Epidermal Growth Factor Receptor Inhibition With Erlotinib in Liver: Dose De-Escalation Pilot Trial as an Initial Step in a Chemoprevention Strategy.

Background And Aims: Effective approaches for prevention of hepatocellular carcinoma (HCC) will have a significant impact on HCC-related mortality. There are strong preclinical data and rationale to support targeting epidermal growth factor receptor (EGFR) for HCC chemoprevention. Small molecule inhibitors of EGFR have been Food and Drug Administration-approved for cancer therapy, which provides an opportunity to repurpose one of these drugs for chemoprevention of HCC.

Diagnosis and staging of hepatobiliary malignancies: Potential incremental value of (18)F-FDG-PET/MRI compared to MRI of the liver.

Objective:  The purpose of the study was to investigate the potential added value of F-FDG-PET/MRI (functional information derived from PET) over standard diagnostic liver MRI (excellent soft tissue characterization) in diagnosing and staging suspected primary hepatobiliary malignancies including extrahepatic cholangiocarcinoma (ECC), intrahepatic cholangiocellular carcinoma (ICC) and gallbladder cancer (GBCA).

Methods:  Twenty consecutive patients with suspected hepatobiliary malignancy were included in this retrospective study. All patients underwent combined whole-body (WB) F-FDG-PET/MRI including contrast-enhanced MRI of the liver, contrast-enhanced WB-MRI and WB F-FDG-PET.

Pretherapy neutrophil to lymphocyte ratio and platelet to lymphocyte ratio do not predict survival in resectable pancreatic cancer.

Background: Pretherapy serum neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR) have both been identified as prognostic in pancreatic ductal adenocarcinoma (PDAC). The aim of this study was to identify the prognostic implication of pretherapy NLR and PLR in patients with resectable PDAC.

Methods: Data were collected retrospectively on patients operated at our institution between 2004 and 2014.

Pyogenic liver abscesses: a contemporary analysis of management strategies at a tertiary institution.

Background: Despite equivocal evidence, non-surgical management for pyogenic liver abscess (PLA) has become the standard of care at most institutions with surgery relegated to salvage therapy for those who fail less invasive means. The aim of this study was to describe the outcomes of a step-up approach to PLA management.

Methods: A retrospective chart review was conducted at a single institution for patients diagnosed with PLA over a 10-year period.

Functional liver tissue engineering by an adult mouse liver-derived neuro-glia antigen 2-expressing stem/progenitor population.

Deaths due to end-stage liver diseases are increasingly registered annually in the world. Liver transplantation is the ultimate treatment for end-stage liver diseases to date, which has been hampered by a critical shortage of organs. The potential of decellularized liver scaffolds (DLS) derived from solid organs as a three-dimensional platform has been evolved as a promising approach in liver tissue engineering for translating functional liver organ replacements, but questions still exist regarding the optimal cell population for seeding in DLS and the preparation of the DLS themselves.

Extended Perioperative Antibiotic Coverage in Conjunction with Intraoperative Bile Cultures Decreases Infectious Complications after Pancreaticoduodenectomy.

Background. Bile contamination from the digestive tract is a well-known risk factor for postoperative complications. Despite the literature concerning prevalence of bacterobilia and fungobilia in patients with biliary pathologies, there are no specific recommendations for perioperative antimicrobial coverage for biliary/pancreatic procedures.

Repair of liver mediated by adult mouse liver neuro-glia antigen 2-positive progenitor cell transplantation in a mouse model of cirrhosis.

NG2-expressing cells are a population of periportal vascular stem/progenitors (MLpvNG2(+) cells) that were isolated from healthy adult mouse liver by using a "Percoll-Plate-Wait" procedure. We demonstrated that isolated cells are able to restore liver function after transplantation into a cirrhotic liver, and co-localized with the pericyte marker (immunohistochemistry: PDGFR-β) and CK19. Cells were positive for: stem cell (Sca-1, CD133, Dlk) and liver stem cell markers (EpCAM, CD14, CD24, CD49f); and negative for: hematopoietic (CD34, CD45) and endothelial markers (CD31, vWf, von Willebrand factor).

Rescue ALPPS: Intraoperative Conversion to ALPPS during Synchronous Resection of Rectal Cancer and Liver Metastasis.

Future liver remnant (FLR) is the most important deciding factor in planning for liver resection. Portal vein embolization (PVE) was first introduced in the 1980s to induce liver hypertrophy, enabling removal of multiple/bilobar tumors. PVE was later combined with sequential hepatectomies with the aim of allowing the liver remnant to hypertrophy (15-20%) between procedures.

Negative regulation of the interferon response by an interferon-induced long non-coding RNA.

Long non-coding RNAs (lncRNAs) play critical roles in diverse cellular processes; however, their involvement in many critical aspects of the immune response including the interferon (IFN) response remains poorly understood. To address this gap, we compared the global gene expression pattern of primary human hepatocytes before and at three time points after treatment with IFN-α. Among ∼ 200 IFN-induced lncRNAs, one transcript showed ∼ 100-fold induction.

The impact of resection margin status and postoperative CA19-9 levels on survival and patterns of recurrence after postoperative high-dose radiotherapy with 5-FU-based concurrent chemotherapy for resectable pancreatic cancer.

Objectives: To analyze the impact of surgical margins and other clinicopathological data on treatment outcomes on 75 patients treated from 1999 to 2006 by initial potentially curative surgery (+/- intraoperative radiotherapy), followed by high-dose 3-dimensional conformal radiation therapy and concomitant fluoropyrimidine-based chemoradiotherapy.

Materials And Methods: All clinical and pathologic data on this patient cohort were analyzed by actuarial Kaplan-Meier survival methodology and by univariate and multivariate Cox proportional hazards methods to measure effects on survival and patterns of failure.

Results: With a median follow-up of 28 months, the median, 2-year and 5-year overall survival (OS) rates were 18.

Comparative lesion sequencing provides insights into tumor evolution.

We show that the times separating the birth of benign, invasive, and metastatic tumor cells can be determined by analysis of the mutations they have in common. When combined with prior clinical observations, these analyses suggest the following general conclusions about colorectal tumorigenesis: (i) It takes approximately 17 years for a large benign tumor to evolve into an advanced cancer but <2 years for cells within that cancer to acquire the ability to metastasize; (ii) it requires few, if any, selective events to transform a highly invasive cancer cell into one with the capacity to metastasize; (iii) the process of cell culture ex vivo does not introduce new clonal mutations into colorectal tumor cell populations; and (iv) the rates at which point mutations develop in advanced cancers are similar to those of normal cells. These results have important implications for understanding human tumor pathogenesis, particularly those associated with metastasis.

Early experience with intraoperative radiotherapy in patients with resected pancreatic adenocarcinoma.

Background: The use of intraoperative radiotherapy (IORT) in patients with resected pancreatic adenocarcinoma has not been clearly defined.

Methods: The medical records of our first 22 patients receiving IORT for resected pancreatic adenocarcinoma (2001 to 2006) were reviewed and compared with the records of 27 consecutive patients not receiving IORT for resected pancreatic adenocarcinoma (2004 to 2006).

Results: There were no 30-day mortalities in either group, and complication rates were similar.

Long-term graft outcomes after steroid withdrawal in African American kidney transplant recipients receiving sirolimus and tacrolimus.

Background: We previously reported excellent short-term outcomes in African American kidney transplant patients receiving tacrolimus/sirolimus and withdrawn from corticosteroid therapy three months after transplantation. We now report the long-term outcomes of patients subjected to this protocol.

Methods: In all, 47 African American kidney transplant recipients were enrolled in an uncontrolled trial in which they were initially treated with sirolimus, tacrolimus, and corticosteroids, without antibody induction therapy.

Food protein sensitivity with partial villous atrophy after pediatric liver transplantation with tacrolimus immunosuppression.

We report three pediatric liver transplant recipients receiving tacrolimus immunosuppression presented with vomiting, heme-positive stools and failure to thrive, who had subtotal villous atrophy in their histology because of food protein sensitivity. Case findings and current literature of the casual relationship between tacrolimus and food allergies briefly reviewed.

Comparative effects of sirolimus and mycophenolate mofetil on erythropoiesis in kidney transplant patients.

Anemia and erythrocytosis (PTE) are common after kidney transplantation. We sought to determine the influence of sirolimus compared to mycophenolate mofetil (MMF) on post-transplant erythropoiesis. A total of 214 patients with recent kidney or kidney-pancreas transplants were treated with either sirolimus-based (n = 87) or MMF-based (n = 127) therapy.

Thrombotic events and markers of oxidation and inflammation in hemodialysis.

The goal of this study was to determine whether antioxidant therapy with vitamin E would alter the rate of vascular access complications or other macrovascular complications in hemodialysis (HD) patients. A secondary goal of the study was to explore the relationship between baseline pretreatment markers of oxidative stress (the advanced glycation end product pentosidine and basal levels of vitamin Ealpha and gamma) and the subsequent development of access failure. Thirty-five stable patients treated by HD were recruited for the study.

Withdrawal of steroid therapy in African American kidney transplant recipients receiving sirolimus and tacrolimus.

Background: Withdrawal of corticosteroids from the immunosuppressive regimens of kidney transplant recipients has been associated with an increased risk of acute and chronic allograft rejection. Previous studies indicate that the risk of rejection is particularly high in African Americans.

Methods: We prospectively enrolled 44 African American kidney transplant recipients to participate in an uncontrolled trial in which they were initially treated with sirolimus, tacrolimus, and corticosteroids.

Comparison of sirolimus vs. mycophenolate mofetil on surgical complications and wound healing in adult kidney transplantation.

Mycophenolate mofetil (MMF) and sirolimus impair wound healing. We compared sirolimus vs. MMF to determine the relative impact on surgical complications and wound healing in adult kidney transplant recipients.

Outcomes of African American kidney transplant recipients treated with sirolimus, tacrolimus, and corticosteroids.

Background: African American kidney transplant recipients generally exhibit poor long-term graft survival compared with other ethnic groups. The combination of sirolimus, tacrolimus, and corticosteroids has proven to be effective in reducing rejection episodes in high-risk organ and islet cell transplant recipients but has not yet been tested in a large number of African American patients.

Methods: The outcomes of 56 African American adult, primary kidney transplant recipients treated with corticosteroids, sirolimus, and tacrolimus targeted to relatively low trough blood levels were compared with those of a concurrent group of 65 white patients treated with steroids, mycophenolate mofetil, and tacrolimus targeted to relatively high blood levels.