion of the hepatic artery from the left atrium and nonpulsatile perfusion of the portal vein via the portal system. Oxygenators are not required. Hepatic vein pressure can be controlled independently of hepatic blood flow and systemic hemodynamics. Pharmacologic studies are not restricted to drugs whose termination of action is limited to hepatic metabolism because normal routes of drug redistribution, metabolism, and excretion are present. The model exhibits normal oxygen metabolism and classic control of hepatic artery resistance by portal vein blood flow. There are rather obvious significant advantages inherent in this model for tightly controlled hepatic physiologic and pharmacologic studies.

Hepatic artery pseudoaneurysm and hemobilia following laser laparoscopic cholecystectomy. A case report.

This report describes injury to the hepatic artery with pseudoaneurysm formation and hemobilia following the use of laser-assisted dissection to perform laparoscopic cholecystectomy. A 57-year-old woman was referred emergently 2 weeks after laser laparoscopic cholecystectomy with upper abdominal pain, upper gastrointestinal bleeding, and jaundice. A selective hepatic arteriogram showed a right hepatic artery pseudoaneurysm which was embolized. Two weeks later the patient had recurrent hemobilia as the result of blood flow restoration in the pseudoaneurysm and a fistula to the cystic duct remnant. She was treated with two additional embolizations and direct injection of the aneurysm with thrombogenic material. Follow-up at 2 years showed no further recurrence. Since the laser has never been shown to have advantages over electrocautery, its use during laparoscopic cholecystectomy is difficult to justify.