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Background: The therapeutic options that provide the best long-term outcome for patients who have a combination of end-stage renal disease and compensated cirrhosis are unknown., Methods: Given the paucity of data and the lack of clinical guidance in this area, a national survey was conducted in the form of an e-mail-based questionnaire addressed to the transplantation surgeons registered with the American Society of Transplant Surgeons., Results: Of the 818 surgeons invited to participate in the survey, 167 (20%) responded. Twenty-one (12.6%) respondents indicated that their program performed <50 kidney transplantations per year, 49 (29.3%) reported performing 50 to 100 kidney transplantations per year, and the majority, 97 (58.1%) of respondents, performed >100 kidney transplantations per year. The majority, 116 (69.5%), believed that compensated cirrhotic patients with end-stage renal disease could be considered for renal transplantation alone, 45 (26.9%) respondents believed that compensated cirrhotic patients on dialysis could only be considered for simultaneous liver-kidney transplantation, and 6 (3.6%) believed that this population of patients was not suitable for kidney transplantation alone., Conclusions: Our findings suggest that there is a substantial heterogeneity of opinion among transplantation surgeons towards transplantation options for compensated cirrhotic patients. Further data is needed to define best practices and clinical guidelines., (Published by Elsevier Inc.)

Liver transplantation with the use of donation after circulatory death (DCD) is associated with ischemic cholangiopathy (IC) often leading to graft loss. We hypothesized that serial postoperative analysis of alkaline phosphatase and bilirubin might identify patients who would later on develop ischemic cholangiopathy and/or graft loss, allowing early recognition and potentially retransplantation. The University of Washington DCD experience totals 89 DCD liver transplantations performed from 2003 to 2011 with Kaplan-Meier estimated 5-year patient and graft survival rates of 81.6% and 75.6%, respectively; 84/89 patients transplanted with DCD livers lived ≥ 60 days after transplantation and were analyzed. Serum bilirubin and alkaline phosphatase levels at 1 week, 2 week, 1 month, and 2 months after transplantation were analyzed. Two-month serum bilirubin and alkaline phosphatase proved to have the strongest associations with development of IC and graft failure. Two-month alkaline phosphatase of <100 U/L had a negative predictive value of 97% for development of IC. Two-month alkaline phosphatase demonstrated an inflection starting at >300 U/L strongly associated with development of IC (P < .0001). Serum bilirubin at 2 months was most strongly associated with graft failure within the 1st year with a strong inflection point at 2.5 mg/dL (P = .0001). All jaundiced recipients at 60 days after transplantation (bilirubin >2.5 mg/dL) developed graft failure within the 1st year (P < .0001). Use of these early surrogate markers could facilitate prioritization and early retransplantation for DCD liver recipients with allografts destined for failure., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Transplantation utilizing donation after circulatory death (DCD) donors is associated with ischemic cholangiopathy (IC) and graft loss. The University of Washington (UW) DCD experience totals 89 DCD liver transplants performed between 2003 and 2011. Overall outcome after DCD liver transplantation at UW demonstrates Kaplan-Meier estimated 5-year patient and graft survival rates of 81.6% and 75.6%, respectively, with the great majority of patient and graft losses occurring in the first-year posttransplant from IC. Our program has almost exclusively utilized either anti-thymocyte globulin (ATG) or basiliximab induction (86/89) for DCD liver transplantations. Analysis of the differential effect of induction agent on graft survival demonstrated graft survival of 96.9% at 1 year for ATG versus 75.9% for basiliximab (p = 0.013). The improved survival did not appear to be from a lower rate of rejection (21.9% vs. 22.2%) but rather a differential rate of IC, 35.2% for basiliximab versus 12.5% for ATG (p = 0.011). Multivariable analysis demonstrated induction agent to be independently associated with graft survival and IC free graft survival when analyzed against variables including donor age, fWIT, donor cold ischemia time and transplant era., (© Copyright 2014 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Background: The protective effect of the liver allograft when simultaneously transplanted with a kidney in the setting of allosensitization is unclear., Methods: We analyzed the significance of sensitization, defined based on positive cytotoxicity crossmatches, positive flow cytometry crossmatches, and/or the presence of high levels of donor-specific antibodies, on the outcomes of simultaneous liver and kidney (SLK) transplantation. We reviewed 56 SLK performed at our center through December 31, 2011 and identified 13 patients who met high sensitization criteria., Results: Median patient survival was not significantly different: 86 months (95% confidence interval [CI], 47-135) for nonsensitized patients versus 151 months (95% CI, 4 to ∞) for sensitized patients (P=0.5). The 5-year survival was 67% (95% CI, 0.5-0.8) in the nonsensitized group and 64% (95% CI, 0.3-0.9) in the sensitized group. There were six renal allograft failures in the nonsensitized group but none in the sensitized group. The adjusted hazard ratios associated with the risk of death or the combined risk of death or renal allograft failure were 0.7 (95% CI, 0.1-3.8) and 0.4 (95% CI, 0.1-2.2) for sensitized versus nonsensitized patients. There were significantly more renal allograft rejections in the sensitized group (5 vs. 1; P=0.002) in the first year after transplantation, only one showing C4d positivity. Creatinine levels at 1 year after transplantation were similar: 1.5 mg/dL in the nonsensitized group versus 1.36 mg/dL in the sensitized group (P=0.6)., Conclusion: Sensitization does not appear to have a significant negative impact on the survival of SLK patients.

When hepatic failure occurs in newborns, most cases are because of viral hepatitis, metabolic diseases, and neonatal hemochromatosis. It is rare to have liver failure presenting in the first day after birth. We report a unique case of a newborn baby with liver failure in the first day of life who received a reduced segment II and III graft when she was 19 days old and became the youngest survivor of LDLT. Common and rare causes of liver failure in this age group were excluded by appropriate testing. She underwent a liver biopsy that showed a liver devoid of hepatocytes. Similar pathological findings were found in the explanted liver. She was discharged from the hospital with normal graft function three months after the transplant., (© 2010 John Wiley & Sons A/S.)

Pancreas transplantation is an effective treatment option for patients with complicated diabetes mellitus. Pancreas allograft recipients are followed with laboratory markers such as serum amylase, lipase and glucose levels. Hyperglycemia may indicate severe acute rejection and has recently been associated with antibody-mediated (humoral) rejection. In this report, we describe a unique case of a pancreas-after-kidney (PAK) transplant recipient with the rare presentation of pancreatic panniculitis, biopsy-proven severe acute cellular and antibody-mediated pancreas allograft rejection and surprisingly well-preserved endocrine function despite treatment with high dose steroids. We discuss the clinicopathologic features of antibody-mediated pancreas rejection, including the importance of correlating pancreas allograft biopsy, C4d staining and donor specific antibodies, to diagnose antibody-mediated rejection and initiate the correct treatment., (©2010 The Authors Journal compilation©2010 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Introduction: The use of hepatitis B core antibody-positive donor livers (HBcAb(+)) has steadily increased. According to a recent multivariate analysis of United Network for Organ Sharing (UNOS) data, there was no significant increase in the risk of using these donors. The increased risk among the hepatitis C virus (HCV)-positive subgroup noted in a univariate model disappeared upon multivariate analysis. However, deeper scrutiny may show that HCV-positive recipients may be at increased risk with HBcAb(+) donor livers, as they require simultaneous treatment with two antiviral regimens there may be deleterious interactions between the two viruses. Thus, the issue of HBcAb(+) donors for HCV-positive recipients merits more detailed analysis., Methods: Using UNOS registry data of all liver transplantations performed during the Model for End-Stage Liver Disease era from February 2002 through November 2007, we analyzed graft survival using Kaplan-Meier and Cox regression analyses., Results: Of the 12,543 HCV-positive recipients, 2,543 received HBcAb(-) livers and 853 received HBcAb(+) livers. While Kaplan-Meier analysis showed significantly lower graft survival among HCV-negative recipients of HBcAb(+) livers (P = .0001), there was no significant effect on graft survival among the HCV-positive population (P = .2). To detect an early effect in HCV-positive recipients, we examined 1-year graft survival, observing no significant difference (P = .3). To exclude a possible late effect, we examined graft survival in the HCV-positive population conditional upon surviving at least 1 year after transplantation; no significant difference was observed (P = .6). The elimination of potentially confounding codiagnoses, such as hepatitis B virus, alcoholism, acute graft failure, and hepatocellular cancer did not alter the findings. On univariate analysis, the lack of a significant effect persisted among the HCV population. However, the significant effect observed in the univariate model for the HCV-negative population became insignificant when combined with other risk factors in the multivariate model., Conclusion: The use of HBcAb(+) livers in recipients with HCV did not appear to have a significant impact on graft survival., (Copyright © 2010. Published by Elsevier Inc.)

Background: Pancreas and kidney allograft function is routinely monitored with serum studies (amylase, lipase, and creatinine). Increased levels commonly prompt tissue biopsy, to diagnose cause of graft dysfunction. Historically, pancreas allografts were infrequently biopsied, although serum enzymes and renal rejection may be poor surrogates for pancreas status., Methods: Pancreas allograft biopsies at our center were reviewed and reclassified according to University of Maryland (UMD) and Banff criteria; C4d immunostaining was performed. Findings were correlated with clinical data and renal allograft biopsies., Results: Fifty-six pancreas allograft biopsies from 27 patients were evaluated. UMD and Banff grading were similar, although two UMD "indeterminate" biopsies were Banff grade 1 rejection. There were 21 concurrent pancreas and renal biopsies, all from simultaneous pancreas-kidney allograft recipients. Thirteen pairs were concordant for rejection; eight pairs were discordant for rejection (38%); six pairs showed pancreas rejection without kidney rejection, and two pairs showed the converse. Fourteen patients had a total of 21 follow-up pancreas allograft biopsies. Seven biopsies showed a lower grade of rejection on follow-up biopsy, 4 biopsies showed more severe rejection, and 10 had unchanged grade. In only 9 of these 21 (43%) cases, did the interval serum amylase or lipase trend parallel the subsequent biopsy diagnosis., Conclusions: With a high biopsy discordance rate, our data suggest that renal allograft rejection is a poor surrogate for pancreas allograft status. Likewise, serum amylase and lipase levels do not predict response to rejection therapy. Surveillance or posttherapy pancreas allograft biopsies may be a useful means to monitor pancreas allograft status.

Objective: Our aim was to determine whether variant hepatic artery anatomy in a liver transplant recipient increases the risk of hepatic artery complications after liver transplantation., Materials and Methods: The study group consisted of 84 patients who underwent gadolinium-enhanced 3D MR angiography before orthotopic liver transplantation in which a branch patch arterial anastomosis at the gastroduodenal takeoff was used. MR angiography studies were retrospectively reviewed and assessed for the presence and type of variant hepatic artery anatomy. The diameter of the distal common hepatic artery was measured. The incidence of posttransplantation hepatic artery stenosis or thrombosis was assessed., Results: Seven (8.3%) of the 84 patients developed hepatic artery complications after transplantation. Of the 24 patients with variant hepatic artery anatomy, five (20.8%) had posttransplantation/ hepatic artery complications. In contrast, only two (3.3%) of the 60 patients with classic hepatic artery anatomy had complications. The higher complication rate in patients with variant hepatic artery anatomy was statistically significant (p < 0.05). The odds ratio was 7.6 (95% confidence interval, 1.4-42.6). The diameter of the distal common hepatic artery was smaller in patients with variant hepatic artery anatomy compared with those with classic hepatic artery anatomy (range, 4.3-7.1 mm [mean, 5.8 mm] vs 4.0-8.9 mm [mean 6.3 mm], p < 0.05), and it was also smaller in patients who had posttransplantation hepatic artery complications compared with those who had no complications (range, 4.2-6.3 mm [mean, 5.2 mm] vs 4.0-8.9 mm, [mean, 6.2 mm], p < 0.01)., Conclusion: Variant hepatic artery anatomy in a liver transplant recipient increased the risk of hepatic artery complications after transplantation. The smaller caliber of the native common hepatic artery may contribute to the higher risk.

Many centers have adopted laparoscopic and hand-assisted laparoscopic (HAL) techniques for live donor nephrectomy. Currently, the majority of laparoscopic living donor kidneys are procured from the left side because of the longer renal vein and improved transplantation. However, indications exist for right donor nephrectomy. We present our technique of HAL right-sided donor nephrectomy. A key feature of our dissection is wide mobilization of adjacent structures to achieve good exposure of the right kidney and inferior vena cava. In addition, the use of the hand permits optimal positioning of the kidney for division of the renal vessels with the vascular stapler. At the time of division of the renal vein, the stapler is placed on the wall of the inferior vena cava in order to gain maximal length. This technique has allowed HAL right-sided donor nephrectomy to be performed safely when indicated.

Jejunoileal bypass (JIB) is a weight loss procedure in which malabsorption is produced by connecting a short length of proximal jejunum to the distal ileum. Because 90% of the small intestine is bypassed, it may have impact on the dose-concentration response of oral cyclosporine (CsA). The authors characterized the dose-adjusted blood concentrations of CsA obtained 2 hours (C2) after oral microemulsion CsA (ME-CsA) in a liver transplant (LTx) subject with an intact JIB, as compared with those from seven LTx controls without JIB. The biliary reconstruction involved choledochocholedochostomy without external drainage in all patients. ME-CsA was administered via a nasogastric tube within 24 hours after graft reperfusion. Oral fluconazole was given prophylactically to the study subject only for 6 days after LTx. During the first week after LTx, the dose-adjusted C2 (mean +/- SD) for the study subject and for controls was 53 +/- 10 and 106 +/- 47 ng/mL, respectively (P < 0.001). The corresponding value during the period from day 7 to day 107 was 105 +/- 40 and 257 +/- 86 ng/mL, respectively (P < 0.001). Multiple linear regression revealed that dosage, days after LTx, and the presence of a JIB were all independent predictors of C2 (R2 = 0.798, P = 0.037). Lack of bile resulting in malabsorption of ME-CsA was not thought to be significant contributor to her low dose-adjusted C2 because there was no external bile drainage and a portion of terminal ileum, where most bile acid reabsorption occurred, was still available after JIB. The fact that fluconazole failed to increase the dose-adjusted C2 in the study subject supports that enteric clearance of CsA may become clinically unimportant after JIB. Therefore, the low dose-adjusted C2 is most likely explained by the reduced bowel length and associated absorptive surface area after JIB. In conclusion, patients with JIB may require higher doses of ME-CsA.

Background: We first introduced the orthotopic liver transplantation utilizing cavaplasty technique in 1994. This paper describes the surgical technique and assesses the outcome of the cavaplasty OLT., Methods: The cavaplasty procedure was used in 115 consecutive orthotopic liver transplantations, including six left lateral and two right lobe transplantations, between November 1994 and September 2000. Fifty-three (66.3%) transplantations required femoro-axillary veno-venous bypass in the initial 4 years, whereas only eight (22.9%) needed VB in the subsequent 2 years. Conversion to piggyback or standard technique was not necessary in any patient., Results: Median results are as follows: operative time 4.5 hr, warm ischemia time 25 min, and blood transfused (packed red blood cells) 6 units. These findings did not differ between first transplantation and retransplantation. There were no perioperative deaths related to the cavaplasty technique. No hepatic venous outflow obstruction was observed, including living-related OLTs. No patient required postoperative hemodialysis for acute renal failure. The median intensive care and hospital stays were 2 days and 10 days, respectively., Conclusions: The cavaplasty technique requires no retrocaval, hepatic vein, or short hepatic vein dissection, and the inferior vena cava can be preserved, which provides advantages for hepatectomy and easy hemostasis, especially during retransplantation. The wide-open triangular caval anastomosis is easy to perform, allowing short implantation time and size matching and avoiding outflow obstruction. The short implantation time reduces the need for veno-venous bypass. Our experience indicates that the cavaplasty technique can be applied to all patients and is justified by minimal technical complications.

A 38-year-old woman with type 1 diabetes underwent kidney-pancreas transplantation. Her postoperative course was complicated due to recurrent acute graft rejections and pancreatitis. After initial immunosuppression with microemulsion cyclosporine, mycophenolate mofetil, and prednisone with muromonab-CD3 induction, cyclosporine was switched to tacrolimus on day 44. The initial dosage was 5 mg twice/day, but it was gradually increased to 10 mg twice/day, aiming at 15-20 ng/ml. On day 17 of tacrolimus therapy the woman developed sudden hearing loss with tinnitus. The serum tacrolimus level was 28.3 ng/ml (therapeutic range 10-20 ng/ml) on day 20 of tacrolimus therapy, and peaked at 34.9 ng/ml on day 28. Two audiograms performed on days 28 and 29 confirmed bilateral hearing loss of 80% for speech perception, characterized as mild to moderate sensorineural hearing loss with speech reception threshold of 35 dB (normal < 20 dB) in both ears. The tacrolimus dosage was gradually reduced to 6 mg twice/day by day 36, with drug level 9.7 ng/ml, after which her hearing gradually recovered.

Introduction: The purpose was to study reentry in a rabbit model of infarction., Methods and Results: A model of an infarct epicardial border zone was produced in Langendorff perfused rabbit hearts by freezing the inner two thirds of the left ventricular wall, allowing only a thin epicardial muscle layer to survive. Reentrant circuits causing stable ventricular tachycardia occurred in the surviving rim of epicardial muscle as shown by mapping impulse propagation with a 196-electrode array. The circuits were functional, and reentry did not occur around an anatomical obstacle. Slow conduction in the circuits was caused by the anisotropic properties of the epicardial muscle. Activation in the circuits was slow transverse to the long axis of the fiber bundles and rapid parallel to the long axis. Other features of the circuits, including orientation of the central functional line of block parallel to the fiber long axis, and an oval shape are also characteristic of anisotropic reentry. Since the slow conduction causing reentry is a result of poor transverse intercellular coupling, we determined whether the "uncoupler" heptanol would cause block in the circuits and terminate tachycardia. Heptanol in concentrations up to 1.2 mM slowed conduction in the transverse and longitudinal directions in the circuits and sometimes extended the central line of functional block. It did not, however, stop reentry because the reentrant impulse was still able to conduct around the ends of the block line., Conclusion: Drugs that decrease intercellular coupling may not be effective antiarrhythmic agents when uniform anisotropy causes functional reentry.