EPI-001 Our study has several limitations This pilot study

Our study has several limitations. This pilot study was unblinded without a control group. We cannot discern if the positive effect is a result of the urologist interviews or the patient\’s own expectations to stem cell therapy or if in fact the stem EPI-001 themselves by differentiation have helped regenerate the erectile function (Gimble et al., 2013; Zuk, 2010) or if a paracrine mechanism is responsible (Fandel et al., 2012; Kimbrel et al., 2014). In general, reported degrees of ED after RP vary greatly (14%–86%) depending on risk stratification and patient selection, the experience of the surgeon, type of operation and the measure and definition of ED (Weyne and Albersen, 2014). The result that 8/11 (73%) of the continent men recovered erectile function after ADRC therapy is promising, although further placebo-controlled trials are needed to differentiate possible stem cell effects from spontaneous regeneration. Regarding spontaneous regeneration, background data from review of 165 medical journals from our urology department showed that only 40/135 (29.6%) continent men and 4/30 (13.3%) incontinent men recovered their erectile function 6months and 1year after RP using conventional therapy. In a previous RCT study of much milder forms of ED from our group (Olsen et al., 2015), only 7/57 (12.3%) men in a placebo control group recovered erectile function (IIEF scores above 10) after 6months. Likewise, others have analyzed all 11 reported, randomized, controlled trials to enclose a penile rehabilitation of 20–25% following RP (Schauer et al., 2015). In the present paper, we report that a much higher number of the stem cell-treated RP-induced ED men with urinary continence had high IIEF scores after 6months. Finally, the nine months\’ IIEF score data from 423 men with ED after RP in the REACTT placebo-controlled study showed relatively low recovery of erectile function after RP; 25.5% had high IIEF scores in the “5mg tadalafil (Cialis®) 3 times a day group” versus 14.2% with high IIEF scores in the placebo group (Montorsi et al., 2014).
We did not include objective measurement for the recovery of erectile function, like measurements of penile hemodynamics or nerve impulse speed. We used EHS and IIEF scores that are generated on the basis of patient questionnaires and thus could be biased by several factors including interviewer effects and differences in the patients\’ understanding of the questions. In order to mitigate interviewer bias, we used the same interviewer throughout the study, and interviewed the patients at different time points using the same questions. A recent study shows correlation between objective measurements and EHS (Matsuda et al., 2014).
The following are the supplementary data related to this article.


Conflicts of Interest


This study was funded by Odense University Hospital (11/31936), The Danish Centre for Regenerative Medicine (14/50427) and the Danish Cancer Society. We thank Lars Melholt Rasmussen, prof. MD, Odense University Hospital and Bruce Conklin, MD, PhD, The Gladstone Inst. USCF, San Francisco, USA for critical reading of the manuscript.

Incorporation of whole genome or exome sequencing (WGS/WES), hereafter referred to as genomic sequencing, in medical practice raises the disquieting issue of incidental findings (IFs), which has important and potentially far-reaching implications (Green et al., 2012; Knoppers et al., 2013; Wolf et al., 2012; Roche and Berg, 2015; Hegde et al., 2015; Ayuso et al., 2015; Krier and Green, 2015). IF, also called secondary findings and occasionally referred to as incidentalomes, are mutations in genes unrelated to the primary condition (phenotype) of the patient (Krier and Green, 2013). As genomic sequencing is a phenotype-agnostic test, it is not surprising that detection of IFs is of major concern and requires the decision of whether and how return of these results to the individual should be practiced (Krier and Green, 2013). Another concern revolves around the additional burden this creates on the healthcare system. Individuals with medically actionable IFs will require long-term surveillance and anticipatory care, which is acceptable when it is appropriate, but may be hard to justify if there is only uncorroborated evidence for the pathogenicity of the mutation in question: e.g. even if the gene is a causal gene for the condition, the mutation could be a novel one and never reported before for the condition.