br Authors Contributions br Conflict of Interest

Authors\' Contributions
Conflict of Interest Jeri Kim, MD, acknowledges receipt of nonfinancial support from Merck, which provided 5-mg tablets of finasteride and matching placebos for the study. For the 3years preceding submission, she has no other conflict of interest to report. Ian Thompson, MD, has received finasteride and matching placebo from Merck for research. No author has any patents—planned, pending, or issued—relevant to the work. No other conflict of interest is reported.
Acknowledgments
Introduction Pancreatic cancer is a highly aggressive disease with dismal prognosis. Patients with localized disease benefit from multimodality therapy including surgical resection. Patients with metastatic disease, however, gain no benefit from a potentially morbid surgical procedure. Staging laparoscopy (SL) has been shown to identify occult metastatic disease in 14% to 31% of patients, effectively sparing these patients unnecessary, aggressive therapies (Ahmed et al., 2006; Doucas et al., 2007; Enestvedt et al., 2008; Jimenez et al., 2000a, b; White et al., 2008). One component of DL that is increasingly acknowledged as important is the cytological analysis of peritoneal LY 2109761 Supplier harvested. Free cancer cells in the peritoneum are thought to arise from exfoliation of malignant cells from the primary tumor and their presence is thought to lead to the peritoneum as a frequent site of recurrence (Foo et al., 1993; Gold et al., 2007). Patients with positive peritoneal cytology (PPC) as the only evidence of metastasis have the same outcome as patients with grossly visible metastases (Ferrone et al., 2006; Merchant et al., 1999). Thus, the American Joint Commission on Cancer (AJCC) staging system for pancreatic cancer includes PPC as a criterion for M1 disease. While conventional cytology is currently the gold standard for detection of malignant cells in peritoneal fluid because it is both highly specific and clinically relevant, it is thought to lack sensitivity, Many patients with negative peritoneal cytology at the time of resection with curative intent still develop early intraperitoneal recurrence(Abe et al., 1995; Kodera et al., 2005; Selvaggi, 2003). Additional techniques including immunohistochemistry (IHC), microarray analysis, and reverse-transcription polymerase chain reaction (RT-PCR) for tumor markers have been investigated to improve the sensitivity of detection of peritoneal cancer cells (Kodera et al., 2002, 2005; Dalal et al., 2007; Fukumoto et al., 2006; Hoffmann et al., 2007; Katsuragi et al., 2007; Mori et al., 2007; Oyama et al., 2004; Tamura et al., 2007; To et al., 2003; Zhang et al., 2006; Schmidt et al., 2001). Limitations of these techniques include cost and time consuming nature of their use, and lack of reproducibility. RT-PCR is also limited by its exquisite sensitivity, which can lead to false-positive, clinically irrelevant results (Timar et al., 2002; Kammula et al., 2004; Wong and Coit, 2012). Viral oncolytic therapy is a field that seeks to genetically design viruses that specifically infect, replicate within, and kill cancers. Many promising viruses so designed are now in clinical trials as cancer therapy (Geevarghese et al., 2010; Heo et al., 2013; Kaufmann and Chiocca, 2014; Kemeny et al., 2006; Reid et al., 2001). The herpes-based virus, T-VEC, recently became the first oncolytic virus approved for clinical use in the Western world for the treatment of metastatic melanoma. NV1066 is a replication-competent, tumor specific herpes virus that carries the marker gene encoding enhanced green fluorescent protein (eGFP). In vitro, NV1066 has been shown to infect over 111 different human cancer cell lines, and can detect as few as 1 cancer cell in a background of 1 million normal cells (Adusumilli et al., 2011). In animal models, NV1066 can circulate the blood stream and identify occult metastatic deposits of cancer (Adusumilli et al., 2005, 2006a, b; Eisenberg et al., 2006; Stanziale et al., 2004). The aim of the current study was to evaluate use of this virus in rapid detection of peritoneal dissemination of pancreatic cancer. This human clinical trial sought to determine if the presence of virally-detected, rare peritoneal cancer cells predict peritoneal recurrence and patient outcome.