Asian Journal of Surgery (2014) 37, 148e153

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ORIGINAL ARTICLE

Nonoperative management for perforated

peptic ulcer: Who can benefit?
Feng Cao a, Jia Li a, Ang Li, Yu Fang, Ya-jun Wang, Fei Li*

Department of General Surgery, Xuanwu Hospital, Capital Medical University, Number 45,
Changchun Street, Beijing 100053, PR China

Received 5 February 2013; received in revised form 5 October 2013; accepted 9 October 2013
Available online 3 January 2014

KEYWORDS Summary Background: Although nonoperative management for perforated peptic ulcer
perforated peptic (PPU) has been used for several decades, the indication is still unclear. A clinicoradiological
ulcer; score was sought to predict who can benefit from it.
surgery; Methods: A clinicoradiological protocol for the assessment of patients presenting with PPU was
treatment used. A logistic regression model was applied to identify determinant variables and construct a
clinical score that would identify patients who can be successfully treated with nonoperative
management.
Results: Of 241 consecutive patients with PPU, 107 successfully received nonoperative man-
agement, and 134 required surgery. In multivariable analysis, the following four variables
correlated with surgery and were given one point each toward the clinical score: age 70
years, fluid collection detection by ultrasound, contrast extravasation detection by water-
soluble contrast examination, and Acute Physiology and Chronic Health Evaluation II (APACHE
II) score 8. Eighty-five percent of patients with a score of 1 or less were successfully treated
with nonoperative management, whereas 23 of 29 patients with a score of 3 or more required
surgery. The area under the receiver operating characteristic curve was 0.804 (95% confidence
interval Z 0.717e0.891).
Conclusion: By combining clinical, radiological parameters, and APACHE II score, the clinical
score allowed early identification of PPU patients who can benefit from nonoperative manage-
ment.
Copyright ª 2013, Asian Surgical Association. Published by Elsevier Taiwan LLC. All rights
reserved.

Conflicts of interest: The authors declare that they have no financial or non-financial conflicts of interest related to the subject matter
or materials discussed in the manuscript.
* Corresponding author. Department of General Surgery, Xuanwu Hospital, Capital Medical University, Number 45, Changchun Street,
Beijing 100053, PR China
E-mail address: feili36@ccmu.edu.cn (F. Li).
a
These two authors contributed equally to this work.

1015-9584/$36 Copyright ª 2013, Asian Surgical Association. Published by Elsevier Taiwan LLC. All rights reserved.
http://dx.doi.org/10.1016/j.asjsur.2013.10.002
Nonoperative management for perforated peptic ulcer
1. Introduction
Because of the widespread clinical use of H2 receptor an-
tagonists and proton-pump inhibitors, significantly less
elective surgery has been carried out for uncomplicated
peptic ulcer. However, the complications associated with
peptic ulcer, especially perforation, are still common in
recent years.1,2 In 1946, Taylor first reported a series of 28
patients with perforated peptic ulcer (PPU) receiving
nonoperative management. The mortality rate was 14%,
which was less than the approximate 20% following a direct
simple closure with omental patch.3 With the development
of critical care medicine, the mortality of PPU treated by
the nonoperative approach has significantly reduced.4e6
However, the indication of nonoperative management is
unclear, and urgent repair of perforation is still the stan-
dard approach for PPU in many clinical centers. The aim of
this study is to establish a clinicoradiological scoring system
to predict who can benefit from it.
2. Materials and methods
2.1. Patients
Between January 2002 and December 2010, all patients
who presented at the general surgery unit of our hospital
with clinical symptoms of PPU confirmed by abdominal
plain film with pneumoperitoneum were evaluated for in-
clusion in this study. Patients with PPU history or suspected
with gastric cancer were excluded from this study. Patients
with severe diffuse peritonitis or septic shock received
direct surgery after fluid resuscitation. Otherwise, the pa-
tients were initially managed nonoperatively. The study
was conducted in accordance with the institutional guide-
lines of the Xuanwu Hospital Ethics Committee, Beijing,
China.
Demographic data were collected for gender and age
(continuous data, divided into the following two categories:
<70 years and 70 years). Clinical variables included
duration of abdominal pain prior to admission, the presence
of fever with a threshold of 38 C, use of steroids or
nonsteroidal anti-inflammatory drugs, the presence of
Helicobacter pylori infection, and satiety during perfora-
tion. Laboratory variables were leukocyte count with a
threshold of 12  109/L and albumin level with a threshold
of 30 g/L. Radiological variables were ultrasound exami-
nation for fluid collection, plain film for pneumo-
peritoneum, and water-soluble contrast examination for
extravasation. In addition, the Acute Physiology and
Chronic Health Evaluation II (APACHE II) scoring system and
Mannheim Peritonitis Index (MPI) were used to evaluate the
general condition of patient and severity of peritonitis.7
2.2. Nonoperative management
Intravenous fluid resuscitation, appropriate antibiotics,
nasogastric suction, and acid-reducing pharmacotherapy
(H2 antagonists or proton-pump inhibitor) were included in
nonoperative management. Patients receiving nonopera-
tive management were treated in intensive care unit. The
149
vital and abdominal signs were rechecked by an experi-
enced surgeon every 4 hours. Operative therapy was indi-
cated for either progression or failure of improvement of
peritonitis within 12 hours. Treatment for H. pylori began
once the patients were able to tolerate oral intake. Follow-
up gastroduodenoscopy was done at 4e6 weeks to monitor
ulcer healing.
2.3. Statistical analysis
Continuous variables were divided into clinically meaning-
ful categories as described earlier and compared between
the two patient groups using Chi-square tests. The logistic
regression analysis was used to identify variables associated
with successful nonoperative treatment, as opposed to
surgery therapy. All variables with univariable p < 0.2 were
considered for the multivariable model. All variables with
an adjusted p < 0.1 were retained in the final model. A
clinical score was constructed based on the final logistic
regression model, in which one point was assigned for the
presence of each predictive factor.
To assess the discriminant ability of this score, a receiver
operating characteristic (ROC) curve was obtained and the
area under the curve (AUC) was calculated. The AUC can be
interpreted as the probability that a randomly chosen pa-
tient having surgical therapy will have a higher score than a
randomly chosen patient with successful nonoperative
treatment. Values of 0.7 or more are often considered
clinically useful.
The sensitivity and specificity of each threshold of the
score were examined, as well as the likelihood ratio for
successful nonoperative treatment for each value of the
score. According to Bayes’ theorem, the likelihood ratio
represents the change in the odds of successful nonopera-
tive treatment between pretest and post-test (post-test
odds Z likelihood ratio  pretest odds). A likelihood ratio
of 1 indicates that the test result does not change the odds
of successful nonoperative treatment, and likelihood ratios
of 5 or more (alternatively, 0.2 or less) are considered to be
clinically useful.8 Statistical analysis was performed with
SPSS version 17.0 (SPSS Inc., Chicago, IL, USA).
3. Results
Between January 2002 and December 2010, 241 patients
with PPU admitted to our hospital were included in this
study. There were 168 male and 73 female patients with a
median age of 45 years (range: 21e92 years). Initially, 132
patients received nonoperative treatment; of these, 25
patients converted to surgery after 12 hours. Finally, 134
patients required surgical therapy. Clinical, laboratory, and
radiological characteristics of the patients are summarized
in Table 1. The clinical results of these two groups including
length of hospital stay, expenditure, and morbidity were
comparable (Table 2). However, the systemic infective
complications were more common in the nonoperative
treatment group than in the surgical group. The incidence
of abdominal abscess and sepsis was 3.7% and 1.9%,
respectively, in the nonsurgical group. In the surgical group,
the incidence rate was 1.5% and 0.7%, respectively
(Table 2).
150 F. Cao et al.

Table 1 Comparison of clinical, biological, and radiolog- Table 1 (continued )

ical parameters of patients with perforated peptic ulcer
Nonoperative Surgery p*
who had nonoperative treatment and surgery.
management (n Z 134)
Nonoperative Surgery p* (n Z 107)
management (n Z 134)
APACHE II 8 <0.001
(n Z 107)
Yes 32 79
Sex 0.691 No 75 55
Female 31 42 MPI 21 0.002
Male 76 92 Yes 22 52
Age 70 y 0.001 No 85 82
Yes 11 37
No 96 97 *Chi-square test.
APACHE II Z Acute Physiology and Chronic Health Evaluation II;
Pain duration 0.064
NSAIDs Z nonsteroidal anti-inflammatory drugs;
prior to
MPI Z Mannheim Peritonitis Index.
admission
12 h
Yes 16 33
No 91 101
3.1. Comparison between the nonoperative group
Fever 38 C 0.058 and the surgical group
Yes 42 69
No 65 65 Patients who received either nonoperative management or
Steroid use 0.172 underwent surgical exploration with PPU were compared.
Yes 2 7 Age 70 years, fluid collection detected by ultrasound,
No 105 127 contrast extravasation detected by gastroduodenal imaging,
NSAIDs use 0.337 and APACHE II 8 were significant variables in the multivar-
Yes 26 40 iable model (Table 3). Because fever and white blood cell
No 81 94 count are factors included in calculating the APACHE II score,
Helicobacter 0.430 we had recalculated the data after excluding them in APACHE
pylori II, and the results were similar. Age (70 years), positive
infection finding for ultrasound, and water-soluble contrast examina-
Yes 65 88 tion were still the independent factors against nonoperative
No 42 46 management. The odds ratio [95% confidence interval (CI)]
Satiety when 0.585 value was 0.293 (0.116e0.721), 0.202 (0.047e0.325), and
perforated 0.029 (0.012e0.089), respectively, in multivariable analysis.
Yes 41 56
No 66 78 3.2. Elaboration of a clinicoradiological score for
Leukocyte count 0.041 prediction of need for surgical therapy
12  109/L
Yes 89 123 One point was given for one clinical criteria (age 70
No 18 11 years), each of two radiological criteria (fluid collection
Albumin level 0.399 detected by ultrasound and contrast extravasation detec-
30 g/L ted by gastroduodenal imaging), and one scoring system
Yes 95 114 (APACHE II 8), leading to a maximum score of 4. The
No 12 20 distribution of patients with PPU according to the predic-
Ultrasound: fluid <0.001 tive score and the proportion of patients with each score
collection value who had nonoperative therapy are shown in Table 4.
Yes 15 76 Fig. 1 shows ROC curves for the logistic regression model
No 92 58 from Table 2 and the clinicoradiological score, for which
Plain film: 0.875 the AUCs were 0.898 (95% CI 0.832e0.963) and 0.804 (95% CI
pneumoperitoneum 0.717e0.891), respectively. The loss of discriminative
None 15 22 ability resulting from simplification of the risk equation was
Unilateral 66 80 therefore minimal.
Bilateral 26 32
Water-soluble <0.001
contrast 4. Discussion
examination:
extravasation The feasibility of nonoperative management of PPU has not
Yes 7 82 been provided until the results of the first randomized
No 100 52 controlled trial was published in 1989. Crofts et al4 showed
that about 72% of the cases (29/40) can be successfully
treated by nonoperative management with similar
Nonoperative management for perforated peptic ulcer 151

Table 2 Clinical results of patients with perforated peptic ulcer who had nonoperative treatment and surgery.
Nonoperative management (n Z 107) Surgery (n Z 134) p
Morbidity 15.9% (17/107) 17.2% (23/134) 0.791
Respiratory infection 7 (6.5) 8 (6.0)
Wound infection 0 (0) 8 (6.0)
Wound dehiscence 0 (0) 3 (2.2)
Abdominal abscess 4 (3.7) 2 (1.5)
Sepsis 2 (1.9) 1 (0.7)
Urinary infection 2 (1.9) 2 (1.5)
Renal failure 1 (0.9) 1 (0.7)
Cardiovascular 1 (0.9) 0 (0)
Length of hospital stay (d) 11.2  1.3 10.9  1.4 0.089
Expenditure (RMB) 11,188.3  2847.4 10,591.9  2733.4 0.099
Data are presented as n (%) or mean  SD, unless otherwise indicated.

morbidity and mortality compared with the immediate
surgical group.4 However, the indication of nonoperative
management for PPU has not been well established. This
study tried to devise a score that would help clinicians
select patients with PPU who can benefit from nonopera-
tive management. Based on univariable and multivariable
analyses, four parameters were significantly correlated
with the therapy approach: age 70 years, fluid collection
detected by ultrasound, contrast extravasation detected by
gastroduodenal imaging, and APACHE II 8. The score
developed by combining these parameters proved accurate
in predicting the need for surgery.
Secondary peritonitis rather than peptic ulcer itself
threaten the life of patients with PPU, and therefore, the
severity of peritonitis should be the major concern when
deciding the treatment approach. However, our study did
not include the MPI score as one of the four parameters that
strongly suggested surgical therapy for PPU. A small amount
of peritoneal effusion is difficult to find due to the large
volume of abdominal cavity, and fluid collection detected
by ultrasound prompts significant leakage of the gastroin-
testinal contents and severe chemical peritonitis leading to
abdominal infection. The water-soluble contrast imaging is
an important examination to determine whether the
perforation is closed, and continuing spillover of contrast
agent suggests that perforation is not closed and that
gastrointestinal contents continue to leak. Positive results
for the two radiological examinations reflect that perito-
neal contamination is severe and aggravating, which are
included in our scoring system. In addition, age and APACHE
II score, which reflect the general condition of patients, are
also the important parameters suggesting surgical therapy.
With the exception of contrast extravasation detected
by gastroduodenal imaging, all determinants in the present
score have previously been identified as independent pre-
dictors of morbidity or mortality, which could explain the
reasonability of our scoring system.4,9,10 In several previous
studies, duration of abdominal pain prior to admission was
an independent factor significantly associating with the
prognosis of PPU patients, which was not proven by our
study.11,12 In our study, the cutoff point of duration of
abdominal pain prior to admission was 12 hours rather than
24 hours, which might lead to the exclusion of pain duration
from our scoring system. The model proposed needs further
validation to determine whether it can be applied to all
patients with PPU. However, the AUC exceeded 0.80,
indicating that this score can help in decision making. This
four-point score is most useful when values are either low

Table 3 Univariate and multivariate analyses for comparison of 107 patients with perforated peptic ulcer who underwent
nonoperative treatment with 134 who had surgery.
Unadjusted Adjusted Score points
OR (95% CI) p OR p
Age 70 y 0.276 (0.148e0.514) 0 0.274 (0.120e0.626) 0.002 1
Fever 38 C 0.519 (0.329e0.819) 0.005 Not retained 0
Steroid use 0.408 (0.129e1.294) 0.128 Not retained 0
Leukocyte count 12  109/L 0.421 (0.204e0.869) 0.019 Not retained 0
Ultrasound: fluid collection 0.126 (0.072e0.220) 0 0.108 (0.054e0.217) 0 1
Water-soluble contrast 0.037 (0.016e0.084) 0 0.031 (0.013e0.077) 0 1
examination: extravasation
APACHE II 8 0.307 (0.191e0.492) 0 0.292 (0.151e0.561) 0 1
MPI 21 0.393 (0.237e0.654) 0 Not retained 0
APACHE II Z Acute Physiology and Chronic Health Evaluation II; CI Z confidence interval; MPI Z Mannheim Peritonitis Index; OR Z odds
ratio.
152 F. Cao et al.

Table 4 Performance statistics for predictive score applied to 95 patients presenting with perforated peptic ulcer.
Score No. of No. of patients Sensitivity (%) Specificity (%) Likelihood ratio Interpretation of likelihood ratio
patients receiving test: test: of successful
nonoperative considered considered nonoperative
management positive negative management
if score if <score at given score
0 10 9 100 0 N Strong evidence for nonoperative
management
1 24 20 82.0 2.2 4.5 Weak evidence for nonoperative
management
2 32 15 42.0 11.1 0.8 Neutral evidence (neither for nor
against nonoperative management)
3 20 6 12.0 48.9 0.4 Moderate evidence against
nonoperative management
4 9 0 0 80.0 0 Strong evidence against
nonoperative management

(0) or high (4). The intermediate values of 2 or 3 require
more careful interpretation. Continued surveillance and
regular reassessment are probably reasonable courses of
action in these patients.
In our series, 44% of cases (107/241) received nonoper-
ative management with the morbidity rate of 15.9%, which
was comparable with the surgical group which had a
morbidity rate of 17.2%. Several factors have been
confirmed to be significantly associated with morbidity
including pain for more than 24 hours, coexistence of major
medical illnesses, amount of abdominal liquid more than
200 mL, preoperative shock, and resection surgery.9,11e13
The overall mortality of our patients was 5.4% (13/241),
which was lower than several previous studies.14,15 In
addition, our study also demonstrated that nonoperative
management did not prolong the hospital stay or increase
the expenditure for selected patients.
Taken together, our study showed that nonoperative
management was effective and safe in selected patients
with PPU. Besides, we proposed a severity model to aid in
Figure 1 Receiver operating characteristic curves for the
multiple logistic regression model and the simplified score.
nonoperative decision making. This severity score, if vali-
dated, does not replace but may supplement individual
clinical judgment. It is a method to assess quantitatively
the severity of PPU and might help in monitoring the evo-
lution of a patient’s condition after admission, when a
nonoperative approach is initially preferred.
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