Beaumont Hospital’s Results of Xiao Procedure Questioned by Peer Experts

By xysergroup | 8月 18, 2010

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.

In their conclusion, they noted that “this procedure should remain on a research protocol, and more patients and longer followup are needed to assess the risk/benefit ratio of this novel procedure.”

The Journal, however, appears to be less than impressed. It published two pieces of editorial comments to accompany the paper, both are quite negative. In one, Dr. Eric Kurzrock of UC Davis Children’s Hospital wrote:

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.

In another, Dr. John Park of University of Michigan was even more blunt:

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.

Along with the editorial comments, Dr. Piet Hoebeke of Ghent University Hospital in Belgium also commented on Beaumont’s results in his editorial:

… in this issue of The Journal the results of the study by Peters et al (page 702) are the first to challenge the excellent, previously published results of nerve rerouting that showed up to 85% success.8 Despite proof that nerve rerouting can create a novel reflex arc generating a detrusor contraction, this group learned that after 1 year no patient became continent and only 2 of 9 were able to stop catheterization. Effects on bladder compliance and cystometric bladder capacity were remarkable despite stopping antimuscarinic treatment. Persistent foot drop cannot be considered a minor complication in children who are already motor disabled. Although promising, this study cautions us that further controlled studies are needed before this nerve rerouting procedure can be used more routinely.

Finally, We cite below how Beaumont described their one-year results in a much more “promising” way in their press release and their project information for the NIH grant they were rewarded in 2009.

Beaumont sees results in nation’s 1st urinary nerve rewiring surgeries for spina bifida patients
4/17/2008

Seven children from across the United States are gaining bladder control through a revolutionary, first-in-the-nation nerve rerouting surgery for patients with spina bifida. The surgeries were conducted in 2007 at Beaumont Hospital in Royal Oak, Mich.

The children previously required the insertion of a catheter to empty their bladder or endured significant incontinence. But as a result of the surgery, they are beginning to void on their own and are also seeing improvement in bowel function. Initially they signaled the bladder to urinate by scratching or pinching their leg or buttocks. But, remarkably, in most patients the brain was able to take over and control urination normally.

This will allow them to attend school without being catheterized and to play with other children without the embarrassment of soiling themselves. It also means fewer urinary tract infections resulting from catheterization, and reduces their need for antibiotics for infection control.


Possible side effects of the surgery include mild postoperative spinal fluid leakage, lower extremity weakness and headache. Recent changes in the surgical technique have dramatically decreased the incidence of these complications. Standard risks associated with any surgery may include bleeding and infection.

Project Information
Project Number: 1R01DK084034-01
Our preliminary data are very promising, and with 9 subjects now 12 months post procedure, 7/9 subjects are voiding either voluntarily or by stimulating the new reflex mechanism.

 

 

Update: Dr. J.W. Thüroff presents a thorough theoretical analysis of the Xiao Procedure in European Urology. 2011 Jan;59(1):173-5. Summary of his comments:

Transection of the lumbar nerve will cause muscle weakness and even permanent muscle paralysis, as in the one reported case with persistent foot drop. Transection of the sacral nerve will cause some improvement of hyperreflexia, but the effect is limited. Reinnervation of the sacral nerve, even if completely successful, will result in limited efficacy, and may cause some DSD.

Dr. Thüroff examined the published urodynamic tracings of Xiao, and found that “voiding is predominantly achieved by abdominal straining with concomitant pelvic floor activity and by only weak detrusor contraction with indiscernible DSD because of the simultaneous abdominal straining.”

Dr. Thüroff concluded that “the important message of the paper by Peters et al is that the functional results of lumbar to sacral nerve rerouting in spina bifida, in their experience, are less favorable in terms of achieving voluntary micturition and urinary continence in children with spina bifida compared with the excellent reports of Xiao… the clinical results of Peters et al are expected based on the theoretical considerations noted.”

 

Update: more comments from peer expets:

http://f1000.com/4390959

Re: Outcomes of lumbar to sacral nerve rerouting for spina bifida.
Peters KM, Girdler B, Turzewski C, Trock G, Feber K, Nantau W, Bush B, Gonzalez J, Kass E, de Benito J, Diokno A. J Urol. 2010 Aug; 184(2):702-7

——————————–

Rosalia Misseri, Indiana University, IN, USA. F1000 Urology
29 Jul 2010 | Clinical Trial, Controversial

The concept of restoring bowel and bladder function by creation of a skin-central nervous system-bladder reflex arc via lumbar to sacral nerve rerouting is curious and has lead to much enthusiasm. This study is the report of the 1-year results of the first North American trial. I found the difference in success between a prior study by Xiao (85%) {1} and the current study interesting.

The authors reported the feasibility of nerve rerouting and their results in subjects at 1 year. No patient achieved complete urinary continence. Most patients had subjective improvement in bowel and bladder function. Despite some improvement in voiding and bowel function, most improvement appeared to be related to bowel function. Transient lower extremity weakness occurred commonly post-operatively, and one patient unfortunately suffered foot drop. The authors are to be applauded for their careful patient follow-up. They stress the importance of a rigorous research protocol and longer follow-up. Despite this innovative neurosurgical approach to neurogenic urinary and fecal incontinence, it is clear that patients undergoing this procedure must be carefully monitored and that very select centers should perform this procedure with strict research protocols in place.

References: {1} Xiao CG, Eur Urol 2006, 49:22-8 [PMID:16314037].

Competing interests: No potential interests relevant to this article were reported.

——————————–

Chris Cooper and Kathleen Kieran, University of Iowa Hospitals and Clinics, IA, USA. F1000 Urology
09 Aug 2010 | Clinical Trial, Controversial

We found this small study of a novel neurosurgical technique for the management of neurogenic bladder and bowel provocative. This paper takes the first steps towards allowing us to more accurately define clinical success rates and identify the subset of patients most likely to benefit from this intervention.

Peters et al. report their single-center experience with lumbar-to-sacral nerve rerouting for the treatment of bladder and bowel incontinence in nine patients with spina bifida. Patients were assessed for continence as well as bowel and bladder symptoms at baseline and at 12 months after surgery. Cutaneous nerve stimulation was begun three months postoperatively. All but one patient had motor weakness, two had substantial gait alterations, and one had foot drop evident early in the postoperative period; all symptoms improved by 12 months except the foot drop. Over the postoperative period, some patients did experience worsening of bladder and bowel incontinence; this was followed by increased awareness of bladder and bowel sensation and the authors postulated that this represented a period of reinnervation. Improvements in bowel function generally preceded improvements in urinary function. At one year, seven out of nine patients had a reproducible bladder reflex with cutaneous stimulation and were able to void spontaneously; their bladder compliance had also improved. Although no patient achieved complete urinary continence, 44% had bowel continence by 12 months, and renal function was stable in all patients. The authors note that the conclusions drawn by their study must be interpreted in light of the small number of patients, relatively short follow-up period, and the limitations of urodynamic studies. Interestingly, the reported success rate in this series was lower than the 87% previously reported in a series of 100 Chinese children, suggesting not only the need for further study of this novel technique but also the importance of carefully selecting patients for study participation as well as establishing a universal operational definition of clinical success.

For further reading, please see refs {1-6}.

References: {1} Xiao et al. J Urol 1990, 143:356A. {2} Xiao CG, Eur Urol 2006, 49:22-9 [PMID:16314037]. {3} Xiao and Godec, Paraplegia 1994, 32:300-7 [PMID:8058346]. {4} Xiao et al. J Urol 1999, 162:936-42 [PMID:10458412]. {5} Xiao et al. J Urol 2003, 170:1237-41 [PMID:14501733]. {6} Xiao et al. J Urol 2005, 173:2112-6 [PMID:15879861].

Competing interests: No potential interests relevant to this article were reported.

——————————–

Bradley Kropp and Blake Palmer, University of Oklahoma, OK, USA. F1000 Urology
20 Jul 2011 | Clinical Trial

I found this article interesting because of the speculation surrounding Dr Xiao’s procedure and reports of 87% sensation and continence at 12 months in spina bifida patients {1}. This is the first report of the procedure and outcomes by someone other than Dr Xiao and done outside of China.

These authors presented their 12-month outcome data on 9 spina bifida patients who underwent an L5 motor root (total in four and partial in five) transection and anastomosis to the transected S3 nerve root. This procedure was done by local neurosurgeons at William Beaumont Hospital in Michigan under the guidance and training of Dr Xiao himself. These patients all underwent thorough preoperative evaluation from a neurology and urology standpoint and were followed closely and studied extensively for the 12 months postoperatively.

They reported no intraoperative complications and a fairly well-tolerated procedure. Lower extremity weakness was expected given the L5 motor root transaction and was seen in 8/9 patients at 1 month. At 12 months, 8/9 were described as at or near baseline function except for one with persistent ipsilateral foot drop and significant worsening of their gait.

The subjective urologic and bowel function seemed to be more improved than the objective evidence to support this. The report does state frankly that the outcomes fall short of what has previously been reported by Dr Xiao as no patient achieved complete urinary continence or stopped intermittent catheterization.

From a neurourologic standpoint, the intended reflex arc was demonstrated objectively in 7/9 patients. This is an extremely important finding that shouldn’t be overlooked, seeing as previous reports falls short of in terms of the amount of clinical data provided. The fact that this procedure failed to show a ‘leap’ forward in the treatment of spina bifida patients shouldn’t mean that it does not contribute to our understanding of the neurogenic bladder in patients with spinal dysraphism and lead to more innovative thinking in terms of neuropathic bladder management.

I also think the rigorously designed study and open reporting of the results should be applauded. I agree with the authors and reviewers that this procedure and others like it should only be done in this manner with the utmost care for the patient and scientific principles applied.

References:

{1} Xiao CG, Eur Urol 2006, 49:22-8 [PMID:16314037].

Competing interests: No potential interests relevant to this article were reported.

 

http://www.spinabifidaassociation.org/site/c.liKWL7PLLrF/b.6701685/k.D5F2/Research_Articles_January_2010_to_January_2011.htm

Research Articles
January 13, 2010 to January 31, 2011

SBA’s National Resource Center is now providing summaries of research on Spina Bifida and related topics. The following topics are frequently requested by Resource Center patrons. The purpose of this list is to highlight professional literature on the subject of spina bifida and related topics.

Urology

Peters KM, Girdler B, Turzewski C, Trock G, Feber K, Nantau W, Bush B, Gonzalez J, Kass E, de BJ, Diokno A. Outcomes of lumbar to sacral nerve rerouting for spina bifida. J Urol 2010 August;184(2):702-7.

[A few years ago Dr. C G Xiao in China described a surgical procedure in which spinal nerves on one side of the body were rerouted, with the ventral lumbar (L5) nerve attached to the sacral (S2) nerve. He reported a success rate of 87%. In the current study the authors reported on the use of this procedure in 9 children who were followed for a year after surgery. The majority of the children in this study had improved bowel continence and improvement in bladder compliance. However, none achieved complete urinary continence. Most also had some weakness of the leg on the side of the surgery. This is a preliminary trial with no comparison group. However, as noted in the two editorials that followed this article, the results are thus far disappointing compared to the glowing reports from China.]

 

http://www.ncbi.nlm.nih.gov/pubmed/22037959

Gregory E. Dean and Christopher Long. Updates in the Management of the Overactive Bladder in Patients with Myelomeningocele. Curr Urol Rep (2011) 12:413–418. Published online: 25 October 2011

Abstract

… Nerve rerouting for neurogenic bladder is a novel, albeit unproven, approach, its use remaining experimental at this point.

Rerouting

Initially developed in China, bladder rerouting is a novel procedure that creates an artificial somatic–autonomic reflex arc to restore neurologic control of bladder filling and emptying in patients with spina bifida [15]. In summary, a midline approach exposes the lumbar and sacral spinal column and a limited laminectomy is performed between L4 and S2. After identification of the L5 and S3 vertebral roots, the arc is created by anastomosing the proximal end of the ventral root of L5 to the distal end of the ventral root of S3. Xiao et al. [15] reported a success rate in 87% of 110 patients at 1 year of follow-up, with nearly all patients achieving continence. Peters et al. [16] were the first group in North America to report their experience with the technique. A total of nine patients enrolled in the study, with seven patients experiencing a response in bladder pressure with dermatome stimulation (suggesting successful rerouting). All patients were able to remain off antimuscarinic therapy postoperatively, although no patients achieved complete continence. The authors also noted improved bowel function for the patient population. Nearly all participants experienced increased bladder and bowel sensation, although consistent improvement documented by urodynamic analysis was lacking [16]. Motor weakness of L5 is a complication highlighted in both studies, ranging from partial weakness (that eventually was shown to recover) to persistent full foot drop [15, 16]. While this approach promises much, no recent published studies have confirmed the degree of success reported by Xiao et al. [15]. Caution should be employed by any clinician who pursues this approach given the lack of confirming data at this point in time.

 

http://www.hindawi.com/journals/au/2012/816274/

Advances in Urology. Volume 2012 (2012), Article ID 816274
Review Article
Neurogenic Bladder

Peter T. Dorsher and Peter M. McIntosh

7.1. Lumbar to Sacral Nerve ReroutingRestoring bladder function in spina bifida by creation of a skin-central nervous system bladder reflex arc via lumbar (L5 motor) to sacral (S3) nerve rerouting has a reported success rate of 87% in 110 children in China [83]. Recently the one-year results of the first North American trial were reported, with 7/9 (87%) of spina bifida subjects having measurable increase in bladder pressure with L5 dermatomal stimulation (>10?cm H2O), most demonstrating a modest increase in bladder compliance, and all stopping antimuscarinic drugs. Two subjects were able to stop catheterization, but none achieved complete urinary continence [84]. One patient had a persistent foot drop after this surgery. These outcomes differ substantially from the Chinese experience, and the improvements in continence and bladder compliance may relate to sectioning of the S3 nerve root in the procedure. This should still be considered an experimental procedure until further prospective data on its efficacy and effects on quality of life can be determined.

 

 

Topics: Xiao Chuanguo, Nerve rerouting |

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