Timothy M. Schmitt

Temporary placement of fully covered self-expandable metal stents in benign biliary strictures: midterm evaluation (with video)

BACKGROUND Benign biliary strictures (BBS) have been endoscopically managed with placement of multiple plastic stents. Uncovered metal stents have been associated with mucosal hyperplasia and partially covered self-expandable metal stents with migration. Recently, fully covered self-expandable metal stents (CSEMSs) with anchoring fins have become available. OBJECTIVE Our purpose was to analyze the efficacy and complication rates of CSEMSs in the treatment of BBS. DESIGN CSEMSs (10-mm diameter) were placed in 44 patients with BBS. CSEMSs were left in place until adequate biliary drainage was achieved, confirmed by resolution of symptoms, normalization of liver function tests, and imaging. SETTING Tertiary care center with long-standing experience with metal stents. PATIENTS A total of 44 patients with BBS (28 men, median age 53.5 years) were included. The preprocedure diagnoses included chronic pancreatitis (n = 19), gallstone-related strictures (n = 14), post liver transplant (n = 9), autoimmune pancreatitis (n = 1), and primary sclerosing cholangitis (n = 1). INTERVENTION ERCP with temporary CSEMS placement. Removal of CSEMSs was performed with a snare or rat tooth. MAIN OUTCOME MEASUREMENTS Stricture resolution and morbidity. RESULTS The median time of CSEMS placement was 3.3 months (interquartile range 3.0-4.8). Resolution of the BBS was confirmed in 34 of 41 patients (83%) after a median postremoval follow-up time of 3.8 months (interquartile range 1.2-7.7). Complications were observed in 6 (14%) patients after CSEMS placement and in 4 (9%) after CSEMS removal. LIMITATION Pilot study from a single center. CONCLUSION Temporary placement of CSEMSs for BBS may offer an alternative to plastic stenting. Further investigation is required to further assess safety and long-term efficacy.

Fully covered self-expandable metallic stents in the management of complex biliary leaks: preliminary data - a case series.

Techniques for management of bile leaks include biliary sphincterotomy and stenting. Partially covered self-expandable metallic stents have been used in complex bile leaks, but they are associated with migration and hyperplasia. A fully covered self-expandable metallic stent (CSEMS) with anchoring fins might be effective in treating bile leaks without these complications. The aim of this study was to investigate the safety and efficacy of temporary placement of a CSEMS for resolving complex bile leaks. Thirteen patients with complex bile leaks underwent endoscopic retrograde cholangiopancreatography (ERCP) with temporary placement of a CSEMS following cholecystectomy (n = 8) or liver transplantation (n = 5). All patients had resolution of their bile leaks. Two patients developed a stricture below the confluence. Three patients died from unrelated causes. Two deaths occurred prior to CSEMS removal. Ten of 11 patients had evidence of biliary debris at the time of CSEMS removal. Overall, temporary placement of CSEMS is efficacious atresolving bile leaks. CSEMS are less prone to migration, but are associated with ulcerations, de novo choledocholithiasis, and strictures.

Pretransplant predictors of recovery of renal function after liver transplantation

The Model for End‐Stage Liver Disease system has given priority on the liver transplant waiting list to candidates with renal failure. This study determined the predictors of spontaneous recovery of renal function after transplantation in 1041 liver transplant recipients on renal replacement therapy (RRT) at the time of transplant (from February 2002 to January 2007). Data from these patients were obtained from the US Organ Procurement and Transplantation Network and US Renal Data System databases. Univariate and multivariate survival models were constructed along with multivariate logistic regression models to find independent predictors of spontaneous renal recovery. Seven hundred seven recipients (67.9%) had spontaneous recovery of renal function after liver transplantation. Those recovering spontaneously had a significantly shorter course of RRT in the pretransplant time period (15.6 versus 36.6 days, P < 0.001). Recovery of renal function was observed in 70.8% and 11.5% of recipients on RRT for less than 30 days and more than 90 days, respectively. Other statistically significant pretransplant variables independently associated with recovery of renal function included recipient age, recipient pretransplant diabetes, and donor age. In conclusion, the duration of pretransplant RRT is highly predictive of spontaneous renal recovery post‐transplant. Liver transplant candidates requiring less than 30 days of pretransplant RRT are likely to spontaneously recover renal function after liver transplantation, whereas those on RRT for more than 90 days are not. Liver Transpl, 2010.

Liver allografts from hepatitis C positive donors can offer good outcomes in hepatitis C positive recipients: a US National Transplant Registry analysis

Organ donors are screened for the hepatitis C antibody (anti‐HCV) and those with positive tests can be used under extended criteria donation. However, there is still a question of long‐term organ viability. The aim of this study was to assess the long‐term outcomes of anti‐HCV positive (HCV+) liver grafts. The US Organ Procurement and Transplantation Network Scientific Registry was reviewed for the period from April 1994 to February 6, 2008 and 56 275 liver transplantations were analyzed. In total, there were 19 496 HCV+ recipients and 934 HCV+ donors. Patient and graft survival were assessed accounting for both donor and recipient anti‐HCV status. Multivariable proportional hazards survival models were developed to adjust for factors known to affect post‐transplant survival. With anti‐HCV negative (HCV−) recipient/HCV− donor as the reference, the adjusted hazard ratio for death was similar for HCV+ recipient/HCV− donor compared with HCV+ recipient/HCV+ donor (1.176 vs. 1.165, P = 0.91). Our results suggest that HCV+ liver donors do not subject the HCV+ recipient to an increased risk for death over the HCV− donor, keeping in mind that careful donor and recipient selection is critical for the proper use of these extended criteria donors.

Combined liver-kidney and liver transplantation in patients with renal failure outcomes in the MELD era.

With the implementation of the Model for End‐Stage Liver Disease (MELD) scoring system, the number of combined liver–kidney transplants (CLKT) has increased dramatically. The United Network for Organ Sharing (UNOS) dataset was analysed for adult recipients with renal failure for the period between February 2002 and April 2006. This group was subdivided into patients on hemodialysis (HD) and to those not on HD prior to transplantation. All recipients in renal failure (serum creatinine ≥2.5 mg/dl) at the time of transplantation were included. A total of 1397 subjects were in renal failure but not on HD (18% received a CLKT, 82% underwent LT alone). Another 1740 subjects were on HD prior to transplantation (41% received a CLKT while 59% received a LT). In dialysis‐dependent recipients, Cox regression analysis demonstrated CLKT had an independent protective effect. In subjects on HD, CLKT had improved survival at 1 year (79.4 vs. 73.7%, P = 0.004). In patients in renal failure without HD, CLKT was not protective. CLKT subjects had a nonsignificant difference in survival as compared with patients who had undergone liver transplantation alone, at 1 year (81.0% vs. 78.8%, P > 0.10). In subjects undergoing CLKT, there was improved survival at 1 year as compared with LT‐alone patients on hemodialysis; however, in patients with renal failure, but not on hemodialysis, there was no difference in survival when comparing CLKT to LT‐alone.

Long-term outcomes of donation after cardiac death liver allografts from a single center.

Abstract:  Organ shortage continues to be a major challenge in transplantation. Recent experience with controlled non‐heart‐beating or donation after cardiac death (DCD) are encouraging. However, long‐term outcomes of DCD liver allografts are limited. In this study, we present outcomes of 19 DCD liver allografts with follow‐up >4.5 years. During 1998–2001, 19 (4.1%) liver transplants (LT) with DCD allografts were performed at our center. Conventional heart‐beating donors included 234 standard criteria donors (SCD) and 214 extended criteria donors (ECD). We found that DCD allografts had equivalent rates of primary non‐function and biliary complications as compared with SCD and ECD. The overall one‐, two‐, and five‐yr DCD graft and patient survival was 73.7%, 68.4%, and 63.2%, and 89.5%, 89.5%, and 89.5%, respectively. DCD graft survival was similar to graft survival of SCD and ECD in non hepatitis C virus (HCV) recipients (p > 0.370). In contrast, DCD graft survival was significantly reduced in HCV recipients (p = 0.007). In conclusion, DCD liver allografts are durable and have acceptable long‐term outcomes. Further research is required to assess the impact of HCV on DCD allograft survival.

Donor factors predicting recipient survival after liver retransplantation : The retransplant donor risk index

The use of extended criteria liver donors (ECD) is controversial, especially in the setting of retransplantation. The aims of this study are to investigate the effects of ECD grafts on retransplantation and to develop a predictive mortality index in liver retransplantation based on the previously established donor risk index. The United Network for Organ Sharing (UNOS) liver transplant dataset was analyzed for all adult, non‐status 1, liver retransplantations occurring in the United States since February 2002. All donors were categorized for multiple characteristics of ECD, and using multivariate survival models a retransplant donor risk index (ReTxDRI) was developed. A total of 1327 retransplants were analyzed. There were 611 (46%) recipients who received livers with at least one ECD criterion. The use of ECD grafts in recipients with HCV did not incur worse survival than the non‐ECD grafts. The addition of the cause of recipient graft failure to the donor risk index formed the ReTxDRI. After adjusting for multiple recipient factors, the ReTxDRI was predictive of overall recipient survival and was a strongly independent predictor of death after retransplantation (HR 2.49, 95% CI 1.89–3.27, p < 0.0001). The use of the ReTxDRI can improve recipient and donor matching and help to optimize posttransplant survival in liver retransplantation.

Sorafenib therapy for hepatocellular carcinoma prior to liver transplant is associated with increased complications after transplant

This study compared post‐transplant outcomes of patients with hepatocellular carcinoma (HCC) who took sorafenib prior to orthotopic liver transplantation (OLT) with those patients who were not treated with sorafenib. Thirty‐three patients with HCC who were listed for liver transplantation were studied: 10 patients were treated with sorafenib prior to transplantation in an attempt to prevent progression of HCC while awaiting transplant. The remaining 23 patients were considered controls. The mean duration of sorafenib use was 19.2 (SD 25.2) weeks. Overall death rates were similar between the sorafenib group and control group (20% vs. 8.7%, respectively, P = 0.56). However, the patients in the sorafenib group had a higher incidence of acute cellular rejection following transplantation (67% vs. 22%, OR = 7.2, 95% CI 1.3–39.6, P = 0.04). The sorafenib group also had a higher rate of early biliary complications (67% vs. 17%, OR = 9.5, 1.6–55.0, P = 0.01). The use of sorafenib was found to be an independent predictor of post‐transplant biliary complications (OR 12.6, 1.4–116.2, P = 0.03). Sorafenib administration prior to OLT appears to be associated with an increase in biliary complications and possibly in acute rejection following liver transplantation. Caution should be taken in this setting until larger studies are completed.

Endovascular Therapy for Hepatic Artery Stenosis and Thrombosis Following Liver Transplantation

Purpose: To evaluate the effectiveness of endovascular management of steno-oclusive disease in liver transplants. Methods: Retrospective review of liver transplant recipients with hepatic artery stenosis (HAS) or thrombosis (HAT) was performed. The HAS group was treated with balloon angioplasty with selective stent placement. The HAT group was treated with catheter-directed thrombolysis. Primary, unassisted, and assisted patency and graft survival rates were calculated. Results: In all, 31 patients were identified (21 males; mean age, 51 years). A total of 25 of 31 (81%) patients had HAS and 6 of 31 (19%) had HAT. Collectively, a total of 35 endovascular procedures were performed to treat HAS in 25 patients. Overall technical success rate was 91%, with 11% major complication rate. Primary-assisted patency rate and graft survival at 6 and 12 months were 87% and 81%, and 76% and 72%, respectively. Only 1 successful thrombolysis of HAT was achieved. Conclusion: Endovascular management is effective for HAS but not for HAT.

Elevated stricture rate following the use of fully covered self-expandable metal biliary stents for biliary leaks following liver transplantation

BACKGROUND Biliary leaks and strictures are common complications after liver transplantation and can be managed surgically or endoscopically. Endoscopic management using fully covered self-expandable metal stents (FCSEMS) might provide some advantages over the commonly used plastic stents in the management of bile leaks after liver transplantation. METHODS Between December 2006 and January 2009, 17 liver transplant recipients underwent placement of a FCSEMS for treatment of biliary leaks. RESULTS FCSEMS were deployed at median of 18 days (range: 6 - 160) after liver transplantation and left in place for a median of 102 days (range: 35 - 427), with a median follow-up after FCSEMS removal of 407 days (range: 27 - 972). Long-term leak control was obtained in all but one patient. Complications included 6 clinically significant biliary strictures (35 %), which were treated with repeat stent placement, and two clinically insignificant strictures (12 %) which required no intervention. Additionally, three patients (18 %) had biliary ulcerations after stent removal, confirmed by choledochoscopy, and were managed conservatively. Two patients required repeat liver transplantation due to hepatic artery thrombosis, and one patient died from sepsis unrelated to FCSEMS stenting. CONCLUSIONS FCSEMS treat biliary leaks effectively, but carry a relatively high stricture risk in patients who have received liver transplants. FCSEMS cannot be recommended for management of biliary leaks following liver transplantation at this point.