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Perforated peptic ulcer - an update

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 Submit a Manuscript: http://www.wjgnet.com/esps/ World J Gastrointest Surg 2017 January 27; 9(1): 1-12
Help Desk: http://www.wjgnet.com/esps/helpdesk.aspx ISSN 1948-9366 (online)
DOI: 10.4240/wjgs.v9.i1.1 © 2017 Baishideng Publishing Group Inc. All rights reserved.

REVIEW

Perforated peptic ulcer - an update

Kin Tong Chung, Vishalkumar G Shelat

Kin Tong Chung, Vishalkumar G Shelat, Department of General of perforation in patients with PUD is about 5%. PPU
Surgery, Tan Tock Seng Hospital, Singapore 308433, Singapore carries a mortality ranging from 1.3% to 20%. Thirty-
day mortality rate reaching 20% and 90-d mortality
Author contributions: Chung KT and Shelat VG contributed rate of up to 30% have been reported. In this review
equally to Manuscript writing. we have summarized the current evidence on PPU to
update readers. This literature review includes the most
Conflict-of-interest statement: None.
updated information such as common causes, clinical
Open-Access: This article is an open-access article which was features, diagnostic methods, non-operative and operative
selected by an in-house editor and fully peer-reviewed by external management, post-operative complications and different
reviewers. It is distributed in accordance with the Creative scoring systems of PPU. With the advancement of medical
Commons Attribution Non Commercial (CC BY-NC 4.0) license, technology, PUD can now be treated with medications
which permits others to distribute, remix, adapt, build upon this instead of elective surgery. The classic triad of sudden
work non-commercially, and license their derivative works on onset of abdominal pain, tachycardia and abdominal
different terms, provided the original work is properly cited and rigidity is the hallmark of PPU. Erect chest radiograph
the use is non-commercial. See: http://creativecommons.org/ may miss 15% of cases with air under the diaphragm
licenses/by-nc/4.0/ in patients with bowel perforation. Early diagnosis,
prompt resuscitation and urgent surgical intervention are
Manuscript source: Invited manuscript
essential to improve outcomes. Exploratory laparotomy
Correspondence to: Vishalkumar G Shelat, FRCS, FICS, Hes­
and omental patch repair remains the gold standard.
peris Diploma in Organ Transplantation (ECOT), Hepatobiliary Laparoscopic surgery should be considered when ex­
Consultant Surgeon, Department of General Surgery, Tan pertise is available. Gastrectomy is recommended in
Tock Seng Hospital, Level 4, Annex 1, 11, Jalan Tan Tock Seng, patients with large or malignant ulcer.
Singapore 308433, Singapore. [email protected]
Telephone: +65-63577807 Key words: Peptic ulcer; Perforation; Laparoscopy;
Fax: +65-63577809 Surgery

Received: July 19, 2016 © The Author(s) 2017. Published by Baishideng Publishing
Peer-review started: July 21, 2016 Group Inc. All rights reserved.
First decision: September 28, 2016
Revised: November 4, 2016
Core tip: The classic triad of sudden onset of abdominal
Accepted: November 27, 2016
Article in press: November 29, 2016 pain, tachycardia and abdominal rigidity is the hallmark
Published online: January 27, 2017 of perforated peptic ulcer. Early diagnosis, prompt resu­
scitation and urgent surgical intervention are essential to
improve outcomes. Exploratory laparotomy and omental
patch repair remains the gold standard and laparoscopic
surgery should be considered when expertise is available.
Abstract Gastrectomy is recommended in patients with large or
Peptic ulcer disease (PUD) affects 4 million people malignant ulcer to enhance outcomes; however the
worldwide annually. The incidence of PUD has been outcomes of patients treated with gastric resections
estimated at around 1.5% to 3%. Perforated peptic ulcer remain inferior.
(PPU) is a serious complication of PUD and patients with
PPU often present with acute abdomen that carries high
risk for morbidity and mortality. The lifetime prevalence Chung KT, Shelat VG. Perforated peptic ulcer - an update. World

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 Chung KT et al . Perforated peptic ulcer

J Gastrointest Surg 2017; 9(1): 1-12 Available from: URL: PPU reduced from 17 per 100000 population in 1996 to
http://www.wjgnet.com/1948-9366/full/v9/i1/1.htm DOI: http:// 12 per 100000 population in 2004 (HR 0.71; 95%CI:
dx.doi.org/10.4240/wjgs.v9.i1.1 0.57-0.88) after the introduction of selective cyclo-
[34]
oxygenase-2 inhibitors into clinical practice .

H. pylori
H. pylori remain one of the commonest infections
INTRODUCTION worldwide. The prevalence of H. pylori has decreased in
Peptic ulcer disease (PUD) results from an imbalance developed countries due to improved hygiene and reduced
between stomach acid-pepsin and mucosal defense transmission in early childhood. The mean prevalence
barriers. It affects 4 million people worldwide an­ of H. pylori in patients with PPU varies between studies
[1]
nually . The incidence of PUD has been estimated at due to different diagnostic methods and geographical
[2]
around 1.5% to 3% . A systematic review of seven variations. Recent studies using histopathological methods
studies from developed countries estimated that the of H. pylori detection have shown that H. pylori prevalence
annual incidence rates of PUD were 0.10%-0.19% in patients with perforated duodenal ulcers ranges from
for physician-diagnosed PUD and 0.03%-0.17% when 50%-80%
[22,35]
. A randomized controlled trial in 2008
[3]
based on hospitalization data . Although 10%-20% of involving 65 patients who underwent simple closure
patients with PUD will experience complications, only of a perforated duodenal ulcer showed one year ulcer
2%-14% of the ulcers will perforate causing an acute recurrence rate of 6.1% in H. pylori treated patients as
[4,5]
illness . Perforation is a serious complication of PUD [36]
opposed to 29.6% in the control group . Recurrent
and patients with perforated peptic ulcer (PPU) often PUD mainly occurs in patients with H. pylori infection
present with acute abdomen that carries high risk for suggesting that H. pylori play an important role in the
[6]
morbidity and mortality . The lifetime prevalence of development of PUD and its complications
[22,37]
. The risk
[7]
perforation in patients with PUD is about 5% . PPU of recurrent H. pylori infection is significantly reduced with
[8-10]
carries a mortality ranging from 1.3% to 20% . proton pump inhibitor therapy, but proton pump inhibitors
Thirty-day mortality rate reaching 20% and 90-d have only a modest efficacy for reduction in ulcers with
[11,12]
mortality rate of up to 30% have been reported . In NSAID users.
this review we have summarized the current evidence
on PPU and we hope our review will assist surgeons Smoking
updated with evidence based practice. Tobacco is thought to inhibit pancreatic bicarbonate
[38,39]
secretion, leading to increased acidity in duodenum .
It also inhibits the healing of duodenal ulcers. A meta-
AETIOLOGY
analysis has indicated that 23% of PUD could be
Although previous studies have indicated that seasonal [40]
associated with smoking . However, in some studies,
variation did influence the incidence of PPU, other studies there was no difference in tobacco use between patients
[13-16]
have failed to prove such a pattern . In developing with non-H. pylori, non-NSAID duodenal ulcers and
world, patients tend to be young male smokers while those with H. pylori related ulcers, indicating a limited
in developed countries; patients tend to be elderly with [41]
role of smoking . This is in agreement with previous
multiple co-morbidities and associated use of non-steroidal studies, which indicated that smoking did not increase
[17,18]
anti-inflammatory drugs (NSAIDs) or steroid . NSAIDs, the risk of ulcer recurrence once the H. pylori had been
Helicobacter pylori (H. pylori), physiological stress, eradicated
[42,43]
.
smoking, corticosteroids and previous history of PUD are
[1,19-27]
risks factors for PPU . In the presence of risk factors, Others
recurrence of ulcer is common despite initial successful A study involving 72 patients investigated the genetic
treatment. A systematic review of 93 studies has shown differences between H. pylori-positive and negative
that the average long-term recurrence of perforation was duodenal ulcer patients. DQA1*0102 allele were sig­
[5]
12.2% (95%CI: 2.5-21.9) . nificantly more common in H. pylori negative pa­tients .
[44]

This study indicated that genotypes might influence the

NSAIDs ability of the host to resist H. pylori infection. A study
NSAIDs are widely used for its analgesic, anti-inflam­ involving 228 patients indicated that steroid use prior
matory and anti-pyretic effects. NSAID use is known to to hospital admission was associated with two fold
[28,29]
increase the risk of PPU . About a quarter of chronic increase in 30 d mortality amongst patients admitted for
[45]
NSAID users will develop PUD and 2%-4% will bleed PPU . Other risk factors may include excessive alcohol
[30-33]
or perforate . Drug interaction with steroids and consumption and excessive acid production such as
[18,46,47]
selective serotonin reuptake inhibitors also increases the gastrinomas and Zollinger-Ellison syndrome (ZES) .
risks of PUD. Selective cyclo-oxygenase-2 inhibitors are Alcohol consumption is known to damage gastric mucosa
less associated with PUD. A study in western Denmark and stimulate gastrin secretion. Despite these acute
showed that the standardized hospitalization rates for effects, there is no evidence that alcohol causes PUD. ZES

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 Chung KT et al . Perforated peptic ulcer

is caused by a gastrin secreting tumor of the pancreas pyrexia leads to compensatory tachycardia. In patients
that stimulates the parietal cells in stomach to increase who delay seeking medical attention, hypotension
the acidity, resulting in gastrointestinal mucosal ulceration. ensues due to total body water deficit. If uninterrupted;
Over 90% of patients with ZES develop peptic ulcers this progresses to mental obtundation and acute kidney
and typically these ulcers are refractory to proton pump injury. This leads to a state where patient becomes
inhibitor therapy. ZES should be suspected in patients with physiologically unfit for operative intervention which is
multiple or refractory peptic ulcers, jejunal ulcers, family absolutely necessary. Hence it is important to establish
history of PUD and associated diarrhea. All patients with prompt confirmatory diagnosis.
ZES should be screened for Multiple Endocrine Neoplasia 1
(MEN1) syndrome.
DIAGNOSIS
An urgent erect chest X-ray and serum amylase/lipase
CLINICAL FEATURES is basic essential test in a patient with acute upper ab­
In 1843 Edward Crisp stated that “the symptoms are so dominal pain. In modern era it is not prudent to perform
typical, I hardly believe that it is possible that anyone an exploratory laparotomy and establish a diagnosis of
[48]
can fail in making a diagnosis” . acute pancreatitis. Seventy-five percent of PPU have
[53]
Symptoms of PUD include abdominal pain, upper free air under diaphragm on erect chest X-ray . In our
abdominal discomfort, bloatedness and feeling of full­ experience of managing 332 patients, erect chest X-ray
[51]
ness. When PUD worsen and eventually perforate, revealed free air in 59.8% of patients . This variation
gastric juice and gas enters the peritoneal cavity leading could reflect the earlier presentation and easy access to
to chemical peritonitis. Sudden onset of abdominal pain healthcare locally. Sixty-one point seven percent of our
or acute deterioration of the ongoing abdominal pain patients presented within 24 h of onset of abdominal
is typical of PPU. Typically the pain never completely pain. In a patient with upper abdominal symptoms, free
subsides despite usual premedical remedies and forces air on an erect chest X-ray establishes a diagnosis of
the patient to seek medical attention. The chemical PPU. In some patients, an abdominal X-ray may have
peritonitis due to efflux of gastroduodenal contents been performed by emergency physician or primary
and severe pain lead to tachycardia. The classic triad medical team. It can show signs such as appearance of
of sudden onset of abdominal pain, tachycardia and gas on both sides of the bowel wall (Rigler’s sign), a large
abdominal rigidity is the hallmark of PPU. volume of free gas resulting in a large round black area
The clinical manifestation can be divided into three (Football sign) and gas outlining soft tissue structures
[49]
phases . In the initial phase within 2 h of onset, such as liver edge or falciform ligament. It is authors’
epigastric pain, tachycardia and cool extremities are practice not to perform an abdominal X-ray in patients
characteristic. In the second phase (within 2 to 12 h), with suspected PPU when chest X-ray does not show free
pain becomes generalized and is worse on movement. air under the diaphragm. CT scan is recommended as
[54]
Typical signs such as abdominal rigidity and right lower it has a diagnostic accuracy as high as 98% . Besides,
quadrant tenderness (as a result of fluid tracking along CT scan can exclude acute pancreatitis that would not
the right paracolic gutter) may be seen. In the third need surgical intervention. CT scan is performed in supine
phase (more than 12 h), abdominal distension, pyrexia position and free air is usually seen anteriorly just below
and hypotension with acute circulatory collapse may be the anterior abdominal wall. The falciform ligament can
evident. sometimes be visible when air is present on both sides. In
A study involving 84 patients with PPU reported that resource poor healthcare facilities, oral gastrograffin can
the commonest presenting symptoms were sudden be used to diagnose PPU. Water-soluble contrast leaking
onset of severe epigastric pain (97.6%), abdominal into the peritoneal cavity can confirm the diagnosis of PPU.
[50]
distention (76.2%) and vomiting (36.9%) . Abdominal Absence of a leak does not exclude PPU as the perforation
[55]
tenderness and classical signs of peritonitis could be may have sealed off spontaneously . Barium study is
elicited in 88.1% and 66.7% of the patients with PPU contraindicated in gastrointestinal perforation and should
in this study. Other symptoms also included nausea be avoided as a tool to diagnose PPU. We consider lateral
(35.7%), severe dyspepsia (33.3%), constipation decubitis abdominal radiographs as obsolete and do not
[50]
(29.8%) and fever (21.4%) . In our experience of recommend. The traditional practice of instilling air via
managing 332 patients with PPU, the most common the nasogastric tube and repeating the erect chest X-ray
presenting symptom was acute onset of abdominal after few minutes is not recommended except in resource
[51]
pain (61.7%) . A recent study in Taiwan has shown poor facilities. It takes time and a repeat negative chest
that patients with PPU were more likely to present to X-ray does not rule out the diagnosis of PPU and still a CT
emergency room on weekends and this needs to be scan would be warranted. Rarely a CT scan is performed
[52]
validated . even when an erect chest X-ray reveals free air under
Tachycardia and abdominal tenderness with rigidity diaphragm. The utility of this CT scan is justified when
are common clinical signs. Severe pain, systemic clinical presentation is not specific to upper gastrointestinal
inflammatory response from chemical peritonitis and pathology or a malignancy is suspected and patients’
fluid deficit either due to poor intake or vomiting or hemodynamics is not deranged. In patients with acute

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 Chung KT et al . Perforated peptic ulcer

Figure 1 Computerized tomography scan shows free air under the Figure 2 Erect chest X-ray image of the same patient with equivocal free
diaphragm with peri-hepatic free fluid. air under the right hemidiaphragm.

[37,59,60]
kidney injury, a non-contrast CT scan is adequate to see ulcer . It is our practice to prescribe intravenous
free air. Oral contrast with CT scan is a useful tool and if proton pump inhibitor for 72-96 h and start oral triple
free leak is seen, diagnosis is certain (Figures 1 and 2). therapy immediately after. We perform urea breath test
Laboratory tests are performed in PPU not to establish to establish H. pylori eradication after completion of
diagnosis but to rule out differential diagnosis and also to medical treatment.
understand the insult to various organ systems. They are
Non-operative management
[56]
non-specific . Serum amylase should be done at index
presentation to emergency unit or after a normal chest Studies have shown that about 40%-80% of PPU will
X-ray. Raised serum amylase may be associated with seal spontaneously with conservative management and
PPU and it’s usually raised less than four times its normal overall morbidity and mortality are comparable
[2,61,62]
.
[57]
level . Tests such as white cell count and C-reactive Conservative management “Taylor method” consists
protein may be done as part of the investigation in PPU. of nasogastric suction, intravenous drip, antibiotics and
Leukocytosis and raised C-reactive protein may be raised repeated clinical assessment. A gastrograffin dye study
[57]
as a result of inflammation or infection . Elevated is essential to confirm absence of leakage in patients
creatinine, urea and metabolic acidosis reflects systemic selected for non-operative management. If patients are
inflammatory response syndrome (SIRS) and prerenal clinically stable and improving, especially with a sealed
[58]
injury . Serum gastrin levels are indicated in patients perforation, surgery may not be warranted. However, if
with history of recurrent ulcers or recalcitrant PUD and they deteriorate, regardless of the presence and size of
can help establish diagnosis of Zollinger Ellison syndrome. the leak, urgent operation is indicated. A Randomized
In patients with suspected parathyroid disorders, serum controlled trial involving 83 patients compared the
calcium levels are indicated. outcome of non-operative treatment with that of operative
[61]
intervention in patients with PPU . Cefuroxime, ampicillin
and metronidazole were administered to all patients.
MANAGEMENT Seventy-two point five percent (29/40) of patients in
PPU is a surgical emergency associated with high conservative group showed clinical improvement and
mortality if left untreated. In general, all patients with were successfully managed without surgery. Covering
PPU require prompt resuscitation, intravenous antibiotics, with an appropriate antibiotic in patients with peritonitis is
analgesia, proton pump inhibitory medications, naso­ associated with an increased chance of resolution of the
gastric tube, urinary catheter and surgical source control. [63]
infection after primary surgery . Another study looking
at 82 patients who were treated conservatively also
Drug treatment in PPU showed that 54% of the patients (44/82) showed clinical
[64]
Omeprazole and triple therapy for H. pylori eradication improvement and did not require a surgical intervention .
are useful adjuncts in treatment of PPU. Evidence has Study also suggests that patients do well without surgery
[55]
shown that omeprazole and triple therapy treatment if spontaneous sealing occurs . A study has shown that
reduces the recurrence rate significantly. Ulcer healing about 40% of PPU had no evidence of leak on upper GI
shown at 8-wk follow up with endoscopy was significantly contrast studies, indicating that the perforation had sealed
[36] [65]
higher in triple therapy eradication group . Eighty-five off spontaneously . The mortality rate for non-operative
point three percent of ulcers were healed in the triple management in patients with a sealed perforation was
therapy group as opposed to 48.4% in the omeprazole 3% as opposed to 6.2% where emergency surgery was
[65]
alone group. Several other studies from different cou­ performed for PPU . This suggests that PPU with a
ntries have also proven triple therapy eradication after sealed perforation can be managed conservatively. The
simple closure of PPU reduced the incidence of recurrent advantages of conservative management include avoidance

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 Chung KT et al . Perforated peptic ulcer

of surgery, risks of general anaesthesia and post-operative that the ulcer recurrence rate was as high as 42% in
complications. On the other hand, disadvantages include perforated duodenal ulcer patients who underwent simple
[72,73]
misdiagnosis and higher mortality rate if conservative omental patch repair . Few prospective randomized
[61,66]
management fails . In clinical practice, non-operative studies also reported substantially less ulcer recurrence in
management strategy is resource intensive and it requires patients who underwent vagotomy in addition to omental
[37,74]
a commitment of active regular clinical examination along patch repair . Nonetheless, vagotomy is now seldom
with round the clock availability of a surgeon and if there is performed for PPU due to the availability of medications
clinical deterioration, emergency surgery is warranted. The such as histamine receptor antagonists, proton pump
essential components of non-operative management of inhibitors and H. pylori eradication.
PPU can be grouped as “R”s: (1) Radiologically undetected
leak; (2) Repeated clinical examination; (3) Repeated
blood investigations; (4) Respiratory and renal support; (5) GASTRECTOMY
Resources for monitoring; and (6) Readiness to operate. Rydiger did a partial gastrectomy for the management
[75]
of PUD in 1880. Unfortunately, it was not successful .
Operative management A year later, Theodor Billroth performed a successful
Management of PPU is primarily surgical and different gastroduodenostomy in a 43-year-old woman with
suture techniques for closure of the perforation are pyloric cancer. He was the first surgeon who did gastric
[76]
described. Johan Mikuliczradecki stated that “every resection for antral carcinoma . Nowadays, emergency
doctor who is faced with a perforated ulcer of stomach gastrectomy is reserved for a giant ulcer or a suspicion of
or duodenum must consider opening the abdomen, malignancy when it is not safe to perform omental patch
[77]
sewing up the hole and averting a possible inflammation repair . A retrospective study reported a mortality rate
by a careful cleansing of the abdominal cavity” . In
[4]
of 24% in 41 patients who underwent gastrectomy for
[78]
[67]
1992, Feliciano also described 5 points of decision that perforated benign gastric ulcers . A study comparing
surgeon needs to take into account. Those decisions outcomes after gastrectomy and simple closure repair
include: (1) Is surgery indicated? (2) Is an omental patch showed that there were no significant differences in
[79]
sufficient or a definitive ulcer operation indicated? (3) Is patient recoveries . Longer operating times, ventilation
the patient stable enough to undergo a definitive ulcer and postoperative blood transfusion are associated with
[80]
operation? (4) Which definitive ulcer operation should be increased mortality . The larger size of perforation
done? (5) Should the availability of newer medical options is associated with higher mortality and post-operative
[81]
influence the choice of operation? With the development anastomotic leak . In a study of 601 patients and
of laparoscopic operation in the past few decades, a sixth including 62 patients treated with gastric resection, we
decision point is proposed; and (6) Should the procedure have shown that serum albumin is the only preoperative
be performed laparoscopically?
[67,68]
. Roscoe Graham factor predictive of mortality (OR 5.57) and outcomes
described PPU to be not a local disease but a local of patients treated with gastric resection are inferior as
[69]
manifestation of a constitutional disturbance . There compared to omental patch repair with mortality risk
[82]
are many operative methods that could be used to treat of 24.2% . Gastric resections for acid reduction have
PPU. Primary closure by interrupted sutures, closure by become less favorable after proton pump inhibitors era
interrupted sutures covered with a pedicled omentum on and in our experience, up to 10% of PPU patients require
top of the repair (Cellan-Jones repair) and plugging the gastric resection.
perforation with a free omental plug (Graham patch) are
the most common techniques.
LAPAROSCOPIC REPAIR
Laparoscopic repair was first performed for a perforated
VAGOTOMY [83]
duodenal ulcer in 1990 . Laparoscopic repair of PPU
Vagus nerve plays an important role in the regulation of is believed to reduce the post-operative morbidity and
[84]
gastrin release and gastric acid secretion by stimulating mortality . A recent systematic review of 3 randomized
[70]
parietal cells via cholinergic receptors . Vagal stimu­ controlled trials with a total of 315 PPU patients com­
[85]
lation also releases histamine and gastrin from entero­ pared laparoscopy with open surgery . This study
chromaffin like cells and G-cells, which in turn, will failed to demonstrate differences in abdominal septic
stimulate the parietal cells to produce acid secretion. complications, pulmonary complications, mortality and
Vagotomy is a procedure that transects the vagal trunks re-operation. However, the operative time was shorter in
[86]
(truncal vagotomy) or distal nerve fibers (highly selective laparoscopic group in contrast with previous study . A
vagotomy). Truncal vagotomy aims to reduce the gastric systematic review of 56 studies comparing laparoscopic
acid secretion, thus reducing the risks of recurrent PUD. vs open approach for PPU concluded that there was
[87]
Selective vagotomy, which spares the hepatic and celiac no consensus on the perfect operating techniques .
divisions of the vagal trunks, are associated with higher The overall conversion rate for laparoscopic surgery
[71]
long-term recurrence rates . Therefore, selective was 12.4% mainly due to the size of perforation. Ulcer
vagotomy is no longer performed. Studies have shown size more than 9 mm is a significant risk factor for

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 Chung KT et al . Perforated peptic ulcer

[88] [102]
conversion to open surgery . The operating time was increased risk of intestinal obstruction . A questionnaire
longer and recurrent leakage was higher in laparoscopic performed by Schein showed that eighty percent of the
group. However, the laparoscopic group also showed surgeons did not leave a drain in after surgery due to
[63]
less postoperative pain and a shorter hospital stay. the reasons discussed above . Nowadays, the tire test
Furthermore, the laparoscopic treatment is also ass­ (watch for bubbles after submerging patch repair under
ociated with equivalent costs compared with the open water) and the dye test (to inject dye via nasogastric
[89]
surgery as it reduces duration of hospital stays . The tube) to look for leakage after closure of PPU are rarely
current evidence remains poor for choosing laparoscopic used (Figure 3).
repair over open surgery for PPU. This review has sug­
gested that patients with a Boey score of 3, age over
70 years and symptoms lasting longer than 24 h should SELF-EXPANDABLE METAL STENTS
have open surgical approach as these patients have Primary stenting and drainage may be used as new
[103]
higher morbidity and mortality. Laparoscopic repair of treatment option for PPU . Eight patients with PPU
[103]
PPU has now been performed by trainee surgeons with were treated with self-expandable metal stents . Two
[90,91]
acceptable results . Our local experience also showed patients were treated with stenting due to postoperative
that strict selection such as Boey score of 0-1, ulcer size leakage after initial surgical closure and six patients were
of less than 10 mm, ulcer located in pyloro-duodenal treated with primary stenting. Seven out of 8 patients
area, haemodynamic stable, no previous abdominal recovered without complications and were discharged
surgeries, not suspected malignant ulcer and excluding 9-36 d after stenting. Another study involving 10 patients
[92]
ASA 3 and above score were safe for training . There with PPU who were treated with stenting also showed
[104]
were no conversions, complications or mortality. good clinical results . This study has indicated stent
Laparoscopic repair techniques mirror techniques treatment as a minimal invasive alternative with fewer
of open surgery and in particular sutureless techniques complications compared to surgical treatment. These
are more prominently described. This may in part due studies indicate that patients with PPU may be treated
to training in intra-corporeal knotting skills. Sutureless with primary stenting and drainage where training and
techniques involve gelatin sponge plug with fibrin glue expertise is available. More data is required to prove the
[68]
sealing or endoscopic clipping . A recent study has effectiveness of this method.
compared the effectiveness of a sutureless onlay omental
[93]
patch with a sutured omental patch method . Forty-
three patients underwent laparoscopic repair of PPU with MARGINAL ULCER PERFORATION
sutureless onlay omental patch and another 64 patients Any form of gastroenteric reconstruction can lead to the
underwent laparoscopic repair of PPU with sutured development of ulcer at the margins of the gastrojejunal
omental patch. There were no leaks in either group. anastomosis, known as marginal ulcer. The incidence
[105,106]
The operating time and length of stay were significantly of marginal ulcer is around 1% to 16% . The ulcer
shorter in sutureless onlay omental patch group. This tends to develop on the jejunal side of the stoma since it
[107]
study has indicated that both techniques are safe and is directly exposed to the gastric acid . Local ischemia,
effective for repair of PPU. Trainees can easily perform NSAIDS, anastomotic tension, chronic irritation due to
laparoscopic sutureless repair with limited experience the suture material and duodenal reflux are implicated
[108]
in laparoscopic surgery. Laparoscopic gelatin sponge in the aetiopathogenesis of marginal ulcer . Marginal
[94] [109]
plug and fibrin glue sealing can be easily performed . ulcer can rarely lead to perforation . The presentation
However, this technique has not been widely accepted of patients with marginal ulcer perforation should be
[95]
as it has been reported to have a higher leak rate . similar to PPU, however it may not be so. The small
Endoscopic clipping of PPU is not widely practiced, as bowel contents has increased bacterial load and will
there are only few centers with technical expertise also neutralize the gastric acid. A prospective study has
and experience is limited with reports showing high shown that 28% of patients with marginal ulcers were
[96,97] [110]
complications and mortality . asymptomatic . Operative management for marginal
“Dilution with solution is the solution to pollution”. ulcer perforation includes anastomotic revision such as
Towards the end of surgery, some surgeons like to converting Billroth Ⅱ gastro-jejunostomy reconstruction
irrigate the peritoneal cavity with 6-10 litres and even into a Roux-en-Y. It can also be treated with simple
[109,111]
up to 30 litres of warm saline although no evidence omental patch repair . In recent time, majority
has been found in literature to support that irrigation of the published studies describe marginal ulcer and
[98,99]
can lower the risk of sepsis . On the other hand, its perforation following bariatric procedures. We have
pneumoperitonuem induced during laparoscopic surgery reported a series of nine patients with marginal ulcer
[100]
may increase the risk of bacterial dissemination . It perforation following previous gastric resections for
[112]
also seems to be a surgeon’s preference whether or not benign and malignant diseases . We have concluded
[101]
to leave a drain at the end of surgery . There is no that patients with marginal ulcer do not present with
evidence to support that leaving a drain in can reduce septic shock. Also, revision of Billroth Ⅱ gastro-jeju­
[101,102]
the incidence of intra-abdominal collections . On nostomy to Roux-en-Y anastomosis is not mandatory
[112]
the contrary, it may lead to infection of drain site and and omental patch repair is sufficient .

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 Chung KT et al . Perforated peptic ulcer

A B

C D

Figure 3 Shows laparoscopic omental patch repair. A: Anterior duodenal perforation; B: Laparoscopic suturing; C: Omental patch; D: Abdominal drain placement.

complications in 96 patients reported that a total of 29

POST-OPERATIVE COMPLICATIONS patients developed a total of 50 events of postoperative
PPU treatment is associated with a significant post­ [119]
complications . The most common complications were
operative morbidity and mortality regardless of whether surgical site infection (32%), respiratory complications
[113]
laparoscopic or open repair is performed . Post- (30%), wound dehiscence (12%) and postoperative
[114]
operative mortality for PPU is estimated to be 6%-10% . fistula (8%). Each additional complication was estimated
Age more than 60 years old, delayed treatment greater to prolong hospital stay by 1.25 d. This study also
than 24 h, shock at presentation with systolic blood reported that age > 40 years, larger size of perforation
pressure less than 100 mmHg and concomitant diseases and history of shock significantly increased the rate of
[2,115]
are the main risk factors influencing outcome . Post- postoperative complications.
[116]
operative mortality in elderly is 3 to 5 times higher . In our local study involving 332 patients who under­
This may be due to the presence of medical comorbidities, went surgery for PPU, post-operative complications
delayed presentation, atypical presentation or delay of > included intra-abdominal collection (8.1%), leakage
[116]
24 h in diagnosis . [51]
(2.1%) and re-operation (1.2%) . Intra-abdominal
Post-operative complications have been reported at abscess remains a serious postoperative complication
[50,117]
around 30% . Complications after surgical closure after PPU surgery. Therefore, good surgical technique
of PPU include surgical site infection, pneumonia, intra- must be adopted to prevent this complication. Our
abdominal collection/abscess, wound dehiscence, enter­ low leak rates (2.1%) could be explained by early
ocutaneous fistula, peritonitis, incisional hernia and presentation, prompt diagnosis, early resuscitation and
ileus. A study has shown the commonest post-operative appropriate surgery. Our data on 30 d mortality was
complications were surgical site infections (48%) and 7.2% which is comparable to a recent study from South
[50] [120]
pneumonia (28%) . However, this study only involved Korea . The lower mortality in our local study could be
25 patients and may not be representative. A more due to younger age (54.7), less co-morbidity (16.2%)
recent study involving 726 PPU patients between 2011 and less patients with pre-operative shock (7.2%).
and 2013 in Denmark indicated the most common post- A recent study looked at the association of mortality
[121]
operative complications were post-operative leak (5.9%) with out of hours admission in patients with PPU .
[118]
and wound dehiscence (4.7%) . Around 1 in every 5 A total of 726 patients who were surgically treated for
patients underwent re-operation due to post-operative PPU were included in this study. This study did not show
complications. This study also indicated that laparoscopic statistically significance between 90-d mortality and
repair was associated with lower risk of re-operation out-of-hours admission in patients surgically treated for
than laparotomy or laparoscopic surgery converted to PPU.
open surgery. Another study assessing postoperative In order to allocate resources appropriately and

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 Chung KT et al . Perforated peptic ulcer

Age Gender
Co-morbidity

History of peptic ulcer Non-steroidal anti-inflammatory medication use

disease

Steroid use
Delay in presentation

American Society of Patient factors

Anesthesiology score

Blood transfusion
Perforated peptic ulcer
Shock at presentation Need for gastric resection

Elevated urea or Disease factors Treatment factors

creatinine Intensive care unit

Gastric vs duodenal
location Anemia or Parenteral nutrition
hypoalbuminemia
Size Complications

Underlying malignancy

Figure 4 Determinants of outcomes in patients with perforated peptic ulcer.

[126]
provide optimal care, it is important to stratify patients PPU. Using the methods described by Ishiguro et al ,
into low and high risk of mortality. There are many it was possible to predict the amount of accumulated
scoring systems available to predict the mortality. intraperitoneal fluid by CT scan. This study has shown
[126]
that the method of Ishiguro et al was useful for
predicting the amount of intraperitoneal fluid in patients
SCORING SYSTEMS TO PREDICT with PPU. It is believed that it will be useful for predicting
OUTCOMES IN PPU the severity of postoperative complications and also
helpful for treatment decision-making (Figure 4).
About 11 different scoring systems used to predict
outcome in PPU can be identified through the literature:
the Boey score, the Americal Society of Anesthesiologists MORTALITY
(ASA) score, the Sepsis score, the Charlson Comorbidity
Mortality is a serious complication in PPU. As we men­
Index, the Mannheim Peritonitis Index (MPI), the Acute
tioned before, PPU carries a mortality ranging from
Physiology and Chronic Health Evaluation Ⅱ (APACHE [9,10]
1.3% to 20% . Other studies have also reported 30-d
Ⅱ), the Simplified Acute Physiology Score Ⅱ (SAPS Ⅱ),
mortality rate reaching 20% and 90-d mortality rate of
The Physiology and Operative Severity Score for the [11,12]
up to 30% .
Enumeration of Mortality and Morbidity Physical Sub-score
(POSSUM-phys score, the Mortality Probability Models Significant risk factors that lead to death are presence
of shock at admission, co-morbidities, resection surgery,
Ⅱ (MPM Ⅱ), Peptic Ulcer Perforation (PULP) score, the
Hacettepe score and the Jabalpur score
[121]
. Amongst female, elderly patients, a delay presentation of more
these 11 scoring systems, the Boey score and ASA score than 24 h, metabolic acidosis, acute renal failure,
[11,127-131]
are the most commonly validated systems
[8,80,122-124]
. hypoalbuminemia, being underweight and smokers .
Other scoring systems are not widely used due a lack The mortality rate is as high as 12%-47% in elderly patients
[132-134]
of validation or their complexity in clinical use. We have undergoing PPU surgery . Patients older than 65
validated ASA score, Boey’s score, MPI and PULP score year-old were associated with higher mortality rate when
[131]
and found that all the four systems have moderate compared to younger patients (37.7% vs 1.4%) . A
accuracy of predicting mortality with area under the study involving 96 patients with PPU also showed that there
[51]
receiver operator curve of 72%-77.2% . In a recent was a ninefold increase in postoperative complications in
[119]
study including 148 patients from two university affiliated patients with comorbidities . In another large population
hospitals in Singapore, Lee et al
[125]
has reported that in study, patients with diabetes had significantly increased
[135]
selected patients with presentation within 48 h and ulcer 30-day mortality from PPU .
size < 2 cm, laparoscopic repair reduces length of hospital
stay compared to open surgery in patients with MPI > 21.
A recent study was looking at 62 patients who CONCLUSION
[126]
underwent emergency surgery for PPU . This study PUD can now be treated with medications instead of
was investigating the correlation between the amount of elective surgery. However, PUD may perforate and PPU
peritoneal fluid and clinical parameters in patients with carries a high mortality risk. The classic triad of sudden

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 Chung KT et al . Perforated peptic ulcer

onset of abdominal pain, tachycardia and abdominal 14 Janik J, Chwirot P. Perforated peptic ulcer--time trends and patterns
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P- Reviewer: Abulezz TA, Lakatos PLL, Lakatos PL, Tambuwala MM,

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