Paraumbilical collateral veins on MRI as possible protection against portal venous thrombosis in candidates for liver transplantation

Background: We retrospectively evaluate the potential protective influence of patent paraumblical vein (PUV) collaterals against portal vein (PV) thrombosis and reduced PV diameter in candidates for orthotopic liver transplant (OLT) Methods: Dynamic 3D contrast-enhanced MRI at 1.5T was obtained in 309 patients with cirrhosis without evidence of malignancy. All MR studies were reviewed by one reader for PUV collaterals, PV thrombosis and PV diameter. Statistical analysis was performed by Fisher exact tests; 50 selected studies were reviewed independently by two additional readers to determine interobserver agreement via intraclass correlation coefficient (ICC). Results: Patent PUV was noted in 119 of 309 patients (38.5%). Mean PV diameter was 13.4 ± 3.0 mm in patients with PUV compared with 11.3 ± 3.6 mm without PUV (P \u3c 0.01). Main PV thrombosis was present in 13 of 309 patients (4.2%) and significantly more frequent in those without PUV than with PUV (6.3% vs. 0.8%, P \u3c 0.05). ICC indicated almost perfect agreement among three readers for presence of PUV collaterals (ICC = 0.91) and PV thrombosis (ICC = 0.96). Conclusion: Our results suggest that patients with patent PUV appear less likely to develop main PV thrombosis or small PV diameter, suggesting a protective effect of PUV on PV patency

Completely steroid-free immunosuppression in liver transplantation: a randomized study.

INTRODUCTION: Corticosteroids (CS) have been standard immunosuppression to prevent and treat rejection. However, CS are associated with increased risk of infection, obesity, hypertension, hyperlipidemia, diabetes, and accelerated hepatitis C virus (HCV) recurrence post-orthotopic liver transplantation (OLT). This study assesses the safety and efficacy of CS-free immunosuppressive regimen in adult OLT. METHODS: A two-yr, prospective, randomized study of CS with delayed withdrawal (CS) or CS-free regimen with basiliximab, tacrolimus, and enteric-coated mycophenolate sodium (EC-MPS) was performed in 39 patients (CS=20; CS-free=19). CS group received intra-operative methylprednisolone weaned by six months. HCV patients had HCV PCR pre-OLT and 0.5, one, three, and six months post-OLT. Protocol liver biopsies were performed at OLT, 2 and 24 wk post-OLT or when indicated. RESULTS: Rejection occurred in two patients. Patient survival at one yr (100% vs. 95%), three yr (85% vs. 63%), and five yr (80% vs. 63%) post-OLT were similar between CS and CS-free group, respectively. Death-censored graft survival at one yr (100% vs. 95%), three yr (85% vs. 63%), and five yr (75% vs. 63%) were also similar. The risk of new-onset DM, hypertension, hypercholesterolemia, and weight gain was similar between groups. CONCLUSION: CS avoidance with basiliximab, calcineurin inhibitor, and EC-MPS is safe and effective as CS- containing immunosuppression in adult OLT

The adipose tissue production of adiponectin is increased in end-stage renal disease.

Adiponectin has antidiabetic properties, and patients with obesity, diabetes, and insulin resistance have low plasma adiponectin levels. However, although kidney disease is associated with insulin resistance, adiponectin is elevated in end-stage renal disease. Here we determine whether adipose tissue production of adiponectin is increased in renal disease in a case-control study of 36 patients with end-stage renal disease and 23 kidney donors. Blood and tissue samples were obtained at kidney transplantation and donation. The mean plasma adiponectin level was significantly increased to 15.6 mg/ml in cases compared with 8.4 mg/ml in controls. Plasma levels of the inflammatory adipokines tumor necrosis factor α, interleukin 6, and high-sensitivity C-reactive protein were significantly higher in cases compared with controls. Adiponectin mRNA and protein expression in visceral and subcutaneous fat were significantly higher in cases than controls, while adiponectin receptor-1 mRNA expression was significantly increased in peripheral blood cells, muscle, and adipose tissue in cases compared with controls. Thus, our study suggests that adipose tissue production of adiponectin contributes to the high plasma levels seen in end-stage renal disease

Initiation of a critical pathway for pancreaticoduodenectomy at an academic institution -- the first step in multi-disciplinary team building

Objective: This study was designed to identify quantifiable parameters to track performance improvements brought about by the implementation of a critical pathway for complex alimentary tract surgery. Background: Pancreaticoduodenectomy (PD) is a complex general surgical procedure performed in varying numbers at many academic institutions. Originally associated with significant perioperative morbidity and mortality, multiple studies have now shown that this operation can be performed quite safely at high volume institutions that develop a particular expertise. Critical pathways are one of the key tools used to achieve consistently excellent outcomes as these institutions. It remains to be determined if implementation of a critical pathway at an academic institution with prior moderate experience with PD will result in performance gains and improved outcomes. Methods: Between January 1, 2004 and October 15, 2006 135 patients underwent PD, 44 before the implementation of a critical pathway on October 15, 2005, and 91 after. Perioperative and postoperative parameters were analyzed retrospectively to identify those that could be used to track performance improvement and outcomes. Key aspects of the pathway include spending the night of surgery in the intensive care unit with careful attention to fluid balance, early mobilization on post-operative day one, aggressive early removal of encumbrances such as nasogastric tubes and urinary catheters, early post-operative feeding, and targeting discharge for postoperative day 6 or 7. Results: The pre- and post-pathway implementation groups were not statistically different with regards to age, sex, race, or pathology (malignant versus benign). Perioperative mortality, operative blood loss, and number of transfused units of packed red blood cells were also similar. As compared to the pre-pathway group, the post-pathway group had a significantly shorter postoperative length of stay (13 versus 7 days, P ≤ 0.0001), operative time (435 ± 14 minutes versus 379 ± 12 minutes, P ≤ 0.0001), and in room non-operative time (95 ± 4 minutes versus 76 ± 2 minutes, P ≤ 0.0001). Total hospital charges were significantly reduced from $240,242 ±$32,490 versus $126,566 ±$4883 (P ≤ 0.0001) after pathway implementation. Postoperative complication rates remained constant (44% pre-pathway versus 37% after, P = NS). Readmission rates were not negatively affected by the reduction in length of stay, with a 7% readmission rate prior to implementation and a 7.7% rate after implementation. Conclusion: Implementation of a critical pathway for a complex procedure can be demonstrated to improve short-term outcomes at an academic institution. This improvement can be quantified and tracked and has implications for better utilization of resources (greater OR and hospital bed availability) and overall cost containment. With a very conservative estimate of 75 pancreaticoduodenectomies per year by this group, this translates to a savings of 450 hospital days and over $8,550,000 in hospital charges on an annual basis. As we enter the pay for performance era, institutions will be required to generate such data in order to retain patient volumes, attract new patients, and receive incentive payments for high quality services rendered

Impact of Obesity on Perioperative Morbidity and Mortality Following Pancreaticoduodenectomy

Background: Obesity has been implicated as a risk factor for perioperative and postoperative complications. The aim of this study was determine the impact of obesity on morbidity and mortality in patients undergoing pancreaticoduodenectomy (PD). Study Design: Between January 2000 and July 2007, 262 patients underwent PD at Thomas Jefferson University Hospital (TJUH), of whom 240 had complete data, including body mass index (BMI) for analysis. Data on BMI, preoperative parameters, operative details, and post-operative course were collected. Patients were categorized as obese (BMI \u3e30 kg/m2), overweight (25≤BMI\u3c30), or normal weight (BMI\u3c25). Complications were graded according to previous published scales. Other endpoints included length of postoperative hospital stay, blood loss, and operative duration. Analyses were performed using univariate and multivariable models. Results: There were 103 (42.9%) normal weight, 71 (29.6%) overweight and 66 (27.5%) obese patients. There were 5 perioperative deaths (2.1%) with no differences across BMI categories. A significant difference in median operative duration and blood loss between obese and normal weight patients was identified (439vs. 362.5minutes, p= 0.0004; 650 vs. 500 ml, p=0.0139). Furthermore, median length of stay was marginally significantly longer for by BMI (9.5 vs. 8 days, p=0.095). While there were no significant differences in superficial wound infections, obese patients did have an increased rate of serious complications compared to normal weight patients (24.2% vs. 13.6%, respectively; p=0.10). Conclusions: Obese patients undergoing PD have a significantly increased blood loss and longer operative time, but do not have a significantly increased length of postoperative hospital stay or rate of serious complications. These findings should be considered when assessing patients for operation and when counseling patients regarding operative risk, but do not preclude obese individuals from undergoing definitive pancreatic surgery

Transplantation of Kidneys from Donors with Acute Renal Failure Five-Year Results from Double Center Experience

Background: Transplantation of kidneys from deceased donors with acute renal failure (ARF) has been described and represents an underutilized source of renal grafts. We reviewed retrospectively our double center experience with transplantation of ARF donor kidneys. Methods: Between January 2009 and June 2014, we performed a total of 397 kidney transplants at the two hospitals. Of which, 65 came from donors with ARF. The outcome was compared with 62 expanded criteria donor kidneys and 270 standard criteria donor kidneys. ARF was defined as donor terminal creatinine higher than 2. All kidneys from ARF donors had acceptable biopsies and were pumped. The immunosuppression was similar in all three groups (Thymoglobulin for induction and Prograf, Cellcept and steroids for maintenance). The outcome measurements included recipient serum creatinine, patient and graft survival at 6 months, 1 year and 3 years. We also reviewed the delayed graft function (DGF) rates and cold ischemic time in all groups. Results: Mean donor creatinine was 3.84±1.3. The 6 month, 1 and 3 year patient survival rates were 98.5%, 96.8% and 92.0% in ARF group, 98.1%, 97.0% and 93.4% SCD group and 98.4%, 93.2% and 77.7% in ECD group. The 6 month, 1 and 3 year death censored graft survival was 96.9%, 96.9%, 96.9% in ARF group, 97.7, 96.5, 91.8 in SCD group and 95.1%, 93.2%, 90.1% in ECD group. The mean 6mo, 1 year and 3 year recipient creatinine was 1.49, 1.46 and 1.51 in ARF group, 1.61, 1.72 and 1.77 in SCD group and 1.91, 1.92 and 2.15 in ECD group, respectively. ARF kidneys are noted to be associated with more DGF (58.5% in ARF group VS 41.5% in non ARF group), longer cold ischemic time (857.79 min in ARF group vs 589.32 min in non ARF group) and younger donor age (32.25 years in ARF group vs 40.65 years in non ARF group). Conclusion: Elevated terminal donor creatinine is not a risk factor for graft loss after deceased donor kidney transplantation. Although there is increased risk of DGF and longer cold ischemic time, transplantation of ARF kidneys provides comparable short and long term graft function and patient survival compared to kidneys from non ARF donors

Fulminant hepatic failure bridged to liver transplantation with molecular adsorbent recirculating system: a single center experience

Purpose: We herein describe the clinical course of a consecutive series of fulminant hepatic failure patients treated with molecular adsorbent recirculating system, a cell-free albumin dialysis technique. From November 2000 to September 2002, 7 adult patients age 22-61 (median 41), one male (14.2%), and 6 females (85.7%), affected by fulminant hepatic failure, underwent 7 courses (1 to 5 session each, six hours in duration) of extracorporeal support using the molecular adsorbent recirculating system technique. Pre and post treatment blood glucose, liver function tests, ammonia, arterial lactate, electrolytes, hemodynamic parameters, arterial blood gases, liver histology, Glasgow Coma Scale, and coagulation studies, were reviewed. No adverse side effects like generalized bleeding on non-cardiogenic pulmonary edema, often seen during MARS treatment, occurred in the patients included in this study. Results: Six patients (85.7%) are currently alive and well, and one (14.2%) died. Four patients (57%) were successfully bridged (two patients in 1 day and two other patients in 4 days) to liver transplantation, while 2 (28.5%) recovered fully without transplantation. All the measured variables stabilized after molecular adsorbent recirculating system commencement. No differences were noted between the pre and post molecular adsorbent recirculating system liver histology. Conclusions: Molecular adsorbent recirculating system is a safe, temporary life support mechanism for patients awaiting liver transplantation or recovering from fulminant hepatic failure

Profiling the circulating mRNA transcriptome in human liver disease

The human circulation contains cell-free DNA and non-coding microRNA (miRNA). Less is known about the presence of messenger RNA (mRNA). This report profiles the human circulating mRNA transcriptome in people with liver cirrhosis (LC) and hepatocellular carcinoma (HCC) to determine whether mRNA analytes can be used as biomarkers of liver disease. Using RNAseq and RT-qPCR, we investigate circulating mRNA in plasma from HCC and LC patients and demonstrate detection of transcripts representing more than 19,000 different protein coding genes. Remarkably, the circulating mRNA expression levels were similar from person to person over the 21 individuals whose samples were analyzed by RNAseq. Liver derived circulating transcripts such as albumin (ALB), apolipoprotein (APO) A1, A2 & H, serpin A1 & E1, ferritin light chain (FTL) and fibrinogen like 1 (FGL1) were significantly upregulated in HCC patient samples. Higher levels of some of these liver-specific transcripts in the plasma of HCC patients were confirmed by RT-qPCR in another cohort of 20 individuals. Several less abundant circulating transcripts associated with cancer were detected in most HCC samples, but not in healthy subjects. Liver specificity of circulating transcripts was confirmed by investigating their expression in HCC tumor and liver cancer cell lines. Liver specific mRNA sequences in the plasma were predominantly present outside circulating extracellular vesicles. Conclusions: The circulating “mRNA” transcriptome is remarkably consistent in diversity and expression from person to person. Detection of transcripts corresponding to disease selective polypeptides suggests the possibility that circulating mRNA can work as a biomarker analyte for cancer detection

Growth inhibition of human hepatocellular carcinoma cells by overexpression of G protein-coupled receptor kinase 2

Summary: In this study, we investigated a novel approach for HCC treatment by inducing overexpression of GRK2 in human HCC cells. We found that overexpression of GRK2 through recombinant adenovirus transduction inhibits the growth of human HCC cells. BrdU incorporation assay showed that the growth inhibition caused by elevated GRK2 level was due tot he reduced cell proliferation but not apoptosis. To examine the anti-proliferative function of increased GRK2 level, we performed cell cycle analysis using propidium iodide staining. We found that the proliferation suppression was associated with G2/M phase cell cycle arrest by the wild type GRK2 but not its kinase-dead K220R mutant. Furthermore, increased levels of wild type GRK2 induced upregulation of phosphor-Ser15 p53 and cyclin B1 in a dose dependent manner. Our data indicate that the anti-proliferative function of elevated GRK2 is associated with delayed cell cycle progression and is GRK2 kinase activity-dependent. Given the public importance of HCC, it is likely that the enforced expression of GRK2 in human HCC by molecular delivery may offer a potential therapeutic approach for the treatment of human liver cancer