Bariatric Surgery for Congestive Heart Failure Patients Improves Access to Transplantation and Long-term Survival.

INTRODUCTION: Obese patients with congestive heart failure (CHF) are often denied access to heart transplantation until they obtain significant weight loss to achieve a certain BMI threshold, often less than 35 kg/m2. It is unknown whether the rapid weight loss associated with bariatric surgery leads to improved waitlist placement, and as such improved survival for morbidly obese patients with CHF. METHODS: A decision analytic Markov state transition model was created to simulate the life of morbidly obese patients with CHF who were deemed ineligible to be waitlisted for heart transplantation unless they achieved a BMI less than 35 kg/m2. Life expectancy following medical weight management (MWM), Roux-en-Y gastric bypass (RYGB), and sleeve gastrectomy (SG) was estimated. Base case patients were defined as having a pre-intervention BMI of 45 kg/m2. Sensitivity analysis of initial BMI was performed. Markov parameters were extracted from literature review. RESULTS: RYGB improved survival compared with both SG and MWM. RYGB patients had higher rates of transplantation, leading to improved mean long-term survival. Base case patients who underwent RYGB gained 2.1 additional years of life compared with patient's who underwent SG and 7.4 additional years of life compared with MWM. SG patients gained 5.3 years of life compared with MWM. CONCLUSIONS: When strict waitlist criteria were applied, bariatric surgery improved access to heart transplantation and thereby increased long-term survival compared with MWM. Morbidly obese CHF patients who anticipate need for heart transplantation should be encouraged to pursue surgical weight management strategies, necessitating discussion between bariatric surgeons, cardiologists, and cardiac surgeons for appropriate perioperative risk management.

Human monoclonal antibody MBL-HCV1 delays HCV viral rebound following liver transplantation: a randomized controlled study.

Rapid allograft infection complicates liver transplantation (LT) in patients with hepatitis C virus (HCV). Pegylated interferon-α and ribavirin therapy after LT has significant toxicity and limited efficacy. The effect of a human monoclonal antibody targeting the HCV E2 glycoprotein (MBL-HCV1) on viral clearance was examined in a randomized, double-blind, placebo-controlled pilot study in patients infected with HCV genotype 1a undergoing LT. Subjects received 11 infusions of 50 mg/kg MBL-HCV1 (n=6) or placebo (n=5) intravenously with three infusions on day of transplant, a single infusion on days 1 through 7 and one infusion on day 14 after LT. MBL-HCV1 was well-tolerated and reduced viral load for a period ranging from 7 to 28 days. Median change in viral load (log10 IU/mL) from baseline was significantly greater (p=0.02) for the antibody-treated group (range -3.07 to -3.34) compared to placebo group (range -0.331 to -1.01) on days 3 through 6 posttransplant. MBL-HCV1 treatment significantly delayed median time to viral rebound compared to placebo treatment (18.7 days vs. 2.4 days, p<0.001). As with other HCV monotherapies, antibody-treated subjects had resistance-associated variants at the time of viral rebound. A combination study of MBL-HCV1 with a direct-acting antiviral is underway.

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.

Accurate estimation of living donor right hemi-liver volume from portal vein diameter measurement and standard liver volume calculation.

Lee et al. recently published a method for estimating right hemi-liver volume (RHLV) by using bedside ultrasound measurement of right (R) and left (L) portal vein (PV) diameters and Urata's standard liver volume (SLV) formula where RHLV = SLV×[R(2) /(R(2) +L(2) )]. We calculated RHLV by substituting SLV from 15 different published formulas in the worldwide literature. We also modified Lee's method using right anterior (RA) and posterior (RP) where RHLV = SLV×[(RA(2) +RP(2) )/(RA(2) +RP(2) +L(2) )] for donors with unusual PV branching. We compared the calculated RHLV with RHLV estimated with software-assisted CT (SACT) volumetry and actual graft weight after right-lobe donation in 200 right-lobe donors. This study confirmed that accurate estimates of RHLV can be achieved by SACT volumetry or by the simple method of Lee but using the SLV of only 3 of the 15 published formulas (Lin or Vauthey using body weight or body surface area) rather than Urata's. Our modification of the Lee's formula using RA and RP, PV diameters was also accurate and not different from Lee's formula. These simplified formulas may be used for donor screening for graft size adequacy before expensive evaluation proceeds.

What defines a transplant surgeon? A needs assessment for curricular development in transplant surgery fellowship training.

This study compares the perceptions of transplant surgery program directors (PDs) and recent fellowship graduates (RFs) regarding the adequacy of training and relevancy to practice of specific curricular content items in fellowship training. Surveys were sent to all American Society of Transplant Surgery approved fellowship PDs and all RFs in practice <5 years. For operative procedures, the RFs considered the overall training to be less adequate than the PDs (p = 0.0117), while both groups considered the procedures listed to be relevant to practice (p = 0.8281). Regarding nonoperative patient care items, although RFs tended to rank many individual items lower, both groups generally agreed that the training was both adequate and relevant. For nonpatient care related items (i.e. transplant-related ethics, economics, research, etc.), both groups scored them low regarding their adequacy of training although RFs scored them significantly lower than PDs (p = 0.0006). Regarding their relevance to practice, while both groups considered these items relevant, RFs generally considered them more relevant than PDs. Therefore, although there is consensus on many items, significant differences exist between PDs and RFs regarding their perceptions of the adequacy of training and the relevance to practice of specific curriculum items in transplant surgery fellowship training.

ASTS recommended practice guidelines for controlled donation after cardiac death organ procurement and transplantation.

The American Society of Transplant Surgeons (ASTS) champions efforts to increase organ donation. Controlled donation after cardiac death (DCD) offers the family and the patient with a hopeless prognosis the option to donate when brain death criteria will not be met. Although DCD is increasing, this endeavor is still in the midst of development. DCD protocols, recovery techniques and organ acceptance criteria vary among organ procurement organizations and transplant centers. Growing enthusiasm for DCD has been tempered by the decreased yield of transplantable organs and less favorable posttransplant outcomes compared with donation after brain death. Logistics and ethics relevant to DCD engender discussion and debate among lay and medical communities. Regulatory oversight of the mandate to increase DCD and a recent lawsuit involving professional behavior during an attempted DCD have fueled scrutiny of this activity. Within this setting, the ASTS Council sought best-practice guidelines for controlled DCD organ donation and transplantation. The proposed guidelines are evidence based when possible. They cover many aspects of DCD kidney, liver and pancreas transplantation, including donor characteristics, consent, withdrawal of ventilatory support, operative technique, ischemia times, machine perfusion, recipient considerations and biliary issues. DCD organ transplantation involves unique challenges that these recommendations seek to address.

Survival benefit-based deceased-donor liver allocation.

Currently, patients awaiting deceased-donor liver transplantation are prioritized by medical urgency. Specifically, wait-listed chronic liver failure patients are sequenced in decreasing order of Model for End-stage Liver Disease (MELD) score. To maximize lifetime gained through liver transplantation, posttransplant survival should be considered in prioritizing liver waiting list candidates. We evaluate a survival benefit based system for allocating deceased-donor livers to chronic liver failure patients. Under the proposed system, at the time of offer, the transplant survival benefit score would be computed for each patient active on the waiting list. The proposed score is based on the difference in 5-year mean lifetime (with vs. without a liver transplant) and accounts for patient and donor characteristics. The rank correlation between benefit score and MELD score is 0.67. There is great overlap in the distribution of benefit scores across MELD categories, since waiting list mortality is significantly affected by several factors. Simulation results indicate that over 2000 life-years would be saved per year if benefit-based allocation was implemented. The shortage of donor livers increases the need to maximize the life-saving capacity of procured livers. Allocation of deceased-donor livers to chronic liver failure patients would be improved by prioritizing patients by transplant survival benefit.

A novel boundary issue: should a patient be an organ donor for their physician?

It is argued that organ donation from a patient to the patient's physician is ethically dubious because donation decisions will be inappropriately influenced and the negative public perceptions will result in more harm than good. It is suggested that to protect the perception of the physician-patient relationship, avoid cynicism about medicine's attitude to patient welfare and maintain trust in the medical profession, a new professional boundary should be established to prevent physicians from receiving organs for transplantation donated by their patients.

Solving the organ shortage crisis: the 7th annual American Society of Transplant Surgeons' State-of-the-Art Winter Symposium.

The 2007 American Society of Transplant Surgeons' (ASTS) State-of-the-Art Winter Symposium entitled, 'Solving the Organ Shortage Crisis' explored ways to increase the supply of donor organs to meet the challenge of increasing waiting lists and deaths while awaiting transplantation. While the increasing use of organs previously considered marginal, such as those from expanded criteria donors (ECD) or donors after cardiac death (DCD) has increased the number of transplants from deceased donors, these transplants are often associated with inferior outcomes and higher costs. The need remains for innovative ways to increase both deceased and living donor transplants. In addition to increasing ECD and DCD utilization, increasing use of deceased donors with certain types of infections such as Hepatitis B and C, and increasing use of living donor liver, lung and intestinal transplants may also augment the organ supply. The extent by which donors may be offered incentives for donation, and the practical, ethical and legal implications of compensating organ donors were also debated. The expanded use of nonstandard organs raises potential ethical considerations about appropriate recipient selection, informed consent and concerns that the current regulatory environment discourages and penalizes these efforts.

Successful algorithm for selective liver biopsy in the right hepatic lobe live donor (RHLD).

Routine versus selective predonation liver biopsy (LBx) remains controversial for assuring the safety of right hepatic lobe live donor (RHLD). Between December 1999 and March 2007, 403 potential RHLD were evaluated; 142 donated. Indications for selective LBx were: abnormal liver function tests or imaging studies, body mass index (BMI) >28, history of substance abuse or family history of immune mediated liver disease. All donors had a LBx at the time of surgery. Of 403 potential RLD, 149(36.9%) were accepted as donors, 25(6.3%) had their recipient receive a deceased donor graft, 94(23.4%) were rejected, 52(12.9%) stopped the evaluation process, 76(18.8%) withdrew from the process and 7(1.7%) are currently completing evaluation. Eighty-seven (21.5%) met criteria and were biopsied. Seventy-three (83.9%) had either normal (n = 24) or macrosteatosis <10% (n = 49); 51 of these donated. Abnormal LBx eliminated 15 potential donors. No significant abnormalities were found in donation biopsies of donors not meeting algorithm criteria. Three of 87 (3.4%) had complications requiring overnight admission (2 for pain, 1 for bleeding; transfusion not required). Use of this algorithm resulted in 78% of potential donors avoiding biopsy and potential complications. No significant liver pathology was identified in donors not meeting criteria for evaluation LBx. Routine predonation LBx is unnecessary in potential RHLD.

Liver and intestine transplantation in the United States, 1996-2005.

The number of liver transplants performed yearly has slowly and steadily increased over the last 10 years, reaching 6441 procedures in 2005. The number of living donor liver transplants performed rose steadily from 1996 to 2001, when it peaked at 519; since 2003 there have been approximately 320 such procedures performed each year. The continual increase in the size of the waiting list for a liver transplant, which peaked in 2001 at 14 897 patients, was interrupted in 2002 by the implementation of the allocation system based on the model for end-stage liver disease and pediatric end-stage liver disease (MELD/PELD). Activity in all areas of intestinal transplantation continues to increase. One-year patient and graft survival following intestine-alone transplantation now seem to be superior to outcomes following liver-intestine transplantation. Other topics covered here include the recent 'Share 15' component of the MELD allocation system; liver transplantation following donation after cardiac death; simultaneous liver-kidney transplantation and waiting list and post-transplant outcomes for both liver and intestine transplantation, broken out by a variety of clinical and demographic factors.

Improved survival after live donor adult liver transplantation (LDALT) using right lobe grafts: program experience and lessons learned.

We present our program experience with 85 live donor adult liver transplantation (LDALT) procedures using right lobe grafts with five simultaneous live donor kidney transplants using different donors performed over a 6-year period. After an "early" 2-year experience of 25 LDALT procedures, program improvements in donor and recipient selection, preoperative imaging, donor and recipient surgical technique and immunosuppressive management significantly reduced operative mortality (16% vs. 3.3%, p = 0.038) and improved patient and graft 1-year survival in recipients during our "later" experience with the next 60 cases (January 2001 and March 2005; patient survival: early 70.8% vs. later 92.7%, p = 0.028; graft survival: Early 64% vs. later 91.1%, p = 0.019, respectively). Overall patient and graft survival were 82% and 80%. There was a trend for less postoperative complications (major and minor) with program experience (early 88% vs. later 66.7%; p = 0.054) but overall morbidity remained at 73.8%. Biliary complications (cholangitis, disruption, leak or stricture) were not influenced by program experience (early 32% vs. later 38%). Liver volume adjusted to 100% of standard liver volume (SLV) within 1 month post-transplant. Despite a high rate of morbidity after LDALT, excellent patient and graft survival can be achieved with program experience.

The Art and Science of Immunosuppression: the Fifth Annual American Society of Transplant Surgeon's State-of-the-Art Winter Symposium.

The 2005 American Society of Transplant Surgeons (ASTS) Winter Symposium entitled 'The Art and Science of Immunosuppression' explored ways to maximize existing immunosuppressive protocols and to develop new strategies incorporating novel agents and emerging diagnostic technologies to customize immunosuppression and reduce side effects. Several presentations evaluated steroid withdrawal or avoidance protocols reflecting the significant difficulties of bone loss, glucose control and growth retardation in children associated with long-term steroid use. Calcineurin-inhibitor related renal dysfunction of both native and transplanted kidneys was identified as significant, but no consensus was reached concerning effective prevention. Similarly, recurrence of Hepatitis C following liver transplantation was identified as problematic without identifying a preferred immunosuppressive regimen in this setting. Control of T-cell mediated rejection was found to be excellent, but recognition and treatment of non-T cell causes of allograft damage (i.e. B- or NK-cell mediated) was identified as an area of current interest. Immunosuppressive agents under development, such as those blocking co-stimulation or cytokine signals, and JAK-3 inhibitors were discussed. Finally, the available technologies for molecular and genetic diagnostics and the clinical correlation in the post-transplant setting were discussed.

Liver regeneration after living adult right lobe transplantation.

BACKGROUND: The purpose of this study was to describe liver regeneration in patients undergoing living-adult liver transplantation. METHODS: This prospective study included 10 donors and eight recipients who had a total of 65 computed tomographic (CT) scans. All patients had preoperative CT ( n = 18), and follow-up CT scans ( n = 47) were obtained for up to 14 months after transplantation. Liver and spleen volumes were measured by hand tracing each organ on the axial portal venous phase images. RESULTS: Both donors and recipients showed immediate increases in liver volume. However, liver regeneration was significantly faster and reached a higher peak in recipients than in donors. Splenic volume in donors demonstrated an initial increase followed by a decline, reaching the preoperative volume after 1 year. Splenic volume in recipients demonstrated immediate decline postoperatively. CONCLUSION: Restoration of liver volume occurred rapidly after transplantation, but followed different patterns in donors and recipients. Deviation from these patterns warrants further investigation.

Life-threatening hypophosphatemia after right hepatic lobectomy for live donor adult liver transplantation.

Life-threatening hypophosphatemia (phosphorus < 1.0 mg/dL) has been reported only once after liver resection for tumor and was associated with a significant increase in postoperative complications. Hypophosphatemia is associated with reversible cardiac dysfunction, hypoventilation, and impaired immunity. The purpose of this study was to determine the incidence of hypophosphatemia after elective right hepatic lobectomy for live donor adult liver transplantation (LDALT), investigate the associated complication rate and surgical outcome of live liver donors, and determine the efficacy of prospective treatment with phosphate repletion as part of total parenteral nutrition (TPN). Evaluation of 30 donors who provided 30 right-lobe grafts between December 1998 and January 2000 was performed. Of the initial 18 live liver donors (group 1), 10 donors were treated with TPN that contained slightly more (35 +/- 8 mmol/d) than the recommended daily allowance (RDA) of phosphorus (30 mmol/d) starting on postoperative day 1. The last 12 donors (group 2) were prospectively studied and administered similar TPN with 2 times the RDA for phosphorus (60 mmol/d). All donors in group 1 developed hypophosphatemia that was either life threatening (phosphorus < 1.0 mg/dL) in 70% or severely depleted (phosphorus, 1.5 to 1.1 mg/dL) in 30%. With more aggressive phosphate repletion (group 2), only 8% developed life-threatening (phosphorus < 1.0 mg/dL) hypophosphatemia and 30% developed severe (phosphorus, 1.1 to 1.5 mg/dL) hypophosphatemia. Results suggest that hypophosphatemia is a universal event after LDALT and may have contributed to the observed complications in this study. Repletion of phosphorus at twice the RDA abrogates the incidence of hypophosphatemia and may reduce donor morbidity. Institutions performing LDALT should carefully monitor live liver donors for hypophosphatemia and correct abnormal phosphate levels. Additional studies are needed to determine whether more aggressive parenteral repletion can prevent postoperative hypophosphatemia and thus improve outcomes.

Live donor adult liver transplantation using right lobe grafts: donor evaluation and surgical outcome.

HYPOTHESIS: Live donor adult liver transplantation (LDALT) is a safe and efficacious treatment for patients with end-stage liver disease. DESIGN: Case-control study. SETTING: Hepatobiliary surgery and liver transplantation unit. PATIENTS: From December 10, 1998, through April 10, 2000, a single team performed 15 LDALT procedures with 2 simultaneous living donor kidney transplants. During this period, 66 potential donors were screened and evaluated. INTERVENTIONS: Potential donors were evaluated with 3-dimensional helical computed tomographic scan, including volume renderings for hepatic lobar volume, vascular anatomy, virtual resection planes, and morphologic features. Suitable donors undergo complete medical and psychiatric evaluation and preoperative arteriography. MAIN OUTCOME MEASURES: Donor demographics, evaluation data, operative data, hospital length of stay, and morbidity. RESULTS: A total of 38 men (58%) and 28 women (42%) were evaluated with 15 donors participating in LDALT. Two additional donors provided kidney grafts for simultaneous transplantation at the time of LDALT. Thirty-two donors (48%) were rejected for either donor or recipient reasons, and 10 patients (15%) elected not to participate after initial screening. Three-dimensional volume renderings by helical computed tomographic scan predicted right lobe liver volume within 92% of actual graft volume. Donor morbidity, including all complications, was 67% with no mortality. Residual liver regenerated to approximately 70% of initial volume within 1 week and 80% within 1 month after surgery. CONCLUSIONS: Donor evaluation is an important component of LDALT. Significant donor morbidity is encountered even with careful selection. To minimize donor morbidity, groups considering initiating living donor programs should have expertise in hepatic resection and vena cava preservation using the "piggyback" technique during liver transplantation.