Epidemiology of Adenosquamous Carcinomas.

Background: Adenosquamous carcinomas (ASCs) are a very rare histology containing cancer cells with both glandular-like (adeno) and squamous cell histologies, comprising typically a fraction of a percent of all solid tumors. The bulk of the literature on ASCs is comprised of case reports and small series, with the general finding that ASCs tend to have worse outcomes than either of their parent histologies. However, there is a lack of pan site-comparative studies in the literature that compare ASC clinicodemographic and survival outcomes with those of conventional adenocarcinomas (ACs) and squamous cell carcinomas (SCCs).

High Ki67 Gene Expression Is Associated With Aggressive Phenotype in Hepatocellular Carcinoma.

Background: Hepatocellular carcinoma (HCC) with high Ki67 protein expression, the most commonly used cell proliferation marker, is associated with an aggressive biologic phenotype; however, conventional immunostaining is hampered by variability in institutional protocol, specific antibody probe, and by assessor subjectivity. To this end, we hypothesized that Ki67 gene () expression would identify highly proliferative HCC, and clarify its association with oncologic outcome, tumor progression, and immune cell population in the tumor microenvironment (TME). Furthermore, we sought to identify the cell-cycle gene expression profile that confers this aggressive phenotype.

First-in-class MKK4 inhibitors enhance liver regeneration and prevent liver failure.

Diminished hepatocyte regeneration is a key feature of acute and chronic liver diseases and after extended liver resections, resulting in the inability to maintain or restore a sufficient functional liver mass. Therapies to restore hepatocyte regeneration are lacking, making liver transplantation the only curative option for end-stage liver disease. Here, we report on the structure-based development and characterization (nuclear magnetic resonance [NMR] spectroscopy) of first-in-class small molecule inhibitors of the dual-specificity kinase MKK4 (MKK4i).

High expression reflects mTOR pathway activity and cancer cell proliferation and is a biomarker for poor breast cancer prognosis.

Eukaryotic translation initiation factor 4E binding protein 1 (EIF4EBP1) is regulated by the mTOR (mammalian target of rapamycin) signaling pathway. Phosphorylated EIF4EBP1 protein leads to pathway activation and correlates with aggressive breast cancer features. However, the clinical relevance of gene expression as a prognostic biomarker in bulk breast tumors is not understood.

Location Has Prognostic Impact on the Outcome of Colorectal Mucinous Adenocarcinomas.

Mucinous (colloid) adenocarcinomas (MAs) are a rare histological subtype of tumors defined by extracellular mucin comprising more than 50% of the tumor. These tumors are on a continuum of mucin-producing malignancies with signet ring cell adenocarcinomas (SRCCs), which instead produce intracellular mucin. Mucin-containing cancers occur primarily in the stomach and colon, where for SRCCs, outcomes are relatively worse in the proximal stomach and the rectum.

Malignant Transformation of Long-Standing Ileal Crohn's Disease Likely Favors Signet Ring Cell Adenocarcinoma Histology.

Signet ring cell adenocarcinomas (SRCCs) are a rare and aggressive histological subtype of adenocarcinomas typically with poor prognosis usually secondary to late stage at detection. In the small bowel, they constitute only 1% of all malignancies. In the last decade, there have been multiple case reports and small case series that have identified SRCCs, typically in the ileum, in patients with Crohn's disease.

Fumarylacetoacetate hydrolase gene as a knockout target for hepatic chimerism and donor liver production.

A reliable source of human hepatocytes and transplantable livers is needed. Interspecies embryo complementation, which involves implanting donor human stem cells into early morula/blastocyst stage animal embryos, is an emerging solution to the shortage of transplantable livers. We review proposed mutations in the recipient embryo to disable hepatogenesis, and discuss the advantages of using fumarylacetoacetate hydrolase knockouts and other genetic modifications to disable hepatogenesis.

Functional characterization of a bioengineered liver after heterotopic implantation in pigs.

Organ bioengineering offers a promising solution to the persistent shortage of donor organs. However, the progression of this technology toward clinical use has been hindered by the challenges of reconstituting a functional vascular network, directing the engraftment of specific functional cell types, and defining appropriate culture conditions to concurrently support the health and phenotypic stability of diverse cell lineages. We previously demonstrated the ability to functionally reendothelialize the vasculature of a clinically scaled decellularized liver scaffold with human umbilical vein endothelial cells (HUVECs) and to sustain continuous perfusion in a large animal recovery model.

Meckel's Enterolith Causing Small Bowel Obstruction: A Useful Solution to a Unique Problem.

Meckel's diverticulum (MD) is the most common congenital anomaly of the gastrointestinal tract. Its course is usually benign but may also result in complications requiring surgical intervention. A diverticulum may also permit the removal of intraluminal objects without bowel resection and anastomosis.

Limited Expansion of Human Hepatocytes in FAH/-Deficient Swine.

The mammalian liver's regenerative ability has led researchers to engineer animals as incubators for expansion of human hepatocytes. The expansion properties of human hepatocytes in immunodeficient mice are well known. However, little has been reported about larger animals that are more scalable and practical for clinical purposes.

Autologous Adipose Tissue-Derived Mesenchymal Stem Cells Introduced by Biliary Stents or Local Immersion in Porcine Bile Duct Anastomoses.

Biliary complications (strictures and leaks) represent major limitations in living donor liver transplantation. Mesenchymal stem cells (MSCs) are a promising modality to prevent biliary complications because of immunosuppressive and angiogenic properties. Our goal was to evaluate the safety of adipose-derived MSC delivery to biliary anastomoses in a porcine model.

Author Correction: Sustained perfusion of revascularized bioengineered livers heterotopically transplanted into immunosuppressed pigs.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Sustained perfusion of revascularized bioengineered livers heterotopically transplanted into immunosuppressed pigs.

Implanted bioengineered livers have not exceeded three days of continuous perfusion. Here we show that decellularized whole porcine livers revascularized with human umbilical vein endothelial cells and implanted heterotopically into immunosuppressed pigs whose spleens had been removed can sustain perfusion for up to 15 days. We identified peak glucose consumption rate as a main predictor of the patency of the revascularized bioengineered livers (rBELs).

Stem Cell-Related Studies and Stem Cell-Based Therapies in Liver Diseases.

Owing to the increasing worldwide burden of liver diseases, the crucial need for safe and effective interventions for treating end-stage liver failure has been a very productive line of inquiry in the discipline of hepatology for many years. Liver transplantation is recognized as the most effective treatment for end-stage liver disease; however, the shortage of donor organs, high medical costs, and lifelong use of immunosuppressive agents represent major drawbacks and demand exploration for alternative treatments. Stem cell-based therapies have been widely studied in the field of liver diseases and are considered to be among the most promising therapies.

Understanding the marvels behind liver regeneration.

Tissue regeneration is a process by which the remaining cells of an injured organ regrow to offset the missed cells. This field is relatively a new discipline that has been a focus of intense research by clinicians, surgeons, and scientists for decades. It constitutes the cornerstone of tissue engineering, creation of artificial organs, and generation and utilization of therapeutic stem cells to undergo transformation to different types of mature cells.

Platelet transfusion increases risk for acute respiratory distress syndrome in non-massively transfused blunt trauma patients.

Purpose: While damage control resuscitation is known to confer a survival advantage in severely injured patients, high-ratio blood component therapy should be initiated only in carefully selected trauma patients, due to the morbidity associated with blood product use. With this project, we aim to identify the effect of platelet transfusion in non-massively transfused bluntly injured patients.

Methods: The Glue Grant database was retrospectively queried and severely injured blunt trauma patients who underwent non-massive transfusion were identified.

Robotic paraesophageal hernia repair: a single-center experience and systematic review.

Robotic Surgery is becoming increasingly used in general surgery. The objective of this study is to evaluate the safety, effectiveness and short-term (less than 1 year) outcomes of Robotic Paraesophageal Hernia (RPEH) Surgery using the DaVinci Surgical Robot system (Intuitive Surgical, CA) in a large community hospital. This is a retrospective cohort study of 28 consecutive patients who underwent robotic paraesophageal hernia repair January 2011-March 2013 in this institution.