Molecular Approach to Colorectal Carcinoma: Current Evidence and Clinical Application.

Colorectal carcinoma is one of the most common cancer types in men and women, responsible for both the third highest incidence of new cancer cases and the third highest cause of cancer deaths. In the last several decades, the molecular mechanisms surrounding colorectal carcinoma's tumorigenesis have become clearer through research, providing new avenues for diagnostic testing and novel approaches to therapeutics. Laboratories are tasked with providing the most current information to help guide clinical decisions. In this review, we summarize the current knowledge surrounding colorectal carcinoma tumorigenesis and highlight clinically relevant molecular testing.

Pathology of Acute and Acute-on-Chronic Liver Failure.

Liver failure can develop as either acute liver failure in the absence of preexisting liver disease, or as acute-on-chronic liver failure in a patient with underlying chronic liver disease or cirrhosis. A timely liver biopsy is helpful to distinguish acute and chronic liver disease, identify precipitating factors, provide prognostic information based on pathologic changes, and aid in making appropriate decisions for patient management. This article will discuss the pathologic features of acute and acute-on-chronic liver failure. Developing an appreciation for the histopathologic patterns of injury observed in these entities is essential for a practical understanding of the diagnostic process.

Molecular Approach to Colorectal Carcinoma: Current Evidence and Clinical Application.

Colorectal carcinoma is one of the most common cancer types in men and women, responsible for both the third highest incidence of new cancer cases and the third highest cause of cancer deaths. In the last several decades, the molecular mechanisms surrounding colorectal carcinoma's tumorigenesis have become clearer through research, providing new avenues for diagnostic testing and novel approaches to therapeutics. Laboratories are tasked with providing the most current information to help guide clinical decisions. In this review, we summarize the current knowledge surrounding colorectal carcinoma tumorigenesis and highlight clinically relevant molecular testing.

Pancreatic Intraductal Papillary Mucinous Neoplasm With Elevated Pre-Operative Cystic Carcinoembryonic Antigen Level: A Histopathologic Correlation.

BACKGROUND: To study the relationship between carcinoembryonic antigen (CEA) level, intraductal papillary mucinous neoplasm (IPMN) subtype, and the presence of invasive carcinoma. METHODS: Cystic CEA level and the following pathologic variables: subtypes of IPMN, size of cystic lesion, presence of dysplasia or carcinoma, and main or branch duct involvement from 45 IPMN cases were analyzed. RESULTS: There was a significant correlation between pre-operative cystic fluid CEA level and the intensity of luminal CEA staining. However, there was no correlation between CEA level and cystic mucinous secretions or mucinous epithelial cytoplasm CEA staining, mucin glycoprotein expression, size of lesion, grade of dysplasia or presence of invasive carcinoma. CEA level was neither sensitive nor specific for the presence of invasive carcinoma. CONCLUSIONS: Cystic CEA level may not be a reliable determinant of the presence or absence of invasive carcinoma in IPMNs, and its use to assess risk of malignancy may be limited.

Cryoglobulinemia as a Possible Primer for TRALI: Report of a Case.

Waldenström macroglobulinemia (WM) is a form of lymphoplasmacytic lymphoma that can cause hyperviscosity syndrome due to unchecked monoclonal antibody production. Some patients are also found to have associated cryoglobulinemia, which can cause systemic complications including vasculitis, renal disease, and pulmonary complications. Cryoglobulins can also serve as a source of interference with various laboratory assays. Therapeutic plasma exchange (TPE) is one of the recommended treatment modalities to manage hyperviscosity. Herein, we present the case of an 84-year-old female patient with Waldenström macroglobulinemia who presented with hyperviscosity syndrome and discrepant laboratory findings, and who then developed transfusion-related acute lung injury (TRALI) during TPE. This case is one of many in the emerging possible linkages observed between cryoglobulinemia and TRALI.

The immunoglobulin superfamily protein differentiation of embryonic stem cells 1 (dies1) has a regulatory role in preadipocyte to adipocyte conversion.

Differentiation of Embryonic Stem Cells 1 (Dies1) was recently identified as a novel type I immunoglobulin (IgG) domain-containing plasma membrane protein important for effective differentiation of a murine pluripotent embryonic stem cell line. In this setting, Dies1 enhances bone morphogenetic protein 4 (BMP4) signaling. Here we show Dies1 transcript expression is induced ∼225-fold during in vitro adipogenesis of 3T3-L1 murine preadipocytes. Immunocytochemical imaging using ectopic expression of Flag-tagged Dies1 in 3T3-L1 adipocytes revealed localization to the adipocyte plasma membrane. Modulation of adipocyte phenotype with with tumor necrosis factor-α (TNFα) treatment or by siRNA knockdown of the master pro-adipogenic transcription factor peroxisome proliferator activated receptor gamma (PPARγ) resulted in a 90% and 60% reduction of Dies1 transcript levels, respectively. Moreover, siRNA-mediated Dies1 knockdown in 3T3-L1 preadipocytes inhibited adipogenic conversion. Such cultures had a 35% decrease in lipid content and a 45%-65% reduction in expression of key adipocyte transcripts, including that for PPARγ. The standard protocol for full in vitro adipogenic conversion of committed preadipocytes, such as 3T3-L1, does not include BMP4 treatment. Thus we posit the positive role of Dies1 in adipogenesis, unlike that for Dies1 in differentiation of embryonic stem cells, does not include its pro-BMP4 effects. In support of this idea, 3T3-L1 adipocytes knocked down for Dies1 did not evidence decreased phospho-Smad1 levels upon BMP4 exposure. qPCR analysis of Dies1 transcript in multiple murine and human tissues reveals high enrichment in white adipose tissue (WAT). Interestingly, we observed a 10-fold induction of Dies1 transcript in WAT of fasted vs. fed mice, suggesting a role for Dies1 in nutritional response of mature fat cells in vivo. Together our data identify Dies1 as a new differentiation-dependent adipocyte plasma membrane protein whose expression is required for effective adipogenesis and that may also play a role in regard to nutritional status in WAT.

Juvenile cobalamin deficiency in a 17-year-old child with autonomic dysfunction and skin changes.

We report a rare case of juvenile cobalamin deficiency who presented at the age of 17 years. He was underweight and had skin changes, normocytic anemia, and autonomic dysfunction, which led to adynamic ileus and acute postrenal failure. The expected macrocytosis was masked by an underlying alpha-thalassemia trait. The patient had an excellent response to parenteral cobalamin treatment.