Association of Recipient APOL1 Kidney Risk Alleles With Kidney Transplant Outcomes.

BACKGROUND: Kidney transplant survival in African American recipients is lower compared with non-African American transplant recipients. APOL1 risk alleles (RA) have been postulated as likely contributors. We examined the graft outcomes in kidney transplant recipients (KTRs) stratified by APOL1 RA status in a multicenter observational prospective study. METHODS: The Renal Transplant Outcome Study recruited a cohort of incident KTRs at 3 transplant centers in the Philadelphia area from 1999-2004. KTRs were genotyped for APOL1 RA. Allograft and patient survival rates were compared by the presence and number of APOL1 RA. RESULTS: Among 221 participants, approximately 43% carried 2 APOL1 RA. Recipients carrying 2 APOL1 RA demonstrated lower graft survival compared with recipients with only 1 or none of APOL1 RA at 1 y posttransplant, independently of other donor and recipient characteristics (adjusted hazard ratio 3.2 [95% confidence interval, 1.0-10.4], P = 0.05). There was no significant difference in overall survival or graft survival after 3 y posttransplantation. There was no difference in death by APOL1 -risk status ( P = 0.11). CONCLUSIONS: Recipients with 2 APOL1 high-risk alleles exhibited lower graft survival 1 y posttransplantation compared with recipients with only 1 or 0 APOL1 RA. Further research is required to study the combined role of the recipient and donor APOL1 genotypes in kidney transplantation.

Circulating messenger RNA variants as a potential biomarker for surveillance of hepatocellular carcinoma.

Background and rationale: Liver derived messenger ribonucleic acid (mRNA) transcripts were reported to be elevated in the circulation of hepatocellular carcinoma (HCC) patients. We now report the detection of high-risk mRNA variants exclusively in the circulation of HCC patients. Numerous genomic alleles such as single nucleotide polymorphisms (SNPs), nucleotide insertions and deletions (called Indels), splicing variants in many genes, have been associated with elevated risk of cancer. Our findings potentially offer a novel non-invasive platform for HCC surveillance and early detection. Approach: RNAseq analysis was carried out in the plasma of 14 individuals with a diagnosis of HCC, 8 with LC and no HCC, and 6 with no liver disease diagnosis. RNA from 6 matching tumors and 5 circulating extracellular vesicle (EV) samples from 14 of those with HCC was also analyzed. Specimens from two cholangiocarcinoma (CCA) patients were also included in our study. HCC specific SNPs and Indels referred as "variants" were identified using GATK HaplotypeCaller and annotated by SnpEff to filter out high risk variants. Results: The variant calling on all RNA samples enabled the detection of 5.2 million SNPs, 0.91 million insertions and 0.81 million deletions. RNAseq analyses in tumors, normal liver tissue, plasma, and plasma derived EVs led to the detection of 5480 high-risk tumor specific mRNA variants in the circulation of HCC patients. These variants are concurrently detected in tumors and plasma samples or tumors and EVs from HCC patients, but none of these were detected in normal liver, plasma of LC patients or normal healthy individuals. Our results demonstrate selective detection of concordant high-risk HCC-specific mRNA variants in free plasma, plasma derived EVs and tumors of HCC patients. The variants comprise of splicing, frameshift, fusion and single nucleotide alterations and correspond to cancer and tumor metabolism pathways. Detection of these high-risk variants in matching specimens from same subjects with an enrichment in circulating EVs is remarkable. Validation of these HCC selective ctmRNA variants in larger patient cohorts is likely to identify a predictive set of ctmRNA with high diagnostic performance and thus offer a novel non-invasive serology-based biomarker for HCC.

From an Incidental Finding to an Emergent Treatment: A Case Report of a Hepatic Adenomatosis and Large Ruptured Hepatic Adenoma.

Introduction. Hepatic adenoma is an uncommon benign liver tumor presenting as solitary lesions or even rarely as hepatic adenomatosis. Large lesions carry a risk of rupture, hemorrhage, and malignant transformation. This case report aims to increase awareness about risk factors for hepatic adenomas, considering the increasing prevalence of obesity and the widespread use of oral contraceptive pills. Case Presentation. A 20-year-old obese female who was taking oral contraceptive pills for seven years presented to the emergency department with vomiting and abdominal pain caused by gastroenteritis. On imaging, multiple hepatic adenomas, including two lesions 6 and 9 cm in diameter, were incidentally found. During the hospitalization, the patient suddenly developed acute anemia and rupture of the largest lesion, which was promptly treated with arterial embolization. Discussion. Obesity and exposure to hormones are well-known risk factors for hepatic adenomas. The incidence of hepatic adenomas is steadily increasing because of the prevalence of obesity, especially among females. Lifestyle interventions for weight loss and discontinuation of oral contraceptive pills are considered a conservative treatment of hepatic adenomas. Large lesions possess the risk of malignant transformation and rupture and require surgical excision.

Municipality and Adjusted Gross Income Influence Outcome of Patients Diagnosed with Pancreatic Cancer in a Newly Developed Cancer Center in Mercer County New Jersey, USA, a Single Center Study.

Socioeconomic status (SES) correlates directly to ZIP code. Mercer County is not atypical as a collection of a dozen municipalities with a suburban/metropolitan population of 370,430 in the immediate vicinity of a major medical center. The purpose of this study for Mercer County, New Jersey, USA is to determine whether a patient's ZIP code is related to the outlook of pancreatic cancer defined as staging at diagnosis, prevalence, overall survival, type of insurance, and recurrence. Our hypothesis was that specific variables such as socio-economic status or race could be linked to the outcome of patients with pancreatic cancer. We interrogated a convenience sample from our cancer center registry and obtained 479 subjects diagnosed with pancreatic cancer in 1998-2018. We selected 339 subjects by ZIP code, representing the plurality of the cases in our catchment area. The outcome variable was overall survival; predictor variables were socio-economic status (SES), recurrence, insurance, type of treatment, gender, cancer stage, age, and race. We converted ZIP code to municipality and culled data using adjusted gross income (AGI, FY 2017). Comparative statistical analysis was performed using chi-square tests for nominal and ordinal variables, and a two-way ANOVA test was used for continuous variables; the p-value was set at 0.05. Our analysis confirmed that overall survival was significantly higher for Whites and for individuals who live in a municipality with a high SES. Tumor stage at the time of diagnosis was not different among race and SES; however, statistically significant differences for race or SES existed in the type of treatment received, with disparities found in those who received radiation therapy and surgery but not chemotherapy. The data may point to a lack of access to specific care modalities that subsequently may lead to lower survival in an underserved population. Access to care, optimal nutritional status, overall fitness, and co-morbidities could play a major role and confound the results. Our study suggests that low SES has a negative impact on overall pancreatic cancer survival. Surgery for pancreatic cancer should be appropriately decentralized to those community cancer centers that possess the expertise and the infrastructure to carry out specialized treatments regardless of race, ethnicity, SES, and insurance.

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.

Pre-Liver Transplant Muscle Loss Is a Risk Factor for Post-Liver Transplantation Left Ventricular Systolic Dysfunction.

BACKGROUND The development of left ventricular systolic dysfunction (LVSD) after liver transplant (LT) can result in increased morbidity and mortality in the immediate period following liver transplant. The aim of this study was to evaluate low muscle mass due to chronic liver disease, as a potential risk factor for LVSD after LT. MATERIAL AND METHODS A retrospective chart review was completed for all adult patients who received a liver transplant between January 2002 and January 2015 at a single academic LT center. Collected data included patient demographics, medical history, laboratory data, radiology results, and pathology. Echocardiograms were reviewed for patients identified as having LVSD diagnosed within 1 year after LT (left ventricular ejection fraction <55%). The total psoas area (TPA), a marker of low muscle mass, was determined by measuring the average cross-sectional area of the psoas muscle on MRI or CT scans before transplant at the level of L4 vertebra. RESULTS Of the 503 post-LT patients reviewed, 144 (28.6%) had pre-and post-LT echocardiograms. Of these 144 patients, 17 developed LVSD, of which 15 (88.2%) occurred within 1 year after LT. The average age at transplant of those with LVSD was 58.9±6 years, with a mean MELD score of 30.7±6. The mean TPA normalized for height for patients with LVSD was 297.68±86.99 mm²/m² compared to 382.1±104.2 mm²/m² for those with normal EF (p= 0.002). BMI, MELD score, and etiology of cirrhosis were not significant risk factors for post-LT LVSD in our study population. During the study period, 35.2% (n=6) of LVSD patients died within 1 year after LT. CONCLUSIONS Although LVSD is thought to be a rare complication after LT, those with muscle loss as predicted by mean TPA measurements normalized for height may be at highest risk.

Hepatic Artery Pseudoaneurysm Following Orthotopic Liver Transplantation: Increasing Clinical Suspicion for a Rare but Lethal Pathology.

BACKGROUND Despite an incidence of between 1% and 2%, the mortality rate in ruptured hepatic artery pseudoaneurysm after orthotopic liver transplantation approaches 69%. Our aim is to report operative and outcomes data for 7 patients with pseudoaneurysm following transplant at 1 institution, with emphasis on suspected risk factors for aneurysm formation. From these risk factors, we performed a systematic review to assess their clinical saliency. MATERIAL AND METHODS Using PRISMA guidelines, we completed a PubMed and online database review to gather studies addressing risk factors for pseudoaneurysm following transplant. We cross-compared infection, Roux-en-Y hepaticojejunostomy, bile leak, and primary sclerosing cholangitis as independent risk factors in order to identify concomitance between each and pseudoaneurysm. RESULTS The incidence of pseudoaneurysm was 0.94%. Of pseudoaneurysm patients, 77.8% had documented infection. Of these, 36.5% had Roux-en-Y hepaticojejunostomy and 33.3% had a documented bile leak. Infection was present in 70% of patients with Roux-en-Y hepaticojejunostomy, 84% of patients with bile leak, and 93% of patients with primary sclerosing cholangitis. CONCLUSIONS Roux-en-Y hepaticojejunostomy, bile leak, and primary sclerosing cholangitis are important risk factors for pseudoaneurysm in the setting of infection. Occurring together, these risk factors should heighten clinical suspicion for their formation in the postoperative period.

Hepatitis B in Solid-Organ Transplant Procedures Other Than Liver.

Transplant is often the best treatment available for patients with end-stage organ failure. Hepatitis B virus infection in transplant procedures other than liver is a major concern because it can be a significant cause of morbidity and mortality after transplant. Due to the increased risk of hepatic complications, such as fibrosing cholestatic hepatitis or histologic deterioration after transplant, systematic use of nucleoside or nucleotide analogues shortly before or at the time of transplant is recommended (tenofovir or entecavir are preferable to lamivudine) in all patients, whatever the baseline histologic evaluation. Sustained viral suppression may result in regression of fibrosis, which in turn may lead to decreased disease-related morbidity and improved survival. Finally, due to the high mortality after nonliver transplant procedures, decompensated cirrhosis from chronic hepatitis B should be considered as a contraindication to nonliver transplant but an indication to combined organ transplant (ie, liver-kidney transplant). Because of the high prevalence of hepatitis B virus exposure in allograft donors and recipients, hepatitis B virus status must be considered during organ allocation. Prevention of hepatitis B virus-related complications in transplant recipients starts with vaccination and donor-recipient matching.

Association of Inflammation prior to Kidney Transplantation with Post-Transplant Diabetes Mellitus.

BACKGROUND/OBJECTIVE: Post-transplant diabetes mellitus (PTDM) is both common and associated with poor outcomes after kidney transplantation. Our objective was to examine relationships of uremia-associated inflammation and adiponectin with PTDM. METHODS: Nondiabetic kidney transplant patients were enrolled with donor controls. Inflammatory cytokines and adiponectin were measured before and after transplantation. Adipose tissue was obtained for gene expression analysis. Glucose transport was quantified in vitro in C2C12 cells following cytokine exposure. The patients were monitored up to 12 months for PTDM. RESULTS: We studied 36 controls and 32 transplant patients, of whom 11 (35%) developed PTDM. Compared to controls, plasma TNFα, IL-6, MCP-1, and CRP levels were higher in transplant patients (p < 0.01). In multivariable analysis, TNFα plasma levels before transplantation were associated with development of PTDM (OR = 2.03, p = 0.04). Visceral adipose tissue TNFα mRNA expression was higher in transplant patients than controls (fold change 1.33; p < 0.05). TNFα mRNA expression was also higher in patients who developed PTDM than in those who did not (fold change 1.42; p = 0.05), and adiponectin mRNA expression was lower (fold change 0.48; p < 0.05). The studies on the C2C12 cells demonstrated an increase in glucose uptake following exposure to adiponectin and no significant change after exposure to TNFα alone. Concomitant TNFα and adiponectin exposure blunted adiponectin-induced glucose uptake (11% reduction; p < 0.001). CONCLUSION: Our in vitro and clinical observations suggest that TNFα could contribute to PTDM through an effect on adiponectin. Our study proposes that inflammation is involved in glucose regulation after kidney transplantation.

Dual Kidney Allocation Score: A Novel Algorithm Utilizing Expanded Donor Criteria for the Allocation of Dual Kidneys in Adults.

BACKGROUND Dual kidney transplantation (DKT) of expanded-criteria donors is a cost-intensive procedure that aims to increase the pool of available deceased organ donors and has demonstrated equivalent outcomes to expanded-criteria single kidney transplantation (eSKT). The objective of this study was to develop an allocation score based on predicted graft survival from historical dual and single kidney donors. MATERIAL AND METHODS We analyzed United Network for Organ Sharing (UNOS) data for 1547 DKT and 26 381 eSKT performed between January 1994 and September 2013. We utilized multivariable Cox regression to identify variables independently associated with graft survival in dual and single kidney transplantations. We then derived a weighted multivariable product score from calculated hazard ratios to model the benefit of transplantation as dual kidneys. RESULTS Of 36 donor variables known at the time of listing, 13 were significantly associated with graft survival. The derived dual allocation score demonstrated good internal validity with strong correlation to improved survival in dual kidney transplants. Donors with scores less than 2.1 transplanted as dual kidneys had a worsened median survival of 594 days (24%, p-value 0.031) and donors with scores greater than 3.9 had improved median survival of 1107 days (71%, p-value 0.002). There were 17 733 eSKT (67%) and 1051 DKT (67%) with scores in between these values and no differences in survival (p-values 0.676 and 0.185). CONCLUSIONS We have derived a dual kidney allocation score (DKAS) with good internal validity. Future prospective studies will be required to demonstrate external validity, but this score may help to standardize organ allocation for dual kidney transplantation.

Listing Practices for Morbidly Obese Patients at Liver Transplantation Centers in the United States.

OBJECTIVES: The effect of morbid obesity on liver transplant outcomes has yielded mixed results. The aim of this study was to determine listing practices for morbidly obese patients at liver transplant centers in the United States. MATERIALS AND METHODS: A 19-item survey was created to assess liver transplant evaluation and listing practices for morbidly obese patients. All adult liver transplant medical and surgical directors in the United States were contacted by e-mail, which provided an Internet link to an online survey. RESULTS: We sent a total of 187 surveys by e-mail, with responses received from 46 physicians (24.7% response rate). A policy on evaluation and listing of obese patients was present at 70.5% of institutions, with most (54.5%) reporting that their body mass index cutoff for transplant was 40 kg/m2, but a range of 35 kg/m2 to unlimited was noted. Most respondents agreed that patients with high body mass index were less likely to be evaluated for transplant. Respondents reported increased complication rates among obese patients, with the most common being poor wound healing and increased infection rates. CONCLUSIONS: Most medical and surgical liver transplant directors have a strong appreciation of the possible morbidity risks associated with performing liver transplants in morbidly obese patients and have policies in effect to minimize these risks.

Liver Retransplantation for Recurrence of HCV-Related Cirrhosis Using Hepatitis C-Positive Allografts: A 19-Year OPTN Analysis.

BACKGROUND Liver re-transplantation (re-OLT) in hepatitis C-infected (HCV+) recipients remains a controversial life-saving procedure, as the process of allograft HCV reinfection is universal. Current literature and practice show that in primary liver transplantations (OLT) in HCV+ recipients, HCV+ grafts have equivalent graft survival as non-infected (HCV-) grafts. MATERIAL AND METHODS Standard Transplant Analysis and Research (STAR) files from the OPTN (Organ Procurement and Transplantation Network) were used to identify HCV+ patients who underwent a second transplant between 3/16/1994 and 6/30/2013. Of 33 816 HCV+ patients who underwent primary OLT during this time 2345 underwent re-OLT; of whom 2079 could be confirmed as second transplants. Out of 2079 HCV+ patients who underwent retransplantation, 75 received HCV+ grafts and 2004 received HCV- grafts. Excluding primary or secondary graft losses within 1 week of transplant, 60 HCV+ donor grafts and 1557 HCV- donor grafts at re-transplantation remained for more focused analysis. RESULTS Graft survival for these patients appeared essentially identical regardless of whether they received an HCV+ or HCV- graft. In addition, using the 33 816 HCV+ patients who underwent primary transplantation during this time, our data agreed with the results of previous studies showing that HCV+ patients who receive HCV+ grafts at first transplant have equivalent graft and patient survival rates. CONCLUSIONS Due to the equivalency of HCV graft survival in re-OLT, selecting HCV+ donor organs for hepatitis C-infected recipients appears to be appropriate.

Synergistic effects of ascorbate and sorafenib in hepatocellular carcinoma: New insights into ascorbate cytotoxicity.

We investigated the mechanism of selective ascorbate-induced cytotoxicity in tumor cells, including Hep G2 cells, compared to primary hepatocytes. H2O2 formation was required for ascorbate cytotoxicity, as extracellular catalase treatment protected tumor cells. H2O2 generated by glucose oxidase treatment also caused cell killing, but treatment with a pharmacologic dose (5-20mM) of ascorbate was significantly more cytotoxic at comparable rates of H2O2 production, suggesting that ascorbate enhanced H2O2 cytotoxicity. This was further supported by the finding that ascorbate at a non-cytotoxic dose (1mM) enhanced cell killing caused by glucose oxidase. Consistent with this conclusion, ascorbate treatment caused deregulation of cellular calcium homeostasis, resulting in massive mitochondrial calcium accumulation. Ascorbate acted synergistically with the chemotherapeutic sorafenib in killing Hep G2 cells, but not primary hepatocytes, suggesting adjuvant ascorbate treatment can broaden sorafenib's therapeutic range. Sorafenib caused mitochondrial depolarization and prevented mitochondrial calcium sequestration. Subsequent ascorbate addition further deregulated cellular calcium homeostasis promoting cell death. Additionally, we present the case of a patient with hepatocellular carcinoma (HCC) who had prolonged regression of a rib metastasis upon combination treatment with ascorbate and sorafenib, indicating that these studies have direct clinical relevance.

Ex vivo resection of hepatic neoplasia and autotransplantation: a case report and review of the literature.

INTRODUCTION: Ex situ liver resection is an uncommon procedure but offers an opportunity for R0 surgical resection of liver tumors that are otherwise unresectable. Liver insufficiency following extensive resections is a risk in this patient population; consequently, all measures should be taken to prevent this highly morbid complication. METHOD: We report a case of a patient with an extensive cholangiocarcinoma involving all three hepatic veins that required ex vivo resection and liver autotransplantation to achieve an R0 resection. Postoperatively, the patient demonstrated signs of worsening liver function that, in addition to standard medical therapy, underwent a brief treatment with molecular adsorbent recirculating system (MARS) therapy. RESULTS: Although the role of MARS remains unclear, the patient tolerated it well and her liver graft dysfunction and hepatic encephalopathy slowly resolved. The patient was discharged to a rehabilitation facility. She is currently alive and well with no evidence of recurrence 3 years later. CONCLUSION: We present a review of the literature on ex situ resection and liver autotransplantation. In addition to numerous case reports, there are a few moderate series of ex situ resection and autotransplantation. We suggest that the use of artificial liver devices, if indicated, in the postoperative ex situ resection liver autotransplant patient may assist in the support of the patient while the transplanted liver remnant recovers.

Expanded criteria donor kidneys where the paired kidney is discarded owing to biopsy results: a concept that needs revision.

OBJECTIVES: We explored the categorizing of expanded criteria donors based on systemic disease processes linked to symmetric bilateral renal injury. MATERIALS AND METHODS: We evaluated expanded criteria donor kidneys where the paired kidney was discarded owing to biopsy results, termed the discard group compared with those expanded criteria donors (where both were transplanted), termed the nondiscard group. Analysis of the Organ Procurement and Transplant Network data was completed focusing on the effect of glomerulosclerosis. RESULTS: Our investigation revealed 754 and 9575 recipients in the discard group and nondiscard groups. Fewer glomerulosclerosis was seen the nondiscard group. An assessment revealed improved 1-, 3-, and 5-year graft (P < .001) and patient (P < .05) survivals in the nondiscard group compared with the discard group. However, multivariate analysis demonstrated glomerulosclerosis had little to no effect on graft and patient survival. Expanded criteria donor kidneys with 0% to 5% glomerulosclerosis had no significant differences in graft function as compared with expanded criteria donor kidneys that had > 10% glomerulosclerosis. In fact, expanded criteria donor kidneys with 0% to 5% glomerulosclerosis showed no statistically significantly protective effect over any biopsy with > 5% glomerulosclerosis in patient survival. CONCLUSIONS: Owing to the limited supply of biopsy results in predicting outcomes when controlled for pertinent variables, relying on biopsy findings for kidney allocation may result in many valuable kidneys being discarded.

Pregnancy after liver transplantation.

Women constitute >30% of patients undergoing liver transplantation (orthotopic liver transplantation, OLT) and about 8% are of reproductive age, and 5% are pediatric females who will mostly survive into adulthood and will consider pregnancy. Although pregnancy in OLT recipients is associated with an increased incidence of hypertension, preeclampsia, anemia, preterm deliveries, and cesarean section, acute rejection and liver allograft loss do not appear to be increased and pregnancy-related maternal death is uncommon. The incidence of structural malformations in the newborn of liver transplant recipients is reported to be 4.4%, which is similar to the rate of 3-5% in the US general population. Patients are advised to defer conception for at least 1-2 years after OLT, while maintaining effective contraception. Pregnancy after OLT usually results in a favorable maternal and neonatal outcome when there is coordinated pre- and perinatal care by a multidisciplinary team composed of obstetric-gynecologists, and a transplant team.

Long-term dosing patterns of enteric-coated mycophenolate sodium or mycophenolate mofetil with tacrolimus after renal transplantation.

MORE was a four-yr, prospective, observational study at 40 transplant centers in the US. Data were analyzed to evaluate changes in mycophenolic acid (MPA) dosing over time in 904 de novo kidney transplant recipients receiving enteric-coated mycophenolate sodium (EC-MPS, n = 616) or mycophenolate mofetil (MMF, n = 288) with tacrolimus. Induction therapy and steroid treatment were similar in the two subpopulations. The proportion of patients receiving the maximal recommended MPA dose was 80.5%, 43.9%, 39.2%, 34.6%, and 30.1% at baseline and years 1, 2, 3, and 4, respectively. More patients received the maximal recommended MPA dose with EC-MPS vs. MMF at month 1 (79.2% vs. 71.7%, p = 0.016), month 3 (68.5% vs. 56.9%, p = 0.001), and month 6 (52.9% vs. 44.0%, p = 0.028). Multivariate analysis showed the risk of biopsy-proven acute rejection, graft loss or death to be similar for EC-MPS vs. MMF. Estimated glomerular filtration rate (GFR) was similar with EC-MPS vs. MMF at all time points. There were no significant differences in any category of adverse event between the EC-MPS and MMF cohorts during follow-up, including gastrointestinal events. In conclusion, MPA dose was maintained more effectively in the first six months after kidney transplantation using EC-MPS vs. MMF, without an increase in adverse events.

Liver resection using cavitron ultrasonic surgical aspirator (CUSA) versus harmonic scalpel: a retrospective cohort study.

BACKGROUND: The aim of this study was to evaluate the safety and efficacy of two device combinations used in parenchymal division during hepatic resections in non-cirrhotic patients and without inflow vascular occlusion. METHODS: We retrospectively analyzed 47 patients who underwent liver resection at our Institution from 2004 to 2010 using the TissueLink with either the Cavitron Ultrasonic Surgical Aspirator (CUSA) or the Harmonic Scalpel. The TissueLink was used with the CUSA in 27 patients and with the Harmonic Scalpel in 20 patients. RESULTS: Median estimated blood loss (EBL) in the Harmonic Scalpel and CUSA groups was 250 and 1035 mL respectively (p < 0.05). Three patients were transfused banked blood perioperatively in the Harmonic Scalpel group and 11 in the CUSA group (p < 0.05). Median operative time in the Harmonic Scalpel and CUSA groups was 185 and 290 min respectively. Length of stay (LOS) was shorter in the Harmonic Scalpel group at 6 days compared to 7 days in the CUSA group (p < 0.05). Perioperative complications were documented in 20% and 26% in the Harmonic Scalpel and CUSA groups, respectively. CONCLUSIONS: Our results show the Harmonic Scalpel with TissueLink to be a safe, effective method of parenchymal division with significantly less EBL and LOS when compared to CUSA with TissueLink.

Targeted therapies in the treatment of advanced hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is the most common liver cancer and the third leading cause of cancer death. It has been a major worldwide health problem with more new cases being diagnosed each year. The current available therapies for patients with advanced HCC are extremely limited. Therefore, it is of great clinical interests to develop more effective therapies for systemic treatment of advanced HCC. Several promising target-based drugs have been tested in a number of clinical trials. One breakthrough of these efforts is the approved clinical use of sorafenib in patients with advanced HCC. Targeted therapies are becoming an attractive option for the treatment of advanced HCC. In this review, we summarize the most recent progress in clinical targeted treatments of advanced HCC.