Transcript The Xiao Procedure - 37th SBA National Conference

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!