CLINICAL OBSTETRICS AND GYNECOLOGY
Volume 48, Number 3, 737–742
Future Considerations
in Pelvic
Reconstructive Surgery
JEFFREY L. CORNELLA, MD
Department of Obstetrics and Gynecology, Mayo Clinic College of
Medicine, Mayo Clinic Scottsdale, Scottsdale, Arizona
Introduction
Management of patients with pelvic floor
dysfunction has become an increasingly
important facet of women’s health care in
the United States. Demographic shifts in
population are increasing the prevalence of
urinary and fecal incontinence, pelvic organ
prolapse, and pelvic muscle dysfunction.
The cost of urinary incontinence manage-
ment is estimated at greater than $26 billion
per year in the American population.1 Luber
et al have estimated that the growth in
demand for services related to female pelvic
floor dysfunction will increase by 45% over
the next 30 years.2 It is estimated that 1 in 9
American women will require pelvic organ
prolapse surgery and that up to 13% may
require an additional procedure resulting
from recurrent relaxation.3 These factors
underscore the need for progress in the pre-
Correspondence: Jeffrey L. Cornella, MD, Associate Pro-
fessor, Department of Obstetrics and Gynecology, Mayo
Clinic College of Medicine, Mayo Clinic Scottsdale,
13400 E Shea Blvd., Scottsdale, AZ 85259-5499. E-mail:
Cornella.Jeffrey@mayo.edu
CLINICAL OBSTETRICS AND GYNECOLOGY / VOLUME 48
Ó 2005, Lippincott Williams & Wilkins
vention of pelvic floor dysfunction and its
surgical management. Basic science investi-
gation in the area of pelvic floor medicine is
increasing and promises to provide needed
advances in this important area of health care.
Basic science research in muscle, nerve, con-
nective tissue will translate to gains in long-
term surgical success. This chapter discusses
current basic science research and surgical
trends that will benefit the subspecialty of
pelvic reconstructive surgery.
Muscle Regeneration
Although the human urethra appears to have
the ability for repair and regeneration of
muscle cells, there appears to be an impor-
tant loss in the number of striated muscle
cells with aging.4 Strasser et al has demon-
strated documented loss of human rhabdos-
phincter cells by apoptosis.5 This study de-
monstrated that 87.6% of the sphincter in the
neonate consisted of striated muscle cells.
The percentage of striated cells decreased
with age with as little as 34.2% noted in 1
senescent sample. This programmed cell
/ NUMBER 3 / SEPTEMBER 2005
737
738 Cornella
death with aging may have a significant affect
on continence.
A possible future management consider-
ation to reverse muscle loss would be the
injection of muscle precursor cells into the
sphincter with the goal of sphincter restora-
tion. A murine model of sphincter injury and
restoration has been described by Yiou.6
Muscle precursor cells were harvested from
limb skeletal muscle and immediately
injected into injured sphincters. The muscle
precursor cells (MPCs) accelerated sphinc-
ter muscle repair and formed new myofibers.
In a separate study, Yiou injected MPC 37
days after sphincter injury to assess repair
and the formation of motor units.7 The re-
generated myotubes carried acetylcholine
receptors and were considered to form ana-
tomic motor units. Urodynamic studies con-
firmed the restoration of 41% sphincter
function 1 month after MPC injection.
Yokoyama has demonstrated persistence of
autologous muscle-derived cells 30 days
after injection into female Sprague-Dawley
rats.8 Muscle-derived stem cells have also
been injected into the rat model with resul-
tant increased leak point pressures.9 Autolo-
gous muscle stem cells may be used for peri-
urethral injection in the future, replacing
current agents with living cells that respond
to pharmacologic agents and nerve stimuli.
Muscle-derived stem cells seeded into acel-
lular scaffolds have been shown to develop
calcium-dependent contractile activity mod-
ulated by nicotinic receptors.10 This would
suggest that matrices or allograft materials
could be created that have contractile func-
tion and a fashioned shape to facilitate
placement at surgery.
Nerve Regeneration
Hale et al compared women with and with-
out urinary stress incontinence who under-
went urethral sphincter electromyography
(EMG) and biopsy.11 The biopsy specimens
were processed for light and electron micro-
scopy. Women with stress incontinence were
noted to differ from continent women in
skeletal muscle volume, amount of fibrosis,
and EMG parameters, supporting a neuro-
genic contribution to stress urinary inconti-
nence. Nerve regeneration may also be a
contributor in the management of pelvic
floor disorders. Biers et al assessed the po-
tential role of nerve regeneration in restoring
urinary tract function.12 Transplantation of
olfactory-ensheathing cells in conjunction
with a biodegradable nerve conduit has been
shown to restore urinary tract function after
spinal cord injury.13
Connective Tissue
Falconer et al conducted biochemical and
morphologic analyses comparing paraure-
thral connective tissue in continent and
incontinent women of childbearing age.14
Significant differences were noted with
collagen concentration 30% higher and col-
lagen fibril diameter 30% larger in the in-
continent group. There was also a lower
proteoglycan/collagen ratio in the inconti-
nent patients. In a separate study, the author
noted paraurethral connective tissue changes
in postmenopausal patients.15 The collagen
concentration was almost doubled in post-
menopausal patients compared with preme-
nopausal control subjects. Higher crosslinking
of collagen fibrils was noted with no change
in the amount of proteoglycans. Subsequent
estrogen replacement resulted in decreased
collagen concentration, decreased crosslink-
ing of collagen, and reversal of the proteo-
glycan/collagen ratio to a premenopausal
level. Tissue engineering may allow colla-
gen regeneration in an organized manner.16
Tissue Engineering
The field of regenerative medicine strives to
relieve the suffering of patients from the
consequences of disease and injury by re-
storing the form and function of damaged
tissues and organs.17 Scientists in the field
of tissue engineering use cell transplanta-
tion, material science, and engineering to
create biologic substitutes that will restore
 Future Considerations in Pelvic Reconstructive Surgery 739

function. The most preferred method for
obtaining cells for tissue engineering is har-
vesting autologous cells and increasing their
number by expansion in culture. The
expanded cells are then reimplanted into
the same host.18 The cells can be expanded
on a 3-dimensional absorbable matrix that
aids in cells reproduction and formation of
subsequent shape. Tubularized collagen
matrices seeded with autologous cells have
been used successfully for total penile ure-
thra replacement (Fig. 1). Vaginal epithelial
and smooth muscle cells have been cultured
and expanded in vitro. Cell-seeded polymer
scaffolds form vascularized vaginal tissue
in vivo (rabbit) that has phenotypic and
functional properties similar to those of nor-
mal vaginal tissues.19 Three-layered tissue
structures of urethra and bladder have been
produced.
Nuclear or therapeutic cloning can also
create materials. Nuclear cloning involves
the introduction of a nucleus from a donor
cell into an enucleated oocyte to generate
an embryo with genetic makeup identical
to the donor.20 Embryonic stem cells lines
are produced and have the potential to be-
come almost any type of cell (Fig. 2). Tissue
engineering for creation of materials used in
pelvic reconstructive surgery will be one of
the most salient future advances in pelvic
floor medicine.

FIGURE 1. Tissue engineering of the urethra using a collagen matrix.

A, Representative case of a patient with a bulbar stricture. B, Urethral repair.
Strictured tissue is excised, preserving the urethral plate on the left side, and
matrix is anastomosed to the urethral plate in an onlay fashion on the right.
C, Urethrogram 6 months after repair. D, Cystoscopic view of the urethra
before surgery on the left side and 4 months after repair on the right side.
Reproduced with permission from KOH. J Am Soc Nephrol. 2004;15:
1113–1125.
740 Cornella
FIGURE 2. Strategy for therapeutic cloning
and tissue engineering. Reproduced with per-
mission from KOH. J Am Soc Nephrol. 2004;
15:1113–1125.
Pharmacogenomics
Genetic differences in metabolism, genetic
polymorphisms, and drug receptors affect
an individual’s response to a given medication.
Pharmacogenomics uses functional genomics
and high-throughput screening methods to
elucidate the constellation of genes that
determine the efficacy and toxicity of a
given medication.21
The overall effects of medications are
determined by the relationship of several
genes encoding proteins involved in multiple
pathways of metabolism. Genetic polymor-
phisms in drug-metabolizing enzymes and
receptors translate into inherited differences
in drug effects. These differences have been
difficult to evaluate in clinical studies to
date. In the near future, additional biomed-
ical research will additionally define the
molecular mechanisms of pharmacologic
effects and gene polymorphisms that deter-
mine drug response. The Human Genome
Project will facilitate the identification of
polymorphisms in drug targets and allow
medications to be used to prevent disease
in individuals who are genetically predis-
posed to them.22 Future drug trials will need
to incorporate comprehensive pharmacoge-
nomic studies coupled with experimental
models that reinforce genotype–phenotype
clinical associations. Pharmacogenomics
will make it possible to select the medica-
tions and doses that are optimal for each per-
son with improved efficacy and decreased
toxicity.23
Neuromodulation
The U.S. Food and Drug Administration has
approved sacral neuromodulation for the treat-
ment of urinary urge incontinence, urgency–
frequency syndrome, and urinary retention.
It has also been used for patients with pelvic
pain, fecal incontinence, and multiple
sclerosis.24 Sacral neuromodulation acts by
the afferent pathway at the cortical site
level.25 Several studies have shown efficacy
of sacral neuromodulation in refractory
urge-incontinent patients.26,27 Long-term
treatment of patients with Fowler’s syn-
drome shows a 77% spontaneous voiding
rate over a 6-year period.28 Future consider-
ations for sacral neuromodulation include
direct stimulation of the pudendal nerve and
expansion of clinical indications to include
pelvic pain, bowel syndromes, and fecal
incontinence.
Robotics
The da Vinci robotic system allows 7
degrees of freedom by adding wrist flexibility
to laparoscopic instrument tips. This opti-
mizes needle placement during intracorporeal
suturing. The robotic tower has a camera
arm and 2 to 3 instrument arms. The surgeon’s
console provides a magnified 3-dimensional
image of the surgical field.29 Future robotic
systems will have improved instrumentation
and a 3-dimensional viewing system for the
assistant. Real-time imaging systems will be
integrated to provide additional information
during dissection.
Prologue
Basic science research in pelvic floor dys-
function is increasing and is required to
 Future Considerations in Pelvic Reconstructive Surgery
meet the needs created by increased num-
bers of patients with pelvic organ prolapse,
incontinence, and other pelvic floor condi-
tions. Surgical innovation is increasing in
the direction of minimally invasive surgery.
Future surgeons will use materials that have
increased benefits to patients as a result of
their sophistication and specialization through
tissue engineering. Future physicians will
complement their management with phar-
macologic agents specific to the patient’s
genetic makeup and metabolism.
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