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Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_5256_Библиотеки_им_академика_М_И_Перельмана.pdf
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phase I/II developments include scaffold-based treatment (NeuroRegen™ scaffold)
and both autologous (fat grafting, stem cell transplantation, and platelet-rich plasma
injection) and heterologous (fecal transplantation) therapies.
NeuroRegen™ scaffold is prepared from bovine aponeurosis by removing resid-
ual muscle, connective tissue, and fat. NeuroRegen™ scaffold is then implanted
into the resection sites and aims to promote axonal growth along collagen bers and
inhibit glial scar formation after spinal cord injury. Findings reported from a previ-
ous non-randomized study in eight patients with spinal cord injury suggests that
NeuroRegen™ scaffold with human umbilical cord mesenchymal stem cells is safe
and feasible for the repair of chronic spinal cord injury. The efcacy and safety of
NeuroRegen™ in scaffold transplantation is currently being assessed in a phase I/II
trial in combination with various types of cell transplantations (bone marrow mono-
nuclear cells, mesenchymal stem cells, or neural stem cells) for spinal cord injury
repair and neurological recovery following such [21, 25]. We identied ve clinical
trials investigating the role of regenerative medicine and cellular therapy in the
treatment and management of fecal incontinence in patients with neurological dis-
orders [26–30]. Novel developments in regenerative medicine may provide sustain-
able surgical techniques that address the limitations of injectable bulking agents and
their need for repeat treatment.
Fat grafting technique using Lipogems is a reconstructive lipoplasty with micro-
fragmented autologous adipose tissue. It is believed to increase circulation, nerve
regeneration, muscle growth and tone in the urethral sphincter and muscles, leading
to a decrease in fecal incontinence with a long-lasting impact [31]. Transplantation
of autologous, puried hematopoietic stem cells (HSC) positive for CD34 and
CD133 (HSC markers) into the spinal cord, using bone marrow or leukapheresis as
sources is currently being trialed. A randomized controlled trial (50 participants)
aimed at assessing this approach, as a potential treatment option for spinal cord
injury is underway. The effect on improving sensory and motor functions, as well as
urinary and fecal incontinence is being evaluated [32].
Another therapeutic intervention under evaluation, in a single arm study with 20
participants, is platelet-rich plasma injection, a thrombocyte enriched liquid portion
of whole blood that increases cell proliferation and the formation of collagen, for
treating incontinent patients after low anterior resection for rectal cancer [33].
Finally, heterologous fecal microbial transplantation, which utilizes infusion of
intestinal microbiota from healthy donors, is also in phase I/II development (single
armed study, 15 participants). This aims to increase microbial diversity, reduce
symptom severity, and improve quality of life [31].
The Gatekeeper™ prosthetic implant and BioSphincter™ bioengineered internal
anal sphincter both aim to reduce the number of soiling episodes in passive fecal
incontinence patients [10, 27]. The Gatekeeper™ implant consists of 4–6 self-
expanding polyacrylonitrile (Hyexpan) implants which are injected into the patient’s
intersphincteric space which has shown evidence of being a safe approach to pas-
sive fecal incontinence management, while being capable of providing a sustained
N. O’Connor et al.
379
improvement in fecal incontinence symptoms [34]. In a phase I clinical trial,
BioSphincters were engineered in a laboratory from smooth muscle and differenti-
ated neural stem cells from the patient’s intestine. Once these engineered sphincters
are prepared, they are implanted into the patient’s anal sphincter where they are
designed to carry out the actions of a normally functioning internal anal sphinc-
ter [27].
We identied several devices with technological innovations and apps to maxi-
mize efcacy of exercises, pelvic oor muscle training, lifestyle and behavior
changes to improve symptoms [30, 35, 36]. One example is the pelvic oor muscle
training or exercise at home, one example currently being evaluated is the LEVA®
Pelvic Health System for treating fecal incontinence, which includes an intravaginal
device that connects to a smartphone app, offering real-time visual feedback, coach-
ing and information sharing with healthcare providers to increase pelvic oor mus-
cle performance [37]. The use of mobile phone apps is also under evaluation for
their use in diagnostic work ups, one trial reported comparison of an electronic
phone-based app stool diary compared to standard paper based in adults with fecal
incontinence and constipation [38].
16.9 Stakeholder Engagement toIdentify Unmet Need
The initial priority-setting exercise involved patients, carers, and healthcare practi-
tioners identifying areas of unmet need for future research through an online survey
and workshop. Sixty-eight people took part in the survey, with the majority from the
UK (n=32), the United States (n=8), and Australia and Canada (n=6). The results
were aligned with the horizon- scanning domains and are also displayed in Fig.16.2,
alongside results from a parallel evidence synthesis component. Participants were
then invited to a workshop to review and rank the top 20 topics of uncertainty identi-
ed by the survey. The top six topics were explored further in facilitated break-out
discussions, which were analyzed using rapid qualitative analysis techniques.
Box 16.1 summarizes the most frequently identied topic uncertainties from the
survey. Patients primarily wanted to know the treatment options that would be most
benecial to help their own fecal incontinence, but many also had a desire to under-
stand the causes or mechanisms, which may help to alleviate fecal incontinence
and its symptoms. Also, the patients emphasized the importance of support (in
addition to treatment options) to help with the psychological consequences of liv-
ing with fecal incontinence. The carers were most concerned with treatment
options particularly for children, for whom constipation was a primary concern.
They, too, emphasized the importance of support for, and awareness of, fecal
incontinence, both from healthcare practitioners and also in their daily lives.
Healthcare practitioners were understandably concerned with the management and
treatment of fecal incontinence, particularly the relative effectiveness of one treat-
ment option over another.
16 Scanning the Horizon for Patient Needs and New Technologies for Fecal…
380
Box 16.1: The 23 Most Frequently Cited Areas of Uncertainty Derived from the
Survey* (Including Areas Which Fell Outside of the Cochrane Incontinence
Scope of Work)
• Mechanisms and causes (n=31)
• Psychological support (n=24)
• Education (patients, carers, healthcare providers) (n=23)
• Drugs (general) (n=21)
• (Self) Managing condition† (n=20)
• PFMT/biofeedback/sphincter exercises (n=20)
• Bowel management (general) (n=19)
• Surgery (general) (n=19)
• Dietary management (n=15)
• Psychological/behavioral/urgency suppression techniques (n=14)
• Clinical pathway to diagnosis (n=13)
• Constipation (including in children) (n=12)
• Evidence-based practice (n=11)
• Fecal Incontinence in children (n=11)
• Pregnant/post-partum women (n=11)
• Lifestyle (n=9)
• Physiotherapy
‡
(n=9
• Prevalence (n=9)
• Electrical stimulation (n=7)
• General models of care (n=7)
• Improvements to physical environments (n=6)
• New devices
§
(intra-rectal diversion devices) (n=6)
*Categories were based on survey responses, sometimes responses were
not very detailed and broad categorizations had to be used. To reect the detail
in the responses, we chose the most precise category based on the description
in the response, for example, if respondents specically mentioned electrical
stimulation this would be the category chosen, whereas if “physiotherapy”
was mentioned with no further description then the “physiotherapy” (not oth-
erwise specied) category was used.
†Patients/carers wanted the tools to be able to self-manage the condition
on a day-to-day basis.
‡Not otherwise specied.
§Respondents wanted new devices to be invented to help divert feces non-
surgically to help with day-to-day management of the condition, for example,
an intra-rectal diversion device). PFMT, Pelvic Floor Muscle Training; SNS,
sacral nerve stimulation.
N. O’Connor et al.
381
The highest-ranking topic uncertainties were discussed further during the break-
out sessions to discuss and prioritize the unmet needs of people living with fecal
incontinence, more detailed results have previously been reported, however, the
eight most discussed cross-cutting themes to come from the breakout sessions were,
education, impact and burden of living with fecal incontinence, healthcare service
improvements, psychological support, stigma and then treatments and management,
cultural management and technology, and accessibility [2].
16.10 Summary andImplications ofResearch Findings
Our review of late-stage clinical trials provides an overview of treatment and man-
agement options for fecal incontinence since 2015. Since the work was originally
funded by Cochrane Incontinence, only treatments relevant to this population were
included, and as such, certain conditions including constipation during pregnancy,
cancer surgery, and Hirschsprung’s disease were excluded due to falling outside of
Cochrane’s remit. Early-stage or licensed treatments were not considered in this
review, and the efcacy of these treatment options was not evaluated. It is likely that
some of the treatments presented here may not advance to regulatory approval.
Our ndings revealed limited development of new pharmaceutical treatments for
fecal incontinence. However, existing drugs were being repurposed for fecal incon-
tinence management, such as linaclotide and colesevelam. This aligns with the high
cost of developing new technologies, which may deter pharmaceutical companies
from investing in fecal incontinence innovations. Stakeholder workshops conducted
as part of a broader priority-setting exercise suggested that research agendas are
often inuenced by funding sponsors and commercial potential. As a result, there
appears to be little interest in creating new, innovative products for fecal inconti-
nence, despite their potential to improve patient care in the long term. Additionally,
stakeholders expressed disappointment in the limited advancements in containment
technologies, which they felt could improve daily life but were being overshadowed
by pharmaceutical research. As noted above, we did identify one feasibility study
that was evaluating leakage performance in an absorbing incontinence product [22].
This study highlighted the growing trend of drug repurposing for fecal inconti-
nence. Given the limited number of drugs currently used to treat fecal incontinence,
it is worthwhile to explore whether existing medications like antidiarrheal agents
can reduce symptoms with minimal side effects. A discrete-choice experiment by
Nafess etal. [39] demonstrated that patients with spinal cord injury preferred treat-
ments offering even modest improvements over current options. Therefore, despite
minimal therapeutic gains, repurposed antidiarrheal drugs could still provide sig-
nicant health-related quality-of-life benets for patients. Other medications, not
originally intended for fecal incontinence, have also been investigated, such as dari-
fenacin, which was tested in women with double incontinence. Although this study
lacked a control group, it may warrant further exploration in a randomized con-
trolled trial [40]. There is also evidence is more recent clinical trials of a shift toward
16 Scanning the Horizon for Patient Needs and New Technologies for Fecal…
382
technology-driven self-monitoring, typically using app-based approaches which
was identied as an area of unmet need by our stakeholders in 2020 [2].
Fecal incontinence is often a symptom of underlying conditions, so its treatment
must be tailored to each patient’s unique circumstances. A range of pharmaceutical
and management options exists and improved access to skilled healthcare profes-
sionals could help more patients experience symptom relief. Increasing education
for healthcare providers and promoting best practices in treating fecal incontinence
would support this effort.
Our horizon scanning approach was comprehensive, covering 11 clinical trial
registries worldwide. However, some trials may have been missed if their registra-
tion records were not accessible through ScanMedicine. Additionally, several trial
records had not been recently updated, complicating efforts to determine their cur-
rent status or whether they had been discontinued prematurely. Our process focused
on trials of products subject to regulatory review for efcacy and safety, which may
have excluded certain medical devices from our search.
16.11 Conclusion
In conclusion, the horizon scan identied promising developments, including repur-
posed drugs, new devices, surgical techniques, and an increase in app-based self-
monitoring for managing/treating fecal incontinence. While drug repurposing
strategies offer hope for incremental improvements, signicant advancements are
likely to come from traditional drug discovery [41]. Raising awareness about fecal
incontinence and increasing proactive screening could lead to more diagnowwes,
potentially spurring innovation. The stigma surrounding fecal incontinence, while
concerning, has prompted some focus on quality-of-life improvements, though
future trials must also consider the psychological support needed alongside medical
treatments. Stakeholder feedback reinforced the importance of addressing this gap.
In the short to medium term, providing psychological support and tools for patients
to cope with fecal incontinence is crucial, as is prioritizing technological advance-
ments to improve symptom management. Only through innovation, combined with
enhanced patient, caregiver, and healthcare provider education, can meaningful
benets for those living with fecal incontinence be realized (Box 16.2).
Box 16.2: Supplementary Material
Search strategy
Updated search of ScanMedicine—conducted on May 6, 2024
An update of the original search run in ScanMedicine (https://scanmedi-
cine.com/) in August 2020 for the original fecal incontinence prioritization
project was conducted on May 6, 2024.
The search covered all 11 of the available registries in ScanMedicine:
Brazil (http://www.ensaiosclinicos), Peru (https://ensayosclinicos- rep), USA
(continued)
N. O’Connor et al.
383
Acknowledgments We would like to thank Alex Inskip, Research Assistant—Information
Specialist, NIHR IO, Newcastle University, UK, for translating this strategy for use in
ScanMedicine.
Disclaimer The views expressed are those of the authors and not necessarily those of the National
Institute for Health and Care Research (NIHR) or the Department of Health and Social Care.
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