Relapsed and De Novo Metastatic HER2-positive Breast Cancer Treated With Trastuzumab: Tumor Genotypes and Clinical Measures Associated With Patient Outcome

Background

We examined tumor genotype characteristics of human epidermal growth factor receptor 2 (HER2)-positive relapsed (R-) and de novo (dn-) metastatic breast cancer (MBC) in trastuzumab-treated patients who were previously not exposed to this agent.

Sclerosing Cholangitis Epidemiology and Etiology

Sclerosing cholangitis represents a spectrum of chronic biliary diseases that either has an unknown etiology (i.e., primary) or is caused by identifiable insults to the biliary tree (i.e., secondary). To date, the epidemiology of primary sclerosing cholangitis has been appraised; however, its etiology continues to be unclear. In contrast, the etiology of secondary sclerosing cholangitis is always known, but the epidemiology of this clinical entity is difficult to study. This paper was originally presented as part of the SSAT/AHPBA Joint Symposium on Sclerosing Cholangitis at the SSAT 48th Annual Meeting, May 2007, in Washington, DC. The other articles presented in the symposium were Schulick RD, Primary Sclerosing Cholangitis: Detection of Cancer in Strictures; Ahrendt SA, Surgical Approaches to Strictures in Primary Sclerosing Cholangitis; and Chapman WC, Primary Sclerosing Cholangitis: Role of Liver Transplantation.     

Aortic and Iliac Fixation of Seven Endografts for Abdominal-aortic Aneurysm Repair in an Experimental Model Using Human Cadaveric Aortas

ObjectiveTo evaluate the proximal and distal (iliac) fixation of seven self-expanding endografts, used in the endovascular treatment (EVAR) of abdominal-aortic aneurysm (AAA), by measuring the displacement force (DF) necessary to dislocate the devices from their fixation sites.MethodsA total of 20 human cadaveric aortas were exposed, left in situ and transected to serve as fixation zones. The Anaconda, EndoFit aorto-uni-iliac, Endurant, Powerlink, Excluder, Talent and Zenith stent grafts were deployed and caudal force was applied at the flow divider, through a force gauge. The DF needed to dislocate each device ≥ 20 mm from the infrarenal neck was recorded before and after moulding-balloon dilatation. Cephalad force was similarly applied to each iliac limb to assess distal fixation before and after moulding-balloon dilatation.ResultsEndografts with fixation hooks or barbs displayed a significantly higher DF necessary to dislocate the proximal portion compared with devices with no such fixation modalities (p < 0.001). Balloon dilatation produced a significant increase in DF in both devices with (p < 0.001) or without (p = 0.003) hooks or barbs. Suprarenal support did not enhance proximal fixation (p = 0.90). Balloon dilatation significantly increased the DF necessary to dislodge the iliac limbs (p = 0.007).ConclusionsDevices with fixation hooks displayed higher proximal fixation. Moulding-balloon dilatation increased proximal and distal fixation. Suprarenal support did not affect proximal fixation.     

Screening and treatment of diabetic nephropathy by primary care physicians

OBJECTIVE: To describe the practices of Indiana primary care physicians related to diabetic nephropathy screening and management. DESIGN: Cross-sectional, observational. SETTING: The state of Indiana. PARTICIPANTS: Active primary care physicians (defined as general internists, family practitioners, and general practitioners) in Indiana who provided care for diabetic patients at the time of the survey (n = 1,018) MEASUREMENTS AND MAIN RESULTS: Practice patterns relevant to microalbuminuria and overt albuminuria screening and management were assessed along two dimensions: the percentage of patients to whom the practices were applied and the frequency with which the practices were performed. Of 1,141 physicians who responded to the survey, 1,018 were eligible for analysis. Eighty-six percent of physicians reported screening more than half of their patients with type 1 diabetes for overt albuminuria, as did 82% of physicians for their patients with type 2 diabetes. Only 17% of physicians indicated performing microalbuminuria testing on more than half of their type 1 patients. Angiotensin-converting enzyme inhibitor agents were used frequently to treat abnormal urinary albumin excretion when hypertension was present, but less often when hypertension was absent. Physician specialty, year of graduation from medical school, practice location, and familiarity with the results of the Diabetes Control and Complications Trial were significant predictors of screening and treatment practice patterns. CONCLUSIONS: Primary care physicians report practices that allow them to detect overt albuminuria but not microalbuminuria. Angiotensin-converting enzyme inhibitors are frequently used by physicians who test for microalbuminuria, but efforts to increase the detection of early renal damage are needed so that these agents and other therapeutic strategies may be employed at the earliest opportunity.     

Alternative splicing of the rat sodium/bile acid transporter changes its cellular localization and transport properties

Bile secretion involves the structural and functional interplay of hepatocytes and cholangiocytes, the cells lining the intrahepatic bile ducts. Hepatocytes actively secrete bile acids into the canalicular space and cholangiocytes then transport bile acids in a vectorial manner across their apical and basolateral plasma membranes. The initial step in the transepithelial transport of bile acids across rat cholangiocytes is apical uptake by a Na(+)-dependent bile acid transporter (ASBT). To date, the molecular basis of the obligate efflux mechanism for extrusion of bile acids across the cholangiocyte basolateral membrane remains unknown. We have identified an exon-2 skipped, alternatively spliced form of ASBT, designated t-ASBT, expressed in rat cholangiocytes, ileum, and kidney. Alternative splicing causes a frameshift that produces a 154-aa protein. Antipeptide antibodies detected the approximately 19 kDa t-ASBT polypeptide in rat cholangiocytes, ileum, and kidney. The t-ASBT was specifically localized to the basolateral domain of cholangiocytes. Transport studies in Xenopus oocytes revealed that t-ASBT can function as a bile acid efflux protein. Thus, alternative splicing changes the cellular targeting of ASBT, alters its functional properties, and provides a mechanism for rat cholangiocytes and other bile acid-transporting epithelia to extrude bile acids. Our work represents an example in which a single gene appears to encode via alternative splicing both uptake and obligate efflux carriers in a bile acid-transporting epithelial cell.     

Primary biliary cirrhosis

Opinion statement  

Primary biliary cirrhosis

Primary biliary cirrhosis (PBC) is an idiopathic chronic autoimmune liver disease that primarily affects women. It is believed that the aetiology for PBC is a combination between environmental triggers in genetically vulnerable persons. The diagnosis for PBC is made when two of the three criteria are fulfilled and they are: (1) biochemical evidence of cholestatic liver disease for at least 6 month's duration; (2) anti-mitochondrial antibody (AMA) positivity; and (3) histologic features of PBC on liver biopsy. Ursodeoxycholic acid (UDCA) is the only FDA-approved medical treatment for PBC and should be administered at a recommended dose of 13-15 mg/kg/day. Unfortunately despite adequate dosing of UDCA, approximately one-third of patients does not respond adequately and may require liver transplantation. Future studies are necessary to elucidate the role of environmental exposures and overall genetic impact not only in the development of PBC, but on disease progression and variable clinical response to therapy.     

The handsewn anastomosis after colon resection due to colonic cancer

Abstracts

1st Biennial Meeting of the Eurasian Colorectal Technologies Association (ECTA), 13-15 November 2009, Guangzhou/Canton, China President: F. Seow-Choen