Parathyroid identification during thyroid and parathyroid operations: A pilot study evaluating a novel low cost autofluorescence based device.

BACKGROUND: The aim of this study was to develop a low-cost prototype near-infrared fluorescence device that enables contrast-free, real time, high-resolution intraoperative visualization of normal and pathological parathyroid glands (PGs) by imaging their autofluorescence (AF). METHODS: A novel near-infrared parathyroid AF (NIR-PAF) imaging device with visible laser PG targeting was developed. The device was evaluated during parathyroid and thyroid operations in a pilot clinical study. RESULTS: Overall, of the 6 parathyroidectomies carried out in the study population a parathyroid adenoma was found to exhibit AF ex vivo in 6/6 (100%) of cases, and in vivo in 3/3 (100%) of these cases. Two of 4 thyroidectomies were evaluated in vivo and all PGs (6 PGs total) were identified by the NIR-PAF device. The NIRPAF device cost less than $1200 Canadian to build. CONCLUSION: The inexpensive NIR-PAF device that we developed can successfully intraoperatively identify both normal and pathological PGs.

The Master Neural Transcription Factor BRN2 Is an Androgen Receptor-Suppressed Driver of Neuroendocrine Differentiation in Prostate Cancer.

Mechanisms controlling the emergence of lethal neuroendocrine prostate cancer (NEPC), especially those that are consequences of treatment-induced suppression of the androgen receptor (AR), remain elusive. Using a unique model of AR pathway inhibitor-resistant prostate cancer, we identified AR-dependent control of the neural transcription factor BRN2 (encoded by POU3F2) as a major driver of NEPC and aggressive tumor growth, both in vitro and in vivo Mechanistic studies showed that AR directly suppresses BRN2 transcription, which is required for NEPC, and BRN2-dependent regulation of the NEPC marker SOX2. Underscoring its inverse correlation with classic AR activity in clinical samples, BRN2 expression was highest in NEPC tumors and was significantly increased in castration-resistant prostate cancer compared with adenocarcinoma, especially in patients with low serum PSA. These data reveal a novel mechanism of AR-dependent control of NEPC and suggest that targeting BRN2 is a strategy to treat or prevent neuroendocrine differentiation in prostate tumors. SIGNIFICANCE: Understanding the contribution of the AR to the emergence of highly lethal, drug-resistant NEPC is critical for better implementation of current standard-of-care therapies and novel drug design. Our first-in-field data underscore the consequences of potent AR inhibition in prostate tumors, revealing a novel mechanism of AR-dependent control of neuroendocrine differentiation, and uncover BRN2 as a potential therapeutic target to prevent emergence of NEPC. Cancer Discov; 7(1); 54-71. ©2016 AACR.This article is highlighted in the In This Issue feature, p. 1.