Xiao Procedure: Lower urinary tract refunctionalization by somatic/autonomic nerve root transposition John S. Wiener, MD Professional Advisory Council What is the Xiao procedure? • Reinnervate bladder by switching nerves • Move nerves that cause lower leg muscles to contract and plug them into nerves that make the bladder contract • Result – reflex stimulation • Stimulation specific part of leg • Invoke bladder contraction (emptying) What is the Xiao procedure? • Nerve transfer between muscles is not new idea • Nerve transfer between somatic and autonomic nervous system is new – Give voluntary nervous system control over involuntary nervous system What is the Xiao procedure? • Who are candidates? – Spinal cord injury patients • REinnervate bladder using normally formed nerves below level of injury – Spina bifida patients • Innervate bladder using nerves that may have not formed normally due to birth defect Normal Bladder Innervation AUTONOMIC NERVES What is the Xiao Procedure? L5 S3 SOMATIC SCRATCH LEG NERVE LEG AUTONOMIC BLADDER NERVE EMPTIES Who is C.G. Xiao, MD? • Chairman of Urology, Tongji Medical Univ. • Fellowship in reconstr. urology in England • Fellowship in U.S. (2 yr.) w/ G. Jordan • Asst Professor of Urology at SUNY & NYU • Received over $3 M in grants from NIH & PVA to estab. neurourology lab to study procedure in rats, cats, & dogs • 1995 began study on humans w/ SCI What motivates C.G. Xiao, MD? • Driven by desire to help multitudes of Chinese with SCI after earthquakes • Northern China has the highest incidence of spina bifida in the world What are Dr. Xiao’s Results? • Presented at special workshop following SBA’s First World Congress on Spina Bifida – March 18-19, 2009 in Orlando – Over 100 pediatric urologists and neurosurgeons from around the world attended – His results in over 1500 patients • 951 cases in 2008 alone What are Dr. Xiao’s Results? • 1320 patients with spina bifida – Follow-up on 431 – 86.2% void spontaneously without cath/med – All gained sensation to void – Many no longer have to scratch leg – Bowel function is normal in 77% (of 26) – Complications • Foot drop – can be treated by shoe or surgery What are Dr. Xiao’s Results? • Criticisms – Follow-up on less than one-third • “If they weren’t having problems, they did not come back to see us.” – Neurosurgeons noted his procedure was a spinal cord detethering • Could explain some of positive results – Complication of foot drop not inconsequential Is Xiao procedure being done in US? • Beaumont Hosp. in MI - first US site Ken Peters with Dr. Xiao • Privately funded • Inclusion criteria – Must be at least 6 years old – Neurogenic bladder requiring cath – Intact lumbar nerve function • All can walk – 4/9 without aids – No prior bladder surgery Do the results equal those in China? • Results – 9 patients with 3 yr F/U – 7/9 demonstrate voiding reflex at 12 months • Now only 2/9 – down-regulation by brain? – 4/9 report improvement in bladder function – 5/9 report improvement in bowel function – 7/9 still required catheters at 12 months • Now only 4/9 require catheters – Only 1/9 still on medication (anticholinergic) • Bladder compliance overall improved – Incontinence “remains a problem” Personal communication – Dr. Peters Do the results equal those in China? • Results – 4 more patients w/ 9 mo F/U – 1/4 demonstrate voiding reflex – 2/4 still require catheters at 12 months Personal communication – Dr. Peters Do the results equal those in China? • Results – early results – Urodynamics show improvement • Increased bladder capacity • Decreased uninhibited contractions • Average voided volume – 133 ml • Average residual urine volume – 119 ml – Bowel improvement • Modest at 6 mo; most better at 12 mo Personal communication – Dr. Peters Do the results equal those in China? • Results – All had temporary leg weakness • One is worse 12 months later with no improvement in bladder-bowel function – Quality of life measures at 12 mo. • 3 better • 5 same • 1 worse – foot drop – 7/9 would do it again Personal communication – Dr. Peters Is Xiao procedure being done in US? • Tampa FL - second US site – Different protocol • Only done on symptomatic patients having spinal cord surgery to detether • Reroute nerves at same time – Funding not an issue • Reimbursed as tethered cord surgery – 16 patients so far randomized to nerve routing or not • No results yet – remain blinded Personal communication – Dr. Homsy Is Xiao procedure being done in US? • Atlanta – third potential US site – Private funding – IRB approved protocol – Ready to start enrollment • On hold after SBA meeting awaiting standardization of protocol Where do go from here? • SBA-sponsored meeting August 2009 – Urologists would not be doing procedure – Develop common protocol • Urology – Entry criteria – Initial evaluation – Follow-up • Neurosurgery – Could not agree Where do go from here? • SBA-sponsored meeting August 2009 – Neurosurgery • Two camps – Purists – enroll only stable ambulatory patients – Pragmatists – perform on patients undergoing detethering » Funding not an issue » Easier to get IRB approval Where do go from here? • SBA-sponsored meeting August 2009 – NIH present at meeting • Recommended multi-institutional study • Fund Dr. Peters (Detroit) • Possibly fund Dr. Smith (Atlanta) • Additional sites dependent on funding NIH - funded Study Nerve Rerouting Treatment for Neurogenic Bladder in Spina Bifida This study is not yet open for participant recruitment. Verified by William Beaumont Hospitals, June 2010 First Received: March 23, 2010 Last Updated: June 4, 2010 History of Changes Sponsor: William Beaumont Hospitals National Institute of Diabetes and Collaborator: Digestive and Kidney Diseases (NIDDK) Information provided by: William Beaumont Hospitals ClinicalTrials.gov NCT01096459 Identifier: NIH - funded Study • Prospective cohort study – No control group • Unoperated side will serve as control for motor & sensory function in legs – Assessment • • • • • Clinical exams Urodynamic studies Testing of cutaneous-voiding reflex Voiding diaries Validated questionnaires – Urinary, bowel, QOL NIH - funded Study • Hypothesis 1 – Patients will show ability to void within 18 mo. so catheterization may be safely stopped – Patients will show bowel control without need for enemas/stimulation – Adverse events not different NIH - funded Study • Hypothesis 2 – Expertise to perform this procedure can be transferred to other qualified centers – At least four cases will be performed at an outside institution • First cases at Beaumont Hospital (MI) • Second group to follow six months later at Children’s Hospital of Atlanta NIH - funded Study • Inclusion Criteria – Males & females aged ≥ 5 years • Spinal dysraphism • Bladder dysfunction • On catheterization for at least 1 year – Atonic or hyperreflexic bladder – No more than one tethered cord release surgery (at least 2 yr prior) – Stable neurogenic bladder dysfunction for at least 1 yr. NIH - funded Study • Inclusion Criteria – Normal renal function • Serum Cr < 1.5 mg/dl • GFR > 75 ml/min – Ambulate independently with or without AFOs – Cath urine volume must be at least 50% of total bladder capacity NIH - funded Study • NIH funding now “on hold” – New Director of NIDDK • Concerned about potential harm • SBA cannot fund a study of this magnitude – Can only offer organizational support Where do go from here? • Lobby NIH to fund study • Prevent backdoor entry • Make study international • Advance the science – Properly-conducted studies – Minimize procedures off protocols – DO NO HARM!