An international pilot study of an internet‐based platform to facilitate clinical research in epilepsy: The EpiNet project

Purpose: We created an epilepsy patient database that can be accessed via the Internet by neurologists from anywhere in the world. The database was designed to enroll and follow large cohorts of patients with specific epilepsy syndromes, and to facilitate recruitment of patients for investigator‐initiated clinical trials. Methods: The EpiNet database records physician‐derived information regarding seizure type and frequency, epilepsy syndrome, etiology, drug history, and investigations. It can be accessed from any country by approved investigators via a secure, password‐protected Website. All data are encrypted. The database is for both research and clinical purposes. Investigators were invited to register any patient with epilepsy, but were particularly encouraged to register patients when uncertain of the optimal management. Participation required approval from investigators’ ethics committees and institutional review boards, and all patients or their caregiver provided written informed consent. Patients were not enrolled in clinical trials in this pilot study. Key Findings: The international pilot study recruited patients from September 2010 to November 2011. Sixty‐four investigators or research assistants from 25 centers in 13 countries registered 1,050 patients. Patients with a wide range of epilepsy syndromes and etiologies were registered. Patients’ ages ranged from 2 weeks to 90 years. Significance: The Website was successfully used by doctors working in different health systems. The pilot study confirmed that this low‐cost, collaborative approach to research has great potential. Large, multicenter cohort studies will commence in 2012, and randomized clinical trials are being planned. All epileptologists are invited to join this project.     

Effects of Histone Deacetylase Inhibitor (HDACi); Trichostatin-A (TSA) on the expression of housekeeping genes

In quantitative RT-PCR (qRT-PCR), analysis of gene expression is dependent on normalization using housekeeping genes such as 18S rRNA, GAPDH and beta actin. However, variability in their expression has been reported to be caused by factors like drug treatment, pathological states and cell-cycle phase. An emerging area of cancer research focuses on identifying the role of epigenetic alterations such as histone modifications and DNA methylation in the initiation and progression of cancer. Histone acetylation is the best studied modification so far and has been probed through the use of histone deacetylase inhibitors (HDACi). Further, modulation of histone acetylation is currently being explored as a therapeutic strategy in the treatment of cancer and HDACis have shown promise in inhibiting tumorigenesis and metastasis. Trichostatin-A (TSA) is the most widely used HDACi. Therefore, we were driven to identify a suitable internal control for RT-PCR following TSA treatment. We performed quantitative RT-PCR analysis using mouse prostate tissue explants, human prostate cancer (LNCaP) cells and human breast cancer (T-47D and ZR-75-1) cells following TSA treatment. Expression of housekeeping genes including 18S rRNA, beta actin, GAPDH and ribosomal highly-basic 23-kDa protein (rb 23-kDa, RPL13A) were compared in vehicle versus TSA treated samples. Our results showed marked variations in 18S rRNA, beta actin mRNA and GAPDH mRNA levels in mouse prostate explants and a human prostate cancer (LNCaP) cell line following TSA treatment. Furthermore, in two human breast cancer cell lines (T-47D and ZR-75-1) 18S rRNA, beta actin mRNA and GAPDH mRNA levels varied significantly. However, RPL13A mRNA levels remained constant in all the conditions tested. Therefore, we recommend use of RPL13A as a standard for normalization during TSA treatment.     

Assessing Trends in Palliative Surgery for Extrahepatic Biliary Malignancies: A 15-Year Multicenter Study

Introduction

Extrahepatic biliary malignancies are often diagnosed at an advanced stage. We compared patients with unresectable perihilar cholangiocarcinoma (PHCC) and gallbladder cancer (GBC) who underwent a palliative procedure versus an aborted laparotomy.

Methods

Seven hundred seventy-seven patients who underwent surgery for PHCC or GBC between 2000 and 2014 were identified. Uni- and multivariable analyses were performed to identify factors associated with outcome.

Results

Utilization of preoperative imaging increased over time (CT use, 80.1 % pre-2009 vs. 90 % post-2009) (p?<?0.001). The proportion of the patients undergoing curative-intent resection also increased (2000–2004, 67.0 % vs. 2005–2009, 74.5 % vs. 2010–2014, 78.8 %; p?=?0.001). The planned surgery was aborted in 106 (13.7 %) patients and 94 (12.1 %) had a palliative procedure. A higher incidence of postoperative complications (19.2 vs. 3.8 %, p?=?0.001) including deep surgical site infections (8.3 vs. 1.1 %), bleeding (4.8 vs. 0 %), bile leak (6.0 vs. 0 %) and longer length of stay (7 vs. 4.5 days) were observed among the patients who underwent a palliative surgical procedure versus an aborted non-therapeutic, non-palliative laparotomy (all p?<?0.05). OS was comparable among the patients who underwent a palliative procedure (8.7 months) versus an aborted laparotomy (7.8 months) (p?=?0.23).

Conclusion

Increased use of advanced imaging modalities was accompanied by increased curative-intent surgery. Compared with patients in whom surgery was aborted, patients who underwent surgical palliation demonstrated an increased incidence of postoperative morbidity with comparable survival.