Mechanical gastric outlet obstruction (GOO) is obstruction of antropyloric, bulbar,
or post-bulbar segments impeding gastric emptying. Both malignant and nonmalignant
etiologies contribute significantly to the disease burden. While surgery has been
the primary modality of management, advent of through-the-scope endoscopic balloon
dilatation (EBD) marked a new era, particularly in the management of benign GOO with
low complication rates and better patient outcomes.
Use of EBD was first reported by Benjamin et al,[1] subsequently multiple studies concreted its place as a first-line therapeutic option
for benign GOO. Adequate dilatation (endpoint of 15 mm) leads to a clinical response
in approximately 75% of the patients.[2] EBD have been described in almost all causes of benign GOO with good clinical outcomes.
In a single-center study by Rana et al,[3] EBD was successful in 84% patients, while a similar retrospective analysis with
large sample size and long-term follow-up by Kochhar et al,[4] showed EBD had a clinical success of 97.3% with no recurrence during a 98-month
follow-up period. In both the studies, the number of endoscopic sessions required
was less in cases of peptic GOO when compared with other etiologies of GOO, particularly
caustic.
This prompts the question why are caustic strictures more difficult to manage then
peptic strictures? It is known that ingestion of a corrosive, both acid and alkali,
causes direct tissue damage on contact. This leads to pylorospasm and prolonged contact
time ultimately leading to more damage to gastric mucosa.[5] This may lead to a more fibrotic response of the underlying tissue, which in turn
leads to a tighter stricture which is less responsive to EBD. Also, fibrosis from
caustic ingestion is deeper then peptic strictures, resulting in more fibrosis and
poorer response to dilatation.
Adjunctive therapies in the form of intralesional steroids, endoscopic incision, and
placement of self-expanding metal stents (SEMS) have been tried for difficult-to-treat
strictures with variable efficacy.[6] While both endoscopic incision and SEMS alleviate the symptoms by widening the luminal
diameter, intralesional steroids block the cross-linking of collagen, prevent scar
contracture, and inhibit stricture formation leading to better endoscopic response.[6]
Sareen et al[7] have conducted a prospective randomized controlled trial in India on endoscopic
management of GOO due to nonsteroidal anti-inflammatory drugs (NSAIDs), caustic, peptic,
and opioids. Novelty of the study is the use of misoprostol as an adjunctive therapy,
which has never been investigated previously. Patients were randomized to receive
2 weeks of misoprostol with proton-pump inhibitor (PPI) and EBD in one arm and PPI
alone in the control arm. Procedural success was defined as achieving 15 mm dilatation
and clinical success as symptomatic resolution till study duration. Misoprostol was
administered via either oral or rectal route. Within the study, there were no procedure-related
adverse events in the groups and both clinical and procedural success was significantly
better in the misoprostol group.
In light of this, an important question arises, does misoprostol changes the behavior
and underlying pathophysiology of gastric mucosa and makes it more responsive to dilatation?
The pathophysiology of stricture development depends on the underlying etiology but
basic pathological changes include persistent damage to mucosal lining leading to
chronic inflammatory changes with subsequent development of intramural fibrosis and
scarring, leading to luminal constriction. In peptic stricture, these pathophysiological
changes occur due to exposure of gastric mucosa to excessive acid.[8] NSAID causes mucosal injury by generation of free radicals via COX-1 inhibition
causing mitochondrial damage.[9] The authors proposed mechanism of stricture formation in opioid users is due to
a combination of delayed gastric emptying causing acid stasis leading to persistent
mucosal injury. Concomitant NSAID abuse may also contribute to stricture formation
in this subgroup of patients. Misoprostol is a synthetic prostaglandin E1 analog that
inhibits basal and nocturnal gastric acid secretion by the parietal cells in the stomach.
It also helps in the secretion of mucin and bicarbonate, enhances mucosal blood flow,
and preserves the mucosa's ability to regenerate new cells.[10]
Sareen et al[7] showed a procedural success rate of 90% in the misoprostol arm, which is significantly
higher than previously published data. The mean number of dilatations required was
3.85 ± 0.8. These results are encouraging as repeated EBD sessions pose a significant
challenge in terms of procedural complications such as pain, bleeding, and perforation.
This also significantly decreases the burden on health care resources and caregiver
burden.
Eradication of Helicobacter
pylori leads to better outcome in peptic stricture.[11] This suggests that there is an inflammatory component similar to inflammatory bowel
disease, which should be dealt in a timely manner and may lead to decrease in the
fibrosis burden leading to better EBD success. Current management options including
EBD, incision, and SEMS for benign GOO address the fibrotic component of a stricture.
Intralesional steroids have been tried for refractory strictures; however, there is
no significant difference in terms of the number of dilatations required for clinical
success or number of patients achieving procedural or clinical success. Misoprostol
in this regard have opened up avenues for further research as it addresses the underlying
inflammatory component and has a different mechanism of action then steroids.
There is no data from Sareen et al[7] demonstrating the difference in outcomes in terms of individual etiologies. It is
important as caustic strictures are more common in countries such as India and endoscopic
management is more difficult than peptic strictures. The sample size is too small
for any meaningful conclusion. There remain many other unanswered questions from the
study, such as timing and optimal dosage of misoprostol and its route of administration.
Studies have shown the role of PPI during the maintenance phase during EBD. Duration
of misoprostol given was too short to impact the number of EBD sessions as they may
go on for weeks to months, whether only 2 weeks of misoprostol therapy would impact
long duration of therapy is up to debate. Even though PPI was given to both arms,
additional contribution of misoprostol in addition to PPI needs further confirmation.
Further, whether misoprostol can be given for long term is one of the important questions
that needs discussion considering its side effect profile. This study was done in
patients with new-onset strictures and as such there was a presumptive inflammatory
component for misoprostol to act on. All patients were either well controlled or abstinent
in terms of underlying etiology, thereby limiting its application to real-world scenario.
Other factors requiring more investigation is the role of misoprostol in refractory
strictures where the disease burden is primarily fibrotic and concurrent use with
triamcinolone injections, radial incisions, and SEMS. Multicentric studies with large
sample size would still be required to establish its definitive role in GOO management.
In conclusion, EBD is successful in ameliorating symptoms in benign GOO and should
be the first-line management for benign strictures as it has relatively low rates
of adverse events, addition of adjunctive therapies and addressing the underlying
etiology may improve the efficacy of EBD, thereby avoiding surgery.
We believe that a slow and safe approach should be used for EBD for benign GOOs. Assessment
of initial luminal diameter should guide the endoscopist for the anticipated number
of attempts that may be required before considering treatment failure. Underlying
etiology should also be kept in mind as the number of sessions required for a caustic
stricture may be more than a peptic stricture. If the patient is clinically well and
has adequate nutritional intake, persistence may be your best friend to avoid invasive
surgery. Our suggested approach for management of benign GOOs is as follows: First
and the most important thing is to maintain nutritional status. It can be achieved
with the insertion of a nasojejunal tube or if not possible, a feeding jejunostomy.
Second, ascertain whether the obstruction is extraluminal or intraluminal. Patients
with extraluminal obstruction/extrinsic compression should be considered for early
surgery. A detailed drug history for the use of NSAIDs and opioids should be taken.
H. pylori should be eradicated and patient should be given long-term PPI. Patient should be
on a 1 to 4 weekly endoscopic dilatation schedule till procedural/clinical success
is achieved. Patient should be followed up clinically and if case of recurrence of
symptoms, repeat dilatations may be required. Use of adjunctive therapies such as
intralesional steroids and SEMS placement should be considered in case of refractory
stricture.
