Henry B. Randall

A Modular Analysis Framework for Blood Genomics Studies: Application to Systemic Lupus Erythematosus

The analysis of patient blood transcriptional profiles offers a means to investigate the immunological mechanisms relevant to human diseases on a genome-wide scale. In addition, such studies provide a basis for the discovery of clinically relevant biomarker signatures. We designed a strategy for microarray analysis that is based on the identification of transcriptional modules formed by genes coordinately expressed in multiple disease data sets. Mapping changes in gene expression at the module level generated disease-specific transcriptional fingerprints that provide a stable framework for the visualization and functional interpretation of microarray data. These transcriptional modules were used as a basis for the selection of biomarkers and the development of a multivariate transcriptional indicator of disease progression in patients with systemic lupus erythematosus. Thus, this work describes the implementation and application of a methodology designed to support systems-scale analysis of the human immune system in translational research settings.

Hepatorenal syndrome: A proposal for kidney after liver transplantation (KALT)

Hepatorenal syndrome (HRS) is a well‐recognized complication of end‐stage liver disease. Once thought to be a reversible condition with liver transplantation (LT) alone, HRS may directly contribute to the requirement for long‐term dialysis posttransplant. As a result, discussion has now focused on whether or when a kidney allograft should be considered for these patients. Using the International Ascites Club guidelines with a pretransplant serum creatinine (SCr) >2.0 mg/dL to define HRS, 130 patients undergoing LT over a 10‐yr period were identified, for an overall incidence of 9%. Patient survival rates at 1, 3, and 5 yr were 74%, and 68%, and 62%, respectively. Survival was significantly worse when compared to non‐HRS patients undergoing LT over the same study period (P = 0.0001). For patients presenting with type 2 HRS, 7 patients (6%) developed irreversible kidney failure posttransplant compared to 0.34% in the non‐HRS population (P < 0.0001). Five of these patients died within 1 yr with a median survival time of 139 days. Combined liver and kidney transplantation (CLKT) for patients with HRS is not recommended. However, an improvement in outcome can be accomplished by addressing those patients who require dialysis greater than 60 days posttransplant. We propose a role for kidney after liver transplantation (KALT) in select HRS patients. Liver Transpl 13:838–843, 2007.

Clinical outcomes from hepatic artery stenting in liver transplantation

Hepatic artery stenosis after liver transplantation may affect liver function and result in hepatic artery thrombosis. Surgical reconstruction has been the first choice for treatment. Interventional radiologic technique can be used, but there is no report on long‐term outcome. The aim of this paper is to assess current outcome and complications of hepatic artery stenting. Twenty‐six adult patients were stented for hepatic artery stenosis between 1998 and 2003. Nine patients had previous surgical reconstruction for hepatic artery stenosis. Seventeen patients suffered newly developed hepatic artery stenosis. Three patients were retransplanted. After stenting, the patients were followed by Doppler ultrasound at day 1, 1 month, and 6 months. Angiography was scheduled in 6 months. Four patients died within 2 months. The other 22 patients were followed for mean 31 ± 14 months (8‐71 months). One of 22 patients died from renal failure 2 years later. Twelve patients hepatic arteries looked normal after stenting. Restenosis was seen in 8 patients (36%). Other complications were artery thrombosis (n = 1) and long segment stricture (n = 1). In 2 patients (25%) restenosis resulted in thrombosis. Six of the 8 patients who developed recurrent stenosis were successfully treated interventionally: restent (n = 5) and balloon dilation (n = 3). However, 3 patients (38%) restenosed. Kaplan‐Meier complication‐free survival was 54% at 1 year after stenting. In conclusion, hepatic artery stenting is a viable treatment for hepatic artery stenosis with reasonable results. Stenting is useful as adjuvant treatment after surgical revision. Liver Transpl 12:422–427, 2006.

Twenty years of follow‐up of aortohepatic conduits in liver transplantation

Arterial problems remain a formidable challenge in liver transplantation. In many situations, an aortohepatic conduit can provide a solution. No long‐term results (over 5 years) have been reported. This study was designed to assess the impact of aortohepatic conduits on graft survival after liver transplantation and the safety of aortohepatic conduits and to establish the long‐term results (up to 20 years) of aortohepatic conduits. Data from 2346 adult liver transplants were prospectively collected into the computerized database and analyzed. In the majority of cases, arterial conduits were constructed from the donor iliac artery obtained at the liver retrieval. Aortohepatic conduits were required in 149 (6.4%) first transplants. The long‐term graft survival after liver transplantation using aortohepatic conduits was excellent and comparable to that of the control group. The graft survival was 59% with the conduit versus 67% without the conduit at 5 years of follow‐up, 50% versus 52% at 10 years, and 33% versus 35% at 15 years. With up to 20 years of follow‐up, there was no statistically significant difference in graft survival, patient survival, hepatic artery complications, or biliary complications. For the same time period, there was no statistically significant difference in graft survival or patient survival for the retransplants with and without aortohepatic conduits. In conclusion, in experienced hands, aortohepatic conduits can be used safely for liver transplantation with no negative impact on long‐term graft survival, patient survival, hepatic artery complications, or biliary complications. Excellent long‐term results can be obtained. Liver Transpl 14:1486–1490, 2008.

Post-liver transplant survival in hepatitis C patients is improving over time.

Outcomes after orthotopic liver transplantation for chronic hepatitis C have been reported to be worsening over the last 2 decades. We analyzed our centers experience over 15 years to identify trends in post–orthotopic liver transplantation survival in patients with and without hepatitis C virus infection. Patient survival and graft survival among adult primary orthotopic liver transplantation recipients who survived more than 90 days from January 1991 to June 2006 at the Baylor Regional Transplant Institute (n = 1901) were evaluated by Kaplan‐Meier analysis. Those with or without hepatitis C virus infection were analyzed by era: era 1, 1991‐1994 (n = 473); era 2, 1995‐1998 (n = 421); era 3, 1999‐2002 (n = 498); and era 4, 2003‐2006 (n = 512). Differences in eras with disparate survivals were assessed by univariate and multivariable analysis. Overall, patient survival and graft survival were significantly lower among hepatitis C virus infection recipients compared to those without hepatitis C virus infection (P < 0.001). This difference was dependent on the era of transplantation, with progressive improvement in hepatitis C virus patient (P < 0.001) and graft (P < 0.001) survival in sequential eras. Several factors accounted for this improvement, notably better selection of hepatocellular carcinoma patients and fewer late cytomegalovirus infections. Improvement occurred despite an increase in the ages of both donors and recipients. In conclusion, posttransplant survival after orthotopic liver transplantation for chronic hepatitis C has improved significantly over the last 15 years despite demographic changes in patients and grafts that have been previously shown to impair survival. A major reason for this improvement is better selection of patients with concurrent hepatocellular carcinoma and fewer late cytomegalovirus infections, although other factors may play a role as well. Liver Transpl 15:360–368, 2009.

Indications for combined liver and kidney transplantation: propositions after a 23‐yr experience

Ruiz R, Jennings LW, Kim P, Tomiyama K, Chinnakotla S, Fischbach BV, Goldstein RM, Levy MF, McKenna GJ, Melton LB, Onaca N, Randall HB, Sanchez EQ, Susskind BM, Klintmalm GB. Indications for combined liver and kidney transplantation: propositions after a 23‐yr experience. u2028Clin Transplant 2010: 24: 807–811.

Intraoperative imaging of pancreas transplant allografts using indocyanine green with laser fluorescence

Vascular thrombosis is a cause of allograft loss after pancreas transplantation. We present the use of intraoperative fluorescence imaging with the SPY imaging device (Novadaq Technologies Inc, Toronto, Canada) in two pancreas transplants as a means to assess patency of the vascular anastomoses. Intravenous indocyanine green 2.5 mg/mL was fluoresced with the device to create the intraoperative video sequences, which were recorded. After 60-day follow-up, real-time SPY imaging on these two pancreas transplants did not demonstrate adverse effects on patients or the transplanted allografts. This method of vascular imaging could prove useful in improving short-term graft survival and possibly lowering the thrombosis rates seen with pancreas transplantation. Long-term correlation studies between intraoperative findings and graft survival must be performed to confirm the utility of this imaging method.

Primary Care Physicians' Attitudes and Practices Regarding Discussing Organ Donation With Their Patients

I first began reading this manuscript and thought, “Wow, how great that would be to involve the primary care physician (PCP) in the organ donation process.” Then, I began to read further and I decided what a wellintentioned disservice this could potentially be. This experiment has been attempted before with poor results. However, not to be discouraging, the authors of the paper have gone an extra step to look at an additional process in an attempt to address the ever-increasing shortage of solid organs for transplantation. To their credit, they identified an interesting set of practice patterns in the United States. They queried PCPs on their practice of discussing end-of-life care and whether or not patients seen in their practice would consider donating their organs. As it has been shown in the paper, very few practicing physicians have ever received any formal training in approaching potential donor families (17%). Most of us are aware that this is just not a skill set one acquires either in medical school or during one’s residency training. Furthermore, very few even discuss issues such as advanced directives and end-of-life care with their patients (30%). Even fewer (4%) have talked about organ donation with their patients. Precariously, only 11% reported having donor information available to patients seen in the office. What is a bit disturbing is the fact that very few physicians in the survey have had any formal training in organ donation discussions, yet 36% say it falls within the purview of their practice. Most (64%) appropriately state they are just not prepared enough to have this discussion. As is often the case, many have more on their plate than they can already handle, and adding more responsibility such as teaching or discussing the particulars of the donation process simply lies outside their practice capabilities and is just a burden most choose not to undertake. The survey also takes for granted that most patients make regular visits to the PCP and thus the visit provides the PCP the opportunity to engage in end-of-life and organ donation discussions. One important factor touched upon in the paper was the philosophical question of how do the physicians themselves feel about the donation and transplant process. Too often, I have encountered a health care provider who still believes organ transplantation to be an “experimental” procedure. Most people in the general public have no idea of the success solid organ transplant has enjoyed over past decade. Far too often, practitioners have diabetic and or hypertensive patients in their practice who may be candidates for transplants but do not know the process to refer the patients for transplant evaluation. Many still believe that finances play a role in getting a patient referred and subsequently listed for transplantation. Therefore, if you are unaware of the success transplant has realized, it makes the task of discussing organ donation that much more ominous. This misconception about the lack of success unfortunately does not reside in the older population of physicians. Physicians, like the greater community, often consider themselves to be religious or spiritual beings and therefore the decision for the PCP to be a donor or not may be in part driven by one’s religious affiliation or beliefs. In the manuscript, for instance, 49% of white physicians reported having designating themselves as a potential organ donor. Compare this to 47% in black or African American physicians despite reporting a higher knowledge of organ transplantation. I find it compelling that black or African American physicians responded favorably to understanding organ donation and transplantation, yet they had such a low self-referral to organ donation in the survey. Several organ procurement organizations around the country have proven over and over that the “uncoupling” Author Affiliation: Baylor Regional Transplant Institute (adult and pediatric transplant surgeon) and Children’s Medical Center-Dallas, Dallas, Texas; and Minority Affairs Committee, United Network for Organ Sharing, Richmond, VA (chair). Corresponding Author: Henry B. Randall, MD, FACS, Adult and Pediatric Transplant Surgeon, Baylor Regional Transplant Institute, Baylor University Medical Center, 3500 Gaston Ave, Dallas, TX 75246 (henryran@ baylorhealth.edu).

Use of two expanded-criteria-donor renal allografts in a single patient

The disparity between the number of available renal donors and the number of patients on the transplant waiting list has prompted the use of expanded-criteria-donor (ECD) renal allografts to expand the donor pool. ECD allografts have shown good results in appropriately selected recipients, yet a number of renal allografts are still discarded. The use of dual renal transplantation may lower the discard rate. Additionally, the use of perfusion systems may improve acute tubular necrosis rates with these allografts. We report a successful case of a dual transplant with ECD allografts using a perfusion system. The biopsy appearance and the pump characteristics were suboptimal for these kidneys, making them unsuitable for single transplantation; however, the pair of transplanted kidneys provided increased nephron mass and functioned well. We recommend that ECD kidneys that are individually nontransplantable be evaluated for potential dual renal transplantation. Biopsy criteria and perfusion data guidelines must be developed to improve the success rates with ECD dual renal allografts. Finally, recipient selection is of utmost importance.