Pediatr Surg Int

DOI 10.1007/s00383-017-4196-y

REVIEW ARTICLE

Pyloric stenosis: an enigma more than a century after the first

successful treatment
Yousef El-Gohary1 · Abdelhafeez Abdelhafeez1 · Elizabeth Paton2 ·
Ankush Gosain1,2 · Andrew J. Murphy1,2

Accepted: 28 September 2017

© Springer-Verlag GmbH Germany 2017

Abstract Despite hypertrophic pyloric stenosis (HPS)

being one of the most frequently treated pediatric surgical
conditions, its etiology remains incompletely understood.
We review the diagnosis and treatment of this condition
with an emphasis on the evolution of surgical techniques
that led to laparoscopic pyloromyotomy, the most frequently
performed technique for HPS today. In addition, we review
key developments in the understanding of HPS etiology and
treatment, including the postulated etiology of work-induced
hypertrophy of the pylorus, its association with prokinetic
macrolide antibiotics, and the emerging role of atropine sulfate as a medical
treatment for HPS or a rescue treatment for
incomplete myotomy.
Keywords Pyloric stenosis · Pyloromyotomy ·
Laparoscopic pyloromyotomy · Macrolide

Introduction
Hypertrophic pyloric stenosis (HPS) is considered one of the
hallmark pediatric surgical diseases. It is the most common
surgical condition causing nonbilious emesis in infancy, and
Electronic supplementary material The online version of this
article (doi:10.1007/s00383-017-4196-y) contains supplementary
material, which is available to authorized users.
* Andrew J. Murphy
[email protected]
1

Department of Surgery, St. Jude Children’s Research

Hospital, 262 Danny Thomas Pl, Memphis, TN 38105, USA

Division of Pediatric Surgery, Department of Surgery,

University of Tennessee Health Sciences Center, Memphis,
TN 38105, USA

pyloromyotomy has remained the treatment of choice ever

since its description more than a century ago [1]. HPS is a
condition that typically manifests between 2 and 12 weeks of
age where the pyloric sphincter becomes abnormally thick,
resulting in gastric outlet obstruction. The classic presentation is an infant more
than two weeks old with postprandial
projectile vomiting who typically becomes hungry afterward. The incidence of HPS is
2–4 per 1000 live births with
geographical variation [2]. It is commonly seen in temperate countries, but rarely
seen in the African population near
the equator, suggesting an environmental contribution to the
etiology [2]. This report will review the historical aspects of
pyloric stenosis followed by a brief overview of its epidemiology, current
treatment and possible etiologies.

History
Hypertrophic pyloric stenosis was first documented by
Harald Hirschsprung, a Danish Pediatrician, in 1888 in
two post-mortem cases [3]. Treatment of pyloric stenosis
in the late nineteenth and early twentieth centuries broadly
entailed three types of surgical interventions: dilatation of
the pylorus, pyloroplasty, and gastroenterostomy [4]. Dilatation of the pyloric
orifice was first described by Professor Loreta, of Bologna, Italy, in 1882 on
adult patients [5].
This was later adopted in pediatric patients with the pyloric
sphincter forcibly dilated using either one or two fingers,
after gaining access to the distal stomach through an incision, or using a
mechanical Hegar dilator [4] (Fig. 1). However, “Loreta’s operation” was later
abandoned due to the
unsatisfactory results with high recurrences and fatal peritonitis due to pyloric
rupture. Dr. Clinton Thomas Dent, an
English surgeon, later performed the first successful pyloroplasty 1902, which
involved incising the pylorus muscle

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Pediatr Surg Int

Fig. 1 Pyloric dilatation. a Orientation of the gastrostomy. b Coronal section

through the stomach depicts the hypertrophied pyloric muscle. c
Hegar dilator inserted through gastrostomy site to forcibly dilate the pyloric
muscle

longitudinally, leaving the mucosa intact and suturing the

muscularis transversely [4] (Fig. 2). This invariably did not
lead to satisfactory results because it did not durably disrupt
the pyloric ring and relieve the obstruction. Last, gastroenterostomy, a procedure
that involves the surgical creation
of a connection between the stomach and the jejunum was
employed to bypass the gastric outlet obstruction; however,
there was an unacceptably high mortality rate associated
with this procedure (Fig. 3). It was reportedly first performed
by Dr. W. Abel [6].
In 1910, Sir Harold Jalland Stiles, a British surgeon,
performed the first pyloromyotomy [7]. However, the procedure came to be known from
the German surgeon, Dr.
Conrad Ramstedt, who in 1911 operated on the first case
of pyloric stenosis that he encountered [1]. He proceeded
with the intent of performing a pyloroplasty. After incising
the pylorus muscle longitudinally, he attempted to close the

defect transversely, however, the sutures tore out through

the muscle and he instead, decided to cover the defect with
an omental patch. This omental patching was done 26 years
before Roscoe Reid Graham of Toronto published his 51
cases of perforated peptic ulcers successfully treated with an
omental ‘Graham’s patch’ [8]. The patient made a successful recovery. Ramstedt
performed another pyloromyotomy
a year later, only this time by incising the pylorus muscle
longitudinally without covering the mucosal bulge with an
omental patch. This operation, now known as Ramstedt’s
pyloromyotomy, has remained unchanged since 1912 [4].
Before Ramstedt’s operation, most infants with pyloric
stenosis died in an emaciated state. While the approach to
achieve a Ramstedt pyloromyotomy has evolved over the
years and is currently most frequently done laparoscopically,
which was first reported in the literature in 1991 [9], the
pyloromyotomy itself has remained unchanged.

Fig. 2 Technique of pyloroplasty. a Longitudinal incision over the pylorus to

split the muscle. b Stay sutures placed superiorly and inferiorly to
apply traction to facilitate transverse closure. c End result of the pyloroplasty
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Pediatr Surg Int

from left to right (Video). The cardinal biochemical profile

in these patients is a hypokalemic, hypochloremic metabolic
alkalosis. Jaundice develops in about 2% of patients secondary to defective hepatic
glucuronyl transferase activity
associated with starvation, which is corrected post-surgery
[14, 15].

Diagnosis

Fig. 3 Gastrojejunostomy to bypass the hypertrophied pyloric

sphincter

Epidemiology
The incidence of HPS is 2–4 per 1000 live births with geographical variation [2].
It is rare or absent in the developing
world and in sub-Saharan Africa, thus it is considered as a
“Western disease” [10, 11]. This strongly suggests an environmental factor. It has
a strongly male predilection, occurring often in first-born males, with a male to
female ratio
6:1 and the median age for presentation is 40 days old [12].
HPS is more common in Whites than Asians, Hispanics or
Blacks. The incidence in Whites is 2.4 per 1000 live births,
1.8 in Hispanics, 0.7 in Blacks, and 0.6 in Asians [13].

Clinical presentation
Classically, patients with pyloric stenosis present with
postprandial, projectile, nonbilious emesis and are typically
hungry after vomiting. This must be differentiated from
the more common cause of vomiting in infancy, gastroesophageal reflux (GER), which
is a physiologic self-limiting
condition that usually resolves by 6 to 12 months of age.
Patients with GER typically regurgitate or “spit up” their
feeds. Significant delay in diagnosing HPS can lead to protracted vomiting which
can eventually lead to blood-tinged
emesis from gastritis. In the past, before the advent of ultrasound, patients often
became so emaciated that the pyloric
‘olive’, a term which describes how the palpable hypertrophied pylorus feels on
physical examination, became visible
on the abdominal wall along with visible gastric peristalsis

The diagnosis of HPS can be established with a good history

and physical examination. It is important when performing physical examination,
that the infant is relaxed and distracted. This can be established with the patient
either breast
feeding in the mother’s arms or while soothing the child with
sucrose solution [16]. Once adequately relaxed, one will be
able to palpate the epigastric hypertrophied pyloric muscle
which has a 99% positive predictive value [17]. Over the past
several decades, there has been a noticeable decline in the art
of performing a skilled clinical examination [18, 19]. Currently, there is a strong
reliance on ultrasound to confirm this
diagnosis, which has a 99.5% sensitivity and 100% specificity [20]. This has
resulted in the decline in the palpation
of the pyloric “olive”, due to presumed earlier presentation
[21]. The ultrasonographic criteria for diagnosing pyloric
stenosis is a pyloric muscle thickness greater than 3 mm and
a pyloric canal length of at least 15 mm [22].
Pre-operative and operative management
Pyloric stenosis is a medical emergency, but not a surgical
emergency and should only undergo operative intervention
once the patient is adequately resuscitated. The classic electrolyte abnormality
seen is a hypokalemic, hypochloremic
metabolic alkalosis as a result of protracted vomiting. Thus,
the aim of resuscitation is to correct these severe electrolyte
derangements. The body tries to physiologically compensate
for the loss of potassium and chloride ions from the gastric
emesis by attempting to conserve potassium at the expense
of hydrogen ions in the kidney, thus leading to paradoxical aciduria, exacerbating
alkalosis even more. The body
attempts to maintain normal pH by excreting excess H
CO3,
but is impaired by chloride depletion. Instead, H
CO3 is
reabsorbed to maintain electrochemical neutrality resulting
in metabolic alkalosis [23]. Baseline maintenance fluid is
calculated at 4 mLs/kg/h for the first 10-kg weight with the
intravenous fluid replacement therapy usually consisting of
5% dextrose in 0.45% saline at 1.5 times maintenance rate.
10 to 20 mEq/L of potassium chloride can be added to the
fluids. At the time of presentation, most patients require one
or more 20-mL/kg normal saline resuscitation boluses. The
electrolyte goal needed to be achieved to be considered safe

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Pediatr Surg Int

for anesthesia is serum bicarbonate less than 28 mEq/dL,

serum potassium more than 3.5 mEq/dL and serum chloride
greater than 100 mEq/dL [20]. It is vital that the metabolic
alkalosis is corrected prior to surgery because it can potentially affect the
respiratory drive, thus leading to difficulties
with extubation at the end of surgery [24].
The routine use of a nasogastric tube (NGT) preoperatively has been debated and is
mostly based on surgeon and/
or institution preference. A recent prospective, randomized
controlled pilot study on the use of a NGT preoperatively
found no effect on postoperative emesis or length of hospital
stay, concluding its use as unnecessary [25].
The surgical approach for pyloric stenosis varies; however, all current techniques
follow the same principle of
extramucosal longitudinal splitting of the pylorus muscle,
first introduced by Ramstedt in 1912 [1]. An adequate pyloromyotomy entails an
incision extending from the vein of
Mayo at the duodenal end to the circular fibers of the stomach proximally. Once the
mucosal bulge is seen with both
edges of the pylorus muscle moving freely either side, an air
leak test can be performed by asking the anesthesiologist to
insufflate air via the NGT into the stomach while dripping
saline on the mucosa.
The three surgical approaches used today are the right
upper abdominal transverse muscle-splitting incision, circumbilical approach
introduced by Tan and Bianchi in 1986
and lastly the laparoscopic approach [12]. Various studies
have compared laparoscopic to open pyloromyotomy, but
both techniques have broadly acceptable similar outcomes
[23]. People who advocate for laparoscopic approach support it because of a shorter
time needed (2.27 h) to achieve
full enteral feeding and an earlier home discharge [26, 27].
The downside to laparoscopic approach is a very small

increased risk of incomplete pyloromyotomy and mucosal

perforation compared to the open approach (Fig. 4) [23, 28].

Postoperative feeding
The optimum feeding regimen is yet to be determined with
feeding strategies varying widely among different institutions. In the past, it was
believed that fasting up to 24 h
postoperatively would decrease the number of emesis based
on early gastric motility studies demonstrating normal gastric peristalsis
returning 24 h after surgery [29, 30]. However, that dogma has changed recently
with most centers
instituting ad libitum postoperative feeding as the enteral
feeding of choice [31]. A recent meta-analysis demonstrated
that ad libitum feeding decreased the length of stay and
decreased time to achieve full enteral feeding when compared to a structured
feeding regimen [31]. The variation in
feeding protocol is based on a surgeon’s preference and the
fear for the development of postoperative emesis. Regardless of the postoperative
feeding regimen chosen, postoperative emesis will occur [23, 31–33]. One of the
important
aspects of the postoperative managements of HPS patients
is parental education regarding the self-limiting nature of
postoperative vomiting.
Intraoperative and perioperative complications
The key intraoperative complications associated with
pyloromyotomy are mucosal perforation and incomplete
myotomy. Mucosal perforation most commonly occurs
at the duodenal end of the pyloric incision because the

Fig. 4 Laparoscopic pyloromyotomy with mucosal bulge seen indicating adequate

myotomy

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mucosal lining balloons out quite rapidly and the serosal surface of the pylorus
substantially thins as it transitions to the duodenal bulb. Intraoperative
recognition of
mucosal perforation is critical, as unrecognized perforation can lead to
postoperative peritonitis, sepsis, and
death. Limited perforation can be repaired by simple
suturing, while more extensive perforations should be
repaired by completely closing the pyloromyotomy, rotating the pylorus ninety
degrees, and repeating the pyloromyotomy at this alternate location. Incomplete
pyloromyotomy is most often caused by insufficient disruption
of the muscular fibers on the gastric end of the pyloric
incision. Incomplete pyloromyotomy will cause persistent
vomiting postoperatively and should be considered when
these symptoms persist beyond one week. The diagnosis (or exclusion) of incomplete
myotomy is most readily
made by an upper gastrointestinal study performed when
postoperative vomiting persists for more than seven days
postoperatively [28]. A study suspicious of incomplete
myotomy will reveal delayed gastric emptying of contrast
and a “string sign” as contrast transits the persistently
narrowed pylorus [34]. As mentioned above, vomiting
may persist postoperatively for up to one week despite
adequate pyloromyotomy due to postoperative pyloric
edema or gastric atony due to chronic obstruction [35].

Non-operative management
The only accepted non-operative management for the
treatment of HPS is the use of atropine sulfate. This medical management is usually
reserved for patients who are
deemed unfit to undergo general anesthesia due to severe
medical co-morbidities. Atropine is a parasympatholytic,
due its competitive, reversible antagonistic binding to the
muscarinic acetylcholine receptors. It inhibits peristalsis
and therefore reduces muscular spasms that are thought
to lead to muscular hypertrophy of HPS [36]. It is also a
very strong inhibitor of meal-induced gastric acid secretion [37]. This presumably
will mitigate the acidic environment and thus prevent pyloric sphincter
contraction. It
has also been used successfully to treat incomplete pyloromyotomy as a ‘rescue
therapy’ [34]. Takeuchi et al. [36]
revealed in their series of 188 patients treated initially
with atropine, (intravenous form, n = 80; oral form, n = 8),
they had an overall success rate of 78.9% (142/180). The
reported median number of days needed for successful
medical treatment is between 12 and 14 days [36] with
most recommending intravenous dose of 0.06 mg/kg/day.

Etiology
The exact cause of the postnatal pyloric muscle thickening
characteristic of HPS is unclear, but it is mostly likely multifactorial. Duodenal
exposure to acid is known to be a potent
stimulus of pyloric sphincter contraction. Furthermore, high
levels of gastrin have been documented after birth in some
patients with pyloric stenosis. Thus, the gastrin theory postulates that the high
gastrin levels will promote hyperacidity,
which stimulates the cycle of pyloric sphincter contraction
and results in muscle hypertrophy [38]. The acid hypersecretion phenomenon has been
reported by Heine et al. [39], who
documented higher histamine-induced gastric acid secretion
in infants with pyloric stenosis before and one week after
pyloromyotomy. In addition, animal studies have induced
pyloric stenosis in newborn dogs after the administration of
maternal pentagastrin shortly before birth [40]. The hypothesis of work-induced
hypertrophy of the pylorus muscle is
further supported by the association between pyloric stenosis and the use of
erythromycin and azithromycin. Both
macrolide antibiotics are known to act as prokinetic agents
due to their stimulation of motilin receptors in the antrum
and pylorus of the stomach, which promotes peristalsis and
gastric emptying [41]. A sevenfold increase in the incidence
of HPS was reported among newborns that received the antibiotic erythromycin for
post-exposure pertussis prophylaxis
[42]. More recently, a cohort study found a strong association between HPS and
infants receiving macrolide antibiotics, especially if received within the first
two weeks of
life, resulting in a 30-fold increased risk of HPS [43, 44].
Infant consumption from two weeks to four months of age
or maternal consumption during the first two weeks of life
also resulted in a threefold increased risk [43]. The strong
male predominance has remained a mystery, but one clue
is the documentation of preterm male babies having more
acid compared to matched females [45]. Another interesting observation is that
bottle-feeding appears to be independently associated with HPS with a 4.6-fold
increase risk
compared to infants who were breastfed [46]. Other theories include deficiency of
nitric oxide synthase containing
neurons within the thickened pylorus [47]. Nitric oxide is a
major cellular signaling molecule produced by endothelial
cells that relaxes smooth muscle and acts as a major vasodilator. Hence, the
abnormal pyloric innervation is postulated to result in inadequate relaxation of
the pylorus muscle
leading to hypertrophy [48]. This led the investigators to
postulate the gene for nitric oxide synthetase, NOS1, as a
candidate gene for HPS [49].
Genetic inheritance for HPS is complex and multifactorial. There is increased
concordance between monozygotic
twins, when compared to dizygotic twins, and patients with
pyloric stenosis occasionally have a family history of this
condition. Pyloric stenosis is associated with several genetic

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Pediatr Surg Int

syndromes, including Apert syndrome, Denys-Drash syndrome, Kallmann syndrome and

Marden-Walker syndrome
[50]. However, a clear genetic predisposition has yet to be
determined [51, 52]. FOXF1 gene mutations have been associated with congenital
anomalies, such as annular pancreas,
malrotation and duodenal stenosis [53]. A recent study on a
single extended family with multiple cases of HPS, possibly
identified a single novel missense variant of the FOXF1 gene
on chromosome 16 as a candidate gene that contributes to
HPS [54].

Conclusion
HPS is one of most frequently treated pediatric surgical conditions, but continues
to have an incompletely understood
etiology. Early diagnosis by physical exam or ultrasound
and appropriate fluid resuscitation followed by pyloromyotomy has transformed HPS
from a lethal condition into
a readily diagnosed and treated malady with nearly 100%
survival. Despite various proposed genetic etiologies, the
widespread geographical and ethnic variations are likely
indicators of a mixed environmental and genetic explanation
for this disease. While the precise etiology remains elusive,
work-induced hypertrophy of the pylorus muscle seems to be
the most plausible, unifying physiologic explanation. This
hypothesis is strongly supported by a recent Danish nationwide cohort study
demonstrating a 30-fold increased risk of
developing HPS with use of prokinetic macrolide antibiotics
in early infancy [43]. This hypothesis is further supported
by the success of atropine sulfate, which reduces muscular
spasms of the pylorus, as a medical treatment for HPS and a
rescue treatment for incomplete pyloromyotomy. Thus, the
administration of macrolide antibiotics to infants during the
first few months of life should be discouraged, unless the
treatment benefits outweigh the risk.
Acknowledgements This research received no specific grant from
any funding agency in the public, commercial, or not-for-profit sectors.
Compliance with ethical standards
Ethical approval This article does not contain any studies with
human participants performed by any of the authors.
Conflict of interest The authors declare no conflict of interest.

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