中秋没事，就丹麦文章给美国泌尿外科杂志主编写了个comment，简言之就是：Do it my way,or get away.留个底。一位世界级神经生理学大佬也来Email表示不可理解丹麦的作法.“Xiao Procedure is not only the surgery." 他除了完全同意我的批评，更进一步指出：这阻断剂不仅阻断神经和逼尿肌之间的联系，还会通过影响 neurotrophic 因子而阻碍反射弧神经再生。

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As the inventor and strong promoter of Xiao Procedure, I am very sorry for the 10 of 10 negative results from Denmark trial, but not surprised at all due to my prior experience in trying to convince other research teams to test the Xiao procedure in the right way. When I was informed of the negative results with only the abstract, I believed that there must be something fundamentally wrong in the trial. I know now that the authors continued anticholinergic treatment following the reinnervation procedure. As I have noted previously (1) this treatment can result in failure of the somatic-autonomic reflex pathway:

“Rigorous criteriafor patient selection have been recommended by Xiao8. These include pre- and preoperative electrophysiological evaluation, patient education, discontinuation of anticholinergics, maintaining bladder capacity below 700mL and leaving a suprapubic catheter in situ until reflex arch voiding was established. Although first published after beginning of the present study most criteria were met,save the upper limit of bladder capacity and cessation of anticholinergic medication, as we judged that the medication was essential for patient wellbeing throughout the 18 month study time. As reinnervation occurs at the level of the preganglionic (nicotinic) receptors, and anticholinergics mainly target postganglionic (muscarinic) receptors, we cannot exclude that treatmentmay have diminished the reflex but do not believe it would have abolished it completely.” (Quote from the article)

Anticholinergics plus CIC have been the “Gold Standard” treatment for neurogenic bladder caused by SCI for more than half a century in developed counties. It aims to block the neural connection between postganglionic nerves and detrusor, to paralyze the detrusor,to inhibit the bladder contraction and to make the bladder a low pressure storage tank for CIC. The Xiao Procedure, however, is to re-establish the neural control of lower urinary tract via the somatic-autonomic reinnervation to allow voluntary voiding. The postganglionic nerve to detrusor connection is the last and most important leg of the somatic-CNS-autonomic reflex arch and if this leg is blocked by anticholinergics continuously, the newly established reflex arch could never be activated to initiate detrusor contraction and voiding, as the case in this report.

This trial is a well designed, rigorously carried out by an outstanding team with credible expertise in multiple specialties related to SCI.  However the anticholinergics issue is a fundamental scientific error, which is very unfortunate and likely makes all of the results meaningless. For example: The baseline as well as the post surgery urodynamic test results are influenced by the anticholinergic treatment and do not reflect the real reflex activity of the bladder. Under the anticholinergics medication,the results should be the same and indeed they were the same. Why the only statistically positive result was the less leaking? It is because external urethra was simultaneously reinnervated by somatic motor axons and became functional which can not be blocked by the anticholinergics

The article, however, should not be the end of the Denmark trail. I am confident on the success of the neural microanastomosis performed by the skilled neurosurgeons I met in China,on the expertise of the electrophysiology and urodynamic staff as showed in the article. So I am also confident that the somatic-autonomic reflex arch has been established and can be activated for voiding after discontinuation of anticholinergics.I suggest the authors discontinue anticholinergics for 2 months and then repeat the post-surgery studies as designed. Nevertheless, discontinuation anticholinergics for a few months under close watch will not affect the “patient wellbeing”, but may prove that anticholinergics are no longer necessary as many other centers have reported. If the results of these suggested studies are quite different from current results, then I wish you to withdraw this article to avoid misleading.  

Finally,I would take this opportunity to advice anyone who may try Xiao Procedure: Do not do it if you are determined to keep using anticholinergics. It makes no sense. 

Chuan-Guo Xiao, M, D,

Chairman

Institute of Neurourology

C.G. XIAO Hospital

Shenzhen, China

cgxiao_hospital@163.com