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This file consists of the Supplementary Materials and Methods and the Supplementary Figure Legends.

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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. Cancer Res; 75(20); 4322–34. ©2015 AACR.

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.

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.

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.

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. Cancer Res; 75(20); 4322–34. ©2015 AACR.

443 Background: Bilimoria et al (2007) reviewed 9,559 patients from the 1995-2004 National Cancer Database (NCDB) showing that 38.2% of patients with early-stage pancreatic cancer without any identifiable contraindications failed to undergo pancreactomy. We used the 2004-2013 NCDB to look at the role of surgery in initial care plans of patients with stage I pancreatic adenocarcinoma. We also assessed differences in practice in this regard at different types of cancer centers. Methods: We analyzed 12,927 patients diagnosed with stage I pancreatic adenocarcinoma between 2004-2013 from the NCDB. Survival differences between patients who received surgery at the primary site versus patients not offered surgery were estimated by the Kaplan-Meier method. Differences in surgery were compared using chi-squared analysis. Results: Of the stage I patients, 27.3% had surgery, 52.8% were not offered surgery, 9.3% were not offered surgery due to risk factors, 4.4% refused surgery. Patients who received surgery had an increased median survival time compared to patients who were not offered surgery (30.2 months versus 7.1 months, p < 0.05). Patients at academic/research programs were most likely to have surgery compared to those at community cancer programs who were least likely to have surgery (39.8% versus 22.9%, p < 0.05). Conclusions: Patients who had surgery of the primary site had a significantly longer median survival time than those that were not offered surgery. Patients were most likely to be offered surgery if they were at an academic/research facility. Future studies should examine other factors that could possibly influence whether a patient is offered surgery or not for early-stage pancreatic adenocarcinoma. [Table: see text]

283 Background: Oldfield et al (2015) showed the conflicting evidence regarding the effect of adjuvant chemotherapy vs. chemoradiation in pancreatic cancer. Using patients identified by the National Cancer Database (NCDB), we are the largest study to compare survival in stage II pancreatic cancer patients who received adjuvant chemotherapy, chemoradiation, radiation, or no adjuvant therapy. Methods: We identified 65,091 patients with stage II pancreatic cancer who received surgery only or surgery in combination with chemotherapy, radiation, or chemoradiation. Between-therapy survival differences were estimated by the Kaplan-Meier method and associated log-rank tests; Tukey-Kramer adjusted p < .05 indicated statistical significance. Results: Patient characteristics were similar between groups; although, patients receiving chemoradiation were younger, had fewer comorbidities, and were more likely to have private insurance compared to all other therapy groups. Statistically significant survival differences were indicated between all therapy groups (all adjusted p< 0.05), as patients receiving chemoradiation had the longest survival followed by patients receiving chemotherapy, patients receiving radiation therapy, and patients receiving no adjuvant therapy (median survival = 22.5, 19.6, 16.9, 14.8 months, respectively). When examining other variables, patients living in an area with a median income < $43,000 were 14% more likely to die compared to patients in an area with a median income ≥ $63,000 (p < 0.001) and those with no comorbidities were 19% less likely to die than patients with two or more comorbidities (p < 0.001). Conclusions: Our data suggests that adjuvant therapy improves median and 3-year survival compared to no adjuvant therapy. Of all adjuvant therapies examined, adjuvant chemoradiation was associated with the greatest increase in survival, followed by adjuvant chemotherapy. Table 1: Median survival and survival rates of stage II pancreatic cancer [Table: see text]