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Rodrigue JR, Mandelbrot DA, Hanto DW, Johnson SR, Karp SJ, Pavlakis M. A cross-sectional study of fatigue and sleep quality before and after kidney transplantation. Clin Transplant 2011: 25: E13-E21. © 2010 John Wiley & Sons A/S. Fatigue and sleep disturbances are common problems for adults with chronic kidney disease or end-stage renal disease. However, these issues have not been examined much in the context of kidney transplantation (KTx). This study characterizes these outcomes in the KTx population and examines their association with psychological functioning and quality of life (QOL). A cross-sectional cohort of 100 wait-listed pre-KTx and 100 post-KTx patients at one transplant center in the United States completed validated fatigue, sleep, mood, and QOL questionnaires, and their medical records were reviewed. Pre-KTx patients had higher levels of fatigue frequency, fatigue severity, and fatigue disruptiveness than post-KTx patients. Also, pre-KTx patients had more difficulty with sleep quality, latency, duration, efficiency, and disturbance and were more likely to have 'poor' sleep quality compared with post-KTx patients. Multivariate predictors of high fatigue severity for both pre- and post-KTx patients were high body mass index (BMI), poor sleep quality, and mood disturbance, while poor sleep quality was predicted by high BMI and mood disturbance. Most sociodemographic and clinical parameters were not associated with fatigue severity or sleep disturbance. Fatigue and sleep disturbances are common before and after KTx, and study findings have important implications for their assessment and management. [ABSTRACT FROM AUTHOR]

Background: Studies have shown that delayed treatment of several non-hepatobiliary (HB) malignancies is associated with adverse effects on disease progression and survival. Delayed treatment of HB malignancies has not been thoroughly investigated. Methods: We performed a retrospective institutional review of patients referred to the Hepatobiliary Surgery Service at Beth Israel Deaconess Medical Center (BIDMC) for hepatobiliary malignancies from 2002 to 2008. Primary outcomes included the time delays (TD) in patient workup. Secondary outcomes were reasons for delay as well as disparities in TD based on demographic factors. Results: Multivariate-adjusted linear regression showed a significant trend of increasing time from presentation until referral to a HB surgeon over the 7-year period (P = 0.001). There were no differences in TD by gender, age or education level. Multivariate-adjusted linear regression showed a significant trend of increasing number of imaging tests performed prior to referral [computerized tomography (CT), magnetic resonance imaging (MRI), positron emission tomography (PET) and ultrasound and endoscopic ultrasound (US/EUS)] (P < 0.001). Multivariate-adjusted linear regression in resectable patients showed a significant difference in overall length of survival in those with a TD1 > 30 days compared with those with a TD1 (TD from presentation until referral) <30 days (P = 0.042). Conclusions: Delays were associated with an increase in imaging studies and delays adversely affect survival in resected patients. Referring physicians are encouraged to expedite the evaluation and early referral of all patients to an HB surgeon for evaluation and treatment. [ABSTRACT FROM AUTHOR]

Pancreas transplantation with enteric drainage avoids the long-term urological complications of bladder drainage. Increasing use of this technique raises the possibility of complications from the enteric reconstruction. This report describes a patient five yr after left-sided pancreas transplant with Roux-en-Y enteric drainage, presenting with abdominal pain, leukocytosis and radiological evidence of bowel obstruction. Exploration revealed a volvulus of the Roux limb as it passed through the mesocolon, with necrosis of the allograft duodenum and marked congestion of the pancreas. This is the first report of pancreas graft loss due to this entity, which should be recognized as an unusual cause of abdominal pain after pancreas transplantation. Potential bowel complications related to the sigmoid mesentery in left-sided pancreas transplantation are additional reasons for right-sided placement of the pancreas allograft. [ABSTRACT FROM AUTHOR]

Equitable distribution of a scarce resource such as kidneys for transplantation can be a challenging task for transplant centers. In this study, we evaluated the association between recipient's employment status and access to renal transplantation in patients with end-stage renal disease ( ESRD). We used data from the United States Renal Data System ( USRDS). The primary variable of interest was employment status at ESRD onset. Two outcomes were analyzed in Cox model: (i) being placed on the waiting list for renal transplantation or being transplanted (whichever occurred first); and (ii) first transplant in patients who were placed on the waiting list. We analyzed 429 409 patients (age of ESRD onset 64.2 ± 15.2 yr, 55.0% males, 65.1% White). Compared with patients who were unemployed, patients working full time were more likely to be placed on the waiting list/transplanted ( HR 2.24, p < 0.001) and to receive a transplant once on the waiting list ( HR 1.65, p < 0.001). Results indicate that recipient's employment status is strongly associated with access to renal transplantation, with unemployed and partially employed patients at a disadvantage. Adding insurance status to the model reduces the effect size, but the association still remains significant, indicating additional contribution from other factors. [ABSTRACT FROM AUTHOR]

Recent changes in Center for Medicare & Medicaid Services ( CMS) condition for participation, using benchmark volume/outcomes requirements for certification, have been implemented. Consequently, the ability of a transplant center to assess its risk tolerance is important in successful management. An analysis of SRTR data was performed to determine donor/recipient risk factors for graft loss or patient death in the first year. Each transplant performed was then assigned a prospective relative risk ( RR) of failure. Using a Monte- Carlo simulation, transplants were selected at random that met the centers' acceptable risk tolerance. Transplant center volume was fixed and its risk tolerance was adjusted to determine the impact on outcomes. The model was run 1000 times on centers with varying volume. The modeling demonstrates that centers with smaller annual volumes must use a more risk taking strategy than larger volume centers to avoid being flagged for CMS volume requirements. The modeling also demonstrates optimal risk taking strategies for centers based upon volume to minimize the probability of being flagged for not meeting volume or outcomes benchmarks. Small volume centers must perform higher risk transplants to meet current CMS requirements and are at risk for adverse action secondary to chance alone. [ABSTRACT FROM AUTHOR]

Background. Social adaptability index (SAI) is the composite index of socioeconomic status based upon employment status, education level, marital status, substance abuse and income. It has been used in the past to define populations at higher risk for inferior clinical outcomes. The objective of this retrospective study was to evaluate the association of the SAI with renal transplant outcome. Methods. We used data from the clinical database at the Beth Israel Deaconess Medical Center Transplant Institute, supplemented with data from United Network for Organ Sharing for the years 2001–09. The association between SAI and graft loss and recipient mortality in renal transplant recipients was studied using Cox model in the entire study population as well as in the subgroups based on age, race, sex and diabetes status. Results. We analyzed 533 end-stage renal disease patients (mean age at transplant 50.8 ± 11.8 years, 52.2% diabetics, 58.9% males, 71.1% White). Higher SAI on a continuous scale was associated with decreased risk of graft loss [hazard ratio (HR) 0.89, P < 0.05, per 1 point increment in the SAI] and decreased risk of recipient mortality (HR 0.84, P < 0.01, per 1 point increment in the SAI). Higher SAI was also significantly associated with decreased risk for graft loss/recipient mortality in some study subgroups (age 41–65 years, males, non-diabetics). Conclusions. SAI has an association with graft and recipient survival in renal transplant recipients. It can be helpful in identifying patients at higher risk for inferior transplant outcome as a target population for potential intervention. [ABSTRACT FROM PUBLISHER]

Goldfarb-Rumyantzev AS, Sandhu GS, Baird BC, Khattak M, Barenbaum A, Hanto DW. Social adaptability index predicts access to kidney transplantation. Clin Transplant 2011: 25: 834-842. © 2011 John Wiley & Sons A/S. Abstract: Identifying the group of subjects prone to disparities in access to kidney transplantation is important for developing potential interventions. Data from the United States Renal Data System (January 1, 1990-September 1, 2007; n = 3407) were used to study association between the Social Adaptability Index (SAI; based upon employment, marital status, education, income, and substance abuse) and outcomes (time to being placed on the waiting list and time to being transplanted once listed). Patients were 56.9 ± 16.1 yr old, 54.2% men, 64.2% white, and 50.4% had diabetes. SAI was higher in whites (7.4 ± 2.4) than African Americans (6.5 ± 2.6) [ANOVA, p < 0.001] and greater in men (7.4 ± 2.4) than in women (6.7 ± 2.5) [ T-test, p < 0.001]. In multivariate model, greater SAI (range 0-12) was associated with increased likelihood of being placed on the waiting list (hazard ratio [HR] 1.19 [95% CI 1.15-1.23] per each point of increase in SAI, p < 0.001) and greater likelihood of receiving a transplant once listed (HR of 1.06 [95% CI 1.03-1.09] per point of increase in SAI, p < 0.001). Similar trends were observed in most of the subgroups (based upon race, sex, diabetic status, age, comorbidities, and donor type). SAI is associated with access to renal transplantation in patients with end-stage renal disease; it may be used to indentify individuals at risk of healthcare disparities. [ABSTRACT FROM AUTHOR]

Rodrigue JR, Dimitri N, Reed A, Antonellis T, BA, Hanto DW, Curry M. Quality of life and psychosocial functioning of spouse/partner caregivers before and after liver transplantation. Clin Transplant 2011: 25: 239-247. © 2010 John Wiley & Sons A/S. Spouse/partner caregivers of liver transplant (LTx) patients play an important role both before and after transplantation. However, very little research has examined the quality of life (QOL), caregiving strain, and psychological functioning of these caregivers. In this study, we examined these outcomes and their correlates in 86 (49 pre-LTx, 38 post-LTx) spouse/partner caregivers. The physical QOL of caregivers was not impaired, and numerous caregiving benefits were identified (e.g., realizing what is important in life, discovering one's own inner strength, giving emotional support to the patient). However, a relatively high proportion of both pre-LTx and post-LTx caregivers had clinically low mental QOL (29% and 35%, respectively), low life satisfaction (45% and 32%, respectively), and high caregiving strain (59% and 81%, respectively). Both pre- and post-LTx caregivers, particularly women, had more total mood disturbance than a normative sample. Higher caregiving strain was significantly correlated with lower mental QOL, lower life satisfaction, and more mood disturbance. Overall, findings suggest that caregiving strain is prominent through the LTx spectrum. There is a need for prospective research to identify the patterns of caregiver outcomes over time and to examine the benefits of clinical interventions for caregivers. [ABSTRACT FROM AUTHOR]

The long-term use of calcineurin inhibitors (CNI) leads to renal dysfunction in many liver transplant (LT) recipients. The purpose of this analysis is to evaluate renal function in patients converted from CNI to sirolimus (SRL). From May 2002–November 2006, 137 LT were performed in 125 patients, 72 of which were converted to SRL. Evaluation of SRL conversion was stratified by early conversion (<90 d from LT) (EC) vs. late conversion (LC). Renal function was evaluated using the six-point modification of diet in renal disease formula (estimated glomerular filtration rate [eGFR]). Forty-two patients on SRL and 40 on CNI had at least three months of follow-up and are included in the eGFR evaluation. At all time points after conversion, the EC group demonstrated a significantly higher mean eGFR than those in the LC group. A significant improvement in eGFR was seen within the EC group when comparing eGFR at time of conversion to eGFR at three, six, nine, and 12 months after conversion and last follow-up. The only improvement in the LC group was from conversion to the three-month time point. We conclude that EC to SRL results in a profound improvement in eGFR that begins at three months and is sustained beyond one yr. [ABSTRACT FROM AUTHOR]

Pancreatic cancer is the fifth most common cause of cancer-related death in the USA. However, the antepartum diagnosis of pancreatic adenocarcinoma in the pregnant patient is exceedingly rare, with only six cases previously reported in the literature. Optimizing both maternal and fetal health outcomes is particularly challenging when surgical procedures are necessary for staging and/or therapeutic purposes--as these interventions often pose significant risks to both the mother and the developing fetus. In this article, we report a case of pancreatic adenocarcinoma diagnosed during pregnancy and review the literature on the management issues confronted in this unique clinical situation. [ABSTRACT FROM AUTHOR]

Websites have emerged to highlight the plight of patients awaiting kidney transplantation and to match them to potential good Samaritan living donors. Little is known about the patients who choose to solicit living donors online, so we examined the 224 profiles of potential kidney transplant recipients who registered on one donor matching website. The number of patients soliciting a living kidney donor is less than 0.5% of those who are awaiting kidney transplantation in the United States. Other than blood type, region, and gender surprisingly few sociodemographic and medical details were posted with most solicitation profiles. The considerable variability in what information is provided in patient profiles suggests that we know very little about who the solicitors are and further highlights one of the inherent ethical problems with public solicitation of living donors. Specifically, in some instances, a Good Samaritan’s pursuit of living kidney donation may be based less on information potentially relevant to transplant outcome and more on the persuasiveness of the appeal. [ABSTRACT FROM AUTHOR]

This article involves the study of a patient with a rare benign schwannoma in the body of the pancreas. After reviewing 39 patient cases previously reported in the literature, a discussion of the schwannoma with regard to clinical presentation, diagnosis, and treatment is examined. A review of the patient''s chart was performed along with a review of the literature using a Medline search. Translations were performed whenever necessary. There are 23 reports of 29 patient cases of pancreatic schwannomas in English and European literature and one report of 10 patient cases in the Japanese literature. The mean age was 57.75 years (range 32–89) and the male-to-female (M:F) ratio was 17:23. The mean reported size was 8.79 cm. The lesion was located in the head in 16 patients (40%), the body in 8 patients (20%), the body and tail in 8 patients (20%), the tail in 6 patients (15%), the head and body in 1 patient (2.5%), and the location was not specified in 1 patient (2.5%). Of the English and European patients, 11 out of 30 patients (36.7%) exhibited solid tumors and 14 out of 30 patients (46.7%) exhibited cystic tumors. The majority of the tumors (35 out of 40) were benign, but there were five reported malignancies. There were no deaths or recurrences reported with a follow-up of 18.68 months ± 24.09 (range 3–108 months). Pancreatic schwannomas are rare, and the preoperative diagnosis is difficult. Intraoperative frozen section can confirm the diagnosis of a benign schwannoma. Enucleation of the tumor from the surrounding parenchyma is recommended, if possible. Patients undergoing resection indicate an excellent long-term prognosis. [Copyright &y& Elsevier]

Competing Interests: P.A., D.E.B., and P.C.K. are the directors for the fellowships mentioned in this article. The remaining authors report no conflicts of interest.

Worsened by the COVID-19 pandemic, alcohol use is one of the leading causes of preventable death in the US, in large part due to alcohol-associated liver disease. Throughout history, liver transplantation for this population has been controversial, and many policies and regulations have existed to limit access to lifesaving transplant for patients who use alcohol. In recent years, the rates of liver transplantation for patients with alcohol-associated liver disease have increased dramatically; however, disparities persist. For instance, many criteria used in evaluation for transplant listing, such as social support and prior knowledge of the harms of alcohol use, are not evidence based and may selectively disadvantage patients with alcohol use disorder. In addition, few transplant providers have adequate training in the treatment of alcohol use disorder, and few transplant centers offer specialized addiction treatment. Finally, current approaches to liver transplantation would benefit from adopting principles of harm reduction, which have demonstrated efficacy in the realm of addiction medicine for years. As we look toward the future, we must emphasize the use of evidence-based measures in selecting patients for listing, ensure access to high-quality addiction care for all patients pretransplant and posttransplant, and adopt harm reduction beliefs to better address relapse when it inevitably occurs. We believe that only by addressing each of these issues will we be able to ensure a more equitable distribution of resources in liver transplantation for all patients., (Copyright © 2023 American Association for the Study of Liver Diseases.)

: The aim of the study was to examine the conflicting duties of a practicing surgeon who is at high risk for morbidity and mortality from Covid-19 infection. Should he opt out of the care of these patients or does his duty to care override other considerations? Older adults and those with serious medical conditions are at much greater risk for severe disease and death from Covid-19 infection. As a practicing frontline surgeon in a high risk group, the hospital offered the author, and other health care providers at high risk, the option to opt out of the care Covid-19 suspected or infected patients before an anticipated surge. What should the surgeon and other health care providers do? This is a question many are asking and having to answer. In this article, the author describes how difficult the situation of having any choice at all was and then how difficult it was to arrive at a decision. The duty to care and its limits, as well as obligations to society, family, co-workers, and to self, are examined. The author considers how he and others can contribute in other ways to patients and providers. The author arrives at a morally permissible and a rational decision to opt out. Health care workers at high risk can contribute in other ways to patients and providers. It still may not feel right.

Social support is a key component of transplantation evaluation in the United States. Social support definitions and evaluation procedures require examination to achieve clear, consistent implementation. We surveyed psychosocial clinicians from the Society for Transplant Social Workers and American Society of Transplant Surgeons about their definitions and evaluation procedures for using social support to determine transplant eligibility. Bivariate statistical analysis was used for quantitative data and content analysis for qualitative data. Among 276 psychosocial clinicians (50.2% response rate), 92% had ruled out patients from transplantation due to inadequate support. Social support definitions varied significantly: 10% of respondents indicated their center lacked a definition. Key domains of social support included informational, emotional, instrumental, motivational, paid support, and the patient's importance to others. Almost half of clinicians (47%) rarely or never requested second opinions when excluding patients due to social support. Confidence and perceived clarity and consistency in center guidelines were significantly associated with informing patients when support contributed to negative wait-listing decisions ( P = .001). Clinicians who excluded fewer patients because of social support offered significantly more supportive health care ( P = .02). Clearer definitions and more supportive care may reduce the number of patients excluded from transplant candidacy due to inadequate social support.

Social support is used to determine transplant eligibility despite lack of an evidence base and vague regulatory guidance. It is unknown how many patients are disqualified from transplantation due to inadequate support, and whether providers feel confident using these subjective criteria to determine eligibility. Transplant providers (n = 551) from 202 centers estimated that, on average, 9.6% (standard deviation = 9.4) of patients evaluated in the prior year were excluded due to inadequate support. This varied significantly by United Network for Organ Sharing region (7.6%-12.2%), and by center (21.7% among top quartile). Significantly more providers used social support in listing decisions than believed it ought to be used (86.3% vs 67.6%). Nearly 25% believed that using social support in listing determinations was unfair or were unsure; 67.3% felt it disproportionately impacted patients of low socioeconomic status. Overall, 42.4% were only somewhat or not at all confident using social support to determine transplant suitability. Compared to surgical/medical transplant providers, psychosocial providers had 2.13 greater odds of supporting the criteria (P = .03). Furthermore, 69.2% supported revised guidelines for use of social support in listing decisions. Social support criteria should be reconsidered in light of the limited evidence, potential for disparities, practice variation, low provider confidence, and desire for revised guidelines., (© 2018 The American Society of Transplantation and the American Society of Transplant Surgeons.)

The United Network for Organ Sharing recently altered current liver allocation with the goal of decreasing Model for End-Stage Liver Disease (MELD) variance at transplant. Concerns over these and further planned revisions to policy include predicted decrease in total transplants, increased flying and logistical complexity, adverse impact on areas with poor quality health care, and minimal effect on high MELD donor service areas. To address these issues, we describe general approaches to equalize critical transplant metrics among regions and determine how they alter MELD variance at transplant and organ supply to underserved communities. We show an allocation system that increases minimum MELD for local allocation or preferentially directs organs into areas of need decreases MELD variance. Both models have minimal adverse effects on flying and total transplants, and do not disproportionately disadvantage already underserved communities. When combined together, these approaches decrease MELD variance by 28%, more than the recently adopted proposal. These models can be adapted for any measure of variance, can be combined with other proposals, and can be configured to automatically adjust to changes in disease incidence as is occurring with hepatitis C and nonalcoholic fatty liver disease., (© 2018 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Background: National guidelines require programmes use subjective assessments of social support when determining transplant suitability, despite limited evidence linking it to outcomes. We examined how transplant providers weigh the importance of social support for kidney transplantation compared with other factors, and variation by clinical role and personal beliefs., Methods: The National survey of the American Society of Transplant Surgeons and the Society of Transplant Social Work in 2016. Using a discrete choice approach, respondents compared two hypothetical patient profiles and selected one for transplantation. Conditional logistic regression estimated the relative importance of each factor; results were stratified by clinical role (psychosocial vs medical/surgical providers) and beliefs (outcomes vs equity)., Results: Five hundred and eighy-four transplant providers completed the survey. Social support was the second most influential factor among transplant providers. Providers were most likely to choose a candidate who had social support (OR=1.68, 95% CI 1.50 to 1.86), always adhered to a medical regimen (OR=1.64, 95% CI 1.46 to 1.88), and had a 15 years life expectancy with transplant (OR=1.61, 95% CI 1.42 to 1.85). Psychosocial providers were more influenced by adherence and quality of life compared with medical/surgical providers, who were more influenced by candidates' life expectancy with transplant (p<0.05). For providers concerned with avoiding organ waste, social support was the most influential factor, while it was the least influential for clinicians concerned with fairness (p<0.05)., Conclusions: Social support is highly influential in listing decisions and may exacerbate transplant disparities. Providers' beliefs and reliance on social support in determining suitability vary considerably, raising concerns about transparency and justice., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Objectives: To evaluate the impact of liver and kidney transplantation on survival in HIV-positive transplant candidates and compare outcomes between HIV-positive and negative recipients., Design: Observational cohort of HIV-positive transplant candidates and recipients and secondary analysis comparing study recipients to HIV-negative national registry controls., Methods: We fit proportional hazards models to assess transplantation impact on mortality among recipients and candidates. We compared time to graft failure and death with HIV-negative controls in unmatched, demographic-matched, and risk-adjusted models., Results: There were 17 (11.3%) and 46 (36.8%) deaths among kidney and liver recipients during a median follow-up of 4.0 and 3.5 years, respectively. Transplantation was associated with survival benefit for HIV-infected liver recipients with model for end-stage liver disease (MELD) greater than or equal 15 [hazard ratio (HR) 0.1; 95% confidence interval (CI) 0.05, 0.01; P < 0.0001], but not for MELD less than 15 (HR 0.7; 95% CI 0.3, 1.8; P = 0.43) or for kidney recipients (HR 0.6; 95% CI 0.3, 1.4; P = 0.23). In HIV-positive kidney recipients, unmatched and risk-matched analyses indicated a marginally significant HR for graft loss [1.3 (P = 0.07) and HR 1.4 (P = 0.052)]; no significant increase in risk of death was observed. All models demonstrated a higher relative hazard of graft loss or death in HIV-positive liver recipients; the absolute difference in the proportion of deaths was 6.7% in the risk-matched analysis., Conclusion: Kidney transplantation should be standard of care for well managed HIV-positive patients. Liver transplant in candidates with high MELD confers survival benefit; transplant is a viable option in selected candidates. The increased mortality risk compared with HIV-negative recipients was modest., Trial Registration: ClinicalTrials.Gov; NCT00074386; http://clinicaltrials.gov/.

Ischemia-reperfusion injury to the kidney is a complex pathophysiological process that has importance during transplantation as it affects graft function and survival. It starts with the physiological changes associated with the death of the donor, including the direct effects of hypoxia and metabolic stress. The injury continues through the organ procurement and preservation procedures. Upon reperfusion, the organ is then further damaged by a reactive inflammatory process which had been primed during the earlier injuries. Clinically, the damage from microvascular dysfunction and cytotoxic agents contributed by the immunologic response results in impaired graft function or graft loss. Recent advances in understanding the specific pathways involved in this injury have helped identify novel therapies. Nevertheless, ischemia-reperfusion injury continues to be a daunting problem even as these treatment strategies are being evaluated for clinical use.

Many liver transplantation (LT) programs require substance abuse (SA) treatment for candidates with a history of alcohol abuse. However, there are no data indicating that SA treatment prevents post-LT alcohol relapse. We examined 118 adults who underwent LT from May 2002 to February 2011 to explore the relationship between SA treatment and post-LT relapse to any alcohol use. Sixty-one patients (52%) with a history of alcohol abuse or dependence received SA treatment before LT. Relapse to any alcohol use was identified in 40 LT recipients (34%). Patients who received SA treatment before LT did not differ significantly in the rate of post-LT alcohol relapse from patients who did not receive treatment before transplantation(30% versus 39%, P = 0.20). However, patients who received SA treatment both before and after transplantation had significantly lower rates of alcohol relapse (16%) than patients who received no SA treatment (41%) or SA treatment only before LT (45%, P = 0.03). Our findings suggest that LT programs should consider placing more emphasis on the continuation of some type of SA treatment after transplantation. Future research should prospectively examine the optimal timing for SA treatment that will attenuate the risk of alcohol relapse after transplantation.

Background: Although cirrhosis is common among Western hepatocellular carcinoma (HCC) patients, a substantial proportion are not cirrhotic. Studies examining surgical outcomes in noncirrhotic patients primarily evaluate Asian populations and liver resections. We describe cirrhotic and noncirrhotic HCC patients undergoing resection and transplantation at a Western institution., Methods: We retrospectively reviewed 188 HCC patients treated surgically from 2000 to 2011 at a single Western institution. The primary endpoint was recurrence. Secondary endpoints included time to recurrence and overall survival., Results: We evaluated 138 cirrhotic and 50 noncirrhotic patients with a median follow-up of 33.8 months. Noncirrhotics mostly underwent liver resection (90%), whereas cirrhotics primarily underwent transplantation (67%). Hepatitis B was the most common underlying liver disease for noncirrhotics (64%), whereas hepatitis C (55%) and alcohol abuse (32%) predominated among cirrhotics. Pathologic evaluation demonstrated tumors in noncirrhotics that were fewer in number, larger, less differentiated, and more likely to have vascular invasion. Recurrence was more common for noncirrhotics (36 vs. 18%; P = .008) and more common after resection compared with transplantation. Overall median survival was 46.9 months for both groups. After resection, noncirrhotics had longer survival times than did cirrhotics (41.6 vs. 32.9 months; P = .04). Vascular invasion was an independent predictor for recurrence; tumor size was a predictor of mortality., Conclusion: Noncirrhotics in our Western cohort had higher risk pathologic features, more frequently underwent resection, and suffered more recurrences than did cirrhotics. Overall survival was similar for both groups. Prospective studies of noncirrhotic HCC patients in Asia and Western countries may inform surveillance and treatment., (Copyright © 2013 Mosby, Inc. All rights reserved.)

Immunoglobulin A (IgA) deposition in the native kidneys of patients with liver disease is well described. Secondary IgA nephropathy usually is thought to be benign, but hematuria, proteinuria, and loss of kidney function have been reported in this context. BK virus nephropathy is an important cause of kidney transplant loss; however, BK virus nephropathy is rare in the native kidneys of patients who underwent transplantation of other organs. We report the case of a patient with alcohol-related end-stage liver disease and chronic kidney disease with hematuria who underwent simultaneous liver-kidney transplantation. His kidney function decreased over the course of several weeks posttransplantation. Biopsy of the transplant kidney showed BK virus nephropathy, but no IgA deposits. In contrast, biopsy of the native kidneys showed IgA deposits, but no BK virus nephropathy. To our knowledge, this is the first reported case of a simultaneous liver-kidney transplantation wherein both the native and transplant kidneys were biopsied posttransplantation and showed exclusively different pathologies. These findings confirm the predilection of BK virus nephropathy for transplant rather than native kidneys., (Copyright © 2013 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Failure of fibrotic liver to regenerate after resection limits therapeutic options and increases demand for liver transplantation, representing a significant clinical problem. The mechanism underlying regenerative failure in fibrosis is poorly understood. Seventy percent partial hepatectomy (PHx) was performed in C57Bl/6 mice with or without carbon tetrachloride (CCl4)-induced liver fibrosis. Liver function and regeneration was monitored at 1 to 14 days thereafter by assessing liver mass, alanine aminotransferase (ALT), mRNA expression, and histology. Progenitor (oval) cell mitogen tumor necrosis factor-like weak inducer of apoptosis (TWEAK) and TWEAK-neutralizing antibody were used to manipulate progenitor cell proliferation in vivo. In fibrotic liver, hepatocytes failed to replicate efficiently after PHx. Fibrotic livers showed late (day 5) peak of serum ALT (3542 ± 355 IU/L compared to 93 ± 65 IU/L in nonfibrotic livers), which coincided with progenitor cell expansion, increase in profibrogenic gene expression and de novo collagen deposition. In fibrotic mice, inhibition of progenitor activation using TWEAK-neutralizing antibody after PHx resulted in strongly down-regulated profibrogenic mRNA, reduced serum ALT levels and improved regeneration. Failure of hepatocyte-mediated regeneration in fibrotic liver triggers activation of the progenitor (oval) cell compartment and a severe fibrogenic response. Inhibition of progenitor cell proliferation using anti-TWEAK antibody prevents fibrogenic response and augments fibrotic liver regeneration. Targeting the fibrogenic progenitor response represents a promising strategy to improve hepatectomy outcomes in patients with liver fibrosis., (Copyright © 2013 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)

Networking between cells is critical for proper functioning of the cellular milieu and is mediated by cascades of highly regulated and overlapping signaling molecules. The enzyme heme oxygenase-1 (HO-1) generates three separate signaling molecules through the catalysis of heme - carbon monoxide (CO), biliverdin, and iron - each of which acts via distinct molecular targets to influence cell function, both proximally and distally. This review focuses on state-of-the art developments and insights into the impact of HO-1 and CO on the innate immune response, the effects of which are responsible for an ensemble of functions that help regulate complex immunological responses to bacterial sepsis and ischemia/reperfusion injury. HO-1 exemplifies an evolutionarily conserved system necessary for the cellular milieu to adapt appropriately, function properly, and ensure survival of the organism., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Background: In this report, we examine the surgical safety and complications (SC) among 125 liver (L) and 150 kidney (K) HIV+ transplantation (TX) recipients in a prospective nonrandomized U.S. multicenter trial., Methods: Subjects were required to have CD4+ T-cell counts >200/100 cells/mm3 (K/L) and undetectable plasma HIV-1 RNA (Viral Load [VL]) (K) or expected posttransplantation suppression (L). Impact of SCs (N ≥ 7) was evaluated by use of the proportional hazards models. Baseline morbidity predictors for SCs (N ≥ 7) were assessed in univariate proportional hazards models., Results: At median 2.7 (interquartile range 1.9-4.1) and 2.3 (1.0-3.7) years after TX, 3-month and 1-year graft survival were [K] 96% (95% CI 91%-98%) and 91% (95% CI 85%-94%) and [L] 91% (95% CI 85%-95%) and 77% (95% CI 69%-84%), respectively. A total of 14 K and 28 L graft losses occurred in the first year; 6 K and 11 L were in the first 3 months. A total of 26 (17%) K and 43 (34%) L experienced 29 and 62 SCs, respectively. In the liver multivariate model, re-exploration was marginally associated (hazard ratio [HR] 2.8; 95% CI 1.0-8.4; P = .06) with increased risk of graft loss, whereas a greater MELD score before transplantation (HR 1.07 per point increase; 95% CI: 1.01-1.14; P = .02), and detectable viral load before TX (HR 3.6; 95% CI 0.9-14.6; P = .07) was associated with an increased risk of wound infections/dehiscence., Conclusion: The rates and outcomes of surgical complications are similar to what has been observed in the non-HIV setting in carefully selected HIV-infected liver and kidney TX recipients., (Copyright © 2012 Mosby, Inc. All rights reserved.)

Clinical pathways (CP) have been developed to aid in the management of many surgical and medical conditions. Studies show the benefits of CP on outcomes including reduction in length of stay (LOS), morbidity, costs, and improvement in patient satisfaction (Arch Surg 2008: 394: 31; J Eval Clin Pract 2007: 13: 920; Arch Otolaryngol Head Neck Surg 2000: 126: 322; Circulation 2000: 101: 461; BMC Pulm Med 2006: 6: 22; Int J Health Care Qual Assur 2006: 19: 237; Am J Med Qual 2005: 20: 83; Am J Surg 2006: 192: 399; Am Surg 2005: 71: 152). Reports of CP in solid organ transplantation are lacking, possibly given the complexity of the transplant procedures that entail a complex, multidisciplinary pre-operative evaluation, inpatient, and post-operative time frames. We have developed CP from presentation for transplant evaluation to post-transplant follow-up for liver, kidney, and pancreas transplantation and live kidney and live liver donation and are making them available online for viewing. Our CPs encompass the pre-operative, peri-operative, and post-operative period, including both outpatient and inpatient care. We propose that transplantation is an ideal forum for successful implementation of CP, given the rigorous process that centers are subject to for CMS approval and the ample opportunity for improving our patients' lives by improvement in and streamlining of the entire process of clinical care from end-stage organ failure to post-transplant long-term management. Our CPs can be found at http://bidmc.org/CentersandDepartments/Departments/TransplantInstitute/TransplantClinicalPathways.aspx., (© 2011 John Wiley & Sons A/S.)

Patient-reported outcomes are important to consider when the relative success of liver transplantation (LT) is being evaluated. Our primary objective was to examine the expectations for LT and the criteria for its success across 4 domains of functioning (pain, fatigue, emotional distress, and interference with daily activities) from the perspective of patients who were wait-listed for LT. One hundred four adult patients with a mean wait-list time of 16.5 ± 13 months completed a semistructured interview with a modified version of the Patient-Centered Outcomes Questionnaire (PCOQ). The patients reported moderate usual levels of pain, fatigue, emotional distress, and interference with daily activities (mean rating range = 3.8-6.2), and they attached great importance to improvements in these domains after LT (mean rating range = 7.3-8.0). Patients considered a mean reduction in pain of 33% to be a successful LT outcome. A reduction in fatigue of 56%, a reduction in emotional distress of 44%, and a reduction in interference with daily activities of 54% represented successful LT across these domains. Patients with more severe illness had higher expectations for fatigue (r = -0.30, P = 0.002) and interference with daily activities (r = -0.24, P = 0.015). Cluster and correlational analyses provided support for the validity of the PCOQ with LT patients. Our findings underscore the importance and value of using patient-centered assessments to better understand the ways in which patients prioritize LT outcomes and define transplantation success. Patient-centered assessments have the potential to facilitate provider-patient communication by helping patients to prioritize their goals for LT and make informed choices on the basis of those priorities., (Copyright © 2011 American Association for the Study of Liver Diseases.)

Hepatocyte proliferation early after liver resection is critical in restoring liver mass and preserving function as the liver regenerates. Carbon monoxide (CO) generated by heme oxygenase-1 (HO-1) strongly influences cellular proliferation and both HO-1 and CO are accepted hepatoprotective molecules. Mice lacking functional HO-1 were unable to mount an appropriate regenerative response following partial hepatectomy (PHTx) compared to wildtype controls. We therefore hypothesized that exogenous administration of CO at low, nontoxic concentrations would modulate hepatocyte (HC) proliferation and liver regeneration. Animals treated with a low concentration of CO 1 hour prior to 70% hepatectomy demonstrated enhanced expression of hepatocyte growth factor (HGF) in the liver compared to controls that correlated with a more rapid onset of HC proliferation as measured by phospho-histone3 staining, increased expression of cyclins D1 and E, phosphorylated retinoblastoma, and decreased expression of the mitotic inhibitor p21. PHTx also increased activation of the HGF receptor c-Met, which was detected more then 9 hours earlier in the livers of CO-treated mice. Blockade of c-Met resulted in abrogation of the CO effects on HC proliferation. Corresponding with increased HC proliferation, treatment with CO maintained liver function with normal prothrombin times versus a 2-fold prolongation in controls. In a lethal 85% PHTx, CO-treated mice showed a greater survival rate compared to controls. In vitro, CO increased HGF expression in hepatic stellate cells, but not HC, and when cocultured together led to increased HC proliferation. In summary, we demonstrate that administration of exogenous CO enhances rapid and early HC proliferation and, importantly, preserves function following PHTx. Taken together, CO may offer a viable therapeutic option to facilitate rapid recovery following PHTx., (Copyright © 2011 American Association for the Study of Liver Diseases.)

Objective: Evaluate recurrence and survival in patients who underwent intraoperative margin re-resection for colorectal cancer liver (CRC) metastases., Design: Retrospective analysis., Setting: University Hospital, Cincinnati, Ohio. Academic medical center., Participants: Cohort of 118 patients who underwent resection of CRC liver metastases between 1992 and 2004. All patients were divided into 3 groups: resection margin (MOR) less than 1 cm (n = 64), MOR greater than 1 cm (n = 33), and re-resection margin (re-MOR) greater than 1 cm (n = 21)., Results: Patients with a margin greater than 1 cm, when compared with re-MOR greater than 1 had decreased incidence of liver and distant recurrence (p < 0.05) as well as improved disease-free survival (39.2 vs 22.9 months, p = 0.023). Differences in overall survival (58.6 vs 44.2 months, p = 0.14) were not significant., Conclusion: Intraoperative re-resection is associated with an increased risk of local and distant recurrence, which may be a reflection of both inadequate surgery and underlying tumor biology.

Progressive multifocal leukoencephalopathy (PML), a demyelinating disease of the brain caused by JC virus (JCV), occurs following transplantation and other conditions associated with immunosuppression. On magnetic resonance imaging (MRI), PML lesions typically appear as hyperintense signal on T2-weighted and FLAIR images located in the subcortical white matter, which are devoid of contrast enhancement or mass effect. The prognosis is poor, but unusual inflammatory forms of PML characterized by contrast enhancement have been associated with a cellular immune response against JCV and a better prognosis. The authors report an atypical presentation of PML with contrast-enhancing lesions and mass effect on the MRI in a liver transplant recipient,who had a progressive course and fatal outcome.

The most significant development in liver transplantation in the USA over the past year was the full implementation of the MELD- and PELD-based allocation policy in March 2002, which shifted emphasis from waiting time within broad medical urgency status to prioritization by risk of waiting list death. The implementation of this system has led to a decrease in pretransplant mortality without increasing post-transplant mortality, despite a higher severity of illness at the time of transplant. The trend over the last few years of rapidly increasing numbers of adult living donor liver transplants was reversed in 2002 by a decline of more than 30% in the number of these procedures. In 2002, a greater percentage of women received livers from living donors (43%) than deceased donors (34%), possibly because of size considerations. From 1993 to 2001, the waiting list increased more than sixfold, from 2902 patients to 18,047 patients. For the first time since 1993, the waiting list size decreased in 2002, dropping 6% to 16,974 candidates. The percentage of temporarily inactive liver candidates also increased from 2001, thus the net decrease in the active waiting list for 2002 was 12%. This may reflect a trend toward less pre-emptive listing practices under MELD. Intestine transplantation remains a low-volume procedure limited to a few transplant centers and is still accompanied by significant pre- and post-transplantation risks. As this procedure matures, its application may increase to include recipients at an earlier stage of their disease with better likelihood of success.