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Laparoscopic repair for perforated peptic ulcer disease

  1. Alvaro Sanabria1,2,*,
  2. Maria Isabel Villegas2,
  3. Carlos Hernando Morales Uribe2

Editorial Group: Cochrane Upper GI and Pancreatic Diseases Group

Published Online: 28 FEB 2013

Assessed as up-to-date: 3 JUL 2012

DOI: 10.1002/14651858.CD004778.pub3


How to Cite

Sanabria A, Villegas MI, Morales Uribe CH. Laparoscopic repair for perforated peptic ulcer disease. Cochrane Database of Systematic Reviews 2013, Issue 2. Art. No.: CD004778. DOI: 10.1002/14651858.CD004778.pub3.

Author Information

  1. 1

    Hospital Pablo Tobon Uribe, School of Medicine, Oncology Unit, Medellín, Antioquia, Colombia

  2. 2

    Universidad de Antioquia, Department of General Surgery, Medellín, Colombia

*Alvaro Sanabria, Oncology Unit, Hospital Pablo Tobon Uribe, School of Medicine, Calle 78B N0 69-240, Medellín, Antioquia, Colombia. alvarosanabria@gmail.com.

Publication History

  1. Publication Status: New search for studies and content updated (no change to conclusions)
  2. Published Online: 28 FEB 2013

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Characteristics of included studies [ordered by study ID]
Bertleff 2009

Methods77 months, multicenter RCT parallel design, randomized using computer-generated random numbers, concealment of allocation using sealed envelopes, outcome assessment was carried out by the treating team, losses to follow up not reported, intention-to-treat analysis


Participants101 patients (52 for laparoscopic group and 49 for open-surgery group).
Sex: 61 men/40 women
Mean age: 61 years
Site of perforation: duodenum (34), juxtapyloric (61)
Size of perforation: 10 mm
Age of inclusion not reported, but probably adults.
Inclusion criteria: clinical diagnosis of perforated peptic ulcer made by the surgeon and confirmed at the operation room.
Exclusions criteria:
Inability to read the Dutch language patient information booklet

Inability to complete informed consent

Prior upper abdominal surgery

Current pregnancy.
Severity assessed by ASA score (mean 1) and Mannheim Peritonitis Index (mean 16-19-5).


InterventionsIntravenous antibiotics at the diagnosis, type and time not specified. All patients were allocated for Helicobacter pylori eradication therapy.
For postoperative analgesia, patients were prescribed opiates. Dose and frequency not specified.
Upper midline incisions were made in patients assigned to open repair. Perforations were repaired with sutures alone or in combination with omental patch.
For laparoscopic repair, pneumoperitoneum was established (pressure not stated) and three trocars were introduced and the ulcer was closed with sutures alone or in combination with omental patch.
The number of participating surgeons, the number of cases previously operated by the surgeon and the number of patients operated by each surgeon or center was not reported.


OutcomesPostoperative complications
Time of nasogastric aspiration
Pain assessed with visual analogue scale
Conversion rate for laparoscopic group
Operation time
Time of analgesic use
Length of hospital stay


NotesSample size was not calculated.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low risk"Surgeons contacted the study coordinator" "The envelope randomisation was based on a computer-generated list provided by the trial statistician"

Allocation concealment (selection bias)Low risk"randomisation took place by opening a sealed envelope"

Blinding (performance bias and detection bias)
All outcomes
High risk"this was an unblinded trial"

Incomplete outcome data (attrition bias)
All outcomes
Low riskNo missing outcome data

Selective reporting (reporting bias)Low riskProtocol published on the Clinicaltrials.gov website

Other biasUnclear riskIn surgical trials, there is always a bias related with learning curve for the new surgical methods. However, we believe this bias is not present in this trial because the experience of surgeons is similar.

In multicenter trials, a bias related with high volume and low volume centers is possible. There is no information about the number of patients by center.

Lau 1996

Methods28 months, RCT parallel design, randomized using computer-generated random numbers by the block method, concealment of allocation using sealed envelopes, outcome assessment was made by two assessors (not stated if independent from the treating team and blind) for pain evaluation and by the treating team for activity, work return evaluation and complications, available to follow-up at 4 weeks: 73% for laparoscopic group versus 69% for open surgery group but all live patients available at 8 weeks for gastroscopy, to intention-to-treat analysis.


Participants93 patients (48 for laparoscopic group and 45 for open surgery group).
Sex: 79 men/14 women
Mean age 47.8 to 52.3 years
Site of perforation: duodenum (76), juxtapyloric (11), gastric (6)
Size of perforation 1-25 mm
Age of inclusion not reported, but probably adults.
Inclusion criteria:
Clinical diagnosis of perforated peptic ulcer made by the surgeon and confirmed at the operation room.
Exclusions criteria:
Complicated ulcers that required definitive surgery (criteria not stated)
Bleeding ulcer
Previous abdominal operations
Serious associated cardiopulmonary diseases
Clinically sealed perforation.
Severity assessed by APACHE II score. Median 6.


InterventionsIntravenous cefuroxime 750 mg and metronidazole 500 mg were given at the time of induction and for the first postoperative day.
For postoperative analgesia, patients were prescribed pethidine 1 mg/kg every 4 hours as required.
Upper midline incisions were made in patients assigned to open repair. Perforations were repaired with the Cellan-Jones method or using a rolled piece of gelatin sponge placed in the perforation and secured with fibrin sealant.
For laparoscopic repair, pneumoperitoneum was established at 15 mm Hg, and three trocars were introduced and the ulcer was sutured with a piece of omentum and non-absorbable suture or using a gelatin and fibrin sealant.
The number of participating surgeons, the number of cases previously operated by the surgeon and the number of patients operated by each surgeon was not reported.
The study divided laparoscopic and open surgery groups in two groups: one repaired with suture and the other repaired with fibrin sealant. We did not consider this distinction to be important and we re-aggregated the data.


OutcomesComplications
Time of nasogastric aspiration
Time of intravenous fluid maintenance
Pain assessed with Visual Analogue Scale
Conversion rate for laparoscopic group
Operation time
Analgesic use
Time to resume oral diet
Length of hospital stay


NotesSample size was calculated using the analgesic doses using a previous study made by the same authors.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low risk"Computer-generated blocked random numbers were used"

Allocation concealment (selection bias)Low risk"to assign the type of surgery, which was written on a card sealed in a completely opaque envelope. Envelopes were drawn randomly by the senior duty nurse in the operating department"

Blinding (performance bias and detection bias)
All outcomes
High risk"All patients were assessed by the treating team approximately 4 weeks postoperatively in the outpatient clinic"

Incomplete outcome data (attrition bias)
All outcomes
Low risk"At the end of 6 to 8 weeks after surgery, gastroscopy showed that the ulcers had healed for all patients", "Similar proportions of patients with laparoscopic repair (group 1 and 2) and open repair (groups 3 and 4) were available at follow-up (73% vs. 69%), respectively", "The data for patients who did not attend this first follow-up visit but who were called back for a check-up gastroscopy were not included in this analysis because there was a delay of at least 1 month in the recording of these data, which made it less reliable"

We believe that lost to follow up at four weeks for measuring returning to work do no affect results of important outcomes for this systematic review.

Selective reporting (reporting bias)Low riskAuthors reported a second study in 1998 that is consistent with data from this study.

Other biasUnclear riskIn surgical trials, there is always a bias related with learning curve for the new surgical methods. However, we believe this bias is not present in this trial because experience of surgeons is similar.

Siu 2002

Methods41 months, RCT parallel design, randomized using computer-generated random numbers by the block method, concealment of allocation using sealed envelopes, outcome assessment was made by assessors independent from the treating team for pain evaluation; by independent surgeons not blinded for discharge and by the treating surgeon not blinded for activity, work return evaluation and complications, intention-to-treat analysis, without losses to follow up


Participants121 patients (63 for the laparoscopic group and 58 for the open surgery group)
Sex: 98 men/ 23 women
Mean age: 53.8 to 56.1 years
Site of perforation: duodenum (93), pyloric-prepyloric (27), gastric (1)
Size of perforation: 4.7 to 5.2 mm
Age: patients older than 16 years old
Inclusion criteria:
Clinical diagnosis of perforated peptic ulcer made by the surgeon and confirmed at the operating room.
Exclusion criteria:
Gastric outlet obstruction
Bleeding ulcer
Previous abdominal operations
Clinically sealed perforation.
Severity assessed by ASA classification and Boey risk factors scale. 81% of patients classified as ASA I and II and 95% as Boey risk scale 0 and 1 (good prognosis).


InterventionsIntravenous cefuroxime 750 mg was given at the time of induction and continued for 5 days.
For postoperative analgesia, patients were prescribed pethidine 1 mg/kg every 4 hours as required.
Upper midline incisions were made in patients assigned to open repair. Perforations were repaired with the Cellan-Jones method.
For laparoscopic repair, pneumoperitoneum was established at 15 mm Hg, and three trocars were introduced and the ulcer was sutured with a piece of omentum and non-absorbable suture.
The number of participating surgeons, the number of cases previously operated by the surgeon and the number of patients operated by each surgeon was not reported.


OutcomesComplications
Analgesic use
Time of nasogastric aspiration
Time of intravenous fluid maintenance
Pain assessed with Visual Analogue Scale
Conversion rate for laparoscopic group
Operation time
Time to resume oral diet
Length of hospital stay


NotesSample size was calculated using the analgesic dose data in a previous study by the authors.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low risk"Randomization was performed after the decision was made for surgery; it took place in the operating room control room by a person not otherwise involved in the clinical setting", "computer-generated random numbers"

Allocation concealment (selection bias)Low risk"Randomization was undertaken by consecutively numbered opaque sealed envelopes containing the treatment options"

Blinding (performance bias and detection bias)
All outcomes
High risk"An independent assessor visited every patient in the morning to record the clinical progress, analgesic requirements, and pain score", "Patients were assessed by independent surgeons for discharge if they could tolerate a normal diet, could fully ambulate, and required only oral analgesics. Both the independent assessor and in-charge surgeons were not blinded with respect to study groups."

Blinding probably do not affect the assessment of hard outcomes as surgical complications, but it is possible that length of stay and pain assessment could be biased by non blinding evaluation of outcomes.

Incomplete outcome data (attrition bias)
All outcomes
Low riskThere were no losses to follow up

Selective reporting (reporting bias)Unclear riskAlthough there is no other information in the report of the trial, analysis of the article offers enough information to assume that any bias due to selective outcome reporting should not greatly affect the results.

Other biasUnclear riskIn surgical trials, there is always a bias related with learning curve for the new surgical methods. However, we believe this bias is not present in this trial because experience of surgeons is similar.

 
Characteristics of excluded studies [ordered by study ID]

StudyReason for exclusion

Bergamaschi 2000Prospective non-randomized clinical trial

Bhogal 2008Prospective non-randomized clinical trial

Katkhouda 1999Prospective non-randomized clinical trial

Lau 1998No data about septic complications

Lemaitre 2005Prospective non-randomized clinical trial

Mehendale 2002Prospective non-randomized clinical trial

Minutolo 2009Prospective non-randomized clinical trial

Nicolau 2008Prospective non-randomized clinical trial

Robertson 2000Prospective non-randomized clinical trial

Vettoretto 2005Prospective non-randomized clinical trial

 
Comparison 1. Laparoscopic surgery versus open surgery

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Septic abdominal complications (presence or absence)2214Odds Ratio (M-H, Fixed, 95% CI)0.66 [0.30, 1.47]

 2 Pulmonary complications (presence or absence)3315Odds Ratio (M-H, Random, 95% CI)0.52 [0.08, 3.55]

 3 Number of septic abdominal complications3315Odds Ratio (M-H, Fixed, 95% CI)0.60 [0.32, 1.15]

 4 Surgical site infection3315Odds Ratio (M-H, Random, 95% CI)0.28 [0.08, 1.00]

 5 Suture dehiscence3315Odds Ratio (M-H, Random, 95% CI)1.52 [0.29, 7.98]

 6 Postoperative ileus3315Odds Ratio (M-H, Fixed, 95% CI)0.54 [0.16, 1.80]

 7 Intra-abdominal abscess3315Odds Ratio (M-H, Fixed, 95% CI)1.15 [0.33, 4.03]

 8 Incisional hernia3315Odds Ratio (M-H, Fixed, 95% CI)0.93 [0.21, 4.15]

 9 Mortality3315Odds Ratio (M-H, Fixed, 95% CI)0.57 [0.18, 1.78]

 10 Number of reoperations2214Odds Ratio (M-H, Fixed, 95% CI)1.89 [0.46, 7.71]

 11 Operative time2214Mean Difference (IV, Random, 95% CI)14.62 [-35.25, 64.49]

 
Summary of findings for the main comparison. Laparoscopic surgery versus open surgery for perforated peptic ulcer disease

Laparoscopic surgery versus open surgery for perforated peptic ulcer disease

Patient or population: patients with perforated peptic ulcer disease
Settings: hospitalized patients from developed countries and availability of laparoscopy equipment
Intervention: laparoscopic surgery versus open surgery

OutcomesIllustrative comparative risks* (95% CI)Relative effect
(95% CI)
No of Participants
(studies)
Quality of the evidence
(GRADE)
Comments

Assumed riskCorresponding risk

ControlLaparoscopic surgery versus open surgery

Septic abdominal complications (presence or absence)
Clinical definition
Follow-up: 30 to 60 days
155 per 1000108 per 1000
(52 to 213)
OR 0.66
(0.3 to 1.47)
214
(2 studies)
⊕⊕⊝⊝
low1,2

Pulmonary complications (presence or absence)
Follow-up: 30 to 60 days
86 per 100046 per 1000
(7 to 249)
OR 0.52
(0.08 to 3.55)
315
(3 studies)
⊕⊕⊝⊝
low

Surgical site infection
Follow-up: 30 to 60 days
72 per 100021 per 1000
(6 to 72)
OR 0.28
(0.08 to 1)
315
(3 studies)
⊕⊕⊕⊝
moderate3

Suture dehiscence
Follow-up: 30 to 60 days
13 per 100020 per 1000
(4 to 96)
OR 1.52
(0.29 to 7.98)
315
(3 studies)
⊕⊕⊝⊝
low3

Postoperative ileus
Follow-up: 30 to 60 days
Study populationOR 0.54
(0.16 to 1.8)
315
(3 studies)
⊕⊕⊝⊝
low4,5

46 per 100025 per 1000
(8 to 80)

Moderate

35 per 100019 per 1000
(6 to 61)

Intra-abdominal abscess
Follow-up: 30 to 60 days
20 per 100023 per 1000
(7 to 75)
OR 1.15
(0.33 to 4.03)
315
(3 studies)
⊕⊝⊝⊝
very low5,6,7

Operative time
Follow-up: 30 to 60 days
The mean operative time in the control groups was
minutes
The mean operative time in the intervention groups was
14.62 higher
(35.25 lower to 64.49 higher)
214
(2 studies)
⊕⊝⊝⊝
very low7,8

*The basis for the assumed risk (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).
CI: Confidence interval; OR: Odds ratio;

GRADE Working Group grades of evidence
High quality: Further research is very unlikely to change our confidence in the estimate of effect.
Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
Very low quality: We are very uncertain about the estimate.

 1 Imprecision is probably because the small sample size of the studies and the lack of reporting form the largest one.
2 There are only three RCTs, all with positive results. Two were from the same city in China. There are no reports from other developed or undeveloped countries where other types of laparoscopic procedures are currently undertaken.
3 For suture dehiscence there are too few events to consider the results precise.
4 The measurement of postoperative ileus is subjective and heterogeneous between groups.
5 The multicenter trial showed no intra-abdominal abscesses. This can be explained because it is the last one published, where the training curve could be already reached.
6 Former trials showed an increase in intra-abdominal abscesses in comparison with the last one. Data are very different between trials.
7 There are only three RCT, all with positive results. Two were from the same city in China. There is no report from other developed or undeveloped countries where other types of laparoscopic procedures are currently undertaken.
8 The operative time has a very large confidence interval that could be explained by the lack of completion of the training curve in the former trials.
 
Table 1. Measures reported in non-parametric form

VariableStudyLaparoscopic groupOpen surgery groupP value

Nasogastric aspiration time (median and range)Bertleff 20092 (3.0) IQR3 (1.3) IQR0.33

Siu 20023 (2-33)3(1-8)0.28

Lau 19962 (1-4)/ 3 (2-1)2 (1-13)/ 3(1-17)No significant (P value not reported)

Time to return to oral dietSiu 20024 (3-35)5 (3-24)0.06

Lau 19964 (3-7)/ 4 (2-11)4 (3-16)/ 4 (3-19)No significant (P value not reported)

Length of stayBertleff 20096.5 (9.3) IQR8 (7.3) IQR0.23

Siu 20026 (4-35)7 (4-39)0.004

Lau 19965 (3-20)/ 6 (3-11)5 (3-19)/ 5 (2-21)No significant (P value not reported)

Analgesic dosesSiu 20020 (0-11)6 (1-30)<0.001

Lau 19961 (0-12)/ 2 (0-17)3 (0-10)/ 4 (1-9)0.03

Bertleff 20091 (1.25) median days of analgesics1 (1.0) median days of analgesics0.007