Surgical management of a massive choledochal cyst.

Choledochal cysts (CC) are congenital bile duct anomalies, typically present in children. The size of CC vary, but they rarely exceed 9 cm. Surgical resection is the mainstay of treatment. This case report presents 18-year-old female with jaundice and abdominal pain. On imaging she was found to have a type I CC versus a type IVa CC. She was taken to the operating room where she was found to have a 20 cm type I CC. The patient experienced complete recovery after total resection of the extrahepatic cyst with reconstruction with a Roux-en-Y hepaticojejunostomy. Preoperative diagnosis of the type of CCs can be challenging. Proper imaging preoperatively can aid in diagnosis of these cysts, but delineation of anatomy and type may not always be possible. If treated in a timely manner, it can help prevent both long- and short-term complications.

Cerebral Sinus Venous Thrombosis in a Patient Using Etonogestrel/Ethinyl Estradiol Vaginal Ring.

A case of 43-year-old female presented to the emergency department (ED) with a new onset grand mal tonic-clonic seizure lasting at least two minutes with post-ictal confusion. Imaging was consistent with cerebral sinus venous thrombosis (CSVT) associated with intracranial hemorrhage. After ruling out most common causes of thrombosis, the etiology was attributed to estrogen vaginal ring. The patient was treated with anticoagulation therapy and had increasing hemorrhagic changes in the first few days, which eventually improved. The estimated annual incidence of cerebral sinus vein thromboses is approximately 3-4 cases per 1 million adults, mostly occurring in females. More than 80% of patients have favorable neurologic outcomes due to increased awareness of the condition as well as availability of advanced imagining and treatment options. The treatment is still controversial due to the high risk of intracranial hemorrhage with sinus thrombosis, especially for patients on anticoagulation. Still, most guidelines support starting anticoagulation. In this report, we highlight the association of CSVT with estrogen vaginal ring and discuss recent management recommendations per different society guidelines.

The Accuracy of Conflict-of-Interest Disclosures Reported by Plastic Surgeons and Industry.

BACKGROUND: The purpose of this study was to analyze the frequency and nature of self-reported conflict-of-interest disclosures in the plastic surgery literature and to compare these findings to the Physician Payments Sunshine Act database. METHODS: All articles published from August of 2013 through December of 2013 in four major plastic surgery journals were analyzed. For every publication, the conflict-of-interest disclosure statement for each investigator was reviewed. These statements were then compared to transactions of value for each investigator as reported by biomedical companies in the Sunshine Act database. An analysis was performed to identify and characterize specific factors associated with conflict-of-interest disclosures. RESULTS: A total of 1002 independent investigators/authors were identified. Of these, 90 investigators (9 percent) self-reported a conflict of interest. In contrast, a total of 428 authors (42.7 percent) were found to have received transactions of value from a biomedical company according to the Sunshine Act database. Conversely, a total of 22 authors (2.2 percent) self-reported a conflict of interest but were not found to have received transactions of value in the Sunshine Act database. Our analysis found that (1) academic investigators, (2) transactions of value in excess of $500, and (3) publishing articles related to the sponsoring biomedical company were all statistically associated with reporting conflicts of interest (p < 0.0001). CONCLUSIONS: Discordance exists between investigator/authors self-reporting in scientific journals and the government-mandated reporting of conflicts of interest by industry. Factors associated with conflict-of-interest disclosure include academic status, transaction amount, and article content related to the sponsoring biomedical company.

Androgen-Regulated SPARCL1 in the Tumor Microenvironment Inhibits Metastatic Progression.

Prostate cancer is a leading cause of cancer death in men due to the subset of cancers that progress to metastasis. Prostate cancers are thought to be hardwired to androgen receptor (AR) signaling, but AR-regulated changes in the prostate that facilitate metastasis remain poorly understood. We previously noted a marked reduction in secreted protein, acidic and rich in cysteine-like 1 (SPARCL1) expression during invasive phases of androgen-induced prostate growth, suggesting that this may be a novel invasive program governed by AR. Herein, we show that SPARCL1 loss occurs concurrently with AR amplification or overexpression in patient-based data. Mechanistically, we demonstrate that SPARCL1 expression is directly suppressed by androgen-induced AR activation and binding at the SPARCL1 locus via an epigenetic mechanism, and these events can be pharmacologically attenuated with either AR antagonists or HDAC inhibitors. We establish using the Hi-Myc model of prostate cancer that in Hi-Myc/Sparcl1(-/-) mice, SPARCL1 functions to suppress cancer formation. Moreover, metastatic progression of Myc-CaP orthotopic allografts is restricted by SPARCL1 in the tumor microenvironment. Specifically, we show that SPARCL1 both tethers to collagen in the extracellular matrix (ECM) and binds to the cell's cytoskeleton. SPARCL1 directly inhibits the assembly of focal adhesions, thereby constraining the transmission of cell traction forces. Our findings establish a new insight into AR-regulated prostate epithelial movement and provide a novel framework whereby SPARCL1 in the ECM microenvironment restricts tumor progression by regulating the initiation of the network of physical forces that may be required for metastatic invasion of prostate cancer.

Total synthesis of a functional designer eukaryotic chromosome.

Rapid advances in DNA synthesis techniques have made it possible to engineer viruses, biochemical pathways and assemble bacterial genomes. Here, we report the synthesis of a functional 272,871-base pair designer eukaryotic chromosome, synIII, which is based on the 316,617-base pair native Saccharomyces cerevisiae chromosome III. Changes to synIII include TAG/TAA stop-codon replacements, deletion of subtelomeric regions, introns, transfer RNAs, transposons, and silent mating loci as well as insertion of loxPsym sites to enable genome scrambling. SynIII is functional in S. cerevisiae. Scrambling of the chromosome in a heterozygous diploid reveals a large increase in a-mater derivatives resulting from loss of the MATα allele on synIII. The complete design and synthesis of synIII establishes S. cerevisiae as the basis for designer eukaryotic genome biology.