美国William Beaumont医院泌尿外科主任Kenneth M. Peters 2010年4月在《当代膀胱功能紊乱报道》杂志发表文章,对肖传国发现的反射弧手术方法予以综述:(附录3) Dr. C. G. Xiao from China was the first to popularize bladder reinnervation through an intradural nerve anastomosis of a lumbar-to-sacral nerve. This concept has gained international attention, and attempts to create other somatic-to-autonomic reflex arcs to assist with voluntary voiding have been studied. In this review, we discuss the current state of the literature in this new field.
2010年8月Peters与同行们在美国泌尿学杂志发表论文。报告9名患者的反射弧手术结果:(附录4) Results At 1 year 7 patients (78%) had a reproducible increase in bladder pressure with stimulation of the dermatome. Two patients were able to stop catheterization and all safely stopped antimuscarinics. No patient achieved complete urinary continence. The majority of subjects reported improved bowel function. One patient was continent of stool at baseline and 4 were continent at 1 year. Of the patients 89% had variable weakness of lower extremity muscle groups at 1 month. One child had persistent foot drop and the remainder returned to baseline by 12 months. Conclusions At 1 year a novel reflex arc with stimulation of the appropriate dermatome was seen in the majority of subjects. Improvements in voiding and bowel function were noted. Lower extremity weakness was mostly self-limited, except in 1 subject with a persistent foot drop. More patients and longer followup are needed to assess the risk/benefit ratio of this novel procedure.
附录1:肖传国论文部分目录 “SKIN-CNS-BLADDER” REFLEX PATHWAY FOR MICTURITION AFTER SPINAL CORD INJURY AND ITS UNDERLYING MECHANISMS CGUO XIAO, WC DE GROAT, CJ GODEC, C DAI, … - The Journal of …, 1999 - Elsevier A detrusor contraction was initiated at short latency by scratching the skin or by percutaneous electrical stimulation in the L7 dermatome. Maximal bladder pressures during this stimulation were similar to those activated by bladder distension in control animals. ... Cited by 57 - Related articles - BL Direct - All 4 versions An artificial somatic-central nervous system-autonomic reflex pathway for controllable micturition after spinal cord injury: preliminary results in 15 patients CG Xiao, MX Du, C Dai, B Li, VW Nitti, WC de … - The Journal of …, 2003 - Elsevier ... Fig. 1. Skin-CNS-bladder reflex pathway. View Within Article. ... Test of skin-CNS-bladder reflex by scratching L5 dermatome caused immediate response of detrusor and external urethral sphincter but voiding was not yet synergic and bladder emptying was incomplete. ... Cited by 48 - Related articles - BL Direct - All 5 versions Reinnervation for neurogenic bladder: historic review and introduction of a somatic-autonomic reflex pathway procedure for patients with spinal cord injury or spina … CG Xiao - European urology, 2006 - Elsevier ... related skin. A new concept may be derived from the skin-CNS-bladder reflex pathway: the impulses delivered from the efferent neurons of a somatic reflex arc can be transferred to initiate responses of an autonomic effector [22]. ... Cited by 20 - Related articles - All 7 versions An artificial somatic-autonomic reflex pathway procedure for bladder control in children with spina bifida CG Xiao, MX Du, B Li, Z Liu, M Chen, ZH Chen, P … - The Journal of …, 2005 - Elsevier ... through the S2, S3 or S4 VR. The efferent impulses of the skin-CNS-bladder reflex pass through the pudendal nerve and should activate the external sphincter before the bladder. Therefore, activation of bladder muscle will be ... Cited by 23 - Related articles - All 3 versions [PDF] 体神经 2 内脏神经吻合后神经纤维再生过程的光镜电镜观察 zhengdasifuyuan.com [PDF]肖传国, 李兵 - 中华实验外科杂志, 2002 - 88889595.zhengdasifuyuan.com 基金项目:国家自然科学基金重点资助项目(39830370) ;国家杰出 青年人才基金资助项目(39925033) 作者单位:430022 武汉,华中科技大学同济医学院附属协和医院泌 尿外科 ... Light microscope and electron microscope study of nerve regenerated ... Cited by 17 - Related articles - View as HTML - All 8 versions [PDF] 人工体神经 2 内脏神经反射弧传出通路神经追踪研究 zhengdasifuyuan.com [PDF]肖传国, 李兵 - 中华实验外科杂志, 2003 - 88889595.zhengdasifuyuan.com 基金项目:国家自然科学基金重点资助项目(39830370) ;国家杰出 青年人才基金项目(39925033) 作者单位:430022 武汉,华中科技大学同济医学院附属协和医院泌 尿外科 ... Neural tracing study of efferent pathway of the artificial somatic2autonomic reflex arc XIAO Chuan2guo ,LI ... Cited by 16 - Related articles - View as HTML - All 6 versions SKIN-CNS-BLADDER REFLEX ARC FOR MICTURITION AFTER SCI Chuan-guo Xiao New York University School Of Medicine New York, Ny 10016 Grant 5R01DK053063-05 from National Institute Of Diabetes And Digestive And Kidney Diseases IRG: ZRG1 Abstract: The neurological bladder caused by spinal cord injury (SCI) presents a significant medical and social problem. There is no satisfactory treatment yet. Supported by the Paralyzed Veterans of America and NIH, a new reflex pathway, \\\\\\\"Skin-CNS-Bladder\\\\\\\" for controlled micturition after SCI has been successfully established in rat, cat and canine models. Preliminary clinical application of 14 SCI patients also provided very promising results. The study proposed here is to transfer the Skin-CNS-Bladder reflex functions. The ventral root (VR) of a lumbar nerve (L5) below the spinal cord lesion will be anastomosed to the sacral VR (S2 and/or S3) which innervate the bladder, while leaving the intact L5 dorsal root (DR) as a started of micturition. After the axonal regeneration, controllable voiding would be initiated by scratching the L4 dermatome. Effect of the new reflex pathway on bladder function will be evaluated by means of electrophysiology and urodynamics. Its effect on bowel and sexual functions will also be studied. The procedure may revolutionize the treatment of neurogenic bladder after SCI, It requires relatively minor surgery on 2 paralyzed nerves. It does not involve implantation of electrodes or other devices but provides unique voluntary control of bladder emptying. Scientifically, the study will further prove the new concept derived from the unique somatic-autonomic reflex that the impulses delivered from the efferent neurons of a somatic reflex arc may be transferred to initiate response of an autonomic effector. This new concept may be widely useful, not only for neurogenic bladder, but also for other problems caused by the spinal cord injury or diseases. Keywords: electrophysiology, human therapy evaluation, neurogenic urinary bladder disorder, neuroregulation, neurosurgery, somatic reflex, spinal cord injury, urination, central nervous system, clinical trial, functional ability, outcomes research, quality of life, skin, urinary electronic stimulator, clinical research, human subject Project start date: 1999-09-30 Project end date: 2007-12-31 5R01DK053063-05 (2004): $642796
附录2:中枢神经外周神经的定义和神经再生的理论 The peripheral nervous system, or PNS, consists of the nerves and ganglia outside of the brain and the spinal cord.[1] The main function of the PNS is to connect the central nervous system (CNS) to the limbs and organs. Unlike the CNS, the PNS is not protected by the bone of spine and skull, or by the blood-brain barrier, leaving it exposed to toxins and mechanical injuries. The peripheral nervous system is divided into the somatic nervous system and the autonomic nervous system; some textbooks also include sensory systems.[2] Neuroregeneration in the PNS occurs to a significant degree.[5] Axonal sprouts form at the proximal stump and grow until they enter the distal stump. The growth of the sprouts are governed by chemotactic factors secreted from Schwann cells. Injury to the peripheral nervous system immediately elicits the migration of phagocytic cells, Schwann cells, and macrophages to the lesion site in order to clear away debris such as damaged tissue. When a nerve axon is severed, the end still attached to the cell body is labeled the proximal segment, while the other end is called the distal segment. After injury, the proximal end swells and experiences some retrograde degeneration, but once the debris is cleared, it begins to sprout axons and the presence of growth cones can be detected. The proximal axons are able to regrow as long as the cell body is intact, and they have made contact with the neurolemmocytes in the endoneurial channel. Human axon growth rates can reach 2 mm/day in small nerves and 5 mm/day in large nerves.[4] The distal segment, however, experiences Wallerian degeneration within hours of the injury; the axons and myelin degenerate, but the endoneurium remains. In the later stages of regeneration the remaining endoneurial tube directs axon growth back to the correct targets. During Wallerian degeneration, Schwann cells grow in ordered columns along the endoneurial tube, creating a band of Bungner (boB) that protects and preserves the endoneurial channel. Also, macrophages and Schwann cells release neurotrophic factors that enhance re-growth. Unlike peripheral nervous system injury, injury to the central nervous system is not followed by extensive regeneration.
附录3:美国William Beaumont医院泌尿外科主任Kenneth M. Peters对肖传国发现的反射弧手术方法予以综述 Bladder Reinnervation: Is it Becoming a Reality? Don Bui, Kevin Feber and Kenneth M. Peters Abstract Management of neurogenic voiding dysfunction presents a clinical challenge. Traditional therapies such as clean intermittent catheterization and antimuscarinics have saved countless lives. However, a desire remains to normalize the voiding in patients suffering from spinal cord injuries. Bladder reinnervation is a novel surgical technique that shows promise in helping those with spinal cord-related neurogenic voiding dysfunction. Dr. C. G. Xiao from China was the first to popularize bladder reinnervation through an intradural nerve anastomosis of a lumbar-to-sacral nerve. This concept has gained international attention, and attempts to create other somatic-to-autonomic reflex arcs to assist with voluntary voiding have been studied. In this review, we discuss the current state of the literature in this new field. Keywords Neurogenic bladder - Nerve transfer - Incontinence - Spina bifida - Spinal cord injury Current Bladder Dysfunction Reports Volume 5, Number 2, 59-62,
附录4:Kenneth M. Peters在美国泌尿学杂志发表论文。报告9名患者的反射弧手术结果: THE JOURNAL OF UROLOGY, Vol. 184, 702-708, August 2010 Outcomes of Lumbar to Sacral Nerve Rerouting for Spina Bifida Kenneth M. Petersa, Benjamin Girdlera, Cindy Turzewskia, Gary Trockc, Kevin Febera, William Nantaub, Brian Bushb, Jose Gonzaleza, Evan Kassa, Juan de Benitoa, Ananias Dioknoa Received 25 November 2009 published online 21 June 2010. Purpose Restoring bladder and bowel function in spina bifida by creation of a skin-central nervous system-bladder reflex arc via lumbar to sacral nerve rerouting has a reported success rate of 87% in China. We report 1-year results of the first North American trial on nerve rerouting. Materials and Methods Nine subjects were enrolled in the study. Intradural lumbar to sacral nerve rerouting was performed. Subjects underwent urodynamic testing with stimulation of the cutaneous dermatome and careful neurological followup. Adverse events were closely monitored along with changes in bowel and bladder function. Results At 1 year 7 patients (78%) had a reproducible increase in bladder pressure with stimulation of the dermatome. Two patients were able to stop catheterization and all safely stopped antimuscarinics. No patient achieved complete urinary continence. The majority of subjects reported improved bowel function. One patient was continent of stool at baseline and 4 were continent at 1 year. Of the patients 89% had variable weakness of lower extremity muscle groups at 1 month. One child had persistent foot drop and the remainder returned to baseline by 12 months. Conclusions At 1 year a novel reflex arc with stimulation of the appropriate dermatome was seen in the majority of subjects. Improvements in voiding and bowel function were noted. Lower extremity weakness was mostly self-limited, except in 1 subject with a persistent foot drop. More patients and longer followup are needed to assess the risk/benefit ratio of this novel procedure. Key Words: nerve transfer, spina bifida cystica, spina bifida occulta, urinary bladder, neurogenic Abbreviations and Acronyms: DR, dorsal root, EMG, electromyography, VR, ventral root http://www.jurology.com/article/S0022-5347(10)03053-3/abstract
附录5:对Kenneth M. Peters论文杂志编辑的评论和论文作者Peter等的回应 EDITORIAL COMMENTS The Beaumont Hospital in Michigan is one of the first American institutes that took up clinical trials of the controversial Xiao Procedure. We have previously questioned their clinical outcomes and their misleading propaganda in our Open Letter of Complaint against the Xiao Procedure.
More recently, the hospital has also become the first institute to publish clinical results of Xiao Procedure in an established scientific journal. Dr. Kenneth Peters and his coauthors wrote in the Journal of Urology of their results: At 1 year 7 patients (78%) had a reproducible increase in bladder pressure with stimulation of the dermatome. Two patients were able to stop catheterization and all safely stopped antimuscarinics. No patient achieved complete urinary continence. The majority of subjects reported improved bowel function. One patient was continent of stool at baseline and 4 were continent at 1 year. Of the patients 89% had variable weakness of lower extremity muscle group at 1 month. One child had persistent foot drop and the remainder returned to baseline by 12 months. The authors present the first North American experience with lumbar to sacral nerve rerouting for patients with spina bifida. The results from this study and previous animal and clinical studies by Xiao clearly demonstrate that nerve rerouting produces a somatic-autonomic or cutaneous/bladder reflex with stimulation of the lower extremity dermatome. What is also clear is that the clinical benefit of the procedure is not at all similar to previous reports. Although the authors did an excellent job of following the patients and characterizing their changes, the results are hard to validate without a control population going through the same rigorous surveillance regimen. In particular the improved bowel continence and minimal changes in bladder compliance may not be statistically significant. The fact that most patients were still on clean intermittent catheterization and none achieved complete urinary continence is troubling in light of the report of 87% success with 110 children with spina bifida presented by Xiao. One has to wonder if most of these children are not voiding volitionally or using the newly developed cutaneous reflex, and how much reinnervation has a role in this surgery. Is it possible that unilateral denervation of the S3 ventral motor nerve produced improved compliance and continence, as previously reported in numerous clinical series? I congratulate the authors for taking on this challenge. I hope this study leads to a rebirth or refocus regarding neurosurgical treatments of neuropathic bowel and bladder. I strongly agree with the authors that this procedure should remain on a research protocol only. Eric A. Kurzrock Pediatric Urology U. C. Davis Children’s Hospital Sacramento, California One of the most curious findings is the discrepancy between urodynamic data and subjective voiding. One patient exhibited a decrease in capacity and an absence of reflex arc, and yet he subjectively reported improved bladder and bowel function! I could not help but speculate that his voiding after the procedure could simply be the bladder emptying via intra-abdominal pressure generation against an open bladder neck, given his preoperative stress incontinence. Xiao reported that more than 87% of 110 patients gained sensation and continence within 1 year (reference 7 in article). In comparison, the current patients undergoing the identical procedure with the help of Xiao himself only showed a modest improvement in objective urodynamic studies and subjective reporting. Unless the innovators provide a sound argument and data for the validity of the procedure, there is a great danger of its improper and rapid adaptation by patients and the medical community at large. John M. Park Department of Urology University of Michigan Medical School Ann Arbor, Michigan REPLY BY AUTHORS We agree this is a challenging study on many levels. The intent of publishing these 1-year data was to understand the potential complications associated with lumbar to sacral nerve rerouting, demonstrate that a cutaneous to bladder reflex is achievable and, given the nationwide interest in this procedure, reinforce the need to continue this rigorous research protocol until more is known about the risk-benefit profile. Hopefully our 36-month data will shed more light on the clinical usefulness of this innovative procedure.